4.4 Article

Resveratrol attenuates lipopolysaccharide-induced hepatitis in D-galactosamine sensitized rats: Role of nitric oxide synthase 2 and heme oxygenase-1

Journal

NITRIC OXIDE-BIOLOGY AND CHEMISTRY
Volume 21, Issue 3-4, Pages 216-225

Publisher

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.niox.2009.09.004

Keywords

Resveratrol; D-galactosamine; Lipopolysaccharide; Nitric oxide synthase; Nitric oxide; Heme oxygenase

Funding

  1. GACR [305/09/0004, 305/07/0061]
  2. IGA MZ [NR/9379-3/2007]
  3. VZ MSM [0021620807]

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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 mu g/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 NO2- was assessed by NO2-/NO3- 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 (TEARS) 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-GaIN 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. (C) 2009 Elsevier Inc. All rights reserved.

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