Fructose diphosphate attenuates the acetaminophen-induced liver injury in the rat evidence for involvement of nitric oxide.
We have previously shown that fructose-1,6-diphosphate (FDP) stimulates the synthesis of nitric oxide probably by stimulating the hepatic inducible nitric oxide synthase (iNOS). The aim of the present study was to evaluate the hepatoprotective role of FDP in acetaminophen-induced liver injury and whether this hepatoprotective effect is mediated by nitric oxide. Liver injury was induced in adult Sprague-Dawley rats by the administration of acetaminophen (1.6 g/kg by gavage) 10 min prior to the intraperitoneal injection of either FDP or normal saline. Liver injury was assessed by alanine aminotransferase (ALT) activity in the serum. iNOS and malondialdehyde (MDA) levels were determined in liver homogenates. Acetaminophen produced striking elevations of serum ALT, high MDA levels and a profound decrease in the liver iNOS. Administration of FDP attenuated the ALT and MDA elevations and prevented the liver iNOS depletion caused by acetaminophen. Pretreatment of the animals with the iNOS inhibitor L-NAME abolished this hepatoprotection. These findings suggest that FDP protects against acetaminophen-induced liver injury, at least partly, by stimulating production of nitric oxide.
Mihas
Anastasios A
AA
Department Of Medicine, University Of Mississippi Medical Center Jackson, Mississippi, USA. anastasios.mihas2@med.va.gov
Kanji
Vijaya K
VK
Mihas
Thanos A
TA
Joseph
Roy M
RM
Markov
Angel K
AK
Heuman
Douglas M
DM
D000082:Acetaminophen / Q000037:antagonists & inhibitors / Q000633:toxicity*; D000410:Alanine Transaminase / Q000097:blood; D018712:Analgesics, Non-Narcotic / Q000037:antagonists & inhibitors / Q000633:toxicity*; D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000201:enzymology / Q000378:metabolism / Q000517:prevention & control*; D005635:Fructosediphosphates / Q000627:therapeutic use*; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D051381:Rats; D017207:Rats, Sprague-Dawley
D018712:Analgesics, Non-Narcotic; D005635:Fructosediphosphates; D009569:Nitric Oxide; D000082:Acetaminophen; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D000410:Alanine Transaminase; C029063:fructose-1,6-diphosphate