Role of liver cytosolic aldehyde dehydrogenase isozymes in control of blood acetaldehyde concentrations.
The role of various cytosolic aldehyde dehydrogenase (ALDH) isozymes in acetaldehyde metabolism was determined. Rats of known genotype (RR, reactor; rr, nonreactor) with respect to induction of a cytosolic enzyme by phenobarbital were used. Animals were treated with either phenobarbital (1.0 mg/ml in drinking water for 3 days) or 75 microng/kg (i.p.) of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) prior to ethanol treatment (2.5 g/kg). TCDD treatment is known to induce a second cytosolic ALDH isozyme in both RR and rr animals. Phenobarbital increased cytosolic ALDH activity 23-fold only in the RR animals, while TCDD increased activity 155-fold in both groups. Phenobarbital-treated RR rats maintained significantly lower blood acetaldehyde levels at 30, 90 and 150 minutes after ethanol injection compared to control RR animals. Blood acetaldehyde levels in phenobarbital-treated rr rats were not significantly different from rr controls. Administration of TCDD to RR or rr rats did not significantly alter blood acetaldehyde levels at 30, 90 or 150 minutes after ethanol treatment compared to appropriate controls. Similarly, phenobarbital significantly increased blood ethanol elimination rate (1.5 times greater than control) only in RR rats. Ethanol elimination rate was not significantly altered by TCDD in either group. Pargyline (100 mg/kg i.p.) did not significantly inhibit cytosolic ALDH activity, while total mitochondrial ALDH activity was inhibited by 28 and 57% in RR animals receiving TCDD and phenobarbital, respectively. Pargyline significantly increased blood acetaldehyde levels after ethanol administration. However, pretreatment with phenobarbital or TCDD significantly decreased elevated blood acetaldehyde levels resulting from pargyline treatment, with the greatest reduction in the phenobarbital-treated RR animals.
D000079:Acetaldehyde / Q000097:blood*; D000445:Aldehyde Oxidoreductases / Q000096:biosynthesis / Q000378:metabolism* / Q000502:physiology*; D000818:Animals; D003600:Cytosol / Q000201:enzymology*; D004790:Enzyme Induction / Q000187:drug effects; D000431:Ethanol / Q000097:blood; D007527:Isoenzymes / Q000096:biosynthesis / Q000378:metabolism* / Q000502:physiology*; D007700:Kinetics; D008099:Liver / Q000201:enzymology / Q000648:ultrastructure*; D051379:Mice; D008815:Mice, Inbred Strains; D008930:Mitochondria, Liver / Q000201:enzymology; D010293:Pargyline / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010634:Phenobarbital / Q000494:pharmacology; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology; D051381:Rats; D013045:Species Specificity; D013997:Time Factors
D007527:Isoenzymes; D000072317:Polychlorinated Dibenzodioxins; D000431:Ethanol; D010293:Pargyline; D000445:Aldehyde Oxidoreductases; D000079:Acetaldehyde; D010634:Phenobarbital