Panax ginseng Ameliorates Pituitary-Ovarian Dysfunction Induced by Radiofrequency Electromagnetic Radiation from Cell Phones via Upregulation of the CREM Signaling Pathway.

BACKGROUND: Panax ginseng (PG) is a plant that contains ginsenosides, which are considered adaptogens that confer cellular protection. However, the impact of PG on pituitary-ovarian dysfunction and subsequent infertility is unknown. This study investigated the hypothesis that PG would attenuate pituitary-ovarian dysfunction associated with mobile phone's Radiofrequency Electromagnetic Radiation (RF-EMR) in experimental rat models and the possible involvement of a cAMP Response Element Modulator (CREM)-dependent pathway. METHODS: Twenty adult female Wistar rats were divided randomly into four groups, each consisting of five rats. The control group was administered a vehicle (distilled water) orally, while the P. ginseng group received 200 mg/kg of P. ginseng extract orally. The RF-EMR group was exposed to 900MHz radiation, and the RF-EMR + PG group was exposed to the same radiation while also being treated with 200 mg/kg of P. ginseng orally. These treatments were administered daily for a period of 56 days. RESULTS: The RF-EMR group exhibited significant reductions in serum levels of LH, FSH, estradiol, and progesterone compared to the control group. Moreover, levels of superoxide dismutase (SOD) and glutathione peroxidase (GPx) were significantly lower in the RF-EMR group compared to the control. Additionally, there was a notable decrease in the expression of the CREM gene, accompanied by disrupted pituitary/ovarian morphology in the RF-EMR group compared to the control. However, the administration of PG mitigated these changes. CONCLUSION: The findings of this study indicate that P. ginseng extract shields against pituitary-ovarian impairment linked to RF-EMR exposure from cell phones by boosting antioxidant capacity and promoting the CREM-dependent pathway.

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.

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.

Repression of HDAC5 by acetate restores hypothalamic-pituitary-ovarian function in type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) accounts for 90-95 % of worldwide diabetes cases and is primarily characterized by insulin resistance. Its progression as a chronic metabolic disease has been largely associated with female reproductive abnormalities, including ovarian dysfunction with consequent infertility. Epigenetic modifications have been suggested as a possible link to metabolic comorbidities. We therefore hypothesized that short chain fatty acids, acetate (ACA), a potential histone deacetylase inhibitor (HDAC) ameliorates hypothalamic-pituitary-ovarian (HPO) dysfunction in T2DM. Female Wistar rats weighing 160-190 g were allotted into three groups (n = 6/group): Control (vehicle; po), T2D and T2D + ACA (200 mg/kg; po). T2DM was induced by fructose administration (10 %; w/v) for 6 weeks and single dose of streptozotocin (35 mg/kg; ip). The present data showed that in addition to insulin resistance, increased fasting blood glucose and insulin, T2DM induced elevated plasma, hypothalamic and ovarian triglyceride, lipid peroxidation, TNF-α and glutathione depletion. Aside, T2DM also led to increased plasma lactate production and γ-Glutamyl transferase as well as decreased gonadotropins/17ß-estradiol. Histologically, hypothalamus, pituitary and ovaries revealed disrupted neuronal cells/moderate hemorrhage, altered morphology/vascular congestions, and degenerated antral follicle/graafian follicle with mild fibrosis and infiltrated inflammatory cells respectively in T2D animals. Interestingly, these alterations were accompanied by elevated plasma/hypothalamic HDAC5 and attenuated when treated with acetate. The present results demonstrate that T2DM induces HPO dysfunction, which is accompanied by elevated circulating/hypothalamic HDAC5. The results in addition suggest that acetate restores HPO function in T2DM by suppression of HDAC5 and enhancement of insulin sensitivity.

Acetate ameliorates nephrotoxicity in streptozotocin-nicotinamide-induced diabetic rats: Involvement of xanthine oxidase activity.

Impaired renal function is a common complication of diabetes mellitus (DM) that often degenerates to cardiovascular disease, contributing to high morbidity and reduced survival worldwide. Short chain fatty acids (SCFAs), including acetate has shown potential benefits in glycemic or metabolic regulation but its effect on diabetes-associated renal toxicity/impairment is not clear. Herein, we investigated the hypothesis that acetate would ameliorate renal toxicity, accompanying DM, possibly by suppression of xanthine oxidase (XO) activity. Adult male Wistar rats (230-260 g) were allotted into groups (n = 6/group) namely: control (vehicle; po), sodium acetate (NaAc)-treated (200 mg/kg), diabetic with or without NaAc groups. DM was induced by intraperitoneal injection of streptozotocin 65 mg/kg after a dose of nicotinamide (110 mg/kg). Diabetic animals showed increased fasting glucose and insulin, renal triglyceride, total cholesterol, atherogenic lipid, malondialdehyde, XO, tissue necrosis factor-α, uric acid, interleukin-6, aspartate transaminase/alanine aminotransferase ratio, gamma-glutamyl transferase and decreased glutathione and nitric oxide concentration. The renal tissue was characterized with disrupted tissue architecture, enlarged Bowman's space, congested glomeruli and adherence of abnormal segments of tuft to Bowman's capsule with consequent elevated serum creatinine and urea concentration. However, these alterations were attenuated by NaAc. The study demonstrates that acetate ameliorates diabetes-induced nephrotoxicity, which is associated with suppressed XO and its accompanied pro-inflammatory mediators. Therefore, SCFAs, acetate would be a promising dietary-derived therapeutic agent for the prevention and management of diabetes-associated renal disturbances.

High fructose-enriched diet synergistically exacerbates endocrine but not metabolic changes in letrozole-induced polycystic ovarian syndrome in Wistar rats.

BACKGROUND: Polycystic Ovarian Syndrome (PCOS) is a multifactorial endocrine-metabolic disorder that highly contributes to the prevalence of infertility globally. The increased consumption of refined carbohydrate, particularly fructose has been associated with pandemic metabolic disorders, including in women of reproductive age. However, the effects of high fructose consumption (FRD) on endocrine and metabolic disorders associated with PCOS are not clear. Therefore, this study investigated the effects of FRD on endocrine/metabolic changes in letrozole-induced PCOS in Wistar rats. MATERIALS AND METHODS: Twenty-eight adult female Wistar rats were randomly allotted into 4 groups and treated with vehicle, letrozole (LET; 0.5 mg/kg), FRD (D-fructose chow pellet mixture) and LET + FRD. The treatment lasted for 21days. RESULTS: Data showed a significant increase in ovarian weight, liver weight, luteinising hormone (LH), testosterone and decrease in follicle stimulating hormone as well as moderate histopathological changes in the fallopian tube, uterus and liver of animals with PCOS. FRD-treated group showed a significant increase in ovarian weight and liver weight but no significant alteration in hormonal profile or histopathological changes in uterus and fallopian tube. However, FRD significantly altered hormonal profile with consequent histopathological changes in fallopian tube and uterus but FRD did not alter ovarian/liver weight or blood glucose in animals with PCOS when compared with animals without PCOS. CONCLUSION: The present results demonstrate that FRD synergistically aggravates endocrine but not metabolic changes in PCOS, suggesting that FRD might deteriorate endocrine-related phenotypes in PCOS.

Hibiscus sabdariffa extract protects against cadmium-induced ovarian toxicity in adult Wistar rats.

Hibiscus sabdariffa (HS) is native to tropical and subtropical regions, and its enrichment as a source of antioxidants and phytoestrogen has been documented. The present study investigated effects of HS on ovarian toxicity induced by cadmium. Adult female Wistar rats were grouped into 4 (n=5/group): Group A received HS (100 mg/kg), group B received cadmium sulphate (5 mg/kg), group C received cadmium sulphate and HS, and group D (control) received 1 ml of distilled water. Cadmium sulphate was administered for five days (i.p) followed by oral administration of HS for 28 days. Results showed distortion in the cytoarchitecture of the follicular cells in the ovary of cadmium-treated rats while there was mild or no distortion recorded for the ovary of the rats treated with cadmium and HS. There was also a significant reduction in the serum level of Luteinizing and follicle stimulating hormone of the rats treated with cadmium (group B) when compared with control rats. However, these alterations were attenuated when treated with HS. We concluded that HS has an ovarian protective effect in cadmium-treated adult female rats. Hence the present results suggest that HS extract would be a potential therapeutic agent in ovarian dysfunction.

Protective role of glutamine against cadmium-induced testicular dysfunction in Wistar rats: Involvement of G6PD activity.

BACKGROUND: Endocrine disruptor such as cadmium has been widely reported to cause testicular toxicity, which contributes to recent decline in male fertility worldwide. Glutamine, the most abundant amino acid in the body has been demonstrated to exert protective effects in cellular toxicity. However, its role in testicular toxicity is unknown. The present study is therefore aimed at investigating the effects of glutamine supplementation on cadmium-induced testicular toxicity, and the possible involvement of glucose-6-phosphate dehydrogenase (G6PD) activity. MATERIALS AND METHOD: Male Wistar rats weighing 160-190 g were allotted into 4 groups (n = 5/group): The groups received vehicle (distilled water; p.o.), glutamine (1gkg-1; p.o.), cadmium chloride (5mgkg-1p.o.) and Cadmium chloride plus glutamine respectively, daily for 30 days. Biochemical and histological analyses were performed with appropriate method. RESULTS: Administration of cadmium significantly decreased body weight, sperm count, motility and viability, as well as altered sperm morphology and progressivity. Cadmium also caused atrophy of the seminiferous tubule in addition to disrupted testicular architecture, lumen, Sertoli cells and spermatogonia. Similarly, serum and testicular aspartate transaminase, and malondialdehyde significantly increased, and G6PD, glutathione, nicotinamide adenine dinucleotide phosphate and nitric oxide significantly decreased with corresponding decrease in follicle stimulating hormone, luteinizing hormone and testosterone in cadmium-treated animals compared with control groups. However, supplementation with glutamine attenuated these alterations. CONCLUSION: The present study demonstrates that cadmium induces testicular dysfunction that is attributable to defective G6PD and accompanied by increased lipid peroxidation and impaired NO-dependent endothelial function. Interestingly, glutamine supplementation ameliorates cadmium-induced testicular dysfunction through enhancement of G6PD activity.