An investigation of the hepato-renal axis and oxidative stress status of Wistar rats treated with counterfeit sildenafil citrate.

Abstract

The liver and kidney being the sites of metabolic biotransformation and excretory route of many agents are known for
their sensitivity or susceptibility to many xenobiotics. Many times the biotransformation results in free radical generation
and leading to tissue damage that is oxidative stress related. Sildenafil citrate, metabolized by CPY-3A4 and excreted by
both the liver and kidney is one of such agents. For this reason, the impact of fake sildenafil citrate is being assessed on
the hepato-renal system as well as the oxidative-stress status of male Wistar rats. Twenty-one rats (250 g) were divided
equally into 3 groups. The rats in the 1st, 2nd, and 3rd groups received 25 mg/kg counterfeit sildenafil citrate tablet, genuine
drug, and distilled water (control) respectively. Hepato-renal indices estimated included total protein, albumin, urea,
creatinine, alkaline phosphatase, ?-glutamyl transferase, alanine and aspartate aminotransferases. Levels and activities of
antioxidant indices such as glutathione peroxidase, superoxide dismutase, catalase and MDA as well as oxidized and
reduced glutathione, glutathione-S-transferase and glutathione reductase were determined. Changes in the histologic
features were assessed using haematoxylin and eosin staining technique. Data obtained were subjected to statistical
analysis using analysis of variance. P ? 0 .05 was considered significant. Results revealed that markers of hepato-renal
damage and oxidative-stress status were significantly different in fake but not genuine drug-administered rats. The results
of this study suggest that at 25 mg/kg genuine sildenafil citrate is not toxic to hepato-renal system but the counterfeit drug
caused hepato-nephrotoxicity, which might have been oxidative stress-induced.