title: Nitric oxide as a mediator of fructose 1,6-bisphosphate protection in galactosamine-induced hepatotoxicity in rats.
abstract: Fructose 1,6-bisphosphate (F1,6BP) has been widely used as a therapeutic agent for different harmful conditions in a variety of tissues. The hypothesis of the present work was that the increase in nitric oxide production and the prevention of oxidative stress induced by exogenous F1,6BP mediate its protective effect against the hepatotoxic action of GalN. Experimental groups used were sham, F1,6BP (2g/kg bw i.p.), GalN (0.4g/kg bw i.p), l-NAME (10mg/kg bw i.v.), F1,6BP+GalN, l-NAME+GalN and l-NAME+F1,6BP+GalN. Animals were killed after 24h of bolus administration. F1,6BP induced an increase in NO and the redox ratio (GSH/GSSG) in liver. Western blot assays pointed to overexpression of liver eNOS in F1,6BP-treated rats. The hepatic injury induced by GalN increased transaminases in plasma and decreased the reduced/oxidized glutathione ratio in liver. The concomitant administration of F1,6BP reversed this damage, while the addition of l-NAME worsened the liver injury. We provided evidence that this F1,6BP-induced protection may be related to the increase in NO production through the positive modulation of eNOS, and the increase in intracellular reduced glutathione, thus providing a higher reducing capacity.
authors.affiliation: Departament de Fisiologia i Immunologia (Biologia), Universitat de Barcelona, Barcelona, Spain.
authors.forename: Norma
authors.initials: N
authors.lastname: Alva
authors.forename: David
authors.initials: D
authors.lastname: Cruz
authors.forename: Sergio
authors.initials: S
authors.lastname: Sanchez
authors.forename: Juana Ma
authors.initials: JM
authors.lastname: Valentín
authors.forename: Jordi
authors.initials: J
authors.lastname: Bermudez
authors.forename: Teresa
authors.initials: T
authors.lastname: Carbonell
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D005635:Fructosediphosphates / Q000494:pharmacology*; D005688:Galactosamine / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D005635:Fructosediphosphates; D009569:Nitric Oxide; D005688:Galactosamine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; C029063:fructose-1,6-diphosphate; D019331:NG-Nitroarginine Methyl Ester