Co-administration of metformin and/or glibenclamide with losartan reverse NG-nitro-l-arginine-methyl ester-streptozotocin-induced hypertensive diabetes and haemodynamic sequelae in rats.

Over the years, there have been opinions on whether to reduced blood pressure (BP) to a different levels in patients with diabetes mellitus. Hence, this study investigated the efficacy of the co-administration of losartan (angiotensin receptor blocking antihypertensive agent) with metformin and/or glibenclamide (antidiabetic agents) on hypertensive-diabetic experimental rats induced by NG-nitro-l-arginine-methyl-ester hydrochloride (l-NAME), and streptozotocin (STZ). STZ (45 mg/kg, i.p.)-induced diabetic rats combined with l-NAME (40 mg/kg, p.o.)-induced hypertension were allotted into different groups. Group 1 received distilled water (10 mL/kg) and served as normal control, group 2 comprised hypertensive diabetic rats with distilled water, groups 3-5 were hypertensive-diabetic rats but received combination treatments of losartan + metformin, losartan + glibenclamide, and losartan + metformin + glibenclamide daily for 8 weeks, respectively. Our finding revealed no changes in the body weights, but there was a significant increase in fasting blood sugar levels in l-NAME - STZ-induced hypertensive-diabetes, which were lowered by losartan + metformin, losartan + glibenclamide, and losartan + metformin + glibenclamide treatments. Moreover, the increased systolic-BP, mean arterial pressure but not diastolic-BP and heart rate by l-NAME + STZ were attenuated more significantly by losartan + metformin + glibenclamide between weeks 2-8 relative to hypertensive-diabetic control. l-NAME + STZ-induced elevated levels of lactate dehydrogenase and creatinine kinase, were differentially reversed by losartan + metformin, losartan + glibenclamide, and losartan + metformin + glibenclamide. However, l-NAME + STZ-induced decreased nitrite level was significantly restored by all treatments, suggesting increased nitrergic transmission. Additionally, l-NAME + STZ-induced degeneration of pancreatic islet and myocardial cells were dramatically alleviated by losartan + metformin + glibenclamide treatments. Our findings suggest hyperglycemia with raised systolic-BP should be managed with losartan combined with both metformin and glibenclamide than single combination of losartan with antidiabetics.

Ascorbic Acid and Alpha-Tocopherol Contribute to the Therapy of Polycystic Ovarian Syndrome in Mouse Models.

Polycystic ovary syndrome (PCOS) affects up to 10% of women within reproductive ages and has been a cause of infertility and poor quality of life. Alteration in the oxidant-antioxidant profile occurs in PCOS. This study, therefore, investigates the contribution of ascorbic acid (AA) and alpha-tocopherol(ATE) on different PCOS parameters. The mifepristone and letrozole models were used, and young mature female mice were randomly assigned to groups of six per group. On PCOS induction with either mifepristone or letrozole, mice were administered AA and ATE at doses ranging from 10-1000mg/kg to 0.1-1000 mg/kg in the respective models. Vaginal cytology, body weights, and temperature, as well as blood glucose, testosterone, and insulin levels, were measured. Total antioxidant capacity and malondialdehyde levels were analyzed. Determination of gene expression of some reactive oxygen species and histomorphological analysis on the ovaries and uteri were performed. At the end of the experiments, AA and ATE restored reproductive cycling, with AA being more effective. AA and ATE increased fasting blood glucose but had no significant effect on serum insulin levels. AA decreased testosterone levels, but ATE caused slight increases. AA and ATE both increased total antioxidant capacity and decreased malondialdehyde levels. AA and ATE also slightly upregulated the mRNA expressions of catalase, superoxide dismutase, and heme oxygenase 1 mainly. AA and ATE also decreased ovarian weight and mostly resolved cysts in the ovaries and congestion in the uterus. This study has shown that AA and ATE are beneficial in the therapy of PCOS.