Protective role of fructose 1,6-bisphosphate during CCl4 hepatotoxicity in rats.
Rats were injected intraperitoneally with CCl4 (2.5 ml/kg body wt.) and the hepatotoxicity was compared with that of rats receiving the same dose of CCl4 and an intraperitoneal injection of fructose 1,6-bisphosphate (2 g/kg body wt.). A 50-70% decrease in plasma aspartate aminotransferase and alanine aminotransferase activities was observed in the latter treatment, indicating a protective role of the sugar bisphosphate in CCl4 hepatotoxicity. The protection was accompanied by elevated hepatic activities of ornithine decarboxylase at 2, 6 and 24 h, S-adenosylmethionine decarboxylase at 6 h, and spermidine N1-acetyltransferase at 2 h. The increase in the enzymes involved in polyamine metabolism was shown in our previous work [Rao, Young & Mehendale (1989) J. Biochem. Toxicol. 4, 55-63] to correlate with increased polyamine synthesis or interconversion, which was related to the extent of hepatocellular regeneration. The hepatic contents of fructose 1,6-bisphosphate and ATP significantly decreased after CCl4 treatment, and administration of the sugar bisphosphate increased hepatic ATP. Fructose 1,6-bisphosphate, an intermediary metabolite of the glycolytic pathway, may decrease CCl4 toxicity by increasing the ATP in the hepatocytes. The ATP generated is useful for hepatocellular regeneration and tissue repair, events which enable the liver to overcome CCl4 injury.
Rao
S B
SB
Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson 39216-4505.
Mehendale
H M
HM
D000123:Acetyltransferases / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D012437:Adenosylmethionine Decarboxylase / Q000378:metabolism; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D002252:Carbon Tetrachloride Poisoning / Q000097:blood*; D056486:Chemical and Drug Induced Liver Injury; D005635:Fructosediphosphates / Q000627:therapeutic use*; D006598:Hexosediphosphates / Q000627:therapeutic use*; D008099:Liver / Q000201:enzymology; D008107:Liver Diseases / Q000517:prevention & control; D008297:Male; D009955:Ornithine Decarboxylase / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D000099228:Diamine N-Acetyltransferase
D000123:Acetyltransferases; D000255:Adenosine Triphosphate; D012437:Adenosylmethionine Decarboxylase; D000410:Alanine Transaminase; D001219:Aspartate Aminotransferases; D005635:Fructosediphosphates; D006598:Hexosediphosphates; D009955:Ornithine Decarboxylase; D000099228:Diamine N-Acetyltransferase; C029063:fructose-1,6-diphosphate