Lack of response of the rat liver "class 3" cytosolic aldehyde dehydrogenase to toxic chemicals, glutathione depletion, and other forms of stress.
One of the rat liver "Class 3" cytosolic aldehyde dehydrogenases (EC 1.2.1.3), ALDH3c, is known to be markedly induced by polycyclic aromatic hydrocarbons and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; dioxin). In the present study we examined whether hepatic ALDH3c induction is a general response to toxicity. Treatment of Wistar rats for 4 days with known toxic doses of hepatotoxic agents--carbon tetrachloride, dimethylnitrosamine, diethylnitrosamine, aflatoxin B1, and D-ethionine--did not induce ALDH3c enzyme activity. Whereas dimethylaminoazobenzene at 100 mg/kg/day for 4 days did not increase ALDH3c, a 10-fold lower dose of dimethylaminoazobenzene for 4 days produced a 20-fold increase in ALDH3c activity. Treatment with phorone, diethylmaleate or L-buthionine-S,R-sulfoximine--which deplete reduced glutathione (GSH) by different mechanisms--did not affect ALDH3c activity. One dose of benzo[a]pyrene for 24 hr increased ALDH3c activity by 25-fold. Treatment with both the GSH-depleting chemicals and benzo[a]pyrene inhibited ALDH3c induction by 45% to 75%, suggesting a role for GSH during ALDH3c induction. After ALDH3c activity had already been induced by benzo[a]pyrene, however, the GSH-depleting chemicals did not affect ALDH3c activity. No changes in ALDH3c activity were seen 24 or 48 hr after partial hepatectomy, on the fifth day following surgical cholestasis, or after guanethidine-induced sympathectomy. These data indicate that hepatic ALDH3c inducibility in the rat is not a general or direct response to chemical toxicity, or to conditions of GSH depletion or other forms of stress.
Pappas
P
P
Department of Pharmacology Medical School, University of Ioannina, Greece.
Vasiliou
V
V
Nebert
D W
DW
Marselos
M
M
D000444:Aldehyde Dehydrogenase / Q000096:biosynthesis*; D000818:Animals; D001564:Benzo(a)pyrene / Q000633:toxicity; D002251:Carbon Tetrachloride / Q000633:toxicity; D003600:Cytosol / Q000201:enzymology; D004052:Diethylnitrosamine / Q000633:toxicity; D004790:Enzyme Induction; D005978:Glutathione / Q000378:metabolism*; D006498:Hepatectomy; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D004124:p-Dimethylaminoazobenzene / Q000633:toxicity
D001564:Benzo(a)pyrene; D004052:Diethylnitrosamine; D004124:p-Dimethylaminoazobenzene; D002251:Carbon Tetrachloride; D000444:Aldehyde Dehydrogenase; D005978:Glutathione