Trichloroethylene inhibits aldehyde dehydrogenase only for aliphatic aldehydes of short chains in rats.
The effects of trichloroethylene (TCE) administration on aldehyde dehydrogenase (ALDH) and cytochrome P450 isozymes were studied in rats and compared with those of methanol. Intragastric administration of TCE to rats at 0.05 or 0.2 ml/kg for 1 week significantly inhibited ALDH activity for aliphatic aldehydes of short chains in the mitochondrial and cytosolic fractions of rat liver, respectively, but had no effect on the activity for long chain aliphatic aldehydes. ALDH activity catalyzing the metabolism of some aromatic aldehydes was even induced by TCE. Microsomal ALDH activity was not decreased by TCE treatment. A kinetic study showed that the low-Km isozyme of ALDH for propionaldehyde in mitochondrial and cytosolic fractions was inhibited by TCE treatment. Addition of TCE, trichloroethanol or trichloroacetic acid to the in vitro assay system did not affect the activity for acetaldehyde, but chloral hydrate at 0.02 mM decreased the activity by 42 and 35% in cytosol and the 700 x g supernatant, respectively. Methanol treatment, on the other hand, had no effect on any ALDH activity. Both TCE and methanol significantly induced CYP2E1 in rat liver. The combined effects of TCE on ALDH and cytochrome P450 may account for the degreasers' flush. Exposure to TCE and methanol may result in a change in the metabolism and toxicity of other chemicals.
Wang
R S
RS
Division of Health Effects Research, National Institute of Industrial Health, Kawasaki, Japan. wang@niih.go.jp
Nakajima
T
T
Honma
T
T
D000426:Alcohol Dehydrogenase / Q000037:antagonists & inhibitors / Q000378:metabolism; D000444:Aldehyde Dehydrogenase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000447:Aldehydes / Q000737:chemistry*; D000818:Animals; D002458:Cell Fractionation; D002697:Chloral Hydrate / Q000633:toxicity; D019392:Cytochrome P-450 CYP2E1 / Q000096:biosynthesis; D003600:Cytosol / Q000201:enzymology; D004338:Drug Combinations; D004347:Drug Interactions; D008297:Male; D000432:Methanol / Q000378:metabolism / Q000633:toxicity; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D008930:Mitochondria, Liver / Q000187:drug effects / Q000201:enzymology*; D051381:Rats; D017208:Rats, Wistar; D012997:Solvents / Q000378:metabolism / Q000633:toxicity*; D014241:Trichloroethylene / Q000378:metabolism / Q000633:toxicity*
D000447:Aldehydes; D004338:Drug Combinations; D012997:Solvents; D014241:Trichloroethylene; D002697:Chloral Hydrate; D000426:Alcohol Dehydrogenase; D019392:Cytochrome P-450 CYP2E1; D000444:Aldehyde Dehydrogenase; D000432:Methanol