Integrity of hypothalamic-pituitary-testicular axis in exceptional longevity.

Hypothalamic integrity increasingly is being recognized as a marker of healthy longevity in rodent models. Insight into hypothalamic function in humans with exceptional longevity can be gained via investigation of the hypothalamic-pituitary-testicular (HPT) axis in men with exceptional longevity. This study aimed to characterize the HPT axis function, defined by levels of testosterone (T) and luteinizing hormone (LH), in 84 Ashkenazi Jewish men aged 90-106 years. We found that 94% of men exhibited preserved hypothalamic-pituitary function, as evidenced by either normal testosterone and LH levels (25%) or an appropriate rise in LH in response to aging-related primary testicular dysfunction (69%), a hormone pattern mirroring female menopause. Total T level was not associated with metabolic parameters or survival. These results demonstrate a high prevalence of testicular dysfunction with preserved hypothalamic-pituitary function in men with exceptional longevity. Thus, the role of hypothalamic integrity and HPT axis in healthy aging warrants further investigation.

Costus afer leaf extract protects against testicle damage caused by cyclosporine A in adult male Wistar rats through an antioxidant mechanism.

Cyclosporine A is one of the most widely used drugs in organ transplant and oncology patients. But its use is accompanied by many toxicities. This study aimed to investigate the possible protective effect of Costus afer (C. afer) leaf extract on cyclosporine A-induced testicular toxicity. This study was carried out on 40 adult male Wistar rats were divided into four groups: control, C. afer, cyclosporine A and cyclosporine A+ C. afer groups. The investigations include genital weight, sperm count and characters, serum luteinising hormone (LH) and testosterone, testicular tissue contents of reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSHPx) and lipid peroxidation (MDA). Besides, a histopathological examination of testicular tissue stained with haematoxylin and eosin (H & E) was performed. Cyclosporine A+ C. afer group showed a significant increase in the genital weight, serum testosterone, sperm count, motility and viability. Besides, the extract significantly decreased testicular content of MDA and increased SOD, CAT and GSHPx. C. afer coadministration significantly decreased serum LH and sperm abnormalities and protected against testicular histopathological alterations. The extract showed a protective effect against testicular toxicity associated with cyclosporine A and that was through an antioxidant mechanism.

Sitagliptin protects male albino rats with testicular ischaemia/reperfusion damage: Modulation of VCAM-1 and VEGF-A.

Twisting of the spermatic cord is considered a popular problem in the urological field, which may lead to testicular necrosis and male infertility. Sitagliptin, a glucose-lowering agent, proved to have a vindicatory function in myocardial and renal ischaemia/reperfusion (I/R), but its role in testicular I/R has not yet been studied. The current work investigates its capability to recover the testicular I/R injury with shedding more light on the mechanism of its action. Four groups were used: sham, sham pretreated with sitagliptin, I/R and sitagliptin/I/R-pretreated groups. The outcomes proved that I/R significantly decreased the serum testosterone, with a major increase in oxidative, inflammatory and nitrosative stress, along with a reduction in testicular vascular endothelial growth factor-A level with marked germinal cell apoptosis. However, pretreatment with sitagliptin significantly reversed the profound testicular I/R damaging effects, on the basis of its antioxidant, anti-inflammatory and anti-apoptotic activities with the ability of recuperation of the testicular vascularity.

Testicular microanatomical and hormonal alterations following use of antiretroviral therapy in Sprague Dawley rats: Role of Naringenin.

Human immunodeficiency virus-infected man may require assisted reproductive technology not just for safer conception but also due to subfertility. The study investigated the effect of antiretroviral drugs on the fertility potentials of males and the possible protective role of Naringenin, using Sprague Dawley rats. Thirty adult male Sprague Dawley rats were grouped into-A: Distilled water; B: Highly Active Antiretroviral Therapy (HAART); C: Naringenin 40 mg/kg; D: Naringenin 80 mg/kg, E: HAART + Naringenin 40 mg/kg; F: HAART + Naringenin 80 mg/kg. The rats were euthanised after 10 weeks. Results showed a significant decrease in sperm count in group B when compared to the control and other groups. Spermatozoa with normal morphology also reduced significantly in the B group and progressive sperm motility reduced when compared to the control, D and the F group. The serum testosterone was not significantly different between groups A and B, however the groups C and D displayed significant increase when compared to groups A and B. The serum luteinising hormone was significantly higher in group B when compared to groups A, E and F. Our data suggest that Naringenin improves the male reproductive anatomy and function, therefore, it promises to be a beneficial adjuvant for mitigating HAART testicular and reproductive perturbations.

Amelioration of diabetes-induced testicular and sperm damage in rats by cerium oxide nanoparticle treatment.

Cerium oxide nanoparticles (CNPs) as an antioxidant have been used frequently to attenuate hyperglycaemia oxidative damage in different organs. We investigated the impact CNPs on the qualitative and quantitative sperm parameters, spermatogenesis and NFE2-related factor 2 (Nrf2) expression as a major contributor of antioxidant defence in the male diabetic rats. Twenty-four male rats were divided into four groups. Controls received only mouse food and water. Second group were treated with CNPs (30 mg kg-1  day-1 ) for 2 weeks. Rats in third group received streptozotocin (STZ) (60 mg/kg). In fourth group, animals became diabetic and received CNPs (30 mg kg-1  day-1 ) for 2 weeks. The results showed a significant abnormality in the sperm parameters and histopathological patterns of testes in the diabetic group compared to the control group and CNPs treatment significantly improved all testicular parameters. Following CNPs administration, sperm DNA fragmentation significantly reduced in the STZ-treated rats. Moreover, after CNPs intake in the STZ-treated rats, Nfr2 expression levels increased significantly. Overall, CNPs administration on the diabetic rates can attenuate detrimental effects of diabetes on the sperm potential fertility, sperm parameters, DNA integrity and Nrf2 expression levels. This study gives a future prospect to determine the role of CNPs in the context of diabetes.

Protective effects of the hydroalcoholic extract of Fumaria parviflora on testicular injury induced by torsion/detorsion in adult rats.

This study was designed to determine the effects of daily oral administration (250 mg/kg) of the hydroalcoholic extract of Fumaria parviflora (FP) for 14 days on the sperm parameters, oxidative stress parameters, serum testosterone levels, expression of Bax and Bcl-2 genes, and apoptosis index of germ cells after testicular torsion-detorsion (ischaemia-reperfusion, IR) injury model in rats. Twenty-eight adult male Wistar rats were divided randomly into four groups of seven each: sham operation, torsion-detorsion (TD), TD plus the hydroalcoholic extract FP (TDFP) and only FP without TD application (FP). Testicular torsion was created by rotating the left testis 720° in a counterclockwise direction; then, after 4 hr, detorsion was performed. The Johnson's score, mean seminiferous tubule diameter (MSTD) and height (thickness) of seminiferous tubule epithelium (HST) were significantly increased in TDFP and FP groups as compared to TD group. The gene expression of Bcl-2, level of serum testosterone hormone and antioxidant parameters-GPx and SOD-were significantly higher in TDFP and FP groups than TD group. The index of apoptosis, the gene expression of Bax and the level of MDA were significantly higher in TD group than TDFP and FP groups. Therefore, F. parviflora could decrease oxidative stress induced by testicular torsion-detorsion.

Effect of Zinc and Melatonin on Oxidative Stress and Serum Inhibin-B Levels in a Rat Testicular Torsion-Detorsion Model.

The present study was aimed to examine the effects of 3-week zinc and melatonin administration on testicular tissue injury and serum Inhibin-B levels caused by unilateral testicular torsion-detorsion in rats. The study was performed on 60 Wistar Albino-type adult male rats. The animals were allocated to 6 groups in equal numbers. 1. Control; 2. Sham; 3. Ischemia-reperfusion; 4. Zinc + ischemia-reperfusion; 5. Melatonin + ischemia-reperfusion; 6. Zinc + melatonin + ischemia-reperfusion. Zinc and melatonin were administered before ischemia-reperfusion at doses of 5 and 3 mg/kg respectively, by intraperitoneal route for a period of 3 weeks. Testicular torsion-detorsion procedures consisted of ischemia for 1 h and then reperfusion for another hour of the left testis. Blood and testicular tissue samples were collected to analyze erythrocyte and tissue GSH and plasma and tissue MDA, Inhibin-B levels. The highest erythrocyte and testis GSH values were found in zinc, melatonin, and zinc + melatonin groups (p < 0.001). Torsion-detorsion group has significantly lower erythrocyte GSH levels and higher plasma MDA values (p < 0.001). Serum inhibin-B and spermatogenic activity levels in the torsion-detorsion group were also significantly lower than those in the other groups (p < 0.001). However, zinc-, melatonin-, and melatonin + zinc-supplemented groups have higher inhibin-B and spermatogenetic activity (p < 0.001). The results of the study show that zinc, melatonin, and melatonin + zinc administration partially restores the increased oxidative stress, as well as the reduced inhibin-B and spermatogenic activity levels in testes ischemia-reperfusion in rats. Suppressed inhibin-B levels in the testicular tissue may be a marker of oxidative stress.

Antioxidants enhance the recovery of three cycles of bleomycin, etoposide, and cisplatin-induced testicular dysfunction, pituitary-testicular axis, and fertility in rats.

OBJECTIVE: To investigate the effects of an antioxidant cocktail (AC) on bleomycin, etoposide, and cisplatin (BEP)-induced testicular dysfunction. DESIGN: In vivo study. SETTING: Research laboratory. ANIMAL(S): Adult male and female Sprague-Dawley rats. INTERVENTION(S): The rats were treated with three cycles of 21 days each of therapeutically relevant dose levels of BEP (0.75, 7.5, and 1.5 mg/kg) with or without the AC (a mixture of α-tocopherol, L-ascorbic acid, Zn, and Se). MAIN OUTCOME MEASURE(S): Sperm parameters, fertility, serum hormone levels (ELISA), testicular histopathology, and expression of proliferating cell nuclear antigen (PCNA), and transferrin (Western blotting and immunohistochemistry) were evaluated at the end of treatment and a 63-day recovery period. RESULT(S): At the end of treatment, the AC improved BEP-induced decrease in sperm motility and increase in abnormality but had no effect on reduced sperm count, fertility, and tubular atrophy, although it up-regulated germ cell proliferation. The AC normalized reduced inhibin B levels, but had no effect on decreased transferrin and testosterone and elevated LH levels. At the end of the recovery period, the AC enhanced the expression of PCNA and transferrin, repopulation of germ cells, LH-testosterone axis, and fertility, but had no effect on reduced FSH and elevated inhibin B levels. CONCLUSION(S): The antioxidants protect and then enhance the recovery of testicular and reproductive endocrine functions when administered concomitantly with BEP therapy. The AC may be beneficial to regain testicular functions after chemotherapy.

Captopril and telmisartan treatments attenuate cadmium-induced testicular toxicity in rats.

The possible protective effect of captopril, an angiotensin-converting enzyme inhibitor, vs. telmisartan, an angiotensin II-receptor antagonist, was investigated in rats with testicular injury induced by a single i.p. injection of cadmium chloride (2 mg/kg). Captopril (60 mg/kg/day, p.o.) and telmisartan (10 mg/kg/day, p.o.) were given for five consecutive days, starting 3 days before cadmium administration. Both agents significantly increased serum testosterone level, which was reduced by cadmium, suppressed lipid peroxidation, restored the depleted reduced glutathione, decreased the elevations of nitric oxide, tumor necrosis factor-α, and cadmium ion levels, and attenuated the reductions of selenium and zinc ions in testicular tissue resulted from cadmium administration. Immunohistochemical analysis revealed that both captopril and telmisartan significantly reduced the cadmium-induced expression of inducible nitric oxide synthase, nuclear factor-κB, Fas ligand, and caspase-3 in testicular tissue. The differences between the results obtained with captopril and telmisartan were insignificant, suggesting that both drugs equally protected the testicular tissue from the detrimental effects of cadmium.

Prophylactic efficacy of Coriandrum sativum (Coriander) on testis of lead-exposed mice.

Lead poisoning is a worldwide health problem, and its treatment is under investigation. The aim of this study was to access the efficacy of Coriandrum sativum (coriander) in reducing lead-induced changes in mice testis. Animal exposed to lead nitrate showed significant decrease in testicular SOD, CAT, GSH, total protein, and tissue lead level. This was accompanied by simultaneous increase in the activities of LPO, AST, ALT, ACP, ALP, and cholesterol level. Serum testosterone level and sperm density were suppressed in lead-treated group compared with the control. These influences of lead were prevented by concurrent daily administration of C. sativum extracts to some extent. Treating albino mice with lead-induced various histological changes in the testis and treatment with coriander led to an improvement in the histological testis picture. The results thus led us to conclude that administration of C. sativum significantly protects against lead-induced oxidative stress. Further work need to be done to isolate and purify the active principle involved in the antioxidant activity of this plant.

Protection of testicular dysfunctions by MTEC, a formulated herbal drug, in streptozotocin induced diabetic rat.

Single injection of streptozotocin (STZ) resulted diabetes mellitus which was reflected here by the levels of fasting blood glucose and serum insulin. Moreover, this experimental diabetes also resulted testicular dysfunctions evaluated by count, viability and motility of sperm as well as by the activities of key enzymes for androgen synthesis. Diabetes induced testicular oxidative stress has been indicated here by the monitoring of testicular peroxidase and catalase activities as well as by quantification of TBARS and CD of testis. Testicular glucose was increased and leydig cell nuclear area was decreased in STZ induced diabetes. Treatment of herbal formulated drug named as MTEC consist of aqueous-methanol extract of Musa paradisiaca, Tamarindus indica, Eugenia jambolana and Coccinia indica to streptozotocin induced diabetic rat at the ratio of 2:2:1:1 at the dose of 60 mg/d for two times a day for 14 d resulted a significant protection in fasting blood glucose and serum insulin levels (p<0.05) along with correction of testicular above parameters towards the control level (p<0.05). This herbal formulated drug has no general toxic effects on the body weight, as well as on the activities of serum glutamate and pyruvate transaminases in serum. The results support the validity of this herbal drug for the management of testicular disorders noted in diabetic state.