Prostanoids and cyclosporin-mediated nephrotoxicity in rats: A critical appraisal

Abstract The involvement of arachidonic acid metabolism in cyclosporin (CsA) nephrotoxicity depending on CsA vehicle has been explored in this study. For this purpose creatinine clearance, urinary excretion and renal levels of eicosanoids were measured in the following rat experimental groups: group I, control; group II, CsA was administered in olive oil by gavage at 15 mg/kg/d for 7 d; group III, same as group II but 30 mg/kg/d; group IV, CsA was administered in fish oil by gavage at 15 mg/kg/d for 7 d; group V, same as group IV but 30 mg/kg/d; group VI, CsA was administered in olive oil at 15 mg/kg/d with prednisolone (1 mg/kg/d). The results indicate that (1) CsA nephrotoxicity and prostanoid alterations seem to be greatly improved when fish oil substitutes olive oil as a vehicle for CsA administration and (2) a correlation was found between eicosanoids measured and renal function, except in group II in which creatinine clearance remains unmodified but eicosanoids were altered, thus suggesting that other factors play a role in mediating nephrotoxicity due to cyclosporin.