N-acetylcysteine attenuates dimethylnitrosamine induced oxidative stress in rats

Eur J Pharmacol. 2011 Mar 5;654(2):181-6. doi: 10.1016/j.ejphar.2010.10.080. Epub 2010 Nov 27.

Abstract

Oxidative stress has been implicated in the pathogenesis and progression of various hepatic disorders and hence screening for a good hepatoprotective and antioxidant agent is the need of the hour. The present study was aimed to investigate the hepatoprotective and antioxidant property of N-acetylcysteine (NAC) against dimethylnitrosamine (DMN) induced oxidative stress and hepatocellular damage in male Wistar albino rats. Administration of single dose of DMN (5mg/kg b.w.; i.p.) resulted in significant elevation in the levels of serum aspartate transaminase and alanine transaminase, indicating hepatocellular damage. Oxidative stress induced by DMN treatment was confirmed by an elevation in the status of lipid peroxidation (LPO) and reduction in the activities of enzymic antioxidants such as superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glutathione-S-transferase and in the levels of non-enzymic antioxidants, reduced glutathione, vitamin-C and vitamin-E in the liver tissue. DMN induced oxidative stress and hepatocellular membrane instability was further substantiated by a decline in the status of the membrane bound ATPases in the liver tissue. Post-treatment with NAC (50mg/kg b.w.; p.o.) for 7days effectively protected against the DMN induced insult to liver by preventing the elevation in the status of the serum marker enzymes and LPO, and restoring the activities of both the enzymic and non-enzymic antioxidants and membrane bound ATPases towards normalcy. These results demonstrate that NAC acts as a good hepatoprotective and antioxidant agent in attenuating DMN induced oxidative stress and hepatocellular damage.

MeSH terms

  • Acetylcysteine / metabolism
  • Acetylcysteine / pharmacology*
  • Animals
  • Antioxidants / metabolism
  • Antioxidants / pharmacology*
  • Ascorbic Acid / metabolism
  • Carcinogens / pharmacology*
  • Catalase / metabolism
  • Dimethylnitrosamine / metabolism
  • Dimethylnitrosamine / pharmacology*
  • Glutathione / metabolism
  • Glutathione Peroxidase / metabolism
  • Glutathione Transferase / blood
  • Glutathione Transferase / metabolism
  • Lipid Peroxidation / drug effects
  • Liver / cytology
  • Liver / drug effects*
  • Liver / enzymology
  • Liver Function Tests
  • Male
  • Malondialdehyde / pharmacology*
  • Oxidative Stress / drug effects*
  • Rats
  • Rats, Wistar
  • Superoxide Dismutase / metabolism
  • Vitamin E / metabolism

Substances

  • Antioxidants
  • Carcinogens
  • Vitamin E
  • Malondialdehyde
  • Catalase
  • Glutathione Peroxidase
  • Superoxide Dismutase
  • Glutathione Transferase
  • Glutathione
  • Dimethylnitrosamine
  • Ascorbic Acid
  • Acetylcysteine