Rat hepatic mitochondria are more sensitive to allyl alcohol than are those of mice.
The hepatotoxic effects of allyl alcohol with particular reference to mitochondrial morphology and function were compared in male CD1 mice and male CD rats 24 h after 0.05 ml/kg i.p. in corn oil. As already noted by others, allyl alcohol-treated rats usually showed histologic evidence of tissue necrosis when hematoxylin-eosin-stained tissue sections were examined whereas mouse tissue sections did not. The serum glutamic pyruvic transaminase (SGPT) activities were significantly elevated in both mice and rats but to a much greater extent in the latter. Pentobarbital sleeping time was significantly increased over that of corn oil control groups in rats but decreased in mice. In rats electron microscopy showed mitochondria which contained flocculent densities. State 4 respiration was not altered by allyl alcohol in rats, but state 3 respiration was significantly depressed indicating an absence of respiratory control and an inability to perform energy coupling. In allyl alcohol-treated mice the isolated mitochondria were found to be primarily in a condensed form. Except for the effect on pentobarbital sleeping time and SGPT, no other findings were different from those in control groups given only corn oil. When the dose of allyl alcohol in mice was increased to 0.15 ml/kg in an attempt to elicit more severe signs of hepatotoxicity, there was a high mortality in the first 24 h period without histologic evidence of liver necrosis. Thus, we confirm that at equivalent doses, male rats are more sensitive to the hepatotoxic effects of allyl alcohol than are male mice, and extend the generalization to the liver mitochondria of the 2 species.
Jacobs
J M
JM
Department of Pharmacology and Toxicology, Dartmouth Medical School, Hanover, NH 03756.
Rutkowski
J V
JV
Roebuck
B D
BD
Smith
R P
RP
D000433:1-Propanol / Q000494:pharmacology / Q000633:toxicity; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D004351:Drug Resistance; D006519:Hepatitis, Alcoholic / Q000201:enzymology / Q000209:etiology / Q000473:pathology; D051379:Mice; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000648:ultrastructure; D009336:Necrosis; D010424:Pentobarbital / Q000494:pharmacology; D020005:Propanols; D051381:Rats; D013045:Species Specificity
D020005:Propanols; C006463:allyl alcohol; D000433:1-Propanol; D000410:Alanine Transaminase; D010424:Pentobarbital