Failure of gentamicin to elevate cellular malondialdehyde content or increase generation of intracellular reactive oxygen species in primary cultures of renal cortical epithelial cells.
The role of lipid peroxidation in gentamicin cytotoxicity was assessed in primary cultures of renal cortical epithelial cells. The cellular content of malondialdehyde (MDA), one of the end products of lipid peroxidation, was determined, and the intracellular generation of reactive oxygen species, one of the events commonly occurring at the beginning of the process of lipid peroxidation, was estimated. Exposures to gentamicin were chosen that preceded or accompanied overt toxicity. MDA was determined by the thiobarbituric acid reactive substances assay. Intracellular generation of reactive oxygen species was estimated by quantitating the fluorescence of 2',7'-dichlorofluorescein (DCF'), a fluorophore formed by the reaction of the deacetylation product (2',7'-dichlorofluorescein, DCF) of the fluorescent probe 2',7'-dichlorofluorescein diacetate (DCFDA) with reactive oxygen species. Neither elevated MDA content nor intracellular generation of reactive oxygen species was observed in primary cultures of renal cortical epithelial cells treated with gentamicin, using exposures which preceded or accompanied overt toxicity. We conclude that lipid peroxidation does not play a role in gentamicin cytotoxicity.
Swann
J D
JD
Division of Pharmacology/Toxicology, College of Pharmacy, University of Texas, Austin 78712.
Acosta
D
D
D000818:Animals; D002478:Cells, Cultured; D002509:Cephaloridine / Q000494:pharmacology; D004848:Epithelium / Q000378:metabolism; D005452:Fluoresceins; D005456:Fluorescent Dyes; D005839:Gentamicins / Q000494:pharmacology*; D007672:Kidney Cortex / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000187:drug effects; D008315:Malondialdehyde / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D010545:Peroxides / Q000494:pharmacology; D020122:tert-Butylhydroperoxide
D005452:Fluoresceins; D005456:Fluorescent Dyes; D005839:Gentamicins; D010545:Peroxides; C029569:diacetyldichlorofluorescein; D008315:Malondialdehyde; C037631:2',7'-dichlorofluorescein; D020122:tert-Butylhydroperoxide; D002509:Cephaloridine; D010100:Oxygen