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

Citation
A. Azad et al., Effect of N-acetylcysteine and L-NAME on aluminium phosphide induced cardiovascular toxicity in rats, ACT PHAR SI, 22(4), 2001, pp. 298-304
Citations number
33
Categorie Soggetti
Pharmacology & Toxicology
Journal title
ACTA PHARMACOLOGICA SINICA
ISSN journal
02539756 → ACNP
Volume
22
Issue
4
Year of publication
2001
Pages
298 - 304
Database
ISI
SICI code
0253-9756(200104)22:4<298:EONALO>2.0.ZU;2-P
Abstract
AIM: To investigate the protective effects of N-acetylcysteine (NAC) and N- omega-Nitro-L-arginine methyl ester (L-NAME) on aluminium phosphide (AlP) p oisoning induced hemodynamic changes, myocardial oxygen free radical injury and on survival time in rats. METHODS: ALP (12.5 mg/kg) was administered i ntragastrically under urethane anaesthesia. The effect of pre- and post-tre atment with NAC and L-NAME alone and in combination was studied on haemodyn amic parameters [blood pressure (BP), heart rate (HR), and electrocardiogra m (ECG)] and biochemical parameters (malonyldialdehyde, catalase, and gluta thione peroxidase). RESULTS: AlP caused significant hypotension, tachycardi a, ECG abnormalities, and finally marked bradycardia. The mean survival tim e was (90 +/- 10) min. There was significant increase in myocardial malonyl dialdehyde (MDA), and decrease in catalase and glutathione peroxidase (GSH Pr) levels. NAC infusion (6.25 mg.kg(-1.)min(-1), iv for 30 min) caused ins ignificant hemodynamic and biochemical changes. Pre- and post-treatment of NAC with AlP significantly increased the survival time, stabilized BP, HR, and EGG, decreased MDA and increased GSH Pr levels compared to AlP group. L -NAME infusion (1 mg.kg(-1).min(-1), iv for 60 min) as such caused signific ant rise in BP but precipitated ECG abnormalities. Pre- and post-treatment of L-NAME with AlP neither improved the survival time nor the biochemical p arameters despite significant rise in BP. Co-administration of both the dru gs with AlP worsened the hemodynamic and biochemical parameters with reduct ion 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.