Scorpion venom: pharmacological analysis and its applications
Keywords:
Scorpion venom, Envenomation, Neurotoxins, Ion channel blockers, Anticancer peptide, Antivenom
Abstract
Scorpions belong to class: Arachnida, order: Scorpionida represented now by approximately 1500 species. These are one of the most ancient group of the animals on the earth conserving their morphology almost unaltered and are the most successful inhabitants of the earth. Scorpions when stimulated secrete venom which is a cocktail of variable concentration of neurotoxins, cardiotoxins, nephrotoxins, hemolytic toxins, phosphodiesterases, phospholipases, hyaluronidase, glucosaminoglycans, histamine, seratonin, tryptophan and cytokine releasers. According to an estimate, frequency of deaths caused by scorpion sting is higher in comparison to that of caused by snake-bite. Almost all of these lethal scorpions except Hemiscorpious species belong to scorpion family Buthidae comprising 500 species. Scorpion venoms show variable reactions in envenomated patients. However, closer the phylogenic relationship among the scorpions, more similar the immunological properties. Furthermore, various constituents of venom may act directly or indirectly and individually or synergistically to exert their effects. Scorpion stings cause a wide range of conditions from severe local skin reactions to neurologic, respiratory and cardiovascular collapse. Lethal members of Buthidae family include Buthus, Parabuthus, Mesobuthus, Tityus, Leiurus, Androctonus and Centruroides. Besides their lethal properties, scorpion venoms have some unique properties beneficial to mankind. These contain anti-insect, antimicrobial and anticancer properties and thus, can play a key role in the insect pest management programmes, treatment of microbial infection and in the treatment of various cancer types.
Downloads
Download data is not yet available.
References
1. Warrel DA. WHO/SEARO Guidelines for the clinical management of snake bites in the South East Asian regions. J Trop Med Pub Hlth. 1999; 30: 1-85.
2. Briggs DEG. Scorpion takes to the water. Nature. 1987; 326: 645-646.
3. Lourenco WR. Diversity and endenism in tropical versus temperate scorpion communities. Biogeogra-phica. 1994; 70: 155-160.
4. Rochat H, Bernard P, Couraud F. Scorpion toxins: chemistry and mode of action. In: Adv. Cyto-pharmacol. Ceccarelli F, ed. New York: Raven, 1979: 325-334.
5. Zlotkin E, Eistan M, Bindokas VP, Adams ME, Moyer M, Burkhart W, Fowler E. Functional duality and structural uniqueness of depressant insect selective neurotoxins. Biochem. 1991; 30: 4814-4821.
6. Gordon D, Maskowitz H, Eitan M, Warner C, Catteral, WA, Zlotkin E. Localization of receptor sites for insect selective toxins on Na+ channels by site directed antibodies. Biochem. 1992; 31: 7622-7628.
7. Zlotkin E. In: Athropods venoms. Bettini S, ed. Springer, New York, 1978: 317-369.
8. Inceoglu B, Lango J, Jing J, Chen L, Doymaz F, Pessah IN, Hammock BD. One scorpion, two venoms: Prevenom of Parabuthus transvaalis acts as an alternative type of venom with distinct mechanism of action. Proc Natl Acad Sci. 2003; 100: 922-927.
9. Corzo G, Escoubas P, Villegas E, Barnham KJ, He W, Norton RS, Nakazima T. Characterization of unique amphipathic antimicrobial peptides from the venom of the scorpion Pandinus imperator. Biochem J. 2001; 359: 35-45.
10. Turkov M, Rashi S, Zilberberg N, Gordon D, Ben Khalifa R, et al. In vitro folding and functional analysis of anti-insect selective scorpion depressant neurotoxin produced in E. coli. Proc Express Purific. 1997; 9: 123-131.
11. Balozet L. Venomous invertebrates. In: Venomous animals and their venoms. Vol. 3, Bucherl W, Buckley EE, eds. Academic New York. 1971: 349-371.
12. Keegan HL. Scorpions of medical importance. University Press of Pississippi Jackson. 1980: 43.
13. Brownell P, Polis G. Scorpion biology and research. Oxford University Press, New York, 2001: 3-13.
14. Polis G. The biology of scorpions. Stanford University Press, Stanford, 1990: 247-193.
15. Possani LD, Becerril B, Delepierre M, Tytgat J. Scorpion toxin specific for Na+ channel. Eur J Biochem. 1999; 264: 287-300.
16. Becceril B, Marangoni S, Possani LD. Toxin and genes isolated from the scorpion of the genus Tityus: a review. Toxicon. 1997; 35: 821-835.
17. Nakagawa Y, Lee YM, Lehmberg E, Herrmann R, Maskowitz H, Jones AD, Hammock BD. Antiscorpion toxin 5 (AaIT5) from Androctonus australis. Eur J Biochem. 1997; 246: 496-501.
18. Murugesan S, Murthy RKK, Noronha OPD, Samuel AM. Tc99m-scorpion venom: labeling, biodistri-bution and scintimaging. J Venom Anim Toxin. 1999; 5: 35-46.
19. Ismail M. The scorpion-envenoming syndrome. Toxicon. 1995; 33: 825-858.
20. Albert D, Rama MB, Karen W, Eddie C. Expression and secretion of a functional scorpion insecticidal toxin in cultured mouse cells. Biotechnol. 1990; 8: 339-342.
21. Stewart LMD, Hirst M, Freber ML, Merryweather AT, Clayley PJ, Posse RD. Construction of an improved baculovirus insecticide containing an insect specific toxin gene. Nature. 1991; 352: 85-88.
22. Mc Cutchen BF, Hammock BD. Recombinant baculovirus expressing an insect-selective neuro-toxin. In: Natural and engineered pest management agent. Hedin PA, Menn JJ, eds. Hallingworth RM, 1994: 348-367.
23. Pelhate M, Stankiewicz M, Ben Khalifa R. Anti-insect scorpion toxins: historical account, activities and prospects. CR Seances Soc Biol Fil. 1998; 192: 463-484.
24. Karbat I, Frolow F, Froy O, Gilles N, Cohen L, Turkov M, et al. Molecular basis of the high insecticidal potency of scorpion α toxins. J Biol Chem. 2004; 279: 31679-31686.
25. Gurevitz M, Karbat I, Cohen L, Ilan N, Kahn R, Turkov M, et al. The insecticidal potential of scorpion β-toxins. Toxicon. 2007; 49: 473-489.
26. Gordon D, Karbat I, Ilan N, Cohen L, Kahn R, Gilles N, et al. The differential preference of scorpion α-toxins for insect or mammalian sodium channels: implications for improved insect control. Toxicon. 2007; 49: 452-472.
27. Pelhate M, Zlotkin E. Action of insect toxin and other toxins derived from the venom of the scorpion Androctonus australis on isolated giant axons of the cockroach (Periplanata americana). J Exp Biol. 1982; 97: 67-77.
28. Ben Khalifa R, Stankiewics M, Lapied B, Turkov M, Zilberberg N, Gurevitz M, Pelhate M. Refined electrophysiological analysis suggests that a depressant toxin is a sodium channel opener rather than a blocker. Life Sci. 1997; 61: 819-830.
29. Wang GK, Strichartz GR. Purification and physiological characterization of neurotoxins from the venoms of the scorpion Centruroides sculpturatus and Leiurus quinquestriatus. Mol Pharmacol. 1983; 23: 519-533.
30. Bontems F, Roumestand C, Gilquin B, Menez A, Toma F. Refined structure of charybdotoxin: common motifs in scorpion toxins and insect defensins. Science. 1991; 254: 1521-1523.
31. Crest M, Jacquet G, Gola M, Zerreouk H, Benslimane A, Rochat H, et al. Kaliotoxin, a novel peptidyl inhibitor of neuronal 13 K-type Ca++-activated K+ channel characterized from Androctonus mauretanicus mauretanicus venom. J Biol Chem. 1992; 267: 1640-1647.
32. Zlotkin A, Fishman Y, Elazar M. AaIT: from neurotoxin to insecticide. Biochiemie. 2000; 82: 869-881.
33. Higgs S, Olson KE, Klimowski L, Powers AM, Carlson JO, Possee RD, Beaty BJ. Mosquito sensitivity to a scorpion neurotoxin expressed using an infectious Snindbis virus vector. Insect Mol Biol. 1995; 4: 97-103.
34. Loret EP, Martin-Eauclaire MF, Mansuelle P, Sampieri F, Granier C, Rochat H. An anti-insect toxin purified from the scorpion Androctonus astralis Hector also acts on the α and β sites of the mammalian sodium channels sequence and circular dichroism study. Biochem. 1991; 30: 633-640.
35. Eitan M, Fowler E, Herrmann R, Duval A, Pelhate M, Zlotkin E. A scorpion venom neurotoxin paralytic to insects that affects sodium current inactivation: purification, primary structure and mode of action. Biochem. 1990; 29: 5941-5947.
36. Krimm I, Gilles N, Sautire P, Stankiewicz M, Pelhate M, Gordon D, Lancelin JM. NMR structures and activity of a novel α-like toxin from the scorpion Leiurus quinquestriatus hebraeus. J Mol Biol. 1999; 285: 1749-1763.
37. Dhawan R, Joseph S, Sethi A, Lala AK. Purification and characterization of a short insect toxin from the venom of the scorpion Buthus tamulus. FEBS Lett. 2003; 528: 261-266.
38. Gawade SP. Excitatory effects of Buthus C56 Drosophila on larval neuromuscular junction. J Venom Anim Toxin Incl Trop Dis. 2003; 9(1): 65-75.
39. Gershburg E, Stockholm D, Froy O, Rashi S, Gurevitz M, Chejanovsky N. Baculovirus mediated expression of a scorpion depressant toxin improve the insecticidal efficacy achieved with excitatory toxin. FEBS Lett. 1998; 422: 132-136.
40. Chhatwal GS, Habbermann E. Neurotoxins, protease inhibitors and histamine releasers in the venom of the red scorpion (Buthus tamulus): isolation and partial characterization. Toxicon. 1981; 19: 807-823.
41. Lala K, Narayanan P. Purification, N-terminal sequence and structural characterization of a toxin protein from the Indian scorpion venom, Buthus tamulus. Toxicon. 1994; 32: 325-338.
42. Wudayagiri R, Inceoglu B, Herrmann R, Choudhary MD, Hammock BD. Isolation and characterization of a novel lepidopteran-selective toxin from the venom of the South Indian scorpion, Mesobuthus tamulus. BMC Biochem. 2001; 2: 11-16.
43. Steiner H, Hultmark D, Engstrom A, Bennich H, Boman HG. Sequence and specificity of two antimicrobial proteins involved in insect immunity. Nature. 1981; 292: 246-248.
44. Bulet P, Cociancich S, Dimarcq JL, Lambert J, Reichhart JM, Hoffmann D, et al. Insect immunity: Isolation from a coleopteran insect of novel inducible antibacterial peptide and of new members of the insect defensin family. J Biol Chem. 1991; 266: 24520-24525.
45. Nicolas P, Mor A. Peptides as weapons against microorganisms in the chemical defense system of vertebrate. Annu Rev Microbiol. 1995; 49: 277-304.
46. Hoffman JA, Kafatos FC, Janeway CA, Ezekowitz RA. Phylogenetic perspective in innate immunity. Science. 1999; 284: 1313-1318.
47. Fennel JF, Shipman WH, Cole LJ. Antibacterial action of melittin, a polypeptide from bee venom. Proc Soc Exp Biol Med. 1968; 127: 707-710.
48. Krishnakumari V, Nagaraj R. Antimicrobial and hemolytic activities of crabrolin, a 13-residue peptide from the venom of the European hornet, Vespa crabro, and its analogs. J Pept Res. 1997; 50: 88-93.
49. Yan L, Adams ME. Lycotoxins, antimicrobial peptides from the venom of the wolf spider Lycosa carolinensis. J Biol Chem. 1998; 273: 2059-2066.
50. Hwang PM, Vogel HJ. Structure-function relation-ship of antimicrobial peptides. Biochem Cell Biol. 1998; 76: 235-246.
51. Larrick JW, Wright SC. Cationic antimicrobial peptides. Drug Future. 1996; 21: 41-48.
52. Hancock RE, Lehrer R. Cationic peptides: a new source of antibiotics. Trends Biotechnol. 1998; 16: 82-88.
53. Zasloff M. Antimicrobial peptides of multicellular organisms. Nature. 2002; 415(6870): 389-395.
54. Hancock RE, Sahl HG. Antimicrobial and host-defense peptides as new anti infective therapeutic strategie. Nature Biotechnol. 2007; 24(12): 1551-1557.
55. Dai L, Yasuda A, Naoki H, Corzo G, Andriantsi-ferana M, Nakajima T. IsCT, a novel cytotoxic linear peptide from scorpion Opisthacanthus madagascariensis. Biochem Biophys Res Commun. 2001; 286: 820-825.
56. Arpornsuwan T, Buasakul B, Jaresitthikunchai J, Roytrakul S. Potent and rapid antigonococcal activity of the venom peptide BmKn2 and its derivatives against different Maldi biotype of multidrug-resistant Neisseria gonorrhoeae. Peptides. 2014; 53: 315-320.
57. Epad RM, Vogel HJ. Diversity of antimicrobial peptides and their mechanism of action. Biochim Biophys Acta. 1999; 1462: 11-28.
58. Mousli M, Bueb JL, Bronner C, Rouot B, Landry Y. G-protein activation: a receptor independent mode of action for cationic amphipathic neuropeptides and venom peptides. Trends Pharmacol Sci. 1990; 11: 358-362.
59. Bulet P, Hetru C, Dimarcq J, Hoffmann D. Antimicrobial peptides in insects: structure and function. Dev Comp Immunol. 1999; 23: 329-344.
60. Cociancich S, Goyffon M, Bontems F, Bulet P, Bouet F, Menez A, Hoffmann J. Purification and characterization of a scorpion defensin, a 4 kD antimicrobial peptide presenting structural similarities with insect defensins and scorpion toxins. Biochem Biophys Res Commun. 1993; 194: 17-22.
61. Ehret-Sabatier L, Loew D, Goyffon M, Fehlbaum P, Hoffman JA, Van Dorsselaer A, Bulet P. Characterization of novel cyteine rich antimicrobial peptides from scorpion blood. Biochem Mol Biol. 1996; 271: 29537-29544.
62. Hetru C, Letellier L, Oren Z, Hoffmann JA, Shai Y. Androctonin, a hydrophilic disulphide-bridged non-haemolytic anti-microbial peptide: a plausible mode of action. Biochem J. 2000; 345: 653-664.
63. Moerman L, Bosteels S, Noppe W, Willems J, Clynen E, Schoofs L. Antibacterial and antifungal properties of alpha-helical, cationic peptides in the venom of scorpions from southern Africa. Eur J Biochem. 2002; 269: 4799-4810.
64. Powers JP, Hancock RE. The relationship between peptide structure and antibacterial activity. Peptides. 2003; 24: 1681-1691.
65. Ramírez-Carreto S, Jiménez-Vargas JM, Rivas-Santiago B, Corzo G, Possani LD, Becerril B. Peptides from the scorpion Vaejovis punctatus with broad antimicrobial activity. Peptides. 2015; 73: 51-59.
66. Bao A, Zhong J, Zeng XC, Nie Y, Zhang L, Peng ZF. A novel cysteinefree venom peptide with strong antimicrobial activity against antibioticsresistant pathogens from the scorpion Opistophthalmus glabrifrons. J Pept Sci. 2015; 21: 758-764.
67. de Melo ET, Estrela AB, Santos EC, Machado PR, Farias KJ, Torres TM. Structural characterization of a novel peptide with antimicrobial activity from the venom gland of the scorpion Tityus stigmurus: stigmurin. Peptides. 2015; 68: 3-10.
68. Bandyopadhyay S, Junjie RL, Lim B, Sanjeev R, Xin WY, Yee CK. Solution structures and model membrane interactions of Ctriporin, an anti-methicillin-resistant Staphylococcus aureus peptide from scorpion venom. Biopolymers. 2014; 101: 1143-1153.
69. Li Z, Xu X, Meng L, Zhang Q, Cao L, Li W. Hp1404, a new antimicrobial peptide from the scorpion Heterometrus petersii. PLoS One. 2014; 9: 97539.
70. Conde R, Zamudio F Z, Rodriguez MH, Possani LD. Scorpine, an antimalarial and antibacterial agent purified from scorpion venom. FEBS Lett. 2000; 471: 165-168.
71. Torres-Larios A, Gurrola GB, Zamudio FZ, Possani LD. Hadrurin, a new antimicrobial peptide from the venom of the scorpion Hadrurus aztecus. Eur J Biochem. 2000; 267: 5023-5031.
72. Verdonck F, Bosteel S, Desmet J, Moerman L, Noppe W, Willems J, et al. A novel class of pore forming peptides in the venom of the Parabuthus schlechteri Purcell (Scorpions: Buthidae). Cinebasia. 2000; 16: 247-260.
73. White SH, Wimley WC, Selsted ME. Structure, function and membrane integration of defensins. Curr Opin Struct Biol. 1995; 5: 521-527.
74. Matsuzaki K. Magainins as paradigm for the mode of action of pore forming peptides. Biochim Biophys Acta. 1998; 1376: 391-400.
75. Du Q, Hou X, Wang L, Zhang Y, Xi X, Wang H, et al. AaeAP1 and AaeAP2: novel antimicrobial peptides from the venom of the scorpion, Androctonus aeneas: structural characterisation, molecular cloning of biosynthetic precursor-encoding cDNAs and engineering of analogues with enhanced antimicrobial and anticancer activities. Toxins. 2015; 7: 219-237
76. Al-Asmari AK, Alamri MA, Almasoudi AS, Abbasmanthiri R, Mahfoud M. Evaluation of the in vitro antimicrobial activity of selected Saudi scorpion venoms tested against multidrug-resistant microorganisms. J Global Antimicrob Resist. 2007; 10: 14-18.
77. Sikora K. Cancer survival in Britain in poorer than that of her comparable European neighbours. BMJ. 1999; 319: 461-462.
78. De Carvalho DD, Schmitmeier S, Novello JC, Markland FS. Effect of BJcuL (a lectin from the venom of the snake Bothropos jararacussu) on adhesion and growth of tumor and endothelial cells. Toxicon. 2001; 39: 1471-1476.
79. Chiang HS, Swaim MW, Huang TF. Characterization of platelet aggregation induced by human breast carcinoma and its inhibition by snake venom peptide, trigramin and rhodostomin. Breast Cancer Res Treat. 1995; 33: 225-235.
80. Maristela P, Daniela DC, Antonio RG, Delwood CC. The effect of lectin from the venom of the snake, Bathrops jararacussu, on tumor cell proliferation. Anticancer Res. 1999; 19: 4023-4026.
81. Zhou Q, Sherwin RP, Parrish C, Richters V, Groshen SG, Tsao-Wei D, Markland FS. Contortrostatin, a dimmer disintegrin from Agkistrodon contortrix contortrix, inhibits breast cancer progression. Breast Cancer Res Treat. 2000; 61: 249-260.
82. Yarom R, Braun K. Myocardiopathology following scorpion venom injection. Isr J Med Sci. 1969; 5: 849-852.
83. Tarasiuk A, Khvatskin S, Sofer S. Effect of antivenom serotherapy on haemodynamic patho-physiology in dogs injected with of Leiurus quinquestriatus scorpion venom. Toxicon. 1998; 36: 963-971.
84. Omran MAA. In vitro anticancer effect of scorpion Leiurus quinquestriatus and Egyptian cobra venom on human breast and prostate cancer cell lines. J Med Sci. 2003; 3: 66-86.
85. Bruses JL, Capaso J, Katz E, Pilar G. Specific in vitro biological activities of snake venom myotoxins. J Neurochem. 1993; 60: 1030-1042.
86. Deshane J, Garner CC, Sontheimer H. Chlorotoxin inhibits glioma invasion via matrix metallo-proteinase-2. J Biol Chem. 2003; 278: 4135-4144.
87. Jager H, Dreker T, Buck A, Giehl K, Gress T, Grissmer S. Blockage of intermediate-conductance Ca2+ activated K+ channels inhibit human pancreatic cancer cell growth in vitro. Mol Pharmacol. 2004; 65: 630-638.
88. Gupta SD, Gomes AN, Debnath A, Saha A, Gomes AP. Apoptosis induction in human leukemic cells by a novel protein Bengalin, isolated from Indian black scorpion venom: through mitochondrial pathway and inhibition of heat shock proteins. Chem Biol Interact. 2010; 183: 293-303.
89. Al-Asmari AK, Islam M, Al-Zahrani AM. In vitro analysis of the anticancer properties of scorpion venom in colorectal and breast cancer cell lines. Oncol Lett. 2016; 2: 1256-1262.
90. Gupta SD, Debnath A, Saha A, Giri B, Tripathi G, Vedasiromoni JR, et al. Indian black scorpion (Heterometrus bengalensis Koch) venom induced antiproliferative and apoptogenic activity against human leukemic cell lines U937 and K562. Leuk Res. 2007; 31: 817-825.
91. Zhang YY, Wu LC, Wang ZP, Wang ZX, Jia Q, Jiang GS, Zhang WD. Antiproliferation effect of polypeptide extracted from scorpion venom on human prostate cancer cells in vitro. J Clin Med Res. 2009; 1: 24-31.
92. Zargan J, Sajad M, Umar S, Naime M, Ali S, Khan HA. Scorpion (Androctonus crassicauda) venom limits growth of transformed cells (SH-SY5Y and MCF-7) by cytotoxicity and cell cycle arrest. Exp Mol Pathol. 2011; 91: 447-454.
93. Almaaytah A, Albalas Q. Scorpion venom peptides with no disulfide bridges: a review. Peptides. 2014; 51: 35-45.
94. Roger JC, Qu Y, Tanada TN, Scheur T, Catterall WA. Molecular determinants of high affinity binding of alpha-scorpion toxin and Sea anemone toxin in S3-S4 extracellular loop in domain IV of the Na+ channel alpha-subunit. J Biol Chem. 1996; 271: 15950-15962.
95. Cestele S, Caterall WA. Molecular mechanism of neurotoxic action on voltage-gated sodium channels. Biochemie (Paris). 2000; 82: 883-892.
96. Martin-Eauclaire MF, Couraud F. Scorpion neurotoxins: effects and mechanism. In: Hand book of neurotoxicology. Chang LW, Dyer RS, eds Marcel Dekker New York, 1995: 683-716.
97. Gwee MC, Nirthanan S, Khoo HE, Gopalkrishnakone P, Kini RM, Cheah LS. Autonomic effect of some scorpion venoms and toxins. Clin Exp Pharmacol Physiol. 2002; 29: 795-801.
98. Couraud F, Jover E, Dubois JM, Rochat H. Two types of scorpion toxin receptor sites, one related to the activation, the other to the inactivation of the action potential Na+ channel. Toxicon. 1982; 20: 9-16.
99. Couto AS, Moreaes-Santos T, Azevedo AD, Almeida AP, Freire-Maia L. Effect of Tsgamma, purified from Tityus serrulatus scorpion venom, on the isolated rat atria. Toxicon. 1992; 30: 339-343.
100. Yatani A, Kirsh GE, Possani LD, Brown AM. Effects of New World ecorpion toxins on single channel and whole cell cardiac sodium currents. Am J Physiol. 1988; 254: 443-451.
101. Romi-Labrun R, Martin-Eauclaire MF, Escoubas P, Wu FQ, Lebrun B, Hisada M, Nakazima T. Characterization of four toxins from Buthus martensi scorpion venom, which act on apaminesensitive Ca++-activated K+ channels. Eur J Biochem. 1997; 245: 457-464.
102. D’ Ajellow A, Zlotkin E, Miranda F, Lissitzky. The effect of the scorpion venom and pure toxin on the cockroach nervous system. Toxicon. 1972; 10: 399-404.
103. Miller C, Moczydlowski E, Latore R, Philips M. Charybdotoxin, a potent inhibitor of single Ca++- activated K+ channels from mammalian skeleton muscle. Nature. 1985; 313: 316-318.
104. Miller C. The charybdotoxin family of K+ channel blocking peptides. Neurons. 1995; 15: 5-10.
105. Hoffmann JA, Hetru C. Insect defensins: inducible antimicrobial peptides. Immunol Today. 1992; 13: 411-415.
106. Bablito J, Jover E, Couraud F. Activation of the voltage sensitive sodium channel by a β-scorpion toxin in the rat brain nerve ending particles. J Neurochem. 1986; 37: 1763-1770.
107. Garcia CM, Leonard RJ, Novik J, Stevens SP, Schmalhofer W. Purification, characterization and biosynthesis of margaritatus venom that selectively inhibits voltage dependent potassium channel. J Biol Chem. 1993; 689(25): 18866-18874.
108. Lin CS, Boltz RC, Blake JT, Nguyen M, Talento A, Fischer PA, et al. Volatge-gated potassium channels regulate calcium dependent pathways involved in human T-lymphocytes activation. J Exp Med. 1993; 177: 637-645.
109. Bednarek MA, Bugianesi RM, Leonard RJ, Felix JP. Chemical synthesis and structurefunction studies of margtoxin, a potent inhibitor of voltage-dependent potassium channel in human T-lymphocytes. Biocem Biophys Res Commun. 1994; 198: 619-625.
110. Garcia ML, Garcia-Calvo M, Hidalgo P, Lee A, Mac Kinnon R. Purification and characterization of three inhibitors of voltage dependent K+ channels from Leiurus quinquestriatus var. hebraeus venom. Biochem. 1994; 33: 6834-6839.
111. Martins JC, Van JC, Borremanus FA. Determination of the three-dimensional solution structure of the scyllatoxin by 1H NMR. J Mol Biol. 1995; 253: 590-603.
112. Pappone PA, Chalan MD. Pandinus imperator scorpion venom blocks voltage-gated K+ channel in nerve fibers. J Neurosci. 1987; 7: 3300-3305.
113. Sands SB, Lewis RS, Chalan MD. Charbdotoxin blocks voltage-gated K+ channel in human and murine T-lymphocytes. J Gen Physiol. 1989; 93: 1061-1074.
114. Valdivia H, Kirby MS, Lederer WJ, Coronado R. Scorpion toxins targated against the sarcoplasmic reticulum Ca++ release channel of skeletal and cardiac muscle. Proc Nat Acad Sci USA. 1992; 89: 12185-12189.
115. el Havek R, Lokuta AJ, Arevalo C, Valdivia HH. Peptide probe of ryanodine receptor function. Imperatoxin A, a peptide from the venom of the scorpion Pandinus imperator, selectively activates skeletaltype ryanodine receptor isoforms. J Biol Chem. 1995; 270: 28696-28704.
116. Pappone PA, Lucero MT. Pandinus imperator scorpion venom blocks voltage gated potassium channels in GH3 cells. J Gen Physiol. 1988; 91: 817-833.
117. Galvez A, Gimenez-Gallego G, Ruben JP, Rov-Contancin L, Feigenbaun P, Kaczorowski GJ, Garcia ML. Purification and characterization of a unique peptidyl probe for the high conductance calcium-activated potassium channel from the venom of the scorpion Buthus tamulus. J Biol Chem. 1990; 265: 11083-11090.
118. Marangoni S, Ghiso J, Sampaio SV, Arantes EC, Giglio JR, Oliviera B, Frangione B. The complete amino acid sequence of toxin TsTX-VI isolated from the venom of the scorpion Tityus serrulatus. J Prot Chem. 1990; 9: 595-601.
119. Grishin EV, Korolkova YV, Kozlov KA, Lipkin AV, Nosyreva ED, Pluzhnikov KA, et al. Structure and function of potassium channel inhibitor from black scorpion venom. Pure Appl Chem. 1996; 68: 2105-2109.
120. More SS, Mirajkar KK, Gadag JR, Menon KS, Mathew MK. A novel Kv1.1 potassium channel-blocking toxin from the venom of Palamneus gravimanus (Indian black scorpion). J Venom Anim Toxin Incl Trop. 2005; 11(3): 315-335.
121. De Bin JA, Maggio JE, Strichartz GR (1993) Purification and characterization of chlorotoxin, a Clchannel ligand from the venom of the scorpion. Am J Physiol Cell Physiol 264:361-369.
122. Lippens G, Najib S, Wodak J, Tartar A. Sequential assignment and solution structure of chlorotoxin, a small peptide from scorpion that blocks chloride channel. Biochem. 1995; 34: 13-21.
123. Zamudio FZ, Conde R, Arevalo C, Becerril B, Martin BM, Valdivia HH, Possani LD. The mechanism of inhibition of ryanodine receptor channel by imperotoxin I, a heterodimeric protein from the scorpion Pandius imperator. J Biol Chem. 1997; 272: 11886-11894.
124. Zamudio FZ, Gurrola GB, Arvalo C, Sreekumar R, Walker JW, Valdivia HH, Possani LD. Primary structure and synthesis of imperotoxin A (Iptxa), a peptide activator of Ca++ release channels/rynodine receptors. FEBS Lett. 1997; 405: 385-389.
125. Chuang RSI, Jaffe H, Cribbs L, Perez-Reyes EJ, Stwartz KJ. Inhibition of T-type voltagegated calcium channels by a new scorpion toxin. Natl Neuro Sci. 1998; 1: 668-674.
126. Freire-Maia L, Pinto GI, Franco I. Mechanism of the cardiovascular effects produced by purified scorpion toxin in the rat. J Pharmacol Exp Ther. 1974; 188: 207-213.
127. Ismail M. The scorpion-envenoming syndrome. Toxicon. 1995; 33: 825-858.
128. Tarasiuk A, Janco J, Sofer S. Effect of scorpion venom on central and peripheral circulatory response in an open-chest dog model. Acta Physiol Scand. 1997; 161: 141-146.
129. Ismail M, Osmon OH, Gumma KA, Karrar MA. Some pharmacological studies with scorpion (Pandinus exitiallis) venom. Toxicon. 1974; 2: 75-82.
130. Almeida AP, Alpoim NC, Freire-Maia L. Effects of purified scorpion toxin (Tityus toxin) on the isolated guinea pig heart. Toxicon. 1982; 20: 855-865.
131. Moss J, Kajik T, Henery DP, Kopin IJ. Scorpion venom induced discharge of catecholamines accompanied by hypertension. Brain Res. 1973; 54: 381-385.
132. Freire-Maia L, Campos JA. Pathophysiology and treatment of scorpion poisoning. In: Ownby LC, Odel GV, eds. Natural toxins, characterizations, pharmacology and therapeutics. Pergamon Press Oxford, 1989: 139-159.
133. Tarasiuk A, Sofer S. Effect of adrenergic blockade and ligation of spleen vessels on haemodynamics of dogs injected with scorpion venom. Crit Care Med. 1999; 27: 365-372.
134. Sofer S. Scorpion envenomation. Int Care Med. 1995; 21: 627-628.
135. Ramchandran LK, Agrawal OP, Achyutan KE, Chudhary L, Vedasiromani JR, Ganguli DK. Fractionation and biological activities of the venom of the Indian scorpions Buthus tamulus and Heterometrus bengalensis. Ind J Biochem Biophys. 1986; 23: 355-358.
136. Russel FE. Toxic effects of animal toxins. In: Idaassen CD, Amdur MO, Doull J, eds. Toxicology basic science of poisons. 3rd edn, New York: Macmillan, 1986: 706-756.
137. Henriques MC, Gassinelli G, Diniz CR, Gomez MV. Effect of the venom of the scorpion Tityus serrulatus on adrenal gland catecholamines. Toxicon. 1968; 5: 175-179.
138. Radha Krishna Murthy K, Vakil AE. Elevation of plasma angiotensin level in dogs by Indian red scorpion (Buthus tamulus) venom and its reversal by administration of insulin and tolazoline. Indian J Med Res. 1988; 88: 376-379.
139. Margulis G, Sofer S, Zalstein E, Zucker N, Ilia R, Gueron M. Abnormal coronary perfusion in experimental scorpion envenomation. Toxicon. 1994; 32: 1675-1678.
140. Wang R, Moreau P, Deschamps A, de Champlain J, Sauve R, Foucart S, et al.Cardiovascular effects of Buthus martensi (Karsch) scorpion venom. Toxicon. 1994; 32: 191-200.
141. Amaral CFS, Lopes JA, Magalhaes RA, de Rezende NA. Electrocardiographic, enzymatic and echocardiographic evidence of myocardial damage after Tityus serrulatus scorpion poisoning. Am J Cardiol. 1991; 67: 655-657.
142. Abroug E, Ayari M, Nouria S, Gamra H, Boujdaria R, Elatrons S, et al. Assessment of left ventricular function in severe scorpion envenomation: combined haemodynamic and echodopller study. Int Care Med. 1995; 21: 629-635.
143. Gueron M, Adolf RJ, Grupp IL, Gabel M, Grupp G, Fowler NO. Haemodynamic and myocardial consequences of scorpion venom. Am J Cardiol. 1980; 45: 1979-1986.
144. Couture R, Harrisson M, Vianna RM, Cloutier F. Kinin receptors in pain and inflammations. Eur J Pharmacol. 2001; 429: 161-176.
145. Campbell DJ, Dixon B, Kladis A, Kemme M, Santmaria, JD. Activation of the kallikrein-kinin system by cardiopulmonary bypass in humans. Am J Physiol. 2001; 281: 1059-1070.
146. Gwee MC, Cheah LS, Nirthanan S, Gopalkri-shnakone P, Wang PT. Pre-junctional action of the venom from the Indian red scorpion Mesobuthus tamulus on adrenergic transmission in vitro. Toxicon. 1994; 32: 201-209.
147. Rowan EG, Vatanpour H, Furman BL, Harvey AL, Tanira MO, Gopalkrishnakone P. The effect of Indian red scorpion Buthus tamulus venom in in vivo and in vitro. Toxicon. 1992; 30: 1157-1164.
148. Murthy RKK, Medh JD, Dave BN, Vakil YE, Billimoria FR. Acute pancreatitis and reduction of H+ ion concentration in gastric secretions in experimental acute myocarditis produced by Indian red scorpion (Buthus tamulus) venom. Indian J Exp Biol. 1989; 27: 242-244.
149. Murthy RKK, Hossein Z. Increased osmotic fragility of red cells of incubation at 370C for 20 hours in dogs with acute myocarditis produced by scorpion (Buthus tamulus) venom. Indian J Exp Biol. 1986; 38: 206-210.
150. Murthy RKK, Anita AG, Dave BN, Billimoria FR. Erythrocyte Na+K+ATPase activity inhibition and increased red cell fragility in experimental myocarditis produced by red scorpion (Buthus tamulus) venom. Indian J Med Res. 1988; 88: 536-540.
151. Murthy RKK, Yeolekar ME. Electrocardiographic changes in acute myocarditis produced by the scorpion (Buthus tamulus) venom. Indian Heart J. 1986; 38: 206-210.
152. Murthy RKK, Hossein Z, Medh JD, Kudalkar JA, Yeolekar ME, Pandit SP, et al. Disseminated intravascular coagulation and disturbances in carbohydrate and fat metabolism in acute myocarditis produced by Indian red scorpion (Buthus tamulus) venom. Indian J Med Res. 1988; 87: 318-325.
153. Murthy RKK, Haghanzari L. The blood level of glucagon, cortisol, and insulin following the injection of venom by the scorpion (Mesobuthus tamulus, Pocock) in dogs. J Venom Anim Toxin. 1999 5: 200-219.
154. Murthy RKK, Zare A. Effect of Indian red scorpion (Mesobuthus tamulus concanesis, Pocock) venom on thyroxine and triiodothyronine in experimental acute myocarditis and its reversible by species-specific antinenom. Indian J Exp Biol. 1998; 36: 16-21.
155. Murthy RKK, Anita AG. Reduced insulin secretion in acute myocarditis produced by scorpion (Buthus tamulus). Indian Heart J. 1986; 38: 467-469.
156. Gwee MC, Nirthanan S, Khoo HE, Gopalkri-shnakone P, Kini RM, Cheah LS. Autonomic effect of some scorpion venoms and toxins. Clin Exp Pharmacol Physiol. 2002; 29: 795-801.
157. Murthy RKK, Zare A. The use of antivenin reverses hematological and osmotic fragility changes of erthrocytes caused by Indian red scorpion Mesobuthus tamulus concanesis, Pocock in experimental envenoming. J Venom Anim Toxins. 2001; 7: 113-138.
158. Freire-Maia L, Campos JA. On the treatment of the cardiovascular manifestations of scorpion envenomation. Toxicon. 1987; 25: 125-130.
159. Freire-Maia L, De Matos IM. Heparin or a PAF antagonist (BN-52021) prevents the acute pulmonary oedema induced by Tityus serrulatus scorpion venom on the rat. Toxicon. 1993; 31: 1207-1210.
160. Gueron M, Ovsyshcher I. What is the treatment for the cardiovascular manifestations of scorpion envenomation? Toxicon. 1987; 25: 121-124.
161. Best CH, Taylor NBA. Textbook in applied physiology of medical practice. Baltimore: Williams and Wilkins, 1967.
162. Pande SV, Mead JF. Inhibition of enzyme activities by free fatty acids. J Biol Chem. 1968; 243: 6180- 6186.
163. de Rezende NA, Dias MB, Campolina D, Chavez-Olortegui C, Diniz C, Amaral CFS. Efficacy of antivenom therapy for neutralizing venom antigen in patients stung by Tityus serrulatus scorpion. Am J Trop Med Hyg. 1995; 52: 277-280.
164. Omran MAA, Abdel-Rahman MS. Effect of the scorpion Leiurus quinquestriatus (H&E) venom on the clinical chemistry parameters of the rat. Toxicol Lett. 1992; 61: 99-109.
165. Ghalim N, El-Hafny B, Sebti F, Heikel J, Lezar N, Moustanir R, Benslimane A. Scorpion venom and serotherpy in Morocco. Am J Trop Med Hyg. 2000; 62: 277-283.
166. Sofer S, Shahak E, Gueron M. Scorpion envenomation and antivenom therapy. J Pediatr. 1994; 124: 973-978.
167. Balozet L. Scorpionism in the Old World. In: Bücherl W, Buckley E, eds. Venomous animals and their venoms. New York: Academic Express, 1971: 349-371.
168. Theakston RD, Warrell DA, Grifithis E. Report of a WHO workshop on the standardization and control of antivenoms. Toxicon. 2003; 41: 541-557.
169. Demagalhaes O. Scorpionism. J Trop Med Hyg. 1938; 41: 393-399.
170. Balozet L. Scorpion venoms and anti-scorpion serum. In: Venom. Buckley EE, Porges N, eds. Washington DC. Public. No. 44. Am Adv Sci. 1956.
171. Mohammed AH, Darwish MA, Honi Ayobe M. Immunological studies on scorpions (Leiurus quinquestriatus) antivenin. Toxicon. 1975; 13: 67-68.
172. Kapadia ZS, Master RWP, Rao SS. Immunological studies in telson extracts of Indian and Egyptian scorpion venom. Indian J Exp Biol. 1964; 2: 75-77.
173. Kankonakar RC, Kulakarni DG, Hulikavi CB. Preparation of a potent anti-scorpion venom serum against the venom of red scorpion (Buthus tamulus). J Postgrad Med. 1998; 44: 85-92.
174. Amaral CFS, Dias MB, Campolina D, Proietti FA, de Rezende NA. Childrens with adrenergic manifestation of envenomation after Tityus serrulatus scorpion sting are protected from early anaphylactic antivenom reaction. Toxicon. 1994; 32: 211-215.
175. Amaral CFS, de Rezende NA. Both cardiogenic and noncardiogenic factors are involved in the pathogenesis of pulmonary oedema after scorpion envenoming. Toxicon. 1997; 35: 997-998.
176. Gueron M, Marquilis G, Sofer S. Echocardiographic and radionucleid angiographic observations following scorpion envenomation by Leiurus quinquestriatus. Toxicon. 1990; 28: 1005-1009.
177. Devaux C, Fourquet P, Granier C. A conserved sequence region of scorpion toxin rendered immunogenic induces broadly cross-reactive, neutralizing antibodies. Eur J Biochem. 1996; 242(3): 727-735.
178. Espino-Solis GP, Riano-Umbarila L, Becerril B, Possani LD. Antidotes against venomous animals: state of the art and prospectives. J Proteomics. 2009; 72(2): 183-199.
179. Holliger PH, Hudson JP. Engineering antibody fragments and the rise of single domains. Nat Biotechnol. 2005; 23: 1126-1136.
180. Riaño-Umbarila L, Contreras-Ferrat G, Olamendi-Portugal T, Morelos-Juárez C, Corzo G, Possani LD, Becerril B. Exploiting cross-reactivity to neutralize two different scorpion venoms with one single chain antibody fragment. J Biol Chem. 2011; 286: 6143-6151.
181. Canul-Tec J-C, Riaño-Umbarila L, Rudinño-Pinera E, Becerril B, Possani LD, Torres-Larios A. Structural basis of neutralization of the major toxic component from the scorpion Centruroides noxius Hoffmann by a human-derived single chain antibody fragment. J Biol Chem. 2011; 286: 20892-20900.
182. Rodríguez-Rodríguez ER, Ledezma-Candanoza LM, Contreras-Ferrat LG, Olamendi-Portugal T, Possani LD, Becerril B, Riaño-Umbarila L. A single mutation in framework 2 of the heavy variable domain improves the properties of diabody and a related single-chain antibody. J Mol Biol. 2012; 423: 337-350.
2. Briggs DEG. Scorpion takes to the water. Nature. 1987; 326: 645-646.
3. Lourenco WR. Diversity and endenism in tropical versus temperate scorpion communities. Biogeogra-phica. 1994; 70: 155-160.
4. Rochat H, Bernard P, Couraud F. Scorpion toxins: chemistry and mode of action. In: Adv. Cyto-pharmacol. Ceccarelli F, ed. New York: Raven, 1979: 325-334.
5. Zlotkin E, Eistan M, Bindokas VP, Adams ME, Moyer M, Burkhart W, Fowler E. Functional duality and structural uniqueness of depressant insect selective neurotoxins. Biochem. 1991; 30: 4814-4821.
6. Gordon D, Maskowitz H, Eitan M, Warner C, Catteral, WA, Zlotkin E. Localization of receptor sites for insect selective toxins on Na+ channels by site directed antibodies. Biochem. 1992; 31: 7622-7628.
7. Zlotkin E. In: Athropods venoms. Bettini S, ed. Springer, New York, 1978: 317-369.
8. Inceoglu B, Lango J, Jing J, Chen L, Doymaz F, Pessah IN, Hammock BD. One scorpion, two venoms: Prevenom of Parabuthus transvaalis acts as an alternative type of venom with distinct mechanism of action. Proc Natl Acad Sci. 2003; 100: 922-927.
9. Corzo G, Escoubas P, Villegas E, Barnham KJ, He W, Norton RS, Nakazima T. Characterization of unique amphipathic antimicrobial peptides from the venom of the scorpion Pandinus imperator. Biochem J. 2001; 359: 35-45.
10. Turkov M, Rashi S, Zilberberg N, Gordon D, Ben Khalifa R, et al. In vitro folding and functional analysis of anti-insect selective scorpion depressant neurotoxin produced in E. coli. Proc Express Purific. 1997; 9: 123-131.
11. Balozet L. Venomous invertebrates. In: Venomous animals and their venoms. Vol. 3, Bucherl W, Buckley EE, eds. Academic New York. 1971: 349-371.
12. Keegan HL. Scorpions of medical importance. University Press of Pississippi Jackson. 1980: 43.
13. Brownell P, Polis G. Scorpion biology and research. Oxford University Press, New York, 2001: 3-13.
14. Polis G. The biology of scorpions. Stanford University Press, Stanford, 1990: 247-193.
15. Possani LD, Becerril B, Delepierre M, Tytgat J. Scorpion toxin specific for Na+ channel. Eur J Biochem. 1999; 264: 287-300.
16. Becceril B, Marangoni S, Possani LD. Toxin and genes isolated from the scorpion of the genus Tityus: a review. Toxicon. 1997; 35: 821-835.
17. Nakagawa Y, Lee YM, Lehmberg E, Herrmann R, Maskowitz H, Jones AD, Hammock BD. Antiscorpion toxin 5 (AaIT5) from Androctonus australis. Eur J Biochem. 1997; 246: 496-501.
18. Murugesan S, Murthy RKK, Noronha OPD, Samuel AM. Tc99m-scorpion venom: labeling, biodistri-bution and scintimaging. J Venom Anim Toxin. 1999; 5: 35-46.
19. Ismail M. The scorpion-envenoming syndrome. Toxicon. 1995; 33: 825-858.
20. Albert D, Rama MB, Karen W, Eddie C. Expression and secretion of a functional scorpion insecticidal toxin in cultured mouse cells. Biotechnol. 1990; 8: 339-342.
21. Stewart LMD, Hirst M, Freber ML, Merryweather AT, Clayley PJ, Posse RD. Construction of an improved baculovirus insecticide containing an insect specific toxin gene. Nature. 1991; 352: 85-88.
22. Mc Cutchen BF, Hammock BD. Recombinant baculovirus expressing an insect-selective neuro-toxin. In: Natural and engineered pest management agent. Hedin PA, Menn JJ, eds. Hallingworth RM, 1994: 348-367.
23. Pelhate M, Stankiewicz M, Ben Khalifa R. Anti-insect scorpion toxins: historical account, activities and prospects. CR Seances Soc Biol Fil. 1998; 192: 463-484.
24. Karbat I, Frolow F, Froy O, Gilles N, Cohen L, Turkov M, et al. Molecular basis of the high insecticidal potency of scorpion α toxins. J Biol Chem. 2004; 279: 31679-31686.
25. Gurevitz M, Karbat I, Cohen L, Ilan N, Kahn R, Turkov M, et al. The insecticidal potential of scorpion β-toxins. Toxicon. 2007; 49: 473-489.
26. Gordon D, Karbat I, Ilan N, Cohen L, Kahn R, Gilles N, et al. The differential preference of scorpion α-toxins for insect or mammalian sodium channels: implications for improved insect control. Toxicon. 2007; 49: 452-472.
27. Pelhate M, Zlotkin E. Action of insect toxin and other toxins derived from the venom of the scorpion Androctonus australis on isolated giant axons of the cockroach (Periplanata americana). J Exp Biol. 1982; 97: 67-77.
28. Ben Khalifa R, Stankiewics M, Lapied B, Turkov M, Zilberberg N, Gurevitz M, Pelhate M. Refined electrophysiological analysis suggests that a depressant toxin is a sodium channel opener rather than a blocker. Life Sci. 1997; 61: 819-830.
29. Wang GK, Strichartz GR. Purification and physiological characterization of neurotoxins from the venoms of the scorpion Centruroides sculpturatus and Leiurus quinquestriatus. Mol Pharmacol. 1983; 23: 519-533.
30. Bontems F, Roumestand C, Gilquin B, Menez A, Toma F. Refined structure of charybdotoxin: common motifs in scorpion toxins and insect defensins. Science. 1991; 254: 1521-1523.
31. Crest M, Jacquet G, Gola M, Zerreouk H, Benslimane A, Rochat H, et al. Kaliotoxin, a novel peptidyl inhibitor of neuronal 13 K-type Ca++-activated K+ channel characterized from Androctonus mauretanicus mauretanicus venom. J Biol Chem. 1992; 267: 1640-1647.
32. Zlotkin A, Fishman Y, Elazar M. AaIT: from neurotoxin to insecticide. Biochiemie. 2000; 82: 869-881.
33. Higgs S, Olson KE, Klimowski L, Powers AM, Carlson JO, Possee RD, Beaty BJ. Mosquito sensitivity to a scorpion neurotoxin expressed using an infectious Snindbis virus vector. Insect Mol Biol. 1995; 4: 97-103.
34. Loret EP, Martin-Eauclaire MF, Mansuelle P, Sampieri F, Granier C, Rochat H. An anti-insect toxin purified from the scorpion Androctonus astralis Hector also acts on the α and β sites of the mammalian sodium channels sequence and circular dichroism study. Biochem. 1991; 30: 633-640.
35. Eitan M, Fowler E, Herrmann R, Duval A, Pelhate M, Zlotkin E. A scorpion venom neurotoxin paralytic to insects that affects sodium current inactivation: purification, primary structure and mode of action. Biochem. 1990; 29: 5941-5947.
36. Krimm I, Gilles N, Sautire P, Stankiewicz M, Pelhate M, Gordon D, Lancelin JM. NMR structures and activity of a novel α-like toxin from the scorpion Leiurus quinquestriatus hebraeus. J Mol Biol. 1999; 285: 1749-1763.
37. Dhawan R, Joseph S, Sethi A, Lala AK. Purification and characterization of a short insect toxin from the venom of the scorpion Buthus tamulus. FEBS Lett. 2003; 528: 261-266.
38. Gawade SP. Excitatory effects of Buthus C56 Drosophila on larval neuromuscular junction. J Venom Anim Toxin Incl Trop Dis. 2003; 9(1): 65-75.
39. Gershburg E, Stockholm D, Froy O, Rashi S, Gurevitz M, Chejanovsky N. Baculovirus mediated expression of a scorpion depressant toxin improve the insecticidal efficacy achieved with excitatory toxin. FEBS Lett. 1998; 422: 132-136.
40. Chhatwal GS, Habbermann E. Neurotoxins, protease inhibitors and histamine releasers in the venom of the red scorpion (Buthus tamulus): isolation and partial characterization. Toxicon. 1981; 19: 807-823.
41. Lala K, Narayanan P. Purification, N-terminal sequence and structural characterization of a toxin protein from the Indian scorpion venom, Buthus tamulus. Toxicon. 1994; 32: 325-338.
42. Wudayagiri R, Inceoglu B, Herrmann R, Choudhary MD, Hammock BD. Isolation and characterization of a novel lepidopteran-selective toxin from the venom of the South Indian scorpion, Mesobuthus tamulus. BMC Biochem. 2001; 2: 11-16.
43. Steiner H, Hultmark D, Engstrom A, Bennich H, Boman HG. Sequence and specificity of two antimicrobial proteins involved in insect immunity. Nature. 1981; 292: 246-248.
44. Bulet P, Cociancich S, Dimarcq JL, Lambert J, Reichhart JM, Hoffmann D, et al. Insect immunity: Isolation from a coleopteran insect of novel inducible antibacterial peptide and of new members of the insect defensin family. J Biol Chem. 1991; 266: 24520-24525.
45. Nicolas P, Mor A. Peptides as weapons against microorganisms in the chemical defense system of vertebrate. Annu Rev Microbiol. 1995; 49: 277-304.
46. Hoffman JA, Kafatos FC, Janeway CA, Ezekowitz RA. Phylogenetic perspective in innate immunity. Science. 1999; 284: 1313-1318.
47. Fennel JF, Shipman WH, Cole LJ. Antibacterial action of melittin, a polypeptide from bee venom. Proc Soc Exp Biol Med. 1968; 127: 707-710.
48. Krishnakumari V, Nagaraj R. Antimicrobial and hemolytic activities of crabrolin, a 13-residue peptide from the venom of the European hornet, Vespa crabro, and its analogs. J Pept Res. 1997; 50: 88-93.
49. Yan L, Adams ME. Lycotoxins, antimicrobial peptides from the venom of the wolf spider Lycosa carolinensis. J Biol Chem. 1998; 273: 2059-2066.
50. Hwang PM, Vogel HJ. Structure-function relation-ship of antimicrobial peptides. Biochem Cell Biol. 1998; 76: 235-246.
51. Larrick JW, Wright SC. Cationic antimicrobial peptides. Drug Future. 1996; 21: 41-48.
52. Hancock RE, Lehrer R. Cationic peptides: a new source of antibiotics. Trends Biotechnol. 1998; 16: 82-88.
53. Zasloff M. Antimicrobial peptides of multicellular organisms. Nature. 2002; 415(6870): 389-395.
54. Hancock RE, Sahl HG. Antimicrobial and host-defense peptides as new anti infective therapeutic strategie. Nature Biotechnol. 2007; 24(12): 1551-1557.
55. Dai L, Yasuda A, Naoki H, Corzo G, Andriantsi-ferana M, Nakajima T. IsCT, a novel cytotoxic linear peptide from scorpion Opisthacanthus madagascariensis. Biochem Biophys Res Commun. 2001; 286: 820-825.
56. Arpornsuwan T, Buasakul B, Jaresitthikunchai J, Roytrakul S. Potent and rapid antigonococcal activity of the venom peptide BmKn2 and its derivatives against different Maldi biotype of multidrug-resistant Neisseria gonorrhoeae. Peptides. 2014; 53: 315-320.
57. Epad RM, Vogel HJ. Diversity of antimicrobial peptides and their mechanism of action. Biochim Biophys Acta. 1999; 1462: 11-28.
58. Mousli M, Bueb JL, Bronner C, Rouot B, Landry Y. G-protein activation: a receptor independent mode of action for cationic amphipathic neuropeptides and venom peptides. Trends Pharmacol Sci. 1990; 11: 358-362.
59. Bulet P, Hetru C, Dimarcq J, Hoffmann D. Antimicrobial peptides in insects: structure and function. Dev Comp Immunol. 1999; 23: 329-344.
60. Cociancich S, Goyffon M, Bontems F, Bulet P, Bouet F, Menez A, Hoffmann J. Purification and characterization of a scorpion defensin, a 4 kD antimicrobial peptide presenting structural similarities with insect defensins and scorpion toxins. Biochem Biophys Res Commun. 1993; 194: 17-22.
61. Ehret-Sabatier L, Loew D, Goyffon M, Fehlbaum P, Hoffman JA, Van Dorsselaer A, Bulet P. Characterization of novel cyteine rich antimicrobial peptides from scorpion blood. Biochem Mol Biol. 1996; 271: 29537-29544.
62. Hetru C, Letellier L, Oren Z, Hoffmann JA, Shai Y. Androctonin, a hydrophilic disulphide-bridged non-haemolytic anti-microbial peptide: a plausible mode of action. Biochem J. 2000; 345: 653-664.
63. Moerman L, Bosteels S, Noppe W, Willems J, Clynen E, Schoofs L. Antibacterial and antifungal properties of alpha-helical, cationic peptides in the venom of scorpions from southern Africa. Eur J Biochem. 2002; 269: 4799-4810.
64. Powers JP, Hancock RE. The relationship between peptide structure and antibacterial activity. Peptides. 2003; 24: 1681-1691.
65. Ramírez-Carreto S, Jiménez-Vargas JM, Rivas-Santiago B, Corzo G, Possani LD, Becerril B. Peptides from the scorpion Vaejovis punctatus with broad antimicrobial activity. Peptides. 2015; 73: 51-59.
66. Bao A, Zhong J, Zeng XC, Nie Y, Zhang L, Peng ZF. A novel cysteinefree venom peptide with strong antimicrobial activity against antibioticsresistant pathogens from the scorpion Opistophthalmus glabrifrons. J Pept Sci. 2015; 21: 758-764.
67. de Melo ET, Estrela AB, Santos EC, Machado PR, Farias KJ, Torres TM. Structural characterization of a novel peptide with antimicrobial activity from the venom gland of the scorpion Tityus stigmurus: stigmurin. Peptides. 2015; 68: 3-10.
68. Bandyopadhyay S, Junjie RL, Lim B, Sanjeev R, Xin WY, Yee CK. Solution structures and model membrane interactions of Ctriporin, an anti-methicillin-resistant Staphylococcus aureus peptide from scorpion venom. Biopolymers. 2014; 101: 1143-1153.
69. Li Z, Xu X, Meng L, Zhang Q, Cao L, Li W. Hp1404, a new antimicrobial peptide from the scorpion Heterometrus petersii. PLoS One. 2014; 9: 97539.
70. Conde R, Zamudio F Z, Rodriguez MH, Possani LD. Scorpine, an antimalarial and antibacterial agent purified from scorpion venom. FEBS Lett. 2000; 471: 165-168.
71. Torres-Larios A, Gurrola GB, Zamudio FZ, Possani LD. Hadrurin, a new antimicrobial peptide from the venom of the scorpion Hadrurus aztecus. Eur J Biochem. 2000; 267: 5023-5031.
72. Verdonck F, Bosteel S, Desmet J, Moerman L, Noppe W, Willems J, et al. A novel class of pore forming peptides in the venom of the Parabuthus schlechteri Purcell (Scorpions: Buthidae). Cinebasia. 2000; 16: 247-260.
73. White SH, Wimley WC, Selsted ME. Structure, function and membrane integration of defensins. Curr Opin Struct Biol. 1995; 5: 521-527.
74. Matsuzaki K. Magainins as paradigm for the mode of action of pore forming peptides. Biochim Biophys Acta. 1998; 1376: 391-400.
75. Du Q, Hou X, Wang L, Zhang Y, Xi X, Wang H, et al. AaeAP1 and AaeAP2: novel antimicrobial peptides from the venom of the scorpion, Androctonus aeneas: structural characterisation, molecular cloning of biosynthetic precursor-encoding cDNAs and engineering of analogues with enhanced antimicrobial and anticancer activities. Toxins. 2015; 7: 219-237
76. Al-Asmari AK, Alamri MA, Almasoudi AS, Abbasmanthiri R, Mahfoud M. Evaluation of the in vitro antimicrobial activity of selected Saudi scorpion venoms tested against multidrug-resistant microorganisms. J Global Antimicrob Resist. 2007; 10: 14-18.
77. Sikora K. Cancer survival in Britain in poorer than that of her comparable European neighbours. BMJ. 1999; 319: 461-462.
78. De Carvalho DD, Schmitmeier S, Novello JC, Markland FS. Effect of BJcuL (a lectin from the venom of the snake Bothropos jararacussu) on adhesion and growth of tumor and endothelial cells. Toxicon. 2001; 39: 1471-1476.
79. Chiang HS, Swaim MW, Huang TF. Characterization of platelet aggregation induced by human breast carcinoma and its inhibition by snake venom peptide, trigramin and rhodostomin. Breast Cancer Res Treat. 1995; 33: 225-235.
80. Maristela P, Daniela DC, Antonio RG, Delwood CC. The effect of lectin from the venom of the snake, Bathrops jararacussu, on tumor cell proliferation. Anticancer Res. 1999; 19: 4023-4026.
81. Zhou Q, Sherwin RP, Parrish C, Richters V, Groshen SG, Tsao-Wei D, Markland FS. Contortrostatin, a dimmer disintegrin from Agkistrodon contortrix contortrix, inhibits breast cancer progression. Breast Cancer Res Treat. 2000; 61: 249-260.
82. Yarom R, Braun K. Myocardiopathology following scorpion venom injection. Isr J Med Sci. 1969; 5: 849-852.
83. Tarasiuk A, Khvatskin S, Sofer S. Effect of antivenom serotherapy on haemodynamic patho-physiology in dogs injected with of Leiurus quinquestriatus scorpion venom. Toxicon. 1998; 36: 963-971.
84. Omran MAA. In vitro anticancer effect of scorpion Leiurus quinquestriatus and Egyptian cobra venom on human breast and prostate cancer cell lines. J Med Sci. 2003; 3: 66-86.
85. Bruses JL, Capaso J, Katz E, Pilar G. Specific in vitro biological activities of snake venom myotoxins. J Neurochem. 1993; 60: 1030-1042.
86. Deshane J, Garner CC, Sontheimer H. Chlorotoxin inhibits glioma invasion via matrix metallo-proteinase-2. J Biol Chem. 2003; 278: 4135-4144.
87. Jager H, Dreker T, Buck A, Giehl K, Gress T, Grissmer S. Blockage of intermediate-conductance Ca2+ activated K+ channels inhibit human pancreatic cancer cell growth in vitro. Mol Pharmacol. 2004; 65: 630-638.
88. Gupta SD, Gomes AN, Debnath A, Saha A, Gomes AP. Apoptosis induction in human leukemic cells by a novel protein Bengalin, isolated from Indian black scorpion venom: through mitochondrial pathway and inhibition of heat shock proteins. Chem Biol Interact. 2010; 183: 293-303.
89. Al-Asmari AK, Islam M, Al-Zahrani AM. In vitro analysis of the anticancer properties of scorpion venom in colorectal and breast cancer cell lines. Oncol Lett. 2016; 2: 1256-1262.
90. Gupta SD, Debnath A, Saha A, Giri B, Tripathi G, Vedasiromoni JR, et al. Indian black scorpion (Heterometrus bengalensis Koch) venom induced antiproliferative and apoptogenic activity against human leukemic cell lines U937 and K562. Leuk Res. 2007; 31: 817-825.
91. Zhang YY, Wu LC, Wang ZP, Wang ZX, Jia Q, Jiang GS, Zhang WD. Antiproliferation effect of polypeptide extracted from scorpion venom on human prostate cancer cells in vitro. J Clin Med Res. 2009; 1: 24-31.
92. Zargan J, Sajad M, Umar S, Naime M, Ali S, Khan HA. Scorpion (Androctonus crassicauda) venom limits growth of transformed cells (SH-SY5Y and MCF-7) by cytotoxicity and cell cycle arrest. Exp Mol Pathol. 2011; 91: 447-454.
93. Almaaytah A, Albalas Q. Scorpion venom peptides with no disulfide bridges: a review. Peptides. 2014; 51: 35-45.
94. Roger JC, Qu Y, Tanada TN, Scheur T, Catterall WA. Molecular determinants of high affinity binding of alpha-scorpion toxin and Sea anemone toxin in S3-S4 extracellular loop in domain IV of the Na+ channel alpha-subunit. J Biol Chem. 1996; 271: 15950-15962.
95. Cestele S, Caterall WA. Molecular mechanism of neurotoxic action on voltage-gated sodium channels. Biochemie (Paris). 2000; 82: 883-892.
96. Martin-Eauclaire MF, Couraud F. Scorpion neurotoxins: effects and mechanism. In: Hand book of neurotoxicology. Chang LW, Dyer RS, eds Marcel Dekker New York, 1995: 683-716.
97. Gwee MC, Nirthanan S, Khoo HE, Gopalkrishnakone P, Kini RM, Cheah LS. Autonomic effect of some scorpion venoms and toxins. Clin Exp Pharmacol Physiol. 2002; 29: 795-801.
98. Couraud F, Jover E, Dubois JM, Rochat H. Two types of scorpion toxin receptor sites, one related to the activation, the other to the inactivation of the action potential Na+ channel. Toxicon. 1982; 20: 9-16.
99. Couto AS, Moreaes-Santos T, Azevedo AD, Almeida AP, Freire-Maia L. Effect of Tsgamma, purified from Tityus serrulatus scorpion venom, on the isolated rat atria. Toxicon. 1992; 30: 339-343.
100. Yatani A, Kirsh GE, Possani LD, Brown AM. Effects of New World ecorpion toxins on single channel and whole cell cardiac sodium currents. Am J Physiol. 1988; 254: 443-451.
101. Romi-Labrun R, Martin-Eauclaire MF, Escoubas P, Wu FQ, Lebrun B, Hisada M, Nakazima T. Characterization of four toxins from Buthus martensi scorpion venom, which act on apaminesensitive Ca++-activated K+ channels. Eur J Biochem. 1997; 245: 457-464.
102. D’ Ajellow A, Zlotkin E, Miranda F, Lissitzky. The effect of the scorpion venom and pure toxin on the cockroach nervous system. Toxicon. 1972; 10: 399-404.
103. Miller C, Moczydlowski E, Latore R, Philips M. Charybdotoxin, a potent inhibitor of single Ca++- activated K+ channels from mammalian skeleton muscle. Nature. 1985; 313: 316-318.
104. Miller C. The charybdotoxin family of K+ channel blocking peptides. Neurons. 1995; 15: 5-10.
105. Hoffmann JA, Hetru C. Insect defensins: inducible antimicrobial peptides. Immunol Today. 1992; 13: 411-415.
106. Bablito J, Jover E, Couraud F. Activation of the voltage sensitive sodium channel by a β-scorpion toxin in the rat brain nerve ending particles. J Neurochem. 1986; 37: 1763-1770.
107. Garcia CM, Leonard RJ, Novik J, Stevens SP, Schmalhofer W. Purification, characterization and biosynthesis of margaritatus venom that selectively inhibits voltage dependent potassium channel. J Biol Chem. 1993; 689(25): 18866-18874.
108. Lin CS, Boltz RC, Blake JT, Nguyen M, Talento A, Fischer PA, et al. Volatge-gated potassium channels regulate calcium dependent pathways involved in human T-lymphocytes activation. J Exp Med. 1993; 177: 637-645.
109. Bednarek MA, Bugianesi RM, Leonard RJ, Felix JP. Chemical synthesis and structurefunction studies of margtoxin, a potent inhibitor of voltage-dependent potassium channel in human T-lymphocytes. Biocem Biophys Res Commun. 1994; 198: 619-625.
110. Garcia ML, Garcia-Calvo M, Hidalgo P, Lee A, Mac Kinnon R. Purification and characterization of three inhibitors of voltage dependent K+ channels from Leiurus quinquestriatus var. hebraeus venom. Biochem. 1994; 33: 6834-6839.
111. Martins JC, Van JC, Borremanus FA. Determination of the three-dimensional solution structure of the scyllatoxin by 1H NMR. J Mol Biol. 1995; 253: 590-603.
112. Pappone PA, Chalan MD. Pandinus imperator scorpion venom blocks voltage-gated K+ channel in nerve fibers. J Neurosci. 1987; 7: 3300-3305.
113. Sands SB, Lewis RS, Chalan MD. Charbdotoxin blocks voltage-gated K+ channel in human and murine T-lymphocytes. J Gen Physiol. 1989; 93: 1061-1074.
114. Valdivia H, Kirby MS, Lederer WJ, Coronado R. Scorpion toxins targated against the sarcoplasmic reticulum Ca++ release channel of skeletal and cardiac muscle. Proc Nat Acad Sci USA. 1992; 89: 12185-12189.
115. el Havek R, Lokuta AJ, Arevalo C, Valdivia HH. Peptide probe of ryanodine receptor function. Imperatoxin A, a peptide from the venom of the scorpion Pandinus imperator, selectively activates skeletaltype ryanodine receptor isoforms. J Biol Chem. 1995; 270: 28696-28704.
116. Pappone PA, Lucero MT. Pandinus imperator scorpion venom blocks voltage gated potassium channels in GH3 cells. J Gen Physiol. 1988; 91: 817-833.
117. Galvez A, Gimenez-Gallego G, Ruben JP, Rov-Contancin L, Feigenbaun P, Kaczorowski GJ, Garcia ML. Purification and characterization of a unique peptidyl probe for the high conductance calcium-activated potassium channel from the venom of the scorpion Buthus tamulus. J Biol Chem. 1990; 265: 11083-11090.
118. Marangoni S, Ghiso J, Sampaio SV, Arantes EC, Giglio JR, Oliviera B, Frangione B. The complete amino acid sequence of toxin TsTX-VI isolated from the venom of the scorpion Tityus serrulatus. J Prot Chem. 1990; 9: 595-601.
119. Grishin EV, Korolkova YV, Kozlov KA, Lipkin AV, Nosyreva ED, Pluzhnikov KA, et al. Structure and function of potassium channel inhibitor from black scorpion venom. Pure Appl Chem. 1996; 68: 2105-2109.
120. More SS, Mirajkar KK, Gadag JR, Menon KS, Mathew MK. A novel Kv1.1 potassium channel-blocking toxin from the venom of Palamneus gravimanus (Indian black scorpion). J Venom Anim Toxin Incl Trop. 2005; 11(3): 315-335.
121. De Bin JA, Maggio JE, Strichartz GR (1993) Purification and characterization of chlorotoxin, a Clchannel ligand from the venom of the scorpion. Am J Physiol Cell Physiol 264:361-369.
122. Lippens G, Najib S, Wodak J, Tartar A. Sequential assignment and solution structure of chlorotoxin, a small peptide from scorpion that blocks chloride channel. Biochem. 1995; 34: 13-21.
123. Zamudio FZ, Conde R, Arevalo C, Becerril B, Martin BM, Valdivia HH, Possani LD. The mechanism of inhibition of ryanodine receptor channel by imperotoxin I, a heterodimeric protein from the scorpion Pandius imperator. J Biol Chem. 1997; 272: 11886-11894.
124. Zamudio FZ, Gurrola GB, Arvalo C, Sreekumar R, Walker JW, Valdivia HH, Possani LD. Primary structure and synthesis of imperotoxin A (Iptxa), a peptide activator of Ca++ release channels/rynodine receptors. FEBS Lett. 1997; 405: 385-389.
125. Chuang RSI, Jaffe H, Cribbs L, Perez-Reyes EJ, Stwartz KJ. Inhibition of T-type voltagegated calcium channels by a new scorpion toxin. Natl Neuro Sci. 1998; 1: 668-674.
126. Freire-Maia L, Pinto GI, Franco I. Mechanism of the cardiovascular effects produced by purified scorpion toxin in the rat. J Pharmacol Exp Ther. 1974; 188: 207-213.
127. Ismail M. The scorpion-envenoming syndrome. Toxicon. 1995; 33: 825-858.
128. Tarasiuk A, Janco J, Sofer S. Effect of scorpion venom on central and peripheral circulatory response in an open-chest dog model. Acta Physiol Scand. 1997; 161: 141-146.
129. Ismail M, Osmon OH, Gumma KA, Karrar MA. Some pharmacological studies with scorpion (Pandinus exitiallis) venom. Toxicon. 1974; 2: 75-82.
130. Almeida AP, Alpoim NC, Freire-Maia L. Effects of purified scorpion toxin (Tityus toxin) on the isolated guinea pig heart. Toxicon. 1982; 20: 855-865.
131. Moss J, Kajik T, Henery DP, Kopin IJ. Scorpion venom induced discharge of catecholamines accompanied by hypertension. Brain Res. 1973; 54: 381-385.
132. Freire-Maia L, Campos JA. Pathophysiology and treatment of scorpion poisoning. In: Ownby LC, Odel GV, eds. Natural toxins, characterizations, pharmacology and therapeutics. Pergamon Press Oxford, 1989: 139-159.
133. Tarasiuk A, Sofer S. Effect of adrenergic blockade and ligation of spleen vessels on haemodynamics of dogs injected with scorpion venom. Crit Care Med. 1999; 27: 365-372.
134. Sofer S. Scorpion envenomation. Int Care Med. 1995; 21: 627-628.
135. Ramchandran LK, Agrawal OP, Achyutan KE, Chudhary L, Vedasiromani JR, Ganguli DK. Fractionation and biological activities of the venom of the Indian scorpions Buthus tamulus and Heterometrus bengalensis. Ind J Biochem Biophys. 1986; 23: 355-358.
136. Russel FE. Toxic effects of animal toxins. In: Idaassen CD, Amdur MO, Doull J, eds. Toxicology basic science of poisons. 3rd edn, New York: Macmillan, 1986: 706-756.
137. Henriques MC, Gassinelli G, Diniz CR, Gomez MV. Effect of the venom of the scorpion Tityus serrulatus on adrenal gland catecholamines. Toxicon. 1968; 5: 175-179.
138. Radha Krishna Murthy K, Vakil AE. Elevation of plasma angiotensin level in dogs by Indian red scorpion (Buthus tamulus) venom and its reversal by administration of insulin and tolazoline. Indian J Med Res. 1988; 88: 376-379.
139. Margulis G, Sofer S, Zalstein E, Zucker N, Ilia R, Gueron M. Abnormal coronary perfusion in experimental scorpion envenomation. Toxicon. 1994; 32: 1675-1678.
140. Wang R, Moreau P, Deschamps A, de Champlain J, Sauve R, Foucart S, et al.Cardiovascular effects of Buthus martensi (Karsch) scorpion venom. Toxicon. 1994; 32: 191-200.
141. Amaral CFS, Lopes JA, Magalhaes RA, de Rezende NA. Electrocardiographic, enzymatic and echocardiographic evidence of myocardial damage after Tityus serrulatus scorpion poisoning. Am J Cardiol. 1991; 67: 655-657.
142. Abroug E, Ayari M, Nouria S, Gamra H, Boujdaria R, Elatrons S, et al. Assessment of left ventricular function in severe scorpion envenomation: combined haemodynamic and echodopller study. Int Care Med. 1995; 21: 629-635.
143. Gueron M, Adolf RJ, Grupp IL, Gabel M, Grupp G, Fowler NO. Haemodynamic and myocardial consequences of scorpion venom. Am J Cardiol. 1980; 45: 1979-1986.
144. Couture R, Harrisson M, Vianna RM, Cloutier F. Kinin receptors in pain and inflammations. Eur J Pharmacol. 2001; 429: 161-176.
145. Campbell DJ, Dixon B, Kladis A, Kemme M, Santmaria, JD. Activation of the kallikrein-kinin system by cardiopulmonary bypass in humans. Am J Physiol. 2001; 281: 1059-1070.
146. Gwee MC, Cheah LS, Nirthanan S, Gopalkri-shnakone P, Wang PT. Pre-junctional action of the venom from the Indian red scorpion Mesobuthus tamulus on adrenergic transmission in vitro. Toxicon. 1994; 32: 201-209.
147. Rowan EG, Vatanpour H, Furman BL, Harvey AL, Tanira MO, Gopalkrishnakone P. The effect of Indian red scorpion Buthus tamulus venom in in vivo and in vitro. Toxicon. 1992; 30: 1157-1164.
148. Murthy RKK, Medh JD, Dave BN, Vakil YE, Billimoria FR. Acute pancreatitis and reduction of H+ ion concentration in gastric secretions in experimental acute myocarditis produced by Indian red scorpion (Buthus tamulus) venom. Indian J Exp Biol. 1989; 27: 242-244.
149. Murthy RKK, Hossein Z. Increased osmotic fragility of red cells of incubation at 370C for 20 hours in dogs with acute myocarditis produced by scorpion (Buthus tamulus) venom. Indian J Exp Biol. 1986; 38: 206-210.
150. Murthy RKK, Anita AG, Dave BN, Billimoria FR. Erythrocyte Na+K+ATPase activity inhibition and increased red cell fragility in experimental myocarditis produced by red scorpion (Buthus tamulus) venom. Indian J Med Res. 1988; 88: 536-540.
151. Murthy RKK, Yeolekar ME. Electrocardiographic changes in acute myocarditis produced by the scorpion (Buthus tamulus) venom. Indian Heart J. 1986; 38: 206-210.
152. Murthy RKK, Hossein Z, Medh JD, Kudalkar JA, Yeolekar ME, Pandit SP, et al. Disseminated intravascular coagulation and disturbances in carbohydrate and fat metabolism in acute myocarditis produced by Indian red scorpion (Buthus tamulus) venom. Indian J Med Res. 1988; 87: 318-325.
153. Murthy RKK, Haghanzari L. The blood level of glucagon, cortisol, and insulin following the injection of venom by the scorpion (Mesobuthus tamulus, Pocock) in dogs. J Venom Anim Toxin. 1999 5: 200-219.
154. Murthy RKK, Zare A. Effect of Indian red scorpion (Mesobuthus tamulus concanesis, Pocock) venom on thyroxine and triiodothyronine in experimental acute myocarditis and its reversible by species-specific antinenom. Indian J Exp Biol. 1998; 36: 16-21.
155. Murthy RKK, Anita AG. Reduced insulin secretion in acute myocarditis produced by scorpion (Buthus tamulus). Indian Heart J. 1986; 38: 467-469.
156. Gwee MC, Nirthanan S, Khoo HE, Gopalkri-shnakone P, Kini RM, Cheah LS. Autonomic effect of some scorpion venoms and toxins. Clin Exp Pharmacol Physiol. 2002; 29: 795-801.
157. Murthy RKK, Zare A. The use of antivenin reverses hematological and osmotic fragility changes of erthrocytes caused by Indian red scorpion Mesobuthus tamulus concanesis, Pocock in experimental envenoming. J Venom Anim Toxins. 2001; 7: 113-138.
158. Freire-Maia L, Campos JA. On the treatment of the cardiovascular manifestations of scorpion envenomation. Toxicon. 1987; 25: 125-130.
159. Freire-Maia L, De Matos IM. Heparin or a PAF antagonist (BN-52021) prevents the acute pulmonary oedema induced by Tityus serrulatus scorpion venom on the rat. Toxicon. 1993; 31: 1207-1210.
160. Gueron M, Ovsyshcher I. What is the treatment for the cardiovascular manifestations of scorpion envenomation? Toxicon. 1987; 25: 121-124.
161. Best CH, Taylor NBA. Textbook in applied physiology of medical practice. Baltimore: Williams and Wilkins, 1967.
162. Pande SV, Mead JF. Inhibition of enzyme activities by free fatty acids. J Biol Chem. 1968; 243: 6180- 6186.
163. de Rezende NA, Dias MB, Campolina D, Chavez-Olortegui C, Diniz C, Amaral CFS. Efficacy of antivenom therapy for neutralizing venom antigen in patients stung by Tityus serrulatus scorpion. Am J Trop Med Hyg. 1995; 52: 277-280.
164. Omran MAA, Abdel-Rahman MS. Effect of the scorpion Leiurus quinquestriatus (H&E) venom on the clinical chemistry parameters of the rat. Toxicol Lett. 1992; 61: 99-109.
165. Ghalim N, El-Hafny B, Sebti F, Heikel J, Lezar N, Moustanir R, Benslimane A. Scorpion venom and serotherpy in Morocco. Am J Trop Med Hyg. 2000; 62: 277-283.
166. Sofer S, Shahak E, Gueron M. Scorpion envenomation and antivenom therapy. J Pediatr. 1994; 124: 973-978.
167. Balozet L. Scorpionism in the Old World. In: Bücherl W, Buckley E, eds. Venomous animals and their venoms. New York: Academic Express, 1971: 349-371.
168. Theakston RD, Warrell DA, Grifithis E. Report of a WHO workshop on the standardization and control of antivenoms. Toxicon. 2003; 41: 541-557.
169. Demagalhaes O. Scorpionism. J Trop Med Hyg. 1938; 41: 393-399.
170. Balozet L. Scorpion venoms and anti-scorpion serum. In: Venom. Buckley EE, Porges N, eds. Washington DC. Public. No. 44. Am Adv Sci. 1956.
171. Mohammed AH, Darwish MA, Honi Ayobe M. Immunological studies on scorpions (Leiurus quinquestriatus) antivenin. Toxicon. 1975; 13: 67-68.
172. Kapadia ZS, Master RWP, Rao SS. Immunological studies in telson extracts of Indian and Egyptian scorpion venom. Indian J Exp Biol. 1964; 2: 75-77.
173. Kankonakar RC, Kulakarni DG, Hulikavi CB. Preparation of a potent anti-scorpion venom serum against the venom of red scorpion (Buthus tamulus). J Postgrad Med. 1998; 44: 85-92.
174. Amaral CFS, Dias MB, Campolina D, Proietti FA, de Rezende NA. Childrens with adrenergic manifestation of envenomation after Tityus serrulatus scorpion sting are protected from early anaphylactic antivenom reaction. Toxicon. 1994; 32: 211-215.
175. Amaral CFS, de Rezende NA. Both cardiogenic and noncardiogenic factors are involved in the pathogenesis of pulmonary oedema after scorpion envenoming. Toxicon. 1997; 35: 997-998.
176. Gueron M, Marquilis G, Sofer S. Echocardiographic and radionucleid angiographic observations following scorpion envenomation by Leiurus quinquestriatus. Toxicon. 1990; 28: 1005-1009.
177. Devaux C, Fourquet P, Granier C. A conserved sequence region of scorpion toxin rendered immunogenic induces broadly cross-reactive, neutralizing antibodies. Eur J Biochem. 1996; 242(3): 727-735.
178. Espino-Solis GP, Riano-Umbarila L, Becerril B, Possani LD. Antidotes against venomous animals: state of the art and prospectives. J Proteomics. 2009; 72(2): 183-199.
179. Holliger PH, Hudson JP. Engineering antibody fragments and the rise of single domains. Nat Biotechnol. 2005; 23: 1126-1136.
180. Riaño-Umbarila L, Contreras-Ferrat G, Olamendi-Portugal T, Morelos-Juárez C, Corzo G, Possani LD, Becerril B. Exploiting cross-reactivity to neutralize two different scorpion venoms with one single chain antibody fragment. J Biol Chem. 2011; 286: 6143-6151.
181. Canul-Tec J-C, Riaño-Umbarila L, Rudinño-Pinera E, Becerril B, Possani LD, Torres-Larios A. Structural basis of neutralization of the major toxic component from the scorpion Centruroides noxius Hoffmann by a human-derived single chain antibody fragment. J Biol Chem. 2011; 286: 20892-20900.
182. Rodríguez-Rodríguez ER, Ledezma-Candanoza LM, Contreras-Ferrat LG, Olamendi-Portugal T, Possani LD, Becerril B, Riaño-Umbarila L. A single mutation in framework 2 of the heavy variable domain improves the properties of diabody and a related single-chain antibody. J Mol Biol. 2012; 423: 337-350.
Published
2017-12-31
How to Cite
(1)
Chaubey, M. Scorpion Venom: Pharmacological Analysis and Its Applications. European Journal of Biological Research 2017, 7, 271-290.
Section
Review Articles
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
