Effect of sildenafil (Viagra) on epidermal growth factor expression in submandibular gland of diabetic male rats: histological and immunohistochemical study

Background:Epidermal growth factor (EGF) is produced in rodents mainly by the granular convoluted tubules in submandibular glands. EGF deficiency in diabetes mellitus could be implicated in the complications of the disease. Sildenafil (Viagra), one of the phosphodiesterase inhibitors, contributes in the protection against diabetes-induced oxidative stress. Aim of the study:To investigate the effect of sildenafil on the level of EGF production by the submandibular gland of diabetic male rats, and the expression of its receptors on the surface of target cells as the testis. Materials and methods:Sixty adult male rats were divided into three equal groups. Group 1: as control. Group 2: rats treated with alloxan (150 mg/kg intraperitoneally once for induction of diabetes). Group 3: treated diabetic group (diabetic rats were treated with sildenafil 1 mg/kg once daily by a gastric tube). Animals were killed 1 month after confirmation of diabetes. Submandibular glands and testes were processed for histological examination. Pancreatic tails were also removed for histological assessment of diabetic changes. Results:Diabetes caused significant reduction in the mean count of granular convoluted tubules. Immunohistochemical detection for EGF showed significant decrease in the mean count of immunopositive cells in diabetic rats and weak staining compared with controls. EGF receptor detection in the testis revealed a weak reaction. After sildenafil treatment, the number of granular convoluted tubules increased significantly. Increased number of immunopositive cells and strong immunoreactivity for EGF compared with the diabetic group was observed. Strong immunoreactivity for the EGF receptor was detected in the testis. Conclusion:These findings suggest that sildenafil reversed the EGF deficiency caused by diabetes.