Allyl alcohol cytotoxicity and glutathione depletion in isolated periportal and perivenous rat hepatocytes.
The mechanism of the periportal (p.p.) toxicity of allyl alcohol (AlOH) was investigated in p.p. and perivenous (p.v.) hepatocytes isolated by digitonin-collagenase perfusion. The distinct origin of the cell preparations was confirmed by the p.p./p.v. ratios of alanine aminotransferase (p.p./p.v. = 1.8), lactate dehydrogenase (1.3) and glutamine synthetase (0.10). The activity of alcohol dehydrogenase (ADH) was not markedly different in p.p. and p.v. cells. Both types of cells oxidized AlOH at a high but equal rate of about 3 mumol/(min.g cells). Concomitantly with rapid oxidation of 0.7 mM AlOH, glutathione (GSH) was depleted by about 95% and its secretion was completely inhibited in both cell types. Although the GSH content was partially restored during a subsequent 3-h incubation, cellular ATP and K+ content gradually decreased and the leakage of lactate dehydrogenase increased in both types of cells. However, the p.p. cells tended to resist AlOH in vitro better, probably due to their 26% higher GSH content after preincubation with L-methionine. Altering the partial pressure of oxygen in physiological range had no effect on the toxicity of AlOH. The results are contrary to the suggestions that the p.p. location of AlOH liver injury is caused by higher ADH activity or higher oxygen tension in the p.p. zone. Rather, the regiospecificity of the injury may be due to rapid uptake and oxidation of AlOH in the p.p. region.
Penttilä
K E
KE
Research Laboratories of the Finnish State Alcohol Company, Alko Ltd., Helsinki, Finland.
D000433:1-Propanol / Q000633:toxicity; D000255:Adenosine Triphosphate / Q000378:metabolism; D000426:Alcohol Dehydrogenase / Q000378:metabolism; D000818:Animals; D004072:Digitonin / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism*; D066298:In Vitro Techniques; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D003012:Microbial Collagenase / Q000494:pharmacology; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism; D020005:Propanols; D051381:Rats
D020005:Propanols; C006463:allyl alcohol; D000255:Adenosine Triphosphate; D000433:1-Propanol; D000426:Alcohol Dehydrogenase; D003012:Microbial Collagenase; D005978:Glutathione; D004072:Digitonin; D010100:Oxygen