Effect of N-acetylcysteine and L-NAME on aluminium phosphide induced cardiovascular toxicity in rats

Acta Pharmacol Sin. 2001 Apr;22(4):298-304.


Aim: To investigate the protective effects of N-acetylcysteine (NAC) and Nomega-Nitro-L-arginine methyl ester (L-NAME) on aluminium phosphide (AlP) poisoning induced hemodynamic changes, myocardial oxygen free radical injury and on survival time in rats.

Methods: AlP (12.5 mg/kg) was administered intragastrically under urethane anaesthesia. The effect of pre- and post-treatment with NAC and L-NAME alone and in combination was studied on haemodynamic parameters [blood pressure (BP), heart rate (HR), and electrocardiogram (ECG)] and biochemical parameters (malonyldialdehyde, catalase, and glutathione peroxidase).

Results: AlP caused significant hypotension, tachycardia, ECG abnormalities, and finally marked bradycardia. The mean survival time was (90 +/- 10) min. There was significant increase in myocardial malonyldialdehyde (MDA), and decrease in catalase and glutathione peroxidase (GSH Px) levels. NAC infusion (6.25 mg . kg-1 . min-1, iv for 30 min) caused insignificant hemodynamic and biochemical changes. Pre- and post-treatment of NAC with AlP significantly increased the survival time, stabilized BP, HR, and ECG, decreased MDA and increased GSH Px levels compared to AlP group. L-NAME infusion (1 mg . kg-1 . min-1, iv for 60 min) as such caused significant rise in BP but precipitated ECG abnormalities. Pre- and post-treatment of L-NAME with AlP neither improved the survival time nor the biochemical parameters despite significant rise in BP. Co-administration of both the drugs with AlP worsened the hemodynamic and biochemical parameters with reduction in the survival time as compared to AlP.

Conclusion: NAC increased the survival time by reducing myocardial oxidative injury whereas L-NAME showed no such protective effects in rats exposed to AlP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcysteine / pharmacology*
  • Aluminum Compounds / antagonists & inhibitors
  • Aluminum Compounds / toxicity*
  • Animals
  • Blood Pressure / drug effects
  • Catalase / metabolism
  • Drug Interactions
  • Electrocardiography / drug effects
  • Free Radical Scavengers / pharmacology
  • Heart Rate / drug effects
  • Male
  • Malondialdehyde / metabolism*
  • Myocardium / metabolism*
  • NG-Nitroarginine Methyl Ester / pharmacology*
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Phosphines / antagonists & inhibitors
  • Phosphines / toxicity*
  • Rats
  • Rats, Wistar


  • Aluminum Compounds
  • Free Radical Scavengers
  • Phosphines
  • Malondialdehyde
  • aluminum phosphide
  • Catalase
  • Nitric Oxide Synthase
  • NG-Nitroarginine Methyl Ester
  • Acetylcysteine