The genus Conus is equipped with a unique venomous mixture of conopeptides which secreted for predation and defense purposes. This work is aiming to explore and determine the effect of the crude venom of Conus flavidus, a worm-hunting cone snail inhabiting the Red Sea, on the oxidant/ antioxidant system in mice using some oxidative stress biomarker assays. In addition to assess its histopathological effects on some treated organs. The LC50 were detected for the crude venom using the hemolytic assay (16.7 mg/ml) and male albino mice were injected intraperitoneally with ½ LC50 (8.3 mg/kg B.Wt). Biochemically, after 2, 4, 6, 12, 24 hours of injection the results revealed significant inhibition of superoxide dismutase (SOD) and catalase (CAT) activities in blood and liver in almost all time intervals comparing with control one. However, it showed elevation in lipid peroxide content (LPC), protein carbonyl content (PCC), nitric oxide level (NO) reduced glutathione content (GSH) and total antioxidant capacity (TAC) contents of both blood and liver in almost all time intervals. Histopathologicaly, liver and heart were dissected after 1, 3 and 7 days of injection. The treated liver showed vacuolar degeneration, karyolosis and pyknosis, mild blood sinusoidal congestion and centrilobular necrosis. The treated heart illustrated degenerated myofibrils, pyknosis, edema, blood vessel congestion, loss of striation normal construction and fascicular pattern in the myocardium. These results revealed that C. flavidus crude venom has distinct effects upon the oxidant/antioxidant cellular system and degenerative pathological effects in some tissues of treated animals, proving that this venom may contain bioactive peptides, which could be purified and used for further pharmacological and drug discovery investigations in the future.
Published in | International Journal of Ecotoxicology and Ecobiology (Volume 2, Issue 1) |
DOI | 10.11648/j.ijee.20170201.15 |
Page(s) | 33-44 |
Creative Commons |
This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited. |
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Copyright © The Author(s), 2017. Published by Science Publishing Group |
Conus flavidus, Hemolytic Assay, Antioxidants, Histopathological Changes, Red Sea
[1] | B. Livett, k. Gayler, & Z. Khalil. (2004). Drugs from the sea: conopeptides as potential therapeutics. Current medicinal chemistry, 11 (13), 1715-1723. |
[2] | S. Conticello, Y. Gilad, N. Avidan, E. Ben-Asher, Z. Levy and M. Fainzilber (2001). "Mechanisms for evolving hypervariability: the case of conopeptides." Molecular Biology and Evolution 18 (2): 120-131. |
[3] | D. Alonso, Z. Khalil, N. Satkunanthan and B. Livett (2003). "Drugs from the sea: conotoxins as drug leads for neuropathic pain and other neurological conditions." Mini reviews in medicinal chemistry, 3 (7): 785-787. |
[4] | O. Buczek, G. Bulaj and B. Olivera (2005). "Conotoxins and the posttranslational modification of secreted gene products." Cellular and Molecular Life Sciences CMLS 62 (24): 3067-3079. |
[5] | J. Jakubowski, W. Kelley, J. Sweedler, W. Gilly and J. Schulz (2005). "Intraspecific variation of venom injected by fish-hunting Conus snails." Journal of Experimental Biology 208 (Pt 15): 2873-2883. |
[6] | C. Pi, Y. Liu, C. Peng, X. Jiang, J. Liu, B. Xu, X. Yu, Y. Yu, X. Jiang, L. Wang, M. Dong, S. Chen and A. L. Xu (2006). "Analysis of expressed sequence tags from the venom ducts of Conus striatus: focusing on the expression profile of conotoxins." Biochimie 88 (2): 131-140. |
[7] | S. Luo, D. Zhangsun, Y. Wu, X. Zhu, L. Xie, Y. Hu, J. Zhang and X. Zhao (2006). "Identification and molecular diversity of T-superfamily conotoxins from Conus lividus and Conus litteratus." Chemical biology & drug design 68 (2): 97-106. |
[8] | S. Norton, and B. Olivera (2006). "Conotoxins down under." Toxicon 48 (7): 780-798. |
[9] | Peng, C., G. Yao, B.-M. Gao, C.-X. Fan, C. Bian, J. Wang, Y. Cao, B. Wen, Y. Zhu, Z. Ruan, X. Zhao, X. You, J. Bai, J. Li, Z. Lin, S. Zou, X. Zhang, Y. Qiu, J. Chen, S. L. Coon, J. Yang, J.-S. Chen and Q. Shi (2016). "High-throughput identification of novel conotoxins from the Chinese tubular cone snail (Conus betulinus) by multi-transcriptome sequencing." GigaScience 5: 17. |
[10] | J. Bingham, P. Jones, A. Lewis, R. Andrews, P. Alewood, In Biochemical Aspects of Marine Pharmacology, Lazarovici, P., Spira, M. E., Zlotkin, E. (Eds.), 1996, 13-27. |
[11] | E. Heading. (2002). Conus peptides and neuroprotection. Current opinion in investigational drugs (London, England: 2000), 3 (6), 915-920. |
[12] | S. McDonough, I. Boland, L. Mintz, I. Bean, 2002. Interactions among toxins that inhibit N-type and P-type calcium channels. J. Gen. The Journal of general physiology. 119, 313–328. |
[13] | S. Staats, T. Yearwood, G. Charapata, W. Presley, S. Wallace, M. Byas-Smith, R. Fisher, A. Bryce, A. Mangieri, R. Luther, M. Mayo, D. McGuire, D. Ellis, 2004. Intrathecal ziconotide in the treatment of refractory pain in patients with cancer or AIDS: a randomized controlled trial. JAMA 291, 63–70. |
[14] | H. Terlau, and B. Olivera (2004). "Conus venoms: a rich source of novel ion channel-targeted peptides." Physiological reviews 84 (1): 41-68. |
[15] | C. Moller, S. Rahmankhah, J. Lauer-Fields, J. Bubis, G. Fields and F. Mari (2005). "A novel conotoxin framework with a helix-loop-helix (Cs alpha/alpha) fold." Biochemistry 44 (49): 15986-15996. |
[16] | B. Aguilar, E. Lopez-Vera, A. Heimer de la Cotera, A. Falcon, M. Olivera and M. Maillo (2007). "I-conotoxins in vermivorous species of the West Atlantic: peptide sr11a from Conus spurius." Peptides 28 (1): 18-23. |
[17] | C. Romeo, L. Di Francesco, M. Oliverio, P. Palazzo, G. Massilia, P. Ascenzi, F. Polticelli and M. E. Schinina (2008). "Conus ventricosus venom peptides profiling by HPLC-MS: a new insight in the intraspecific variation."Journal of separation science, 31 (3): 488-498. |
[18] | L. Cruz, A. Ramilo, P. Corpuz, B. Olivera, 1992. Conus peptides: phylogenetic range of biological activity. The Biological Bulletin.183, 159–164. |
[19] | M. Almaaytah, L. Zhou, T. Wang, B. Chen, B. Walker and C. Shaw (2012). "Antimicrobial/cytolytic peptides from the venom of the North African scorpion, Androctonus amoreuxi: Biochemical and functional characterization of natural peptides and a single site-substituted analog." Peptides 35 (2): 291-299. |
[20] | K. Yagi, (1987). Lipid peroxides and human disease. Chemistry and physics of lipids 45, 337–351. |
[21] | Z. Reznick, L. Packer, (1994). Oxidative damage to proteins: spectrophotometric method for carbonyl assay. Methods in enzymology. 233, 357–363. |
[22] | C. Green, A. Wagner, J. Glogowski, L. Skipper, J. Wishnok, R. Tannenbaum,1982. Analysis of nitrate, nitrite and [15N] nitrate in biological fluids. Analytical biochemistry. 126, 131–138. |
[23] | E. Biutler, O. Doron, B. Kelly, (1963). Improved method for determination of blood glutathione. Journal of laboratory and clinical medicine 61: 882-888. |
[24] | P. Misra, I. Fridovich,, (1972). The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase. Journal of Biological chemistry, 247 (10): 3170–3175. |
[25] | H. Aebi, Catalase in vitro. In Oxygen radicals in biological systems: Meths Enzymol. Edited by Packer L. Orlando: Academic; 1984: 121–126. |
[26] | G. Cohen, D. Dembiec, J. Marcus J (1970). Measurement of catalase activity in tissue extracts. Analytical biochemistry, 34: 30–38. |
[27] | D. Koracevic, G. Koracevic, V. Djordjevic, V., Andrejevic, S., Cosic, V., (2001). Method for the measurement of antioxidant activity in human fluids. Journal of clinical pathology. 54, 356–361. |
[28] | P. Dancey, J. Reidy, (2002). Statistics without maths for psychology (Eds.), Harlow: Pearson Education. |
[29] | W. Snedecor, (1956). Statistical Methods, 4th Eds. The Iowa Collage Press, Iowa State, USA. |
[30] | S. Dutertre, H. Jin, I. Vetter, B. Hamilton, K. Sunagar, V. Lavergne, & F. Alewood. (2014). Evolution of separate predation-and defence-evoked venoms in carnivorous cone snails. Nature communications, 5. |
[31] | M. Olivera, (2002). "Conus" Venom Peptides: Reflections from the Biology of Clades and Species. Annual Review of Ecology and Systematics, 25-47. |
[32] | M. Olivera, (1997). EE Just lecture, 1996 Conus venom peptides, receptor and ion channel targets, and drug design: 50 million years of neuropharmacology. Molecular biology of the cell, 8 (11), 2101-2109.. |
[33] | M. Olivera, & W. Teichert, (2007). Diversity of the neurotoxic Conus peptides. Molecular Interventions, 7 (5), 251. |
[34] | M. McIntosh, & M. Jones, (2001). Cone venom–from accidental stings to deliberate injection. Toxicon, 39 (10), 1447-1451. |
[35] | B. Aguilar, E. Lopez-Vera, E. Ortiz, B. Becerril, D. Possani, M. Olivera, and P. Heimer de la Cotera,. (2005). A novel conotoxin from Conus delessertii with post-translationally modified lysine residues. Biochemistry, 44: 11130–11136. |
[36] | M. Loughnan,, A. Nicke, A. Jones, I. Schroeder, T. Nevin, J. Adams, F. Alewood, and J. Lewis, R. J. (2006). Identification of a Novel Class of Nicotinic Receptor Antagonists. The Journal of Biological Chemistry, 281 (34): 24745–24755. |
[37] | A. Zugasti-Cruz, M. Maillot, E. Lopez-Vera, A. Falcon, Heimer de la Cotera, E. P., Olivera, B. M. and Aguilar, M. B. (2006). Amino acid sequence and biological activity of a gamma-conotoxin-like peptide from the worm-hunting snail Conus austini. Peptides, 27: 506–51. |
[38] | R. Saminathan, S. Babuji, S. Sethupathy, P. Viswanathan, T. Balasubramanian and P. Gopalakrishanakone (2006). "Clinico-toxinological characterization of the acute effects of the venom of the marine snail, Conus loroisii." Acta Trop 97 (1): 75-87. |
[39] | S. Biggs, Y. Rosenfeld, Y. Shai, and M. Olivera, (2007). Conolysin-Mt: a Conus peptide that disrupts cellular membranes. Biochemistry, 46 (44), 12586-12593. |
[40] | C. Oviedo-Gómez, M. Galar-Martínez, S. García-Medina, C. Razo-Estrada, and M. Gómez-Oliván, (2010). Diclofenac-enriched artificial sediment induces oxidative stress in Hyalella azteca. Environmental Toxicology and Pharmacology, 29 (1), 39-43. |
[41] | R. Endean, G. Parrish, and P. Gyr, (1974). Pharmacology of the venom of Conus geographus. Toxicon, 12: 131–138. |
[42] | J. Cruz, and J. White, (1995). Clinical toxicology of Conus snail stings. In: Handbook of Clinical Toxicology of Animal Venoms and Poisons, 117-127. |
[43] | D. Fegan, and D. Andresen (1997). "Conus geographus envenomation." Lancet 349(9066): 1672. |
[44] | D. Annadurai, R. Kasinathan, and S. Lyla, (2007). Acute toxicity effect of the venom of the marine snail, Conus zeylanicus. Journal of environmental biology, 28 (4), 825-828. |
[45] | M. Olivera, R. Hillyard, J. Rivier, S. Woodward, R. Gray, G. Corpuz, and J. Cruz, (1990). Conotoxins: targeted peptide ligands from snail venoms. In: Hall, S., Strichartz, G. (Eds.), Marine Toxins. American Chemical Society Washington, DC, pp. 256–278. |
[46] | A. Santamaria, S. Rodriguez, A. Zugasti, A. Martinez, S. Galvan-Arzate, and S. Puertas, (2002). A venom extract from the sea anemone Bartholomea annulata produces haemolysis and lipid peroxidation in mouse erythrocytes. Toxicology, 173:221–228. |
[47] | I. Dalle-Donne, R. Rossi, R. Colombo, D. Giustarini, & A. Milzani, (2006). Biomarkers of oxidative damage in human disease. Clinical Chemistry, 52 (4), 601-623. |
[48] | I. Dalle-Donne, R. Rossi, D. Giustarini, A. Milzani, and R. Colombo. (2003). Protein carbonyl groups as biomarkers of oxidative stress. Clinica chimica acta, 329 (1), 23-38. |
[49] | I. Fedorova, A. Mikov, E. Maleeva, A. Andreev, E. Bocharov, D. Tikhonov, and A. Kozlov, S. A. (2014). Novel insect-toxin from Tibellus oblongus spider venom. In FEBS Journal (281), 414-415. |
[50] | T. Mayne. (2003). Antioxidant nutrients and chronic disease: use of biomarkers of exposure and oxidative stress status in epidemiologic research. The Journal of nutrition, 133 (3), 933S-940S. |
[51] | L. Petricevich. (2004). Cytokine and nitric oxide production following severe envenomation. Current Drug Targets-Inflammation and Allergy, 3 (3), 325-332. |
[52] | I. Alayash. (1999). Hemoglobin-based blood substitutes: oxygen carriers, pressor agents, or oxidants? Nature Biotechnology, 17: 545–549. |
[53] | T. Kawano, R. Pinontoan, H. Hosoya, & S. MUTO. (2002). Monoamine-dependent production of reactive oxygen species catalyzed by pseudoperoxidase activity of human hemoglobin. Bioscience, biotechnology, and biochemistry, 66 (6), 1224-1232. |
[54] | N. Jiang, S. Tan, B. Ho, and L. Ding. (2007). Respiratory protein–generated reactive oxygen species as an antimicrobial strategy. Nature Immunology, 8 (10): 1114-1122. |
[55] | G. Reyes, & J. Cruz. (1983). Haemolytic factors from Conus textile venom. Acta Med. Phillips, 17-25. |
[56] | S. Kreger. (1989). Cytolytic activity in the venom of the marine snail Conus californicus. Toxicon, 27 (1): 56. |
[57] | M. McIntosh, F. Ghomashchi, H. Gelb, J. Dooley, J. Stoehr, B. Giordani, R. Naisbitt, and M. Olivera, (1995). Conodipine-M, a novel phospholipase A2 isolated from the venom of marine cone snail Conus magus. The Journal of Biological Chemistry, 270 (8): 3518-3526. |
[58] | M. Adibhatla, F. Hatcher, and J. Dempsey. (2003). Phospholipase A2, hydroxyl radicals, and lipid peroxidation in transient cerebral ischemia. Antioxidant and Redoxy Signaling 5: 647–654. |
[59] | F. El-Asmar, M. Farag, S. Shoukry, and R. El-Shimi. (1979). Effect of scorpion Leiurus quinquestriatus venom on lipid peroxidation. Toxicon, 17: 279. |
[60] | B. Halliwell, and M. Gutteridge. (1989). Free Radicals in Biology and Medicine, second ed. Oxford Univeristy Press, New York. |
[61] | M. Gutteridge, J. M. and Mitchell, J. (1999). Redox imbalance in the critically ill. British Medical Bulletin, 55 (1), 49-75. |
[62] | D. Nikitovic, and A. Holmgren. (1996). S-nitrosoglutathione is cleaved by the thioredoxin system with liberation of glutathione and redox regulating nitric oxide. Journal of Biological Chemistry, 271 (32), 19180-19185. |
[63] | J. Wetscher, M. Bagchi, D. Bagchi, G. Perdikis, R. Hinder, K. Glaser, and A. Hinder. (1995). Free radical production in nicotine treated pancreatic tissue. Free Radical Biology and Medicine, 18 (5), 877-882. |
[64] | A. Abdel-Rahman, M. Abdel-Nabi, A. Nassier, and J. Schemerhorn. (2010). Neurotoxic and cytotoxic effects of venom from different populations of the Egyptian Scorpio maurus palmatus. Toxicon, 55, 298-306. |
[65] | W. Wester, and H. Canton. (1991). the usefulness of histopathology in aquatic toxicity studies. Comparative Biochemistry and Physiology Part C: Comparative Pharmacology, 100 (1), 115-117. |
[66] | S. Thophon, M. Kruatrachue, S. Upatham, P. Pokethitiyook, S. Sahaphong, & S. Jaritkhuan, (2003). Histopathological alterations of white seabass, Lates calcarifer, in acute and subchronic cadmium exposure. Environmental Pollution, 121 (3), 307-320. |
[67] | J. Schwaiger, R. Wanke, S. Adam, M. Pawert, W. Honnen, & R. Triebskorn. (1997). The use of histopathological indicators to evaluate contaminant-related stress in fish. Journal of Aquatic Ecosystem Stress and Recovery, 6 (1), 75-86. |
[68] | J. Teh, S. Adams, and E. Hinton. (1997). Histopathological biomarkers in feral freshwater fish populations exposed to different types of contaminant stress. Aquatic Toxicology, 37 (1), 51-70. |
[69] | M. Gernhofer, M. Pawet, E. Schramm, Müller & R. Triebskorn. 2001. Ultrastructural biomarkers as tools to characterize the health status of fish in contaminated streams. Journal of Aquatic Ecossystem, Stress and Recovery, 8: 241-260. |
[70] | E. Fanta, A. Rios, S. Romão, C. Vianna, & S. Freiberger. (2003). Histopathology of the fish Corydoras paleatus contaminated with sublethal levels of organophosphorus in water and food. Ecotoxicology and environmental safety, 54 (2), 119-130. |
[71] | E. Hinton, J. Lauren, L. Holliday, and S. Giam, (1988). Liver structural alterations accompanying chronic toxicity in fishes: potential biomarkers of exposure. In Preprints of Papers Presented at National Meeting, Division of Water, Air and Waste Chemistry, American Chemical Society;(USA) (Vol. 28). |
[72] | P. Kumar, K. Venkateshvaran, P. Srivastava, K. Nayak, M. Shivaprakash, and K. Chakraborty. (2013). Toxicity and histopathological observations on albino mice on intra-peritoneal injection of three species of Conus. International Journal of Advanced Research in Pharmaceutical and Bio Sciences, 3 (1). |
[73] | D. Uchitel. (1997). Toxins affecting calcium channels in neurons. Toxicon, - 11911161.8(35). |
[74] | M. Bahloul, H. Kallel, N. Rekik, C. Ben Haminda, H. Chelly, and M. Bouaziz. (2005). Cardiovascular dysfunction following severe scorpion envenomation. Mechanisms and physiopathology. Presse Medicale, 34, 115-120. |
[75] | M. Fainzilber, and E. Zlotkin. (1992). A new bioassay reveals mollusc-specific toxicity in molluscivorous Conus Venoms. Toxicon, 30 (4): 465-469. |
APA Style
Mona F. Abou-Elezz, Alaa Y. Moustafa, Mohamed S. El-Naggar. (2017). Assessment of Biochemical and Histopathological Effects of Crude Venom of Cone Snail Conus flavidus on albino Mice. International Journal of Ecotoxicology and Ecobiology, 2(1), 33-44. https://doi.org/10.11648/j.ijee.20170201.15
ACS Style
Mona F. Abou-Elezz; Alaa Y. Moustafa; Mohamed S. El-Naggar. Assessment of Biochemical and Histopathological Effects of Crude Venom of Cone Snail Conus flavidus on albino Mice. Int. J. Ecotoxicol. Ecobiol. 2017, 2(1), 33-44. doi: 10.11648/j.ijee.20170201.15
AMA Style
Mona F. Abou-Elezz, Alaa Y. Moustafa, Mohamed S. El-Naggar. Assessment of Biochemical and Histopathological Effects of Crude Venom of Cone Snail Conus flavidus on albino Mice. Int J Ecotoxicol Ecobiol. 2017;2(1):33-44. doi: 10.11648/j.ijee.20170201.15
@article{10.11648/j.ijee.20170201.15, author = {Mona F. Abou-Elezz and Alaa Y. Moustafa and Mohamed S. El-Naggar}, title = {Assessment of Biochemical and Histopathological Effects of Crude Venom of Cone Snail Conus flavidus on albino Mice}, journal = {International Journal of Ecotoxicology and Ecobiology}, volume = {2}, number = {1}, pages = {33-44}, doi = {10.11648/j.ijee.20170201.15}, url = {https://doi.org/10.11648/j.ijee.20170201.15}, eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ijee.20170201.15}, abstract = {The genus Conus is equipped with a unique venomous mixture of conopeptides which secreted for predation and defense purposes. This work is aiming to explore and determine the effect of the crude venom of Conus flavidus, a worm-hunting cone snail inhabiting the Red Sea, on the oxidant/ antioxidant system in mice using some oxidative stress biomarker assays. In addition to assess its histopathological effects on some treated organs. The LC50 were detected for the crude venom using the hemolytic assay (16.7 mg/ml) and male albino mice were injected intraperitoneally with ½ LC50 (8.3 mg/kg B.Wt). Biochemically, after 2, 4, 6, 12, 24 hours of injection the results revealed significant inhibition of superoxide dismutase (SOD) and catalase (CAT) activities in blood and liver in almost all time intervals comparing with control one. However, it showed elevation in lipid peroxide content (LPC), protein carbonyl content (PCC), nitric oxide level (NO) reduced glutathione content (GSH) and total antioxidant capacity (TAC) contents of both blood and liver in almost all time intervals. Histopathologicaly, liver and heart were dissected after 1, 3 and 7 days of injection. The treated liver showed vacuolar degeneration, karyolosis and pyknosis, mild blood sinusoidal congestion and centrilobular necrosis. The treated heart illustrated degenerated myofibrils, pyknosis, edema, blood vessel congestion, loss of striation normal construction and fascicular pattern in the myocardium. These results revealed that C. flavidus crude venom has distinct effects upon the oxidant/antioxidant cellular system and degenerative pathological effects in some tissues of treated animals, proving that this venom may contain bioactive peptides, which could be purified and used for further pharmacological and drug discovery investigations in the future.}, year = {2017} }
TY - JOUR T1 - Assessment of Biochemical and Histopathological Effects of Crude Venom of Cone Snail Conus flavidus on albino Mice AU - Mona F. Abou-Elezz AU - Alaa Y. Moustafa AU - Mohamed S. El-Naggar Y1 - 2017/02/18 PY - 2017 N1 - https://doi.org/10.11648/j.ijee.20170201.15 DO - 10.11648/j.ijee.20170201.15 T2 - International Journal of Ecotoxicology and Ecobiology JF - International Journal of Ecotoxicology and Ecobiology JO - International Journal of Ecotoxicology and Ecobiology SP - 33 EP - 44 PB - Science Publishing Group SN - 2575-1735 UR - https://doi.org/10.11648/j.ijee.20170201.15 AB - The genus Conus is equipped with a unique venomous mixture of conopeptides which secreted for predation and defense purposes. This work is aiming to explore and determine the effect of the crude venom of Conus flavidus, a worm-hunting cone snail inhabiting the Red Sea, on the oxidant/ antioxidant system in mice using some oxidative stress biomarker assays. In addition to assess its histopathological effects on some treated organs. The LC50 were detected for the crude venom using the hemolytic assay (16.7 mg/ml) and male albino mice were injected intraperitoneally with ½ LC50 (8.3 mg/kg B.Wt). Biochemically, after 2, 4, 6, 12, 24 hours of injection the results revealed significant inhibition of superoxide dismutase (SOD) and catalase (CAT) activities in blood and liver in almost all time intervals comparing with control one. However, it showed elevation in lipid peroxide content (LPC), protein carbonyl content (PCC), nitric oxide level (NO) reduced glutathione content (GSH) and total antioxidant capacity (TAC) contents of both blood and liver in almost all time intervals. Histopathologicaly, liver and heart were dissected after 1, 3 and 7 days of injection. The treated liver showed vacuolar degeneration, karyolosis and pyknosis, mild blood sinusoidal congestion and centrilobular necrosis. The treated heart illustrated degenerated myofibrils, pyknosis, edema, blood vessel congestion, loss of striation normal construction and fascicular pattern in the myocardium. These results revealed that C. flavidus crude venom has distinct effects upon the oxidant/antioxidant cellular system and degenerative pathological effects in some tissues of treated animals, proving that this venom may contain bioactive peptides, which could be purified and used for further pharmacological and drug discovery investigations in the future. VL - 2 IS - 1 ER -