Casas A, Hotter G, Roselló-Catafau J, Fernández-Cruz L, Gelpí E
Molecular Pathology Unit, Centro de Investigación y Desarrollo (CSIC), Barcelona, Spain.
Prostaglandins Leukot Essent Fatty Acids. 1995 Jan;52(1):49-53. doi: 10.1016/0952-3278(95)90096-9.
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 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.
本研究探讨了取决于环孢素（CsA）载体的花生四烯酸代谢在CsA肾毒性中的作用。为此，在以下大鼠实验组中测量了肌酐清除率、类二十烷酸的尿排泄和肾脏水平：第一组，对照组；第二组，以15mg/kg/d的剂量通过灌胃给予橄榄油中的CsA，持续7天；第三组，与第二组相同，但剂量为30mg/kg/d；第四组，以15mg/kg/d的剂量通过灌胃给予鱼油中的CsA，持续7天；第五组，与第四组相同，但剂量为30mg/kg/d；第六组，以15mg/kg/d的剂量给予橄榄油中的CsA和泼尼松龙（1mg/kg/d）。结果表明：（1）当鱼油替代橄榄油作为CsA给药的载体时，CsA肾毒性和前列腺素改变似乎得到了极大改善；（2）在所测量的类二十烷酸与肾功能之间发现了相关性，但在第二组中除外，该组肌酐清除率未改变，但类二十烷酸发生了改变，因此表明其他因素在介导环孢素引起的肾毒性中起作用。
