Inhibition of hepatic aldehyde dehydrogenase by carbon tetrachloride: an in vitro study.
In vitro inhibition of rat liver mitochondrial and microsomal aldehyde dehydrogenase (ALDH) under conditions of active CCl4 metabolism was investigated. Incubation of microsomes or mitochondria in the presence of NADPH alone caused significant, time-dependent inhibition of mitochondrial and microsomal ALDH. EDTA partially protected ALDH from inhibition. Incubation of microsomes or microsomes plus mitochondria in the presence of NADPH and CCl4 resulted in marked inhibition of microsomal and mitochondrial ALDH activity. The inhibition was both dose- and time-dependent and was relatively less in the presence of EDTA. It is proposed that the inhibition of membrane-bound ALDH may be one of the early events responsible for the genesis of CCl4-hepatotoxicity.
D000444:Aldehyde Dehydrogenase / Q000037:antagonists & inhibitors*; D000818:Animals; D002251:Carbon Tetrachloride / Q000378:metabolism / Q000494:pharmacology*; D004492:Edetic Acid / Q000494:pharmacology; D066298:In Vitro Techniques; D008099:Liver / Q000201:enzymology*; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D008930:Mitochondria, Liver / Q000201:enzymology; D009243:NAD / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D009243:NAD; D009249:NADP; D004492:Edetic Acid; D002251:Carbon Tetrachloride; D000444:Aldehyde Dehydrogenase