Erectile dysfunction drugs and oxidative stress in the liver of male rats

Abstract

Erectile dysfunction (ED) affected the lives of more than 300 million men worldwide. Erectile dysfunction drugs (EDD), known as phosphodiesterase inhibitors (PDEIs), have been used for treatment of ED. It has been shown that oxidative stress plays an important role in the progression of erectile dysfunction. Oxidative stress can be alleviated or decreased by antioxidant enzymes. Therefore, the present study aims at investigating the changes in the activity of antioxidant enzymes such as superoxide dismutase, catalase, and glutathione reductase as well as protein expression of glutathione peroxidase and glutathione S-transferase 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, levels of reduced glutathione and malondialdyhyde (MDA) were assayed. The present study showed that sildenafil, vardenafil, and tadalafil treatments significantly decreased the levels of glutathione, MDA and the activity of glutathione reductase. In addition, vardenafil and sildenafil increased the activity of superoxide dismutase and catalase. Interestingly, western immunoblotting data showed that vardenafil induced the activity of glutathione peroxidase (GP_X) and its protein expression, whereas tadalafil and sildenafil inhibited such enzyme activity and its protein expression. In addition, the protein expression of GST π isozyme was markedly reduced after treatment of rats with sildenafil. It is concluded that ED drugs induced the activities of both SOD and catalase which consequently decreased MDA level. Therefore, decrement in MDA levels could increase nitric oxide-cGMP level which in turn promotes the erection mechanism.

Keywords: CAT, catalase; Catalase; ED, erectile dysfunction; EDD, erectile dysfunction drugs; GPx, glutathione peroxidase; GR, glutathione reductase; GSH, glutathione; GST, glutathione S-transferase; Glutathione; Glutathione peroxidase; Glutathione reductase; MDA, malondialdyhyde; Oxidative stress; PDE-5, phosphodiesterase type-5; PDEIs, phosphodiesterase inhibitors; ROS, reactive oxygen species; SOD, superoxide dismutase.

Fig. 1

Western immunoblotting analysis showed the influence of tadalafil, vardenafil, and sildenafil on the protein expression of (A) Glutathione S-transferase π isozyme, (B) Glutathione peroxidase (GPx3 isozyme). In both figures A and B, Lanes 1–4 represented the pooled proteins of matched control, tadalafil, vardenafil, and sildenafil-treated rats, respectively. The band intensity was measured using Quantity one software program.

Fig. 2

Histopathological examination showed moderate inflammation and marked fibrosis in the liver tissues of male rats after treatment with vardenafil and sildenafil with no changes in the liver of tadalafil-treated rats.