The consequences of nitrofurantoin-induced oxidative stress in isolated rat hepatocytes: evaluation of pathobiochemical alterations.
Oxidative stress was induced in isolated rat hepatocytes by incubation with nitrofurantoin in the absence and presence of the GSSG reductase inhibitor BCNU. In both cases nitrofurantoin markedly reduced glutathione but exerted cytotoxicity as measured by LDH release and loss of intracellular potassium only in BCNU pretreated cells. The onset of cytotoxicity was accompanied by an increase of lipid peroxidation. Oxidation of protein thiols, however, could not be detected in the early phase of cell damage. The cytoprotective activity of N-acetyl-cysteine > dithiothreitol = deferoxamine revealed the substantial importance of glutathione for cellular defence and the sensitivity of not yet identified thiol-dependent targets of oxidative stress.
Klee
S
S
Institute of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Free University of Berlin, Germany.
Nürnberger
M C
MC
Ungemach
F R
FR
D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D002330:Carmustine / Q000494:pharmacology; D003676:Deferoxamine / Q000494:pharmacology; D004229:Dithiothreitol / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism; D005980:Glutathione Reductase / Q000037:antagonists & inhibitors; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000187:drug effects*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009582:Nitrofurantoin / Q000494:pharmacology*; D010084:Oxidation-Reduction; D051381:Rats; D017208:Rats, Wistar; D013312:Stress, Physiological / Q000139:chemically induced* / Q000378:metabolism
D008315:Malondialdehyde; D009582:Nitrofurantoin; D007770:L-Lactate Dehydrogenase; D005980:Glutathione Reductase; D005978:Glutathione; D003676:Deferoxamine; D004229:Dithiothreitol; D002330:Carmustine; D000111:Acetylcysteine