Effects of aldehyde dehydrogenase and glutathione on the degradation of (E)-4-hydroxy-2-nonenal and N-hexanal in rat liver.
The relative contribution of the aldehyde dehydrogenase (EC 1.2.1.3, ALDH) and glutathione (GSH) conjugate system to the degradation of (E)-4-hydroxy-2-nonenal (4HN), a toxic breakdown product arising from lipid peroxidation, was investigated in rat liver. Significant increases in the contents of 4HN and hexanal (HA) and a decrease of ALDH but not alcohol dehydrogenase (EC 1.1.1.2, ADH) activity were recognized in rat liver following administration of carbon tetrachloride (3 ml/kg, p.o.). Hepatic ALDH activity was correlated with HA production (r = -0.82, P < 0.01) but not with 4HN. When lipid peroxidation was induced by t-butyl hydroperoxide, the ratio of HA to 4HN production in the liver of rats pretreated with the ALDH inhibitor, cyanamide (100 mg/kg, i.p.) was higher than that in controls, whereas the ratio was lower in the liver of rats pretreated with the glutathione-depleting agent, phorone (250 mg/kg, i.p.). These results suggest that 4HN in rat liver is metabolized by the GSH-conjugate system in preference to degradation by ALDH.
Laboratory of Health Science, School of Pharmaceutical Sciences, University of Shizuoka, Japan.
M
M
Fujita
M
M
Sano
K
K
Yoshino
I
I
Tomita
D000426:Alcohol Dehydrogenase / Q000378:metabolism; D000444:Aldehyde Dehydrogenase / Q000378:metabolism*; D000447:Aldehydes / Q000378:metabolism*; D000818:Animals; D001673:Biodegradation, Environmental; D002251:Carbon Tetrachloride / Q000494:pharmacology; D003484:Cyanamide / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism*; D007659:Ketones / Q000494:pharmacology; D007700:Kinetics; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010545:Peroxides / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000494:pharmacology; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis; D020122:tert-Butylhydroperoxide
D000447:Aldehydes; D007659:Ketones; D010545:Peroxides; D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances; D003484:Cyanamide; C018637:phorone; D020122:tert-Butylhydroperoxide; C010463:n-hexanal; D002251:Carbon Tetrachloride; D000426:Alcohol Dehydrogenase; D000444:Aldehyde Dehydrogenase; D005978:Glutathione; C027576:4-hydroxy-2-nonenal