Protective effect of fosfomycin on gentamicin-induced lipid peroxidation of rat renal tissue |
| |
Authors: | Yanagida Chie Ito Kousei Komiya Izumi Horie Toshiharu |
| |
Institution: | Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, 260-8675, Japan. |
| |
Abstract: | Fosfomycin is clinically recognized to reduce the aminoglycoside antibiotics-induced nephrotoxicity. However, little has been clarified why fosfomycin protects the kidney from the aminoglycosides-induced nephrotoxicity. Gentamicin, a typical aminoglycoside, is reported to cause lipid peroxidation. We focused on lipid peroxidation induced by gentamicin as a mechanism for the aminoglycosides-induced nephrotoxicity. The aim of this study is to investigate the effect of fosfomycin on the gentamicin-induced lipid peroxidation. In rat renal cortex mitochondria, fosfomycin was shown to depress the gentamicin-induced lipid peroxidation, which was evaluated by formation of thiobarbituric acid reactive substances (TBARS). Interestingly, this effect was observed in rat renal cortex mitochondria, but not in rat liver microsomes. However, fosfomycin did not affect lipid peroxidation of arachidonic acid caused by gentamicin with iron. Fosfomycin inhibited the gentamicin-induced iron release from rat renal cortex mitochondria. These results indicated that fosfomycin inhibited the gentamicin-induced lipid peroxidation by depressing the iron release from mitochondria. This may possibly be one mechanism for the protection of fosfomycin against the gentamicin-induced nephrotoxicity. |
| |
Keywords: | TBARS thiobarbituric acid reactive substances AGs aminoglycoside antibiotics BSA bovine serum albumin EGTA ethylene glycol-bis (β-aminoether)-N N N′ N′-tetraacetic acid TCA trichloroacetic acid MDA malondialdehyde |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|