Zinc protects against lead-induced testicular damage via modulation of steroidogenic and xanthine oxidase/uric acid/caspase 3-mediated apoptotic signaling in male Wistar rats.

AIM: This study evaluated the effect of lead, with or without zinc co-administration, on steroidogenic and xanthine oxidase (XO)/uric acid (UA)/caspase 3-mediated apoptotic signaling in the testis. MATERIALS AND METHODS: Forty male Wistar rats were divided into four groups at random; vehicle-treated control, zinc-treated, lead-treated, and lead + zinc-treated groups. RESULTS: Lead exposure significantly lowered overall weight gain, testicular, epididymal, seminal vesicle, and prostate weights. Also, lead decreased sperm count, viability and motility but increased the fraction of sperm with aberrant morphology. In addition, lead caused a marked rise in the level of UA and XO activity but a decrease in nuclear factor erythroid 2-related factor 2 (Nrf2), reduced glutathione (GSH) as well as total antioxidant capacity (TAC) levels, and superoxide dismutase (SOD) and catalase activities. Furthermore, lead increased the testicular levels of nuclear factor kappa B (NFkB), interleukin-1beta (IL-1ß), and tumour necrotic factor-alpha (TNF-α), which were associated with an increase in testicular caspase 3 activity and DNA fragmentation as well as a decline in circulating gonadotropin releasing hormone (GnRH), luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, and testicular 3ß-hydroxysteroid dehydrogenase (3ß-HSD) and 17ß-hydroxysteroid dehydrogenase (17ß-HSD). These were associated with lead-induced degenerative changes in testicular tissues evidenced by shrunken seminiferous tubules, degeneration and sloughing of germ cells. Co-administration of zinc prevented lead-induced testicular injury by ameliorating oxidative stress, apoptosis, and inflammation through downregulation of XO/UA/caspase 3 pathway and upregulation of testicular 3ß-HSD/17ß-HSD. CONCLUSION: This study demonstrated that zinc protected against lead-induced testicular toxicity via the downregulation of XO/UA/caspase 3 signaling.

Impact of COVID 19 on erectile function.

Purpose: COVID-19, a novel infection, presented with several complications, including socioeconomical and reproductive health challenges such as erectile dysfunction (ED). The present review summarizes the available shreds of evidence on the impact of COVID-19 on ED.Materials and methods: All published peer-reviewed articles from the onset of the COVID-19 outbreak to date, relating to ED, were reviewed. Results: Available pieces of evidence that ED is a consequence of COVID-19 are convincing. COVID-19 and ED share common risk factors such as disruption of vascular integrity, cardiovascular disease (CVD), cytokine storm, diabetes, obesity, and chronic kidney disease (CKD). COVID-19 also induces impaired pulmonary haemodynamics, increased ang II, testicular damage and low serum testosterone, and reduced arginine-dependent NO bioavailability that promotes reactive oxygen species (ROS) generation and endothelial dysfunction, resulting in ED. In addition, COVID-19 triggers psychological/mental stress and suppresses testosterone-dependent dopamine concentration, which contributes to incident ED.Conclusions: In conclusion, COVID-19 exerts a detrimental effect on male reproductive function, including erectile function. This involves a cascade of events from multiple pathways. As the pandemic dwindles, identifying the long-term effects of COVID-19-induced ED, and proffering adequate and effective measures in militating against COVID-19-induced ED remains pertinent.

Effects of methotrexate on serum testosterone level in sleep deprived male Wistar rats.

BACKGROUND: Sleep deprivation has been reported to decrease testosterone levels but the mechanism remains unclear. Studies have shown that sleep deprivation increases interleukin 1 beta (IL-1ß), a pro-inflammatory cytokine and that increased IL-1ß levels cause reductions in Leydig cell production of testosterone. This study was therefore designed to determine the effects of methotrexate, an IL-1ß blocker on serum testosterone levels in sleep deprived male Wistar rats. METHODS: Twenty male Wistar rats were randomly assigned into four groups (n = 5); group I (Control) received the vehicle (1% tween 80 solution); group II (methotrexate) received 0.5 mg/kg body weight methotrexate; group III (SD) was sleep deprived and received the vehicle; group IV (SD+Methotrexate) was sleep deprived and received 0.5 mg/kg body weight methotrexate. Sleep deprivation was induced using the modified multiple platform technique for 14 days. Treatments were administered twice weekly by oral gavage for 14 days. Blood was collected on day 14 and serum was obtained for analyses of testosterone, LH and FSH levels. IL-1ß level and histology of the testis were also determined. Data were expressed as Mean ± SEM and analysed using ANOVA. p < 0.05 was considered significant. RESULTS: Serum testosterone levels were significantly decreased while testicular IL-1ß was increased in SD and SD+Methotrexate compared with Control. FSH and LH levels were not significantly different among the groups. CONCLUSION: Results of this study suggest that reduction in serum testosterone level in sleep deprived rats is not dependent on increased level of IL-1ß.

Effects of vitamin E and melatonin on serum testosterone level in sleep deprived Wistar rats.

BACKGROUND: Sleep deprivation affects a significant proportion of the global population. It has been reported to induce oxidative stress in the testes and reduce serum testosterone levels. Exogenous anti-oxidants have been known to prevent damages and diseases associated with oxidative stress but there is dearth of knowledge on their effectiveness during sleep deprivation. AIM: This study was designed to investigate the effects of two anti-oxidants; melatonin and vitamin E on serum testosterone concentration in sleep deprived male Wistar rats. METHODS: Thirty (30) male Wistar rats were used for this study. Animals were divided into six (6) groups (n = 5). Group 1 was the control, group 2 rats were sleep deprived, group 3 received vitamin E (200 mg/ kg bwt) only, group 4 rats received vitamin E and were sleep deprived, group 5 received melatonin only (10 mg/kg bwt), and group 6 rats received melatonin (10 mg/kg bwt) and were sleep deprived. Sleep deprivation was induced using the modified multiple platform technique. Body weights were taken on days 7, 14 and 21. Blood was collected at sacrifice and serum was obtained for analyses of testosterone, corticosterone and melatonin. Testicular malondialdehyde, superoxide dismutase and catalase levels were determined by the methods of Adam-Vizi and Seregi (1982), Misra and Fridovich (1972), and Sinha, (1972) respectively. Data obtained were analyzed using one way ANOVA and p < 0.05 was considered significant. RESULTS: Serum testosterone (nmol/l) of the sleep deprived animals (0.6 ± 0.3) reduced significantly (p < 0.05) compared with control group (3.3 ± 0.04), sleep deprived+vitamin E group (2.8 ± 0.5) and sleep deprived+melatonin group (2.0 ± 0.3). Also, melatonin+sleep deprived group had reduced testosterone compared with control. There were no significant changes in the serum corticosterone (nmol/l) and melatonin levels in all the groups compared with the sleep deprived group. However, corticosterone was increased in the sleep deprived+Vitamin E group (51.6 ± 20.5) compared with control (6.3 ± 0.6) Sleep deprived group had increased testicular malondialdehyde (MDA) (1.6 ± 0.1 unit/mg), superoxide dismutase (SOD) (3.2 ± 0.2 unit/mg), and catalasel evels (44.3 ± 1.1 unit/ mg) compared with control (0.9 ± 0.0 µmg). MDA, and catalase were significantly reduced in sleep deprived+vitamin E (1.1 ± 0.2, 2.4 ± 0.3, 39 ± 1.0 unit/ mg) compared with sleep deprived while melatonin alone had increased MDA. level (1.7 ± 0.2unit/mg) compared with control. SOD in the sleep deprived+melatonin group (2.7 ± 0.2 µ/mg) as compared with control increased (p < 0.05) while MDA and catalase levels as compared with control and sleep deprived groups showed no difference. Histological findings showed that the pathology in the testes of sleep deprived rats was ameliorated by vitamin E. CONCLUSION: Vitamin E had a more potent effect than melatonin in maintaining testosterone level in sleep deprived Wistar rat.

Sodium acetate ameliorates doxorubicin-induced cardiac injury via upregulation of Nrf2/HO-1 signaling and downregulation of NFkB-mediated apoptotic signaling in Wistar rats.

Despite the effectiveness of doxorubicin (DOX) in the management of a wide range of cancers, a major challenge is its cardio-toxic effect. Oxidative stress, inflammation, and apoptosis are major pathways for the cardiotoxic effect of DOX. On the other hand, acetate reportedly exerts antioxidant, anti-inflammatory, and anti-apoptotic activities. This particular research assessed the impact of acetate on cardiotoxicity induced by DOX. Mechanistically, acetate dramatically inhibited DOX-induced upregulation of xanthine oxidase and uric acid pathway as well as downregulation of Nrf2/HO-1 signaling and its upstream proteins (reduced glutathione peroxidase, superoxide dismutase, glutathione-S-transferase, glutathione, and catalase, glutathione reductase). In addition, acetate markedly attenuated DOX-driven rise inTNF-α, NFkB IL-6 and IL-1ß expression, and myeloperoxidase activity. Furthermore, acetate significantly ameliorated DOX-led suppression of Bcl-2 and Ca2+-ATPase activity and upregulation of Bax, caspase 3, and caspase 9 actions. Improved body weight, heart structural integrity, and cardiac function as depicted by cardiac injury markers convoyed these cascades of events. Summarily, the present study demonstrated that acetate protects against DOX-induced cardiotoxicity by upregulating Nrf2/HO-1 signaling and downregulating NFkB-mediated activation of Bax/Bcl-2 and caspase signaling.

Acetate attenuates cyclophosphamide-induced cardiac injury via inhibition of NF-kB signaling and suppression of caspase 3-dependent apoptosis in Wistar rats.

AIM: The goal of the current study was to examine the potential therapeutic effects of sodium acetate on cardiac toxicities caused by cyclophosphamide in Wistar rats. The possible involvement of NF-kB/caspase 3 signaling was also explored. MAIN METHODS: Thirty-two male Wistar rats were divided into four groups at random. (n = 8). The control animals received 0.5 mL of distilled water orally for 14 days, the acetate-treated group received 200 mg/kg/day of sodium acetate orally for 14 consecutive days, and cyclophosphamide-treated rats received 150 mg/kg /day of cyclophosphamide i.p. on day 8, while cyclophosphamide + acetate group received sodium acetate and cyclophosphamide as earlier stated. KEY FINDINGS: Results showed that cyclophosphamide-induced cardiotoxicity, which manifested as a marked drop in body and cardiac weights as well as cardiac weight/tibial length, increased levels of troponin, C-reactive protein, lactate, and creatinine kinase, and lactate dehydrogenase activities in the plasma and cardiac tissue. Histopathological examination also revealed toxic cardiac histopathological changes. These alterations were associated with a significant increase in xanthine oxidase and myeloperoxidase activities, uric acid, malondialdehyde, TNF-α, IL-1ß, NFkB, DNA fragmentation, and caspase 3 and caspase 9 activities in addition to a marked decline in Nrf2 and GSH levels, and SOD and catalase activities in the cardiac tissue. Acetate co-administration significantly attenuated cyclophosphamide cardiotoxicity by its antioxidant effect, preventing NFkB activation and caspase 9/caspase 3 signalings. SIGNIFICANCE: This study shows that acetate co-administration may have cardio-protective effects against cyclophosphamide-induced cardiotoxicity by inhibiting NF-kB signaling and suppressing caspase-3-dependent apoptosis.

Buchholzia coriacea seed induce antifertility by interfering with steroidogenic enzymes and inflammatory cytokines in rat testis.

Buchholzia coriacea has been reported to possess antifertility activities but little is known of the mechanisms responsible. This study was therefore designed to examine the mechanism responsible for the action of Buchholzia coriacea. Eighteen male Wistar rats (180-200 g) were used for this study. They were grouped into 3 (n = 6) namely, Control, Methanolic fraction of Buchholzia coriacea (MFBC) 50 mg/kg, and MFBC 100 mg/kg administered orally with respective dosage. After 6 weeks of administration, rats were euthanized, serum collected, while testes, epididymis and prostate were excised and homogenized. Testicular protein and testosterone, aromatase and 5α-reductase enzyme, 3ß hydroxysteroid dehydrogenase (HSD), 17ß-HSD, interleukin (IL) 1ß, IL-10 and Prostatic specific enzyme antigen (PSA) were assessed and data analyzed with ANOVA. There were significant increases in 3ß-HSD and 17ß-HSD levels in the MFBC 50 mg/kg with corresponding decreases in MFBC 100 mg/kg when compared to control. IL-1 was decreased in both doses while IL-10 increased in both doses compared to control. 5-α reductase enzyme was significantly decreased in the MFBC 100 mg/kg relative to the control. Testicular protein, testosterone and aromatase enzyme were not significantly different at both doses compared to control. PSA was significantly increased in the MFBC 100 mg/kg but not the 50 mg/kg relative to control. MFBC exhibits antifertility properties by interfering with testicular enzymes and inflammatory cytokines.

Glutamine prevents upregulation of NF-kB signaling and caspase 3 activation in ischaemia/reperfusion-induced testicular damage: An animal model.

AIM: Testicular ischaemia/reperfusion (I/R) injury is a major consequence of testicular torsion with possible attendant risk of male infertility. Glutamine, on the other hand, is a known antioxidant with anti-inflammatory potential. The present study evaluated whether or not glutamine would improve I/R-induced testicular injury in torsion/detorsion (T/D). The possible associated mechanisms were also investigated. METHODS: Wistar rats were randomly allotted into four groups (n = 10); sham-operated, glutamine-treated, T/D, and T/D + glutamine. Testicular torsion was induced and reperfusion established after two and a half hour under ketamine/xylazine anaethesia. Glutamine was administered one hour before reperfusion and continued daily for 3 days. At the end of the study, animals were euthanized, blood samples obtained, epididymal sperm suspension collected, and the testes harvested for biochemical and histopathological assays using established methods. RESULTS: Glutamine prevented T/D-driven I/R-induced reduced sperm quality, impaired testicular histoarchitecture, and suppressed circulating testosterone. Also, glutamine abated I/R-induced oxidative stress (evidenced by reduced hydrogen peroxide and MDA generation and enhanced concentrations and activities of antioxidants), inflammation (evidenced by suppression of TNF-α and IL-1ß), and apoptosis (evidenced by reduced DNA fragmentation) by down-regulating NF-kB and caspase 3 activity. CONCLUSION: For the first time, this study demonstrated that glutamine administration improved testicular I/R injury in T/D rat model by maintaining testicular redox balance, and testicular integrity and function via inhibition of I/R-induced upregulation of NF-kB signaling and caspase 3 activation.

Atorvastatin-mediated downregulation of VCAM-1 and XO/UA/caspase 3 signaling averts oxidative damage and apoptosis induced by ovarian ischaemia/reperfusion injury.

BACKGROUND: Oxidative damage is critical in the pathogenesis of ovarian ischaemia/reperfusion (I/R) injury, and statins have been reported to exert antioxidant activity. However, the role of VCAM-1 and xanthine oxidase (XO)/uric acid (UA) in ovarian I/R injury is not known. Also, whether or not atorvastatin exerts antioxidant activity like other statins is unclear. OBJECTIVES: This study investigated the involvement of VCAM-1 and XO/UA in ovarian I/R injury and the likely protective role of atorvastatin. METHODS: Forty female Wistar rats were randomized into sham-operated, ischaemia, ischaemia/reperfusion (I/R), ischaemia and atorvastatin, and I/R and atorvastatin. RESULTS: In comparison with the sham-operated group, atorvastatin blunted ischaemia and I/R-induced distortion of ovarian histoarchitecture and follicular degeneration. Also, atorvastatin alleviated ischaemia and I/R-induced rise in XO, UA, and malondialdehyde, which was accompanied by inhibition of ischaemia and I/R-induced reductions in reduced glutathione level, enzymatic antioxidant activities and increase in myeloperoxidase activity and TNF-α and IL-6 levels by atorvastatin treatment. Additionally, atorvastatin blocked ischaemia and I/R-induced increase in VCAM-1 expression, caspase 3 activity, 8-hydroxydeoxyguanosine level and ovarian DNA fragmentation index. CONCLUSION: For the first time, this study revealed that atorvastatin-mediated downregulation of VCAM-1 and XO/UA/caspase 3 signaling averts oxidative injury, inflammation, and apoptosis induced by ovarian ischaemia/reperfusion injury.