Resveratrol attenuates lipopolysaccharide-induced hepatitis in D-galactosamine sensitized rats: role of nitric oxide synthase 2 and heme oxygenase-1.
The goal of study was directed to investigate the effects of resveratrol (RES) pretreatment on the enhancing action of D-galactosamine (D-GalN; 800 mg/kg) on lipopolysaccharide (LPS; 0.5 microg/kg) inducing liver failure in rats. Liver function was assessed by determination of plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST), alpha-glutathione S-transferase (alpha GST) and bilirubin (BILI). Plasma NO(2)(-) was assessed by NO(2)(-)/NO(3)(-) colorimetric kit. The estimation of nonenzymatic and enzymatic antioxidants (glutathione and catalase) was performed in plasma and liver homogenate. Lipid peroxidation was evaluated by the thiobarbituric acid reacting substances (TBARS) and the conjugated dienes (CD). Morphological examinations using light and electron microscopy were performed. Observations related to pharmacological increases of inducible nitric oxide synthase (NOS-2)/nitric oxide (NO) and inducible heme oxygenase (HO-1) in fulminant hepatic failure and modulation by resveratrol were followed up by real-time reverse transcription PCR (RT-PCR) in liver tissue. In the present study we found that among the mechanisms responsible for the hepatoprotective effect of resveratrol in the LPS/D-GalN liver toxicity model are reduction in NO, downregulation of NOS-2, modification of oxidative stress parameters and modulation of HO-1 which led to overall improvement in hepatotoxic markers and morphology after the hepatic insult.
Institute of Pharmacology, 1st Faculty of Medicine, Charles University, Prague, Albertov 4, 128 00 Prague 2, Czech Republic. hfarg@lf1.cuni.cz
Hassan
H
Farghali
Dalibor
D
Cerný
Ludmila
L
Kameníková
Jindrich
J
Martínek
Ales
A
Horínek
Eva
E
Kmonícková
Zdenek
Z
Zídek
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D056486:Chemical and Drug Induced Liver Injury / Q000473:pathology / Q000517:prevention & control*; D019610:Cytoprotection; D005688:Galactosamine / Q000633:toxicity; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000187:drug effects; D008070:Lipopolysaccharides / Q000633:toxicity; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D017093:Liver Failure / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*
D000975:Antioxidants; D008070:Lipopolysaccharides; D013267:Stilbenes; D005688:Galactosamine; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat; D000077185:Resveratrol