Role of oxidative/nitrative stress in hepatic encephalopathy induced by thioacetamide

Pharmazie. 2011 May;66(5):378-81.

Abstract

The study was designed to reveal the pathogenic mechanism of peroxynitrite in hepatic encephalopathy (HE), assess oxidative/nitrative stress in relation to HE induced by thiacetamide (TAA) and provide new ideas and scientific basis for the etiology and treatment of HE. Male Wistar rats were divided into four groups randomly: A (control), B (model), C (ebselen) and D (solvent). All the groups were treated with TAA by intraperitoneal (i.p.) except group A (treated with saline i.p.) to manufacture the model of HE. When rats treated with TAA came to the second stage of HE the four groups were administered intragastrically (i.g.) with saline (A, B), ebselen (C) and dimethyl sulfoxide (DMSO) (D), respectively. Plasma was collected to detect the levels of 3-nitrotyrosine (3-NT), NO, T-SOD and MDA. The results showed that the levels of 3-NT, NO, MDA significantly increased and T-SOD decreased obviously in rats suffering from HE. With the development and progression of HE the extent of oxidative/nitrative stress increased. When treated with ebselen the symptoms of HE mitigated and the levels of biochemical indicators ameliorated significantly. This indicates that oxidative/nitrative stress is involved in the mechanisms of hepatic encephalopathy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinogens / toxicity*
  • Chromatography, High Pressure Liquid
  • Hepatic Encephalopathy / metabolism*
  • Hepatic Encephalopathy / pathology
  • Liver / pathology
  • Male
  • Malondialdehyde / metabolism
  • Nitric Oxide / metabolism
  • Oxidative Stress / drug effects*
  • Peroxynitrous Acid / chemistry
  • Peroxynitrous Acid / toxicity
  • Rats
  • Rats, Wistar
  • Reactive Nitrogen Species
  • Spectrometry, Fluorescence
  • Stress, Physiological / drug effects*
  • Superoxide Dismutase / metabolism
  • Superoxides / metabolism
  • Thioacetamide / toxicity*
  • Thiobarbituric Acid Reactive Substances / metabolism
  • Tyrosine / analogs & derivatives
  • Tyrosine / chemistry
  • Tyrosine / metabolism

Substances

  • Carcinogens
  • Reactive Nitrogen Species
  • Thiobarbituric Acid Reactive Substances
  • Thioacetamide
  • Superoxides
  • Peroxynitrous Acid
  • Nitric Oxide
  • 3-nitrotyrosine
  • Tyrosine
  • Malondialdehyde
  • Superoxide Dismutase