European Journal of Biomedical and Pharmaceutical Sciences

ATTENUATION OF AMIODARONE-INDUCED LUNG, LIVER AND KIDNEY TOXICITY BY NITRIC OXIDE SYNTHASE INHIBITOR, AMINOGUANIDINE IN RATS

Walaa I. Mohammed* and Eman M. Ali

ABSTRACT

Amiodarone (AM) is one of the most important antiarrhythmic drugs. Despite the use of this drug is widespread, it is associated with unwanted systemic effects. The present study was conducted to investigate whether aminoguanidine (AG), an inhibitor of nitric oxide synthase (iNOS) can protect against amiodarone-induced lung, liver and kidney toxicity in rats. Rats divided into four groups, control group: rats received saline. AG- treated group: rats received AG (100 mg/kg, i.p) daily for 15 days. AM- treated group: rats received saline daily for 5 days, followed by AM (100 mg/kg, i.p) for 10 days. AG+AM- treated group: rats received AG (100 mg/kg i.p.) daily for 5 days before and 10 days concomitant with AM (100 mg/kg, i.p). In this study, AM- treated group showed significant decrease in the body weight and significant increase in organs/body weight ratio compared to the control group. Furthermore, there was significant increase in serum AST, ALT, bilirubin, urea and creatinine levels, with a significant decrease in serum albumin level. Moreover, total leukocyte count and protein levels in BALF were significantly increase. In addition, there was significant increase in TNF-α , NO and MDA levels in lung, liver and kidney tissues and, there were histopathological abnormalities in them. The present study demonstrated that AG has a protective effect against AM induced lung, liver and kidney toxicity via its iNOS inhibition, antioxidant and anti-inflammatory effects.

Keywords: Amiodarone, Aminoguanidine, Lung Toxicity, Liver Toxicity, Kidney Toxicity, Tumor Necrosis Factor, Antioxidant.