Therapeutic potential of virgin coconut oil in mitigating sodium benzoate- model of male infertility: Role of Nrf2/Hmox-1/NF-kB signaling pathway.

Objectives: Male infertility is a major public health issue due to increased prevalence, so there is an urgent need for a therapeutic solution. The search for a natural dietary substance that could modulate redox balance and inflammation and protect testicular function is in demand. Virgin Coconut Oil (VCO) has found use in the treatment of diabetes, and cancer owing to the presence of polyphenols. However, there is a dearth of information on its effect on testicular toxicity. The present study investigated VCO as a possible treatment for testicular toxicity in the Sodium Benzoate (SB) model of male infertility by evaluating the oxidative and inflammatory status, circulating hormonal levels, and key sperm indices. Materials and Methods: Twenty adult male rats were randomly assigned to four groups of 5 rats each and were treated with normal saline, sodium benzoate, sodium benzoate+5% VCO, and sodium benzoate+15% VCO for 30 days respectively. Biochemical analysis of reproductive hormones was assessed. Sperm parameters assessed include sperm function tests and sperm kinematics. One-way analysis of variance (ANOVA) followed by post hoc Tukey tests was performed. Results: 5% VCO reverts the deranged serum reproductive hormones caused by sodium benzoate. 5% VCO was more potent as an antioxidant and anti-inflammatory treatment than 15% VCO. However, both doses prevented SB's effect on the sperm function test and kinematics. Conclusion: VCO-supplemented diet can ameliorate SB-induced testicular toxicity by inhibiting its mechanisms of toxicity that are related to oxidative stress, apoptosis, and inflammation.

Zinc ameliorates acrylamide-induced oxidative stress and apoptosis in testicular cells via Nrf2/HO-1/NfkB and Bax/Bcl2 signaling pathway.

BACKGROUND: Acrylamide is a toxic substance formed in some foods that require high-temperature cooking processes and has been implicated as a gonadotoxic agent. Zinc, on the other hand, is a known antioxidant with fertility-enhancing properties. Hence, this study was designed to explore the possible ameliorative effect of zinc in acrylamide-induced gonadotoxicity. METHODS: Twenty-four male Wistar rats were randomized into control, acrylamide (10 mg/kg of acrylamide), acrylamide + 1 mg/kg of zinc, and acrylamide + 3 mg/kg of zinc. The administration was via the oral route and lasted for 56 days. RESULTS: Zinc treatment ameliorated acrylamide-impaired sperm quality, normal testicular histoarchitecture, and hormonal balance, which was accompanied by increased testicular malondialdehyde and interleukin-1ß and decreased testicular superoxide dismutase (SOD) and catalase (CAT). Furthermore, zinc prevented acrylamide-induced downregulation of testicular nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and B-cell lymphoma 2 (BCl2) expression and upregulation of testicular nuclear factor kappa B (NF-κB) and bcl-2-like protein 4 (bax) expression. CONCLUSION: In conclusion, zinc may protect against acrylamide-induced testicular toxicity, mediated by its antioxidant, anti-inflammatory, and antiapoptotic effects.

Naringin from sweet orange peel improves testicular function in high fat diet-induced diabetic rats by modulating xanthine oxidase/uric acid signaling and maintaining redox balance.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a metabolic disorder affecting many organs, including the testis. Naringin from orange peel extract (OPE) is a flavanone with fertility-enhancing properties. Hence, this study was designed to establish the effect of naringin on T2DM-induced testicular dysfunction. Thirty male (30) Wistar rats were randomized into five groups control, diabetes, diabetes + naringin, diabetes + OPE, and diabetes + metformin. The administrations were via the oral route and lasted for 28 days. RESULTS: Naringin ameliorated T2DM-induced increase in FBS and decrease in serum insulin. It also abrogated T2DM-induced decrease in sperm quality, gonadotropin-releasing hormone, luteinizing hormone, follicle-stimulating hormone, testosterone, estradiol, prolactin, catalase, superoxide dismutase, and total antioxidant capacity. Furthermore, naringin prevented a T2DM-induced increase in malonaldehyde, tumor necrosis factor-alpha, C-reactive protein, xanthine oxidase (XO), and uric acid (UA), it was accompanied by the restoration of normal testicular histoarchitecture. CONCLUSIONS: Naringin prevented T2DM-induced testicular dysfunction by modulating XO/UA and restoring redox balance. Also, while the animals treated with OPE exhibited better ameliorative effects than their counterparts treated with naringin, the findings from this study showed that naringin would be a promising supplement for treating T2DM-induced male infertility.

Omega 3 fatty acid improves sexual and erectile function in BPF-treated rats by upregulating NO/cGMP signaling and steroidogenic enzymes activities.

Bisphenol F (BPF) is an environmental pollutant that has been implicated in sexual dysfunction. Omega 3 fatty acid (O3FA), on the other hand, is an antioxidant with the ability to improve fertility indices. However, no study has explored the possible ameliorative effect of O3FA on BPF-induced sexual dysfunction. Thus, the effect of BPF and/or O3FA on male sexual performance was investigated. Male Wistar rats were randomized into 6 groups, corn oil-treated, O3FA low and high dose (100 and 300 mg/kg), BPF-treated, BPF + O3FA low and BPF + O3FA high dose. BPF significantly impaired male sexual competence, evidenced by a reduction in motivation to mate, prolonged mount, intromission and ejaculation latency, and post-ejaculatory index. Furthermore, a reduction in mount, intromission, and ejaculation frequency were observed. Also, BPF caused a decrease in gonadotropin releasing hormone, follicle stimulating hormone, luteinizing hormone, testosterone, nitric oxide (NO) cyclic guanosine monophosphate (cGMP), 3beta-hydroxysteroid dehydrogenase (3ß-HSD), 17beta-hydroxysteroid dehydrogenase (17ß-HSD), dopamine, and acetylcholine esterase. Furthermore, it was accompanied by a significant increase in prolactin and estrogen and poor pregnancy outcomes. These observed BPF-led alterations were abolished by O3FA administration. This study showed that O3FA ameliorates BPF-induced sexual dysfunction by upregulating NO/cGMP signaling and steroidogenic enzymes activities.

Omega-3 fatty acid ameliorates bisphenol F-induced testicular toxicity by modulating Nrf2/NFkB pathway and apoptotic signaling.

Introduction: Bisphenol F (BPF) has been shown to disrupt testicular functions via perturbation of testicular redox balance, while omega-3 fatty acid (O3FA) has been established to exert antioxidant and anti-inflammatory activities. Therefore, this study focused on the role and associated molecular mechanism of O3FA in BPF-induced testicular dysfunction in male Wistar rats. Methods: Twenty-four (24) rats were randomly grouped after two weeks of acclimatization into four (4) groups (n=6/group); the vehicle-treated control group, BPF treated group received 30 mg/kg of BPF, and the intervention groups received 30 mg/kg BPF + 100 mg/kg O3FA (BPF+O3FA-L) and 30 mg/kg BPF + 300 mg/kg of O3FA (BPF+O3FA-H). All treatment lasted for 28 days. Results: Low and high doses of O3FA ameliorated BPF-impaired sperm quality, and induced hormonal imbalance, accompanied by a distortion in testicular histology and elevated testicular injury markers. Furthermore, co-administration of BPF with both doses of O3FA blunted BPF-induced redox imbalance, inflammatory response, and apoptosis. Discussions: In conclusion, our present findings show that O3FA improves testicular functions in BPF-treated rats by improving sperm quality and reproductive hormones via the maintenance of testicular redox balance.

In vivo exposure to bisphenol F induces oxidative testicular toxicity: role of Erß and p53/Bcl-2 signaling pathway.

Introduction: Bisphenol F (BPF), an alternative to bisphenol A has been implicated as a gonadotoxic substance. BPF has been shown to induce hormonal imbalance and testicular oxidative damage. However, the mechanism associated with BPF-induced testicular toxicity has not been fully explored. This study was designed to explore the role of tumor protein (p53)/ B-cell lymphoma 2 (BCl-2) signaling and oestrogen receptor beta (Erß) in BPF-induced testicular toxicity. Methods: Male Wistar rats were randomized into control (Cntrl), BPF-treated (10, 30, and 50 mg/kg for low dose (BPF-L), medium dose (BPF-M), and high dose (BPF-H) respectively), and BPF-treated recovery (Cntrl-R, BPF-L-R, BPF-M-R, and BPF-H-R). The administration was via gavage and lasted for 28 days and the animals in the recovery groups were allowed 28-days exposure free period for recovery from BPF exposure. Results: BPF resulted in the distortion of the testicular histoarchitecture, which was accompanied by a significant rise in testicular gamma-lutamyl transferase and lactate dehydrogenase activities but a decline in sorbitol dehydrogenase activities. Also, BPF caused a significant reduction in plasma gonadotropin-releasing hormone, luteinising hormone, follicle-stimulating hormone, and testosterone, which was associated with the downregulation of testicular 3beta-hydroxysteroid dehydrogenase and 17beta-hydroxysteroid dehydrogenase activities. Furthermore, BPF induced testicular inflammation, redox imbalance, and apoptosis, accompanied by distortion in p53/BCl-2 signaling and overexpression of Erß. Again, the observed toxic effects of BPF were dose-dependent and not completely reversed by BPF cessation. Discussion: Bisphenol F induced gonadotoxicity by distorting p53/BCl2 signaling and the expression of Erß. These observed alterations were not completely reversed after the cessation of BPF exposure.

Orange Peel Extract and Physical Exercise Synergistically Ameliorate Type 2 Diabetes Mellitus-Induced Dysmetabolism by Upregulating GLUT4 Concentration in Male Wistar Rats.

Diabetes mellitus (DM) is a chronic disease and one of the oldest known disorders. It is characterized by dysglycemia, dyslipidemia, insulin resistance (IR), and pancreatic cell dysfunction. Although different drugs, metformin (MET), glipizide, glimepiride, etc., have been introduced to treat type 2 DM (T2DM), these drugs are not without side effects. Scientists are now seeking natural treatments such as lifestyle modification and organic products known with limited side effects. Thirty-six male Wistar rats were randomized into six groups (n = 6 per group): control, DM untreated rats, DM+orange peel extract (OPE), DM+exercise (EX), DM+OPE +EX, and DM+MET. The administration was once daily through the oral route and lasted for 28 days. EX and OPE synergistically ameliorated the diabetic-induced increase in fasting blood sugar, homeostatic model assessment for insulin resistance (HOMA IR), total cholesterol (TC) and triglyceride (TG), TC/high-density lipoprotein (HDL), TG/HDL, triglyceride glucose (TyG) index, and hepatic lactate dehydrogenase, alanine transaminase, malondialdehyde, c-reactive protein, and tumour necrosis factor α when compared with the diabetic untreated group. Also, EX+OPE blunted DM-induced decrease in serum insulin, homeostasis model assessment of ß-cell function (HOMA-B), homeostasis model assessment of insulin sensitivity (HOMA S), quantitative insulin-sensitivity check index (QUICK 1), HDL, total antioxidant capacity, superoxide dismutase, and hepatic glycogen. Furthermore, EX+OPE ameliorated the observed DM-induced decrease in glucose transporter type 4 (GLUT 4), expression. This study showed that OPE and EX synergistically ameliorate T2DM-induced dysglycaemia, dyslipidaemia, and down-regulation of GLUT4 expression.

Restoration of Hepatic and Intestinal Integrity by Phyllanthus amarus Is Dependent on Bax/Caspase 3 Modulation in Intestinal Ischemia-/Reperfusion-Induced Injury.

Ethnopharmacological relevance: Oxidative stress is a key player in intestinal ischemia/reperfusion (I/R) injury (IIRI) with a tendency to trigger systemic inflammatory response, resulting in progressive distal organ injury. To date, the role of Bax/caspase 3 signaling in IIRI has not been reported. Furthermore, the discovery of a safe and effective drug remains pertinent in improving the outcome of IIRI. Therefore, this study investigated the role of Bax/caspase 3 signaling in intestinal I/R-induced intestinal and hepatic injury. In addition, the protective effect and possible associated mechanism of action of methanolic Phyllanthus amarus leaf extract (PA) against intestinal I/R-induced intestinal and hepatic injury were evaluated. Materials and methods: Fifty male Wistar rats were randomized into five groups (n = 10). The sham-operated group was received 0.5 mL of distilled water for seven days prior to the sham surgery, while the IIRI, febuxostat (FEB) + IIRI, low-dose PA (LDPA) + IIRI, and high-dose PA (HDPA) + IIRI groups underwent the I/R procedure. In addition to the procedure, IIRI, FEB + IIRI, LDPA + IIRI, and HDPA + IIRI received 0.5 mL of distilled water, 10 mg/kg of febuxostat, 200 mg/kg of PA, and 400 mg/kg of PA, respectively, for seven days prior to the I/R procedure. Results: Administration of methanolic Phyllanthus amarus leaf extracts attenuated the intestinal I/R-induced rise in intestinal and hepatic injury markers, malondialdehyde, nitric oxide, TNF-α, IL-6, and myeloperoxidase activities. In addition, Phyllanthus amarus ameliorated I/R-induced suppression of reduced glutathione, thiol and non-thiol proteins, and superoxide dismutase, catalase, and glutathione peroxidase activities in intestinal and hepatic tissues. These were coupled with the suppression of I/R-induced bacterial translocation, downregulation of I/R-induced activation of Bax/caspase 3 signaling, and improvement of I/R-induced distortion of intestinal and hepatic histoarchitecture by Phyllanthus amarus. Conclusion: Methanolic Phyllanthus amarus leaf extract protects against intestinal and hepatic injuries associated with intestinal I/R by suppressing oxidative-stress-mediated activation of Bax/caspase 3 signaling. The beneficial effects of Phyllanthus amarus may be ascribed to its constituent bioactive molecules, especially tannins, anthocyanin, alkaloids, and phenolics.

HAART and anti-Koch's impair sexual competence, sperm quality and offspring quality when used singly and in combination in male Wistar rats.

This study investigated the impact of the administration of HAART and anti-Koch's, singly and in combination, on sexual competence and birth statistics. Adult male Wistar rats were randomised into distilled water-treated control, HAART-treated, anti-Koch's-treated and HAART + anti-Koch's-treated groups. The 56-day oral treatment led to impaired sexual competence evident by significantly reduced motivation to mate, prolonged latencies of mount, intromissions, ejaculations and post-ejaculatory interval, as well as reduced frequencies of mount, intromissions and ejaculations. This was accompanied by significant reductions in penile erection reflex and penile grooming. HAART and anti-Koch's, when administered singly or in combination, also led to significant reductions in the circulatory follicle-stimulating hormone, luteinizing hormone, testosterone and intratesticular testosterone, but a significant rise in prolactin. Also, HAART and/or anti-Koch's significantly reduced sperm count, sperm motility, sperm viability and spermatozoa with normal morphology. Furthermore, HAART and anti-Koch's, separately or in combination, significantly lowered fertility capacity, litter size and litter weight and offspring survival. The deleterious effects of these drugs were more pronounced when combined. Findings of the present study revealed that HAART and/or anti-Koch's impair sexual competence via a testosterone-dependent hyperprolactinemia-mediated mechanism. These events are associated with reduced fertility capacity, poor sperm quality and lowered offspring survival.