Impaired expression of sex hormone receptors in male reproductive organs of diabetic rat in response to oral antidiabetic drugs

Introduction. Few oral antidiabetic drugs have been evaluated for their reproductive complication. This study aimed to evaluate the effect of metformin, pioglitazone and sitagliptin on the structure of male reproductive system through an immunohistopathological study. Material and methods. Sprague-Dawley male rats were injected with streptozotocin. The diabetic rats were divided into four groups (n = 8/each group); diabetic control, metformin-, pioglitazone- and sitagliptin-treated groups in addition to a normal control group (n = 8). At the end of the experiment, blood samples were collected for biochemical assessment. Testis, epididymis and seminal vesicle were dissected and processed for histopathological examination using routine and immune-staining. Results. All drugs significantly (p < 0.05) decreased fasting blood glucose, glycated hemoglobin, total cholesterol, triglycerides and malondialdehyde compared to the diabetic control group. Metformin has induced the least pathologic changes on the structure of the testis, epididymis and seminal vesicle among the studied drugs. Metformin succeeded to restore weights of testis, epididymis and seminal vesicle as well as testosterone hormone level back to values of the NC group while the pioglitazone and sitagliptin failed to do that. A significant reduction (p < 0.05) in testicular ERa and ERb immunoexpression of pioglitazone-treated group as well as suppression of ERb and AR immunoreactivity in in epididymus and seminal vesicles of pioglitazone- and sitagliptin-treated rats were observed compared to the control animals. Conclusions. Histological structure as well ER and AR expression in the system organs were negatively and significantly affected with all studied drugs. Metformin has the least effect on the structure of the studied male reproductive organs. Thus, pioglitazone and sitagliptin treatment should be avoided in young male diabetic patients

Oral thearubigins do not protect against acetaminopheninduced hepatotoxicity in mice

Purpose: To investigate the potential protective effect of oral repeated doses of thearubigins against acetaminophen-induced hepatotoxicity in mice.Methods: Mice were randomly divided into six groups (n=8) and administered the following: Control group (saline), acetaminophen group (saline), N-acetylcysteine group (500 mg/kg/day), and thearubigins groups (60, 70, 100 mg/kg/day). The drugs were given orally by gavage for seven days. On day 7, 1 h after the last dose of treatment, the mice (except control group) were given a single dose of acetaminophen (n-acetyl-p-aminophenol, APAP) orally by gavage (350 mg/kg) and then sacrificed 4 h post-APAP intake. Blood was collected for biochemical measurements and their liver were subjected to biochemical and histopathological assessment.Results: The acetaminophen group showed significant increases (p < 0.001) in serum alanine aminotransferase level, hepatic cytochrome P2E1 level, and serum and hepatic malondialdehyde levels. Moreover it showed significant decrease (p < 0.001) in serum and hepatic glutathione levels. Morphologically, the liver sections showed cellular necrosis, vacuolization, and degeneration around the centrilobular veins. Pretreatment with N-acetylcysteine reversed all acetaminophen-induced changes (p < 0.001 for all biomarkers except for hepatic MDA (p = 0.014) while pretreatment with thearubigins failed to reverse any of them.Conclusion: Oral repeated doses of thearubigins failed to protect against acetaminophen-induced hepatotoxicity in mice and didn't affect hepatic cytochrome P2E1 level.Keywords: Acetaminophen, Hepatotoxicity, Thearubigins, N-acetylcysteine, Cellular necrosis, Vacuolization, Hepatic cytochrome P2E