Erectile Dysfunction Drugs and Protein Expression of Glutathione S- transferase and Glutathione Peroxidase in the Liver of Male Rats

Erectile dysfunction (ED) drugs have been used for treatment of erectile dysfunction which affects the lives of approximately 300 million men worldwide. It is well known that the cytosolic glutathione Stransferase (GST) and glutathione metabolizing enzymes play an important role in the detoxification of many endogenous and exogenous compounds. Therefore, the present study aims at investigating the changes in activities and expression of glutathione S-transferase, and glutathione peroxidase (GPx) enzymes as well as antioxidant enzymes after treatment of male rats with a daily dose of sildenafil (1.48 mg/kg), tadalafil (0.285 mg/kg) and vardenafil (0.285 mg/kg) for three weeks. In addition, glutathione reductase (GR) activity, levels of both reduced glutathione and free radicals (measured as malondialdyhyde, MDA), and histopathological examinations were assayed in the liver tissues of rats. The data of the present study showed that sildenafil, vardenafil, and tadalafil treatments significantly decreased the levels of glutathione, MDA and the activity of glutathione reductase in liver tissue of male rats. In addition, vardenafil and sildenafil increased superoxide dismutase and catalase activity. The total activity of GST was only decreased after treatment of rats with vardenafil, whereas the other two drugs did not change such activity. Interestingly, western immunoblot showed that protein expression of GST π isozyme was markedly reduced after treatment of rats with sildenafil. In addition, the activity and expression of glutathione peroxidase were significantly reduced after treatment of rats with either sildenafil or tadalafil, whereas vardenafil induced the activity and expression of this enzyme. It is concluded that ED drugs induced changes in the activity and protein expression of both GPx and GST π. In addition, these drugs have shown antioxidant activities which might be a new mechanism that can be added to the previous action of these drugs. Key-words: Glutathione S-transferase, glutathione, free radicals, glutathione peroxidase, and glutathione reductase