Influence of ethanol on glutathione-S-transferase activity and glutathione content in the isolated perfused rabbit lung.
The induction of pulmonary glutathione-S-transferase (GST) by ethanol was investigated using the isolated perfused rabbit lung (IPRL) preparation with particular attention paid to the duration and route of ethanol administration. For perfusion with buffer containing 0.2% ethanol or acute ethanol treatment (4 g/kg by gastric intubation) 4 h before the IPRL preparation, there were no differences in the rate of glutathione (GSH) conjugation with 1-chloro-2,4-dinitrobenzene (CDNB) at low substrate concentrations (100-400 microM) but a decrease was observed in the rate at high substrate concentrations (500-1000 microM). Lungs from rabbits treated acutely showed the lowest maximal rate of GSH conjugation in the IPRL. Prolonged treatment with ethanol (10% in drinking water for 3 weeks) increased GSH conjugation (CDNB concentration of 300-750 microM). None of these ethanol treatments altered GSH conjugation with 1,2-epoxy(p-nitrophenoxy)propane (ENP). Upon termination of perfusion, there were no differences in pulmonary GSH concentration between control and ethanol-treated groups. Therefore, the effect of altered GSH level as a co-substrate on GST activity in lung might be excluded as an explanation for the effects of ethanol. These data suggest that ethanol has differential effects on GST activity depending upon the substrate and duration of ethanol administration.
Yang
C M
CM
Department of Pharmacology and Toxicology, School of Pharmacy and Pharmacal Sciences, Purdue University, West Lafayette, IN 47907.
Carlson
G P
GP
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004137:Dinitrochlorobenzene / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D004852:Epoxy Compounds / Q000378:metabolism; D000431:Ethanol / Q000097:blood / Q000494:pharmacology*; D005978:Glutathione / Q000032:analysis / Q000378:metabolism*; D005982:Glutathione Transferase / Q000378:metabolism*; D008168:Lung / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D009596:Nitrophenols / Q000378:metabolism; D011817:Rabbits; D013379:Substrate Specificity; D014361:Trypsin Inhibitors / Q000378:metabolism
D004137:Dinitrochlorobenzene; D004852:Epoxy Compounds; D009596:Nitrophenols; D014361:Trypsin Inhibitors; D000431:Ethanol; C007606:1,2-epoxy-3-(p-nitrophenoxy)propane; D005982:Glutathione Transferase; D005978:Glutathione