Hepatoprotective effects of salidroside on fulminant hepatic failure induced by D-galactosamine and lipopolysaccharide in mice

J Pharm Pharmacol. 2009 Oct;61(10):1375-82. doi: 10.1211/jpp/61.10.0015.

Abstract

Objectives: The aim was to investigate the protective effect of salidroside isolated from Rhodiola sachalinensis A. Bor. (Crassulaceae) on D-galactosamine/lipopolysaccharide-induced fulminant hepatic failure.

Methods: Hepatotoxicity was induced by an intraperitoneal injection of D-galactosamine (700 mg/kg) and lipopolysaccharide (10 mug/kg); salidroside (20, 50 and 100 mg/kg) was administered intraperitoneally 1 h before induction of hepatoxicity. Liver injury was assessed biochemically and histologically.

Key findings: Salidroside attenuated the induced acute increase in serum aspartate aminotransferase and alanine aminotransferase activities, and levels of tumour necrosis factor-alpha levels and serum nitric oxide. It restored depleted hepatic glutathione, superoxide dismutase, catalase and glutathione peroxidase activities, decreased malondialdehyde levels and considerably reduced histopathological changes. Histopathological, immunohistochemical and Western blot analyses also demonstrated that salidroside could reduce the appearance of necrotic regions and expression of caspase-3 and hypoxia-inducible factor-1alpha in liver tissue.

Conclusions: Salidroside protected liver tissue from the oxidative stress elicited by D-galactosamine and lipopolysaccharide. The hepatoprotective mechanism of salidroside appear to be related to antioxidant activity and inhibition of hypoxia-inducible factor-1alpha.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine Transaminase / blood
  • Animals
  • Antioxidants / metabolism
  • Aspartate Aminotransferases / blood
  • Caspase 3 / metabolism
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Galactosamine
  • Glucosides / therapeutic use*
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Lipopolysaccharides
  • Liver / drug effects
  • Liver / metabolism
  • Liver / pathology
  • Liver Failure, Acute / chemically induced
  • Liver Failure, Acute / drug therapy*
  • Liver Failure, Acute / metabolism
  • Liver Failure, Acute / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nitric Oxide / blood
  • Oxidative Stress / drug effects
  • Phenols / therapeutic use*
  • Tumor Necrosis Factor-alpha / blood
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Antioxidants
  • Glucosides
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Lipopolysaccharides
  • Phenols
  • Tumor Necrosis Factor-alpha
  • Nitric Oxide
  • Galactosamine
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • Caspase 3
  • rhodioloside