Modulation of GABA by sodium butyrate ameliorates hypothalamic inflammation in experimental model of PCOS.

Polycystic ovarian syndrome (PCOS) is a known endocrine disorder that has affected many women of childbearing age, and is accompanied by various neurodegenerative conditions. Hence, this study investigates the impact of butyrate in reversing hypothalamic-related disorder, possibly through γ aminobutyric acid (GABA) in a rat model of PCOS. Eight-week-old female Wistar rats were allotted into four groups (n = 5), which include control, butyrate, letrozole, and letrozole + butyrate groups. PCOS was induced by administering 1 mg/kg of letrozole (oral gavage) for 21 days. After confirmation of PCOS, 200 mg/kg of butyrate (oral gavage) was administered for 6 weeks. Rats with PCOS were characterized by elevated levels of plasma insulin and testosterone. Increases in plasma and hypothalamic triglyceride levels, inflammatory biomarker (SDF-1), apoptotic marker (caspase-6), and decreased plasma GnRH were observed. Additionally, a decrease in hypothalamic GABA was revealed. Nevertheless, the administration of butyrate attenuated these alterations. The present study suggests that butyrate ameliorates hypothalamic inflammation in an experimental model of PCOS, a beneficial effect that is accompanied by enhanced GABA production.

Flavonoid glycoside fraction of Ginkgo biloba extract modulates antioxidants imbalance in vanadium-induced brain damage.

Human and animal diseases have always been reported to be treated by medicinal herbs owing to their constituents. Excess sodium metavanadate is a potential environmental toxin when consumed and could induce oxidative damage leading to various neurological disorders and Parkinsons-like diseases. This study is designed to investigate the impact of the flavonoid Glycoside Fraction of Ginkgo Biloba Extract (GBE) (at 30 mg/kg body weight) on vanadium-treated rats. Animals were divided randomly into four groups: Control (Ctrl, normal saline), Ginkgo Biloba (GIBI, 30mg/kg BWT), Vanadium (VANA, 10 mg/kg BWT) and Vanadium + Ginkgo biloba (VANA + GIBI). Markers of oxidative stress (Glutathione Peroxidase and Catalase) were assessed and found to be statistically increased with GIBI when compared with CTRL and treatment groups. Results from routine staining revealed that the control and GIBI group had a normal distribution of cells and a pronounced increase in cell count respectively compared to the VANA group. When compared to the VANA group, the NeuN photomicrographs revealed that the levels of GIBI were within the normal range (***p < 0.001; ** p < 001). The treatment with GIBI showed a better response by increasing the neuronal cells in the VANA+GIBI when compared with the VANA group. The NLRP3 Inflammasome photomicrographs denoted that there was a decrease in NLRP3-positive cells in the control and GIBI groups. The treatment group shows fewer cells compared to that of the VANA group. The treatment group shows fewer cells compared to that of the VANA group. The findings of the study confirmed that ginkgo biloba extract via its flavonoid glycoside fraction has favorable impacts in modulating vanadium-induced brain damage with the potential ability to lower antioxidant levels and reduce neuroinflammation.

Low-dose spironolactone combats dyslipidemia and hepatic inflammation by modulating PCSK9 in rat model of polycystic ovarian syndrome.

Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder among women and it is associated with overt metabolic derangement. Circulating lipids are regulated by proprotein convertase subtilisin/kexin type 9 (PCSK9) which blocks low density lipoprotein (LDL) receptors especially in the liver. The liver is highly vulnerable in dyslipidemia as lipid accumulation leads to progression of non-alcoholic fatty liver disease (NAFLD). An array of scientific endeavours hold that low-dose spironolactone (LDS) is beneficial as intervention for PCOS traits, but this claim is yet to be fully elucidated. The aim of this study was to investigate the effect of LDS on dyslipidemia and hepatic inflammation in rats with letrozole (LET)-induced PCOS and to assess the possible involvement of PCSK9 in these effects. Eighteen female Wistar rats were randomly assigned into 3 groups. The control group received vehicle (distilled water; p.o.), LET-treated group received letrozole (1 mg/kg; p.o.), LET+LDS-treated group received LET plus LDS (0.25 mg/kg, p.o.) for 21 days. Exposure to LET increased body and hepatic weights, plasma and hepatic total cholesterol (TC), TC/HDL, LDL, interleukin-6, MDA, PCSK9, ovarian degenerated follicles and hepatic NLRP3 intensity, reduced GSH and normal ovarian follicles. Interestingly, LDS averted dyslipidemia, NLRP3-dependent hepatic inflammation and ovarian PCOS traits. It is evident herein that LDS ameliorates PCOS traits and combats dyslipidemia and hepatic inflammation in PCOS by a PCSK9-dependent mechanism.

Acetate-mediated-obestatin modulation attenuates adipose-hepatic dysmetabolism in high fat diet-induced obese rat model.

PURPOSE: Approximately 650 million of world adult population is affected by obesity, which is characterized by adipose and hepatic metabolic dysfunction. Short chain fatty acids (SCFAs) have been linked to improved metabolic profile. However, the effect of SCFAs, particularly acetate on adipose-hepatic dysfunction is unclear. Therefore, the present study investigated the role of acetate on adipose-hepatic metabolic dysfunction and the possible involvement of obestatin in high fat diet-induced obese Wistar rats. METHODS: Adult male Wistar rats (160-190 g) were allotted into groups (n = 6/group): Control, acetate-treated, obese and obese + acetate-treated groups received vehicle (distilled water), sodium acetate (200 mg/kg), 40% HFD and 40% HFD plus sodium acetate respectively. The administration lasted for 12 weeks. RESULTS: HFD caused increased body weight gain and visceral adiposity, insulin resistance, hyperinsulinemia and increased pancreatic-ß cell function and plasma/hepatic triglyceride and total cholesterol as well as decreased adipose triglyceride and total cholesterol, increased plasma, adipose, and hepatic malondialdehyde, TNF-α, uric acid, lactate production and plasma/adipose but not gamma-glutamyl transferase and decreased plasma, adipose, and hepatic nitric oxide, glucose-6-phosphate dehydrogenase (G6PD), glutathione (GSH) and obestatin concentration compared to the control group. Notwithstanding, treatment with acetate attenuated the alterations. CONCLUSIONS: The results demonstrate that high fat diet-induced obesity is characterized with adipose and hepatic lipid dysmetabolism, which is associated with obestatin suppression. Findings also suggest that acetate provide protection against adipose and hepatic metabolic perturbations by restoring obestatin as well as G6PD/GSH-dependent antioxidant system.

Naringin ameliorates motor dysfunction and exerts neuroprotective role against vanadium-induced neurotoxicity.

Exposure to vanadium has been known to lead to a progressive neurodegenerative disorder like Parkinson's disease. Naringin is a known flavonoid glycoside that is mostly seen in the flesh of grapefruit and orange and is believed to have protective effects for the treatment of neurodegenerative disorders. This study sought to investigate the role of Naringin in the treatment of vanadium-induced neurotoxicity. Vanadium (10 mg/kg BW) was injected intraperitoneally to induce motor dysfunction, followed by treatment with Naringin (30 mg/kg BW) intraperitoneally for 14 days. Oxidative stress imbalance was monitored by checking Glutathione Peroxidase (GPX) and Catalase levels. Histological and immunohistochemical alterations were observed using RBFOX3 polyclonal antibody to determine neuronal cell distribution and NLRP3 inflammasome antibody as a marker of inflammation. Exposure to vanadium induces neurotoxicity by significantly increasing the Catalase and Glutathione Peroxidase (GPX) levels. Vanadium administration also led to increased inflammatory cells and a significant reduction of the viable neuronal cells in the SNc and CPu. Treatment with Naringin showed a neuroprotective role by dependently restoring the Catalase and Glutathione Peroxidase (GPX) levels, inflammasome activation, and neuronal damage in the SNc and CPu. Naringin demonstrated anti-oxidative, and anti-inflammatory responses by inhibiting oxidative stress, and inflammation and exerts neuroprotective effects by inhibiting apoptosis following vanadium-induced neurotoxicity in adult Wistar rats.

Acetate supplementation restores testicular function by modulating Nrf2/PPAR-γ in high fat diet-induced obesity in Wistar rats.

PURPOSE: Several studies have established impaired testicular function in obese male population, including the young males with childhood obesity, contributing to increased male infertility, which is a universal trend in the last few decades. Short chain fatty acids (SCFAs) have been recently demonstrated to inhibit progression to metabolic comorbidities. The present study therefore hypothesized that SCFAs, acetate attenuates testicular dysfunction in high fat diet (HFD)-induced obese rat model, possibly by modulating Nrf2/PPAR-γ. METHODS: Adult male Wistar rats weighing 160-190 g were randomly allotted into three groups (n = 6/group): The groups received vehicle (distilled water), 40% HFD and sodium acetate (200 mg/kg) plus 40% HFD respectively. The administration lasted for 12 weeks. RESULTS: HFD caused obesity, which is characterized with increased body weight and visceral adiposity and insulin resistance/hyperinsulinemia. In addition, it increased testicular lipid deposition, malondialdehyde, pro-inflammatory mediators, lactate/pyruvate ratio, γ-Glutamyl transferase, and circulating leptin as well as decreased testicular glutathione, nitric oxide, Nrf2, PPAR-γ and circulating follicle stimulating hormone and testosterone without a significant change in testicular lactate dehydrogenase, blood glucose and luteinizing hormone when compared to the control group. Nevertheless, administration of acetate reversed the HFD-induced alterations. CONCLUSION: The present results demonstrates that HFD causes obesity-driven testicular dysfunction, associated with testicular lipid deposition, oxidative stress, and inflammation. The study in addition suggests the restoration of testicular function in obese animals by acetate, an effect that is accompanied by elevated Nrf2/PPAR-γ.