Comparison of N-Methylformamide-Induced Hepatotoxicity and Metabolism in Rats and Mice
N-Methylformamide (NMF) is a solvent and a potential anticancer drug which is hepatotoxic in man (1); mice (2) and rats (3) causing centrilobular hepatic necrosis. However, the mechanism underlying this hepatotoxicity is currently unknown. NMF is extensively metabolised in mice in vivo (4)(Fig. 1). However, no metabolism has been detected in vitro in liver fractions or isolated hepatocytes (2). N-hydroxymethyl formamide (NMFOH) has been indirectly identified as a urinary metabolite of NMF (4). NMF causes depletion of non-protein thiols in vivo in mice (5) and in mouse hepatocytes (2) and also causes lipid peroxidation in hepatocytes (2). Although NMF has been reported to be hepatotoxic in rats (3) as well as mice, in our hands, rats were very much less sensitive. Consequently we have investigated the metabolism and toxicity of NMF in both rats and mice, to determination the possible correlation between metabolism and toxicity.
KeywordsCovalent Binding Urinary Metabolite Aspartate Transaminase Radioactive Metabolite NADPH Generate System
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