Allyl alcohol toxicity in isolated renal epithelial cells: protective effects of low molecular weight thiols.
The toxicity of allyl alcohol was studied in freshly isolated renal epithelial cells prepared from male and female rats. Cells from female rats demonstrated a greater susceptibility to allyl alcohol toxicity as assessed by glutathione depletion and loss of cell viability. The sensitivity of female rat renal cells appears to relate to the higher activity of alcohol dehydrogenase found in the female rat kidney, which metabolizes allyl alcohol to the highly reactive aldehyde, acrolein. Pyrazole, an inhibitor of alcohol dehydrogenase, abolished the cytotoxic effects of allyl alcohol whereas inhibition of aldehyde dehydrogenase by disulfiram treatment was found to increase the sensitivity of renal cells to the effects of allyl alcohol. The toxicity of allyl alcohol was decreased by a number of treatments which resulted in increased levels of glutathione or other low molecular weight thiols. These results indicate that acrolein is the toxic metabolite responsible for the renal cell injury following exposure to allyl alcohol, and unless immediately inactivated acrolein interacts with critical nucleophilic sites of the cell and initiates cell injury. These studies demonstrate that freshly isolated kidney cells represent a convenient model system for studies of thiol-mediated protective mechanisms against toxic renal cell injury.
Ohno
Y
Y
Jones
T W
TW
Ormstad
K
K
D000433:1-Propanol / Q000378:metabolism / Q000633:toxicity; D000426:Alcohol Dehydrogenase; D000429:Alcohol Oxidoreductases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D004221:Disulfiram / Q000494:pharmacology; D004347:Drug Interactions; D005260:Female; D005978:Glutathione / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D020005:Propanols; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012737:Sex Factors; D013438:Sulfhydryl Compounds / Q000494:pharmacology
D020005:Propanols; D011720:Pyrazoles; D013438:Sulfhydryl Compounds; C031280:pyrazole; C006463:allyl alcohol; D000433:1-Propanol; D000429:Alcohol Oxidoreductases; D000426:Alcohol Dehydrogenase; D005978:Glutathione; D004221:Disulfiram