The renal effects of Bothrops jararacussu venom and the role of PLA(2) and PAF blockers.
The most common complication in the lethal cases of ophidian bites in Brazil is acute renal failure, but its pathogenesis is obscure. The effects of Bothrops jararacussu venom (3, 10 and 30 microg/ml) were examined using the isolated perfused kidney from Wistar rats. Dexamethasone, and WEB 2086, a triazolobenzodiazepine substance, which is a platelet activating factor receptor antagonist, were tested for a possible blockade of the renal effects in the presence of 10 microg/ml of venom. The most intense effects of the venom were noticed at 120 min after using 30 microg/ml. We observed a decrease in the perfusion pressure and in the renal vascular resistance. However, the glomerular filtration rate (GFR) and the urinary flow (UF) increased significantly. The percent of sodium (%Na(tot)(+)) and potassium (%K(tot)(+)) tubular transport were also decreased. Dexamethasone was unable to block the effects of B. jararacussu in the kidney, while WEB 2086 blocked its effect in glomerular filtration rate, urinary flow and in the percentage of total tubular potassium reabsorption. We suggest that this venom promotes diuresis independently of perfusion pressure drop. The alterations in GFR, UF and %K(tot)(+) are probably mediated by platelet activating factor. Dexamethasone did not block the renal effects maybe because of the concentration used in this work or maybe the renal effects are promoted by the myotoxin, which does not have PLA(2) activity.
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Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceara, Rua Cel. Nunes de Melo 1127, 60430-270 Fortaleza, CE, Brazil.
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Monteiro
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D000818:Animals; D016824:Antigens, Human Platelet / Q000502:physiology*; D001381:Azepines / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D017837:Bothrops / Q000502:physiology*; D003435:Crotalid Venoms / Q000633:toxicity*; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D007668:Kidney / Q000098:blood supply / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D010477:Perfusion; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000502:physiology*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D011312:Pressure; D051381:Rats; D017208:Rats, Wistar; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology; D012964:Sodium / Q000378:metabolism; D014230:Triazoles / Q000494:pharmacology; D014554:Urination / Q000187:drug effects / Q000502:physiology; D014563:Urodynamics
D016824:Antigens, Human Platelet; D001381:Azepines; D003435:Crotalid Venoms; D004338:Drug Combinations; D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors; D014230:Triazoles; C083451:human platelet antigen 1b; C052518:WEB 2086; D003907:Dexamethasone; D012964:Sodium; D011188:Potassium