The effects of alpha, beta-unsaturated aldehydes on hepatic thiols and thiol-containing enzymes.
The effects of series of alpha, beta-unsaturated aldehydes on hepatic glutathione, cytochrome P450, and NADPH-cytochrome c reductase activity were compared with time. Male F-344 rats were dosed with muconaldehyde (36 mumol/kg), acrolein (89 mumol/kg), crotonaldehyde (450 mumol/kg), or the saturated aldehyde propionaldehyde (89 mumol/kg) and terminated 0.5, 4, or 24 hr later. Acrolein or muconaldehyde reduced glutathione to 51 and 75% of controls, respectively, at 4 hr; glutathione returned to 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). Propionaldehyde changed none of these activities. Acrolein (44.5 mumol/kg) given 4 hr prior to phenobarbital (50 mg/kg) for two consecutive days decreased the phenobarbital induction of cytochrome P450 to 45% of phenobarbital alone. This treatment also decreased the 2 alpha, 2 beta, 6 beta, 16 alpha, and 16 beta 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.
Cooper
K O
KO
Joint Graduate Program in Toxicology, Rutgers University, Robert Wood Johnson Medical School/UMDNJ, Piscataway 08903.
Witz
G
G
Witmer
C
C
D000171:Acrolein / Q000378:metabolism; D000447:Aldehydes / Q000633:toxicity*; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects; D005952:Glucose-6-Phosphatase / Q000378:metabolism; D006651:Histocytochemistry; D007527:Isoenzymes; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D006899:Mixed Function Oxygenases / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D013250:Steroid Hydroxylases / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000378:metabolism*; D013739:Testosterone / Q000378:metabolism
D000447:Aldehydes; D007527:Isoenzymes; D013438:Sulfhydryl Compounds; D013739:Testosterone; D000171:Acrolein; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D013250:Steroid Hydroxylases; D001189:Aryl Hydrocarbon Hydroxylases; C022724:testosterone 7-alpha-hydroxylase, hamster; D005952:Glucose-6-Phosphatase