© 1992 Oxford University Press
research-article |
The Effects of 
,ß-Unsaturated Aldehydes on Hepatic Thiols and Thiol-Containing Enzymes
The Joint Graduate Program in Toxicology, Rutgers University, Robert Wood Johnson Medical School/UMDNJ New Jersey 08903
Received November 13, 1991; accepted April 10, 1992
The effects of series of 
,ß-unsaturated aldehydes on hepatic giutathione, cytochrome P450, and NADPH-cytochrome c reductase activity were compared with time. Male F-344 rats were dosed with muconaldehyde (36 µmol/kg), acrolein (89 µmol/ kg), crotonaldehyde (450 µmol/kg), or the saturated aldehyde propionaldehyde (89 µmol/kg) and terminated 0.5, 4, or 24 hr later. Acroiein or muconaldehyde reduced glutathione to 51 and 75% of controls, respectively, at 4 hr; glutathione returned control values at 24 hr. Only at 24 hr, acrolein, muconaldehyde, or crotonaldehyde decreased cytochrome P450 to 61, 71, and 67% of control values, respectively; ethylmorphine N-demethylation was decreased to a greater extent, i.e., to 35, 60, and 23% of controls. The reductase activity was unchanged at any time following the treatment with reactive aldehydes which were not hepatotoxic (as shown by glucose 6-phosphatase activity, histological changes, or serum enzymes). Propionaidehyde changed none of these activities. Acroiein (44.5 µmol/kg) given 4 hr prior to phenobarbital (50 mg/kg) for two consecutive days decreased the phenobarbital induction of cytochrome P450 45% of phenobarbital alone. This treatment also decreased the 2, 2ß, 6ß, l6, and 16ß hydroxylation of testosterone as well as androstenedione formation showing effects on individual cytochrome P450 isozymes. NADPH-cytochrome c reductase induction was not decreased by this treatment, thus indicating that in vivo these changes are due to a mechanism other than generalized inhibition of protein synthesis.