Grape seed extract improved the fertility-enhancing effect of atorvastatin in high-fat diet-induced testicular injury in rats: involvement of antioxidant and anti-apoptotic effects.

OBJECTIVES: Reduced male fertility is highly prevalent with hypercholesterolaemia. Though statins are drugs of choice for hypercholesterolaemia, their effect on male fertility is still controversial and dose-dependent. Grape seed extract (GSE) possess hypocholesterolemic and testicular protective effects. Thus, this study aimed to investigate the effects of low-dose atorvastatin (ATV) on male infertility in hypercholesterolaemic rats and assess the additional value of combining ATV with GSE. METHODS: Male rats were randomized into four groups. The normal group was fed a standard diet. The remaining groups were fed a high-fat diet (HFD) for 1 month to induce hypercholesterolaemia. Two HFD groups were administered either ATV (1 mg/kg) alone or combined with GSE (200 mg/kg) orally for 65 days, while the third group served as HFD control. KEY FINDINGS: Treatment with ATV or ATV/GSE attenuated dyslipidemia-induced alteration in serum HDL-cholesterol, LDL-cholesterol, and total cholesterol. ATV enhanced serum testosterone, sperm count and motility and fertility index. The effect on testosterone and sperm count was more pronounced by ATV/GSE. Moreover, ATV reduced testicular malondialdehyde, nitric oxide, caspase-9 and caspase-3 while elevated reduced glutathione and superoxide dismutase along with catalase activity. Noteworthy, GSE/ATV induced more powerful antioxidant and anti-apoptotic effects. CONCLUSION: GSE enhanced ATV's protective effect against hypercholesterolaemia-induced infertility via antioxidant and anti-apoptotic mechanisms.

Geraniol ameliorates diabetic nephropathy via interference with miRNA-21/PTEN/Akt/mTORC1 pathway in rats.

Deregulated activity of protein kinase B/mammalian target of rapamycin complex-1 (Akt/mTORC1) incites crucial pathological characteristics of diabetic nephropathy. The acyclic monoterpene geraniol has been recently reported to possess antidiabetic effects; however, its potential renoprotective effect in diabetes has not yet been elucidated. This study aimed to assess the possible modulatory effect of geraniol on the Akt/mTORC1 pathway in diabetes-induced nephropathy in rats compared to the standard antidiabetic drug gliclazide. Geraniol and gliclazide was administered daily to diabetic rats for 6 weeks starting on the 3rd-day post diabetes induction by streptozotocin (STZ). Geraniol amended the deteriorated renal function (serum creatinine; blood urea nitrogen). It exerted a remarkable antihyperglycemic effect that is comparable to that of gliclazide and suppressed the fibrotic marker, transforming growth factor-ß. Geraniol restored redox balance and inhibited lipid peroxidation by reducing nicotine amide adenine dinucleotide phosphate oxidase and enhancing the antioxidant enzyme, superoxide dismutase. These beneficial effects were associated with a robust downregulation of miRNA-21 and consequently, reversion of tumor suppressor protein phosphatase and tension homolog (PTEN)/Akt/mTORC1 cue and its downstream proteins required for mesangial cell proliferation and matrix protein synthesis. The current study indicates that geraniol interfered with miRNA-21/ PTEN/AKT/mTORC1 pathway signaling that contributes largely to the progression of mesangial expansion and extracellular matrix deposition in diabetic nephropathy.

The Role of Vildagliptin in Treating Hypertension Through Modulating Serum VEGF in Diabetic Hypertensive Patients.

BACKGROUND: Several trials have reported that dipeptidyl peptidase-4 (DPP-4) inhibitors are used to improve endothelial function in addition to treating type 2 diabetes (T2DM). The current study investigated the effects of vildagliptin, DPP-4 inhibitor, compared to metformin on endothelial function and blood pressure through vascular endothelial growth factor (VEGF) modulation in patients with T2DM and hypertension. METHODS: This study was designed as a randomized controlled parallel study. A total of 120 volunteers were recruited and allocated into 4 groups: healthy volunteers, patients recently diagnosed with hypertension and diabetes, patients treated with captopril for hypertension in addition to metformin, and patients treated with captopril in addition to vildagliptin. The percentage change in body weight was calculated in addition to serum VEGF levels, blood pressure, glycated hemoglobin (HbA1c), total lipid profile, and insulin resistance. RESULTS: At the end of the therapeutic period, the results showed that vildagliptin significantly decreased blood pressure and increased serum VEGF levels, while metformin was more effective at lowering body weight. In comparison with metformin, vildagliptin showed a promising action through its antihypertensive effect via elevating VEGF levels and improving physiological angiogenesis and vasculature. WHAT IS NEW AND CONCLUSION: Vildagliptin showed a promising action through its blood pressure-regulating effect via modulating VEGF levels and improving physiological angiogenesis and vasculature, in addition to improving the lipid profile of patients, while metformin was better in reducing body weight.

Protective effect of ursodeoxycholic acid, resveratrol, and N-acetylcysteine on nonalcoholic fatty liver disease in rats.

CONTEXT: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. Resveratrol (RSV) and N-acetylcysteine (NAC) are safe representatives of natural and synthetic antioxidants, respectively. OBJECTIVE: The objective of this study was to evaluate protective effects of RSV and NAC, compared with ursodeoxycholic acid (UDCA), on experimental NAFLD. MATERIALS AND METHODS: NAFLD was induced by feeding rats a methionine choline-deficient diet (MCDD) for four cycles, each of 4 d of MCDD feeding and 3 d of fasting. Animals were divided into normal control, steatosis control, and five treatment groups, receiving UDCA (25 mg/kg/d), RSV (10 mg/kg/d), NAC (20 mg/kg/d), UDCA + RSV, and UDCA + NAC orally for 28 d. Liver integrity markers (liver index and serum transaminases), serum tumor necrosis factor-α (TNF-α), glucose, albumin, renal functions (urea, creatinine), lipid profile (total cholesterol; TC, triglycerides, high density lipoproteins, low density lipoproteins; LDL-C, very low density lipoproteins, leptin), and oxidative stress markers (hepatic malondialdehyde; MDA, glutathione; GSH, glutathione-S-transferase; GST) were measured using automatic analyzer, colorimetric kits, and ELISA kits, supported by a liver histopathological study. RESULTS: RSV and NAC administration significantly improved liver index (RSV only), alanine transaminase (52, 52%), TNF-α (70, 70%), glucose (69, 80%), albumin (122, 114%), MDA (55, 63%), GSH (160, 152%), GST (84, 84%), TC (86, 86%), LDL-C (83, 81%), and leptin (59, 70%) levels compared with steatosis control values. A combination of RSV or NAC with UDCA seems to ameliorate their effects. DISCUSSION AND CONCLUSION: RSV and NAC are effective on NAFLD through antioxidant, anti-inflammatory, and lipid-lowering potentials, where as RSV seems better than UDCA or NAC.