Hepatotoxicity due to allyl alcohol in deermice depends on alcohol dehydrogenase.
The role of alcohol dehydrogenase in the hepatic necrosis due to allyl alcohol was studied in two strains of the deermouse, Peromyscus maniculatus. Mice of the alcohol dehydrogenase-negative (AdhN) strain which lack alcohol dehydrogenase activity were resistant to allyl alcohol toxicity. In contrast, dose-dependent necrosis of periportal regions of the liver and increases in plasma levels of lactate dehydrogenase, sorbitol dehydrogenase and SGOT were observed in plasma from alcohol dehydrogenase-positive deermice (AdhF) 24 hr following administration of allyl alcohol (21 to 84 mg per kg). Half-maximal damage to periportal areas was observed with about 52 mg per kg allyl alcohol. Thus, these data demonstrate that metabolism of allyl alcohol to acrolein by alcohol dehydrogenase is obligatory for the hepatotoxicity of allyl alcohol.
Belinsky
S A
SA
Bradford
B U
BU
Forman
D T
DT
Glassman
E B
EB
Felder
M R
MR
Thurman
R G
RG
D000433:1-Propanol / Q000633:toxicity; D000426:Alcohol Dehydrogenase; D000429:Alcohol Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D004305:Dose-Response Relationship, Drug; D007064:L-Iditol 2-Dehydrogenase / Q000097:blood; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D009336:Necrosis; D010084:Oxidation-Reduction; D010542:Peromyscus / Q000235:genetics; D020005:Propanols
D020005:Propanols; C006463:allyl alcohol; D000433:1-Propanol; D000429:Alcohol Oxidoreductases; D000426:Alcohol Dehydrogenase; D007064:L-Iditol 2-Dehydrogenase; D001219:Aspartate Aminotransferases