Role of cyclooxygenases in oedema-forming activity of bothropic venoms

The venoms of Bothrops asper (BaV) and Bothrops jararaca (BjV), two of the most medically important poisonous snakes of Latin America, cause pronounced oedema in the victims through poorly understood mechanisms. In the present study, we examined the possible role of cyclooxygenases (COX) in the gene...

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Bibliographic Details
Published in:	Toxicon (Oxford) Vol. 49; no. 5; pp. 670 - 677
Main Authors:	Olivo, Renata do A., Teixeira, Catarina F.P., Wallace, John L., Gutierrez, Jose M., Zamuner, Stella R.
Format:	Journal Article
Language:	English
Published:	Oxford Elsevier Ltd 01-04-2007 Elsevier Science
Subjects:	Analysis of Variance Animal poisons toxicology. Antivenoms Animals Anti-Inflammatory Agents - therapeutic use Biological and medical sciences Blotting, Western Bothrops Bothrops asper Bothrops jararaca COX-2 Crotalid Venoms - toxicity Cyclooxygenase Cyclooxygenase 2 Inhibitors - therapeutic use Dexamethasone - therapeutic use Edema - drug therapy Edema - enzymology Edema - etiology Indomethacin - therapeutic use Inflammation Lactones - therapeutic use Male Medical sciences Mice PGE 2 Prostaglandin-Endoperoxide Synthases - metabolism Snake Bites - complications Snake Bites - drug therapy Snake Bites - enzymology Sulfones - therapeutic use Toxicology Bothrops asper Cyclooxygenase COX-2 Bothrops jararaca BaV PG PGE 2 Inflammation COX BjV Edema Prostaglandin-endoperoxide synthase PGE2 Enzyme Toxicity Animal origin Ophidia Vertebrata Venom Reptilia Oxidoreductases Mechanism of action
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Summary:	The venoms of Bothrops asper (BaV) and Bothrops jararaca (BjV), two of the most medically important poisonous snakes of Latin America, cause pronounced oedema in the victims through poorly understood mechanisms. In the present study, we examined the possible role of cyclooxygenases (COX) in the genesis of mouse paw oedema caused by BaV and BjV injections. BaV at 2.5 μg/paw and BjV at 0.75 μg/paw induced significant oedema that persisted for up to 6 h following subplantar injection. Treatment with indomethacin (2 mg/kg), rofecoxib, (10 mg/kg), or dexamethasone (2 mg/kg) significantly reduced the BaV- and BjV-induced oedema formation. Treatment with SC-560 (30 mg/kg) significantly reduced the oedema formation induced by BjV but had no effect on that induced by BaV. Both venoms induced significant increases in the levels of prostaglandin E 2 (PGE 2) and the expression of COX-1 and COX-2 in paw tissue. The peak of oedema formation and PGE 2 release correlated with marked expression of COX-2 in the paw tissue. These results demonstrate that injection of BaV and BjV results in a rapid increase in oedema formation that is, at least partially, mediated by arachidonic acid metabolites formed by COX-2. In the case of BjV, COX-1-derived prostanoids also appear to contribute significantly to the inflammatory changes.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0041-0101 1879-3150
DOI:	10.1016/j.toxicon.2006.11.006