The effects of dichloroacetate on liver damage and circulating fuels in rats exposed to carbon tetrachloride.
It has been known that carbon tetrachloride-induced liver damage in starved rats is ameliorated simply by restoration of feeding. An analogue of dichloroacetate has been reported to ameliorate carbon tetrachloride-induced liver damage, and dichloroacetate has been shown to have a variety of effects on fuel metabolism. We investigated simultaneously the effects of dichloroacetate on liver damage and on circulating fuels in rats exposed to carbon tetrachloride. The effects of carbon tetrachloride varied with the rat's condition. In starved rats, the liver damage was more severe, and serum ketone body concentration decreased. In non-starved rats, the liver damage was not as severe and the serum ketone body concentration increased. The administration of dichloroacetate ameliorated liver damage both in starved and in non-starved rats given carbon tetrachloride: the administration of dichloroacetate protected from the liver damage particularly in starved rats. There were associated changes in the concentrations of circulating fuels. When the pyruvate-lowering effect of dichloroacetate was diminished in carbon tetrachloride-injected, starved rats, the alanine aminotransferase-lowering effect of dichloroacetate was also diminished. We propose that dichloroacetate's effect on fuel metabolism may produce a hepato-protective effect.
Irita
K
K
Department of Anesthesiology and Critical Care Medicine, Kyushu University School of Medicine, Fukuoka, Japan.
Okabe
H
H
Koga
A
A
Yamakawa
M
M
Yoshitake
J
J
Takahashi
S
S
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001769:Blood / Q000378:metabolism*; D002251:Carbon Tetrachloride / Q000494:pharmacology*; D003999:Dichloroacetic Acid / Q000494:pharmacology*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005978:Glutathione / Q000097:blood; D007274:Injections, Intraperitoneal; D008099:Liver / Q000187:drug effects* / Q000473:pathology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013217:Starvation
D005230:Fatty Acids, Nonesterified; D003999:Dichloroacetic Acid; D002251:Carbon Tetrachloride; D000410:Alanine Transaminase; D005978:Glutathione