Melatonin ameliorates endocrine dysfunction and defective sperm integrity associated with high-fat diet-induced obesity in male Wistar rats.

Obesity (OBS) has been established as a link to male hypogonadism with consequent infertility. Previous studies have shown that melatonin (MEL) modulates hypothalamic-pituitary-gonadal function. The present study therefore investigated the hypothesis that MEL supplementation would attenuate spermatogenic and steroidogenic dysfunctions associated with obesity induced by high-fat diet (HFD). Twenty-four adult male Wistar rats (n = 6/group) were used: control group received vehicle (normal saline), obese group received 40% high-fat diet and distilled water, MEL-treated group received MEL (4 mg/kg), and OBS + MEL group received MEL and 40% HFD and the treatment lasted for 12 weeks. HFD caused increased body weight, glucose intolerance, plasma triglyceride and low-density lipoprotein cholesterol/ very low-density lipoprotein cholesterol and malondialdehyde, as well as decreased antioxidant capacity, high-density lipoprotein cholesterol, gonadotrophin-releasing hormone, follicle-stimulating hormone and testosterone and altered sperm parameters. However, all these alterations were attenuated when supplemented with MEL. Taken together, these results indicate that HFD exposure causes endocrine dysfunction and disrupted sperm parameters in obese animals, which are accompanied by lipid peroxidation/defective antioxidant capacity. In addition, the present results suggest that melatonin supplementation restores endocrine function and sperm integrity in obese rat model by suppression of oxidative stress-dependent mechanism.

Low dose spironolactone-mediated androgen-adiponectin modulation alleviates endocrine-metabolic disturbances in letrozole-induced PCOS.

Polycystic ovarian syndrome (PCOS), is a multifactorial endocrine disorder in women of reproductive age. It usually associates with metabolic disorders (MDs), which aggravates the risk of infertility, cardiometabolic events and associated comorbidities in women with PCOS. Adiponectin, a circulating protein produced by adipocytes, which has been suggested to inversely correlate with MDs. Spironolactone, a non-selective mineralocorticoid receptor (MR) antagonist, has been in wide clinical use for several decades. Herein, we investigated the effects of low dose spironolactone (LDS) and the role of adiponectin in endocrine-metabolic disturbances in experimentally-induced PCOS rats. Eighteen female Wistar rats (160-180 g) were randomly allotted into 3 groups and treated with vehicle (p.o.), letrozole (LET; 1 mg/kg) and LET + LDS (0.25 mg/kg), once daily for 21 days, respectively. The results showed that LET-treated animals had features of PCOS, characterized by elevated plasma testosterone and prolactin, increased body weight gain and ovarian weight as well as disrupted ovarian cytoarchitecture and degenerated follicles. Additionally, elevated fasting blood glucose, 1 h-postload glucose and plasma insulin, impaired glucose tolerance, insulin resistance, reduced insulin sensitivity, increased plasma and ovarian lipid profile, plasma lipid peroxidation, TNF-α, IL-6 and decreased plasma glutathione peroxidase and glutathione content were observed. These alterations were associated with decreased circulating adiponectin and were reversed when treated with LDS. The present results suggest that LDS ameliorates endocrine-metabolic disturbances and inflammation-related comorbidities associated with LET-induced PCOS by modulating circulating androgen-adiponectin status.

Glia activation and its role in oxidative stress.

Glia activation and neuroinflamation are major factors implicated in the aetiology of most neurodegenerative diseases (NDDs). Several agents and toxins have been known to be capable of inducing glia activation an inflammatory response; most of which are active substances that can cause oxidative stress by inducing production of reactive oxygen species (ROS). Neurogenesis on the other hand involves metabolic and structural interaction between neurogenic and glia cells of the periventricular zone (PVZ); a region around the third ventricle. This study investigates glia activation (GFAP), cell proliferation (Ki-67) and neuronal metabolism (NSE) during neurogenesis and oxidative stress by comparing protein expression in the PVZ against that of the parietal cortex. Adult Wistar Rats were treated with normal saline and 20 mg/Kg KCN for 7 days. The tissue sections were processed for immunohistochemistry to demonstrate glia cells (anti Rat-GFAP), cell proliferation (anti Rat-Ki-67) and neuronal metabolism (anti Rat-NSE) using the antigen retrieval method. The sections from Rats treated with cyanide showed evidence of neurodegeneration both in the PVZ and cortex. The distribution of glia cells (GFAP), Neuron specific Enolase (NSE) and Ki-67 increased with cyanide treatment, although the increases were more pronounced in the neurogenic cell area (PVZ) when compared to the cortex. This suggests the close link between neuronal metabolism and glia activation both in neurogenesis and oxidative stress.

Acetate attenuates hypothalamic pyroptosis in experimentally induced polycystic ovarian syndrome.

This study hypothesized that SCFA, acetate impacts positively on hypothalamic pyroptosis and its related abnormalities in experimentally induced PCOS rat model, possibly through NrF2/HIF1-α modulation. Eight-week-old female Wister rats were divided into groups (n = 5), namely control, PCOS, acetate and PCOS + acetate groups. Induction of PCOS was performed by administering 1 mg/kg body weight of letrozole for 21 days. After PCOS confirmation, the animals were treated with 200 mg/kg of acetate for 6 weeks. Rats with PCOS were characterized with insulin resistance, leptin resistance, increased plasma testosterone as well as degenerated ovarian follicles. There was also a significant increase in hypothalamic triglyceride level, triglyceride-glucose index, inflammatory biomarkers (SDF-1 and NF-kB) and caspase-6 as well as plasma LH and triglyceride. A decrease was observed in plasma adiponectin, GnRH, FSH, and hypothalamic GABA with severe inflammasome expression in PCOS rats. These were accompanied by decreased level of NrF2/HIF1-α, and the alterations were reversed when treated with acetate. Collectively, the present results suggest the therapeutic impact of acetate on hypothalamic pyroptosis and its related comorbidity in PCOS, a beneficial effect that is accompanied by modulation of NrF2/HIF1-α.

Counteractive effects of extracts of Mangifera indica on testes of Wistar Rat exposed to cyclophosphamide.

Introduction: Infertility may have a variety of causes that can affect both the male and female reproductive systems. Cyclophosphamide is a drug used in chemotherapy and immune system suppression. Leaf extracts of Mangifera indica exhibit a wide spectrum of pharmacological properties which have been shown in studies, including antioxidant and protective advantages. This study evaluate the antagonistic implications of leaf extracts of Mangifera indica on the testis following the exposure to cyclophosphamide. Methods: 25 male Wistar rats were assigned to five groups with five rats in each. Group A (Control), Group B (administered 150 mg of cyclophosphamide only), Group C (administered 50 mg of extracts of leaf extracts of Mangifera indica only), Group D (administered 150 mg of cyclophosphamide and 50 mg of leaf extracts of Mangifera indica) and Group E (administered 150 mg of cyclophosphamide and 100 mg of leaf extracts of Mangifera indica) for two weeks. The rats were euthanized under the anesthetic of ketamine (30 mg/kg IP). Blood was taken by cardiac puncture for biochemical examination. Testes were excised, preserved in 10% Neutral Buffered Formalin for histological investigation. One-way analysis of variance was used to examine the data, and then the Student Newman-Keul post-hoc analysis was performed. The significance of the result was assessed using p < 0.05. Results: The study showed statistically significant differences (p < 0.05) in the hormonal assay, including LH, FSH, and testosterone across all test groups, with group B (cyclophosphamide only) having significantly lower levels. Cyclophosphamide administration was observed to have a negative effect on the testicular histology and immunohistochemical results and leaf extracts of Mangifera indica attenuated the damage induced by cyclophosphamide in groups D and E. Conclusion: Leaf Extracts of Mangifera indica considerably reduced the effects of cyclophosphamide-induced changes in testis.

Effects of Combined Garcinia kola and Kigelia africana on Insulin and Paraoxonase 1 (PON1) Levels in Type 2 Diabetic Rats.

BACKGROUND: Individual extracts of Garcinia kola and Kigelia africana have been shown to have therapeutic effects against a variety of variables linked to the development of diabetes mellitus. However, there is still a lack of information about the combined effects of these extracts on Insulin and Paraoxonase 1 (PON-1) in Streptozotocin-Nicotinamide-induced type-2 diabetic Wistar rats. METHODS: Forty-two young male rats (180-200g) were randomly divided into six groups (n = 7/group). Diabetes was intraperitoneally induced with 110 mg/kg of nicotinamide constituted in distilled water and fifteen minutes later with 65 mg/kg of streptozocin freshly prepared in 0.1M citrate buffer (pH of 4.5) and treated for six weeks as follows: the control rats received either 0.9% normal saline (NS) or 250 mg/kg extract by gavage. The remaining animals were diabetes induced and subsequently treated with either NS, graded doses of the extract (250 mg/kg and 500 mg/kg), or 5 mg/kg Glibenclamide + 100mg/kg Metformin. Gas chromatography-mass spectrometry (GCMS) of the combined extracts was also analyzed to identify the bioactive compounds present in it. Insulin, PON-1 levels, lipid profiles, and atherogenic index were assessed. RESULTS: Our findings show that Insulin and PON-1 levels in the plasma of diabetic rats treated with the combined extracts were significantly increased when compared to the control rats. Moreover, the GCMS of the extract shows the presence of both monounsaturated (oleic acid) and polyunsaturated (linoleic acid) fatty acids. CONCLUSION: The current findings suggest that the extract may help improve glucose homeostasis and prevent atherosclerosis through the established mechanism of the identified bioactive compounds.

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.