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


CONCLUSIONS
NAC increased the survival time by reducing myocardial oxidative injury whereas L-NAME showed no such protective effects in rats exposed to AlP.
Azad
A
A
Department of Pharmacology All India Institute of Medical Sciences New Delhi-110029, India.
Lall
S B
SB
Mittra
S
S
D000111:Acetylcysteine / Q000494:pharmacology*; D017607:Aluminum Compounds / Q000037:antagonists & inhibitors / Q000633:toxicity*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002374:Catalase / Q000378:metabolism; D004347:Drug Interactions; D004562:Electrocardiography / Q000187:drug effects; D016166:Free Radical Scavengers / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010720:Phosphines / Q000037:antagonists & inhibitors / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar
D017607:Aluminum Compounds; D016166:Free Radical Scavengers; D010720:Phosphines; D008315:Malondialdehyde; C001864:aluminum phosphide; D002374:Catalase; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester; D000111:Acetylcysteine