N-Acetylcysteine Ameliorates Experimental Autoimmune Myocarditis in Rats via Nitric Oxide

J Cardiovasc Pharmacol Ther. 2015 Mar;20(2):203-10. doi: 10.1177/1074248414547574. Epub 2014 Aug 20.

Abstract

Background: Oxidative stress may play an important role in the development of myocarditis. We investigated the effects of N-acetylcysteine (NAC), a potent antioxidant, on experimental autoimmune myocarditis (EAM) in rats.

Methods and results: A rat model of porcine myosin-induced EAM was used. After the immunization with myosin, NAC (20 mg/kg/d) or saline was injected intraperitoneally on days 1 to 21. Additional myosin-immunized rats treated with NAC were orally given 25 mg/kg/d of N(G)-nitro-l-arginine methylester (l-NAME), an inhibitor of nitric oxide (NO) synthase, and N(G)-nitro-d-arginine methylester (d-NAME), an inactive enantiomer. The NAC treatment improved cardiac pathology associated with reduced superoxide production. In the EAM rats treated with NAC associated with oral l-NAME, but not with oral d-NAME, the severity of myocarditis was not reduced. Expression of intercellular adhesion molecule 1 was reduced by NAC treatment. Myocardial c-kit(+) cells were demonstrated only in the NAC-treated group. Hemodynamic study showed that the increased left ventricular mass produced by myocardial inflammation tended to be reduced by NAC treatment.

Conclusion: Treatment with NAC ameliorated myocardial injury via NO system in a rat model of myocarditis.

Keywords: N-acetylcysteine; autoimmune myocarditis; free radicals; nitric oxide; oxidative stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcysteine / pharmacology
  • Acetylcysteine / therapeutic use*
  • Animals
  • Autoimmune Diseases / drug therapy*
  • Autoimmune Diseases / physiopathology
  • Disease Models, Animal
  • Intercellular Adhesion Molecule-1 / physiology
  • Myocarditis / drug therapy*
  • Myocarditis / physiopathology
  • Nitric Oxide / physiology*
  • Rats
  • Rats, Inbred Lew
  • Superoxides / metabolism

Substances

  • Superoxides
  • Intercellular Adhesion Molecule-1
  • Nitric Oxide
  • Acetylcysteine