Protective effect of fosfomycin on gentamicin-induced lipid peroxidation of rat renal tissue.
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.
Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, 260-8675, Japan.
Chie
C
Yanagida
Kousei
K
Ito
Izumi
I
Komiya
Toshiharu
T
Horie
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005578:Fosfomycin / Q000494:pharmacology*; D005839:Gentamicins / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007501:Iron / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D000900:Anti-Bacterial Agents; D005839:Gentamicins; D017392:Thiobarbituric Acid Reactive Substances; D005578:Fosfomycin; D007501:Iron