Background: The reproductive potential declines with age. Late-onset hypogonadism is characterized by reduced serum testosterone. Humanin is a mitochondrial-derived signaling peptide encoded by short open reading frames within the mitochondrial genome. It may protect against some age-related diseases such as atherosclerosis by its cytoprotective effects. Objective: it aimed to investigate the potential anti-aging effects of humanin on the testicular architecture, oxidative stress, some apoptotic and inflammatory markers in the hypogonadal aged male rats Methods: Forty male albino rats were divided into 4 groups: normal adult controls, aged vehicle-treated group, aged testosterone-treated group, and aged humanin-treated group. Twenty-month-old male rats with declined serum testosterone were selected to be the animal models of late-onset hypogonadism. Testicular weights, serum testosterone, and some sperm parameters were measured. Testicular tissue IL-6 and TNF-α, superoxide dismutase activity, glutathione peroxidase, and malondialdehyde were assessed. The activity of caspase-3, BCL2, PCNA, and the nuclear factor erythroid 2-related factor 2-antioxidant response element pathway were evaluated. Testes were subjected to histopathological and immunohistochemical examination. Statistical analysis was executed using One Way Analysis of variance (ANOVA) followed by Post hoc (LSD) test to compare means among all studied groups. Result: humanin treatment significantly improved serum testosterone, some sperm characteristics, and antioxidant defenses. It decreased active caspase-3, pro-apoptotic BAX expression, and increased antiapoptotic BCL2 and proliferating cell nuclear antigen (PCNA) possibly via activating the (Nrf2-ARE) pathway. Conclusion: humanin might be a promising therapeutic modality in late-onset hypogonadism as it ameliorated some age-related testicular and hormonal adverse effects.

Background: Vitamin D receptors (VDR) are expressed in many reproductive tissues indicating a potential role of vitamin D3-VDR in the regulation of reproductive functions. Nevertheless, the data about the effect of vitamin D 3 in the uterus are scarce. Aim of Study:This study was designed to evaluate the potential effects of vitamin D 3 on spontaneous, KCl-induced and oxytocin-induced contractions in the rat uterus in vitro. Material and Methods:The study was conducted on 10 healthy adult female albino non-pregnant rats. Full-thickness longitudinal muscle strips were dissected from each nonpregnant rat and then myometrial tension was recorded. The strips were mounted vertically in organ baths and exposed to vitamin D3 and different uterotonic agents to delineate the potential action of vitamin D 3 on the rat myometrial contractility. Spontaneous contractions were recorded using mechanical activity recording system. We evaluated the effects of 3 different dosed of vitamin D3 on spontaneous uterine contractions; then on concentrated KCl-induced uterine contractions and oxytocin (OT)-induced uterine contractions. Furthermore, the effects of vitamin D3 on spontaneous uterine contractions pretreated with nifedipine; a voltage-gated L-type Ca 2 + channel antagonist were investigated.Results: Vitamin D3 significantly inhibited the spontaneous uterine contractions in a dose dependent manner. Moreover, vitamin D3 inhibited the uterine contractions whether induced by oxytocin or concentrated KCl. Administration of nifedipine resulted in a significant decline in the force amplitude of spontaneous uterine contractions. In the presence of vitamin D3 , the uterine relaxant effect of nifedipine was significantly augmented. Conclusions:The inhibitory effects of the in vitro administration of vitamin D 3 on rat uterus may yield novel insights into its therapeutic use. Further, it may be recommended to be used as a novel tocolytic agent for preventing unwanted uterine contractions in early pregnancy and relieving pain related to dysmenorrhea.

A prevalent clinical problem including sepsis, shock, necrotizing enterocolitis, and mesenteric thrombosis is intestinal ischemia/reperfusion (I/R) injury. Humanin (HN), a recently identified mitochondrial polypeptide, exhibits antioxidative and antiapoptotic properties. This work aimed to study the role of HN in a model of experimental intestinal I/R injury and its effect on associated dysmotility. A total of 36 male adult albino rats were allocated into 3 equal groups. Sham group: merely a laparotomy was done. I/R group: for 1 h, clamping of the superior mesenteric artery was done, and then reperfusion was allowed for 2 h later. HN-I/R group: rats underwent ischemia and reperfusion, and 30 min before the reperfusion, they received an intraperitoneal injection of 252 μg/kg of HN. Small intestinal motility was evaluated, and jejunal samples were got for biochemical and histological analysis. I/R group showed elevation of intestinal NO, MDA, TNF- α, and IL-6 and decline of GPx and SOD levels. Furthermore, histologically, there were destructed jejunal villi especially their tips and increased tissue expression of caspase-3 and i-NOS, in addition to reduced small intestinal motility. Compared to I/R group, HN-I/R group exhibited decrease intestinal levels of NO, MDA, TNF- α, and IL-6 and increase GPx and SOD. Moreover, there was noticeable improvement of the histopathologic features and decreased caspase-3 and iNOS immunoreactivity, beside enhanced small intestinal motility. HN alleviates inflammation, apoptosis, and intestinal dysmotility encouraged by I/R. Additionally, I/R-induced apoptosis and motility alterations depend partly on the production of nitric oxide.

Background and purpose: Intestinal ischemia-reperfusion (I/R) injury is a common clinical issue involving sepsis, shock, necrotizing enterocolitis, mesenteric thrombosis. Inflammatory reactions and cellular apoptosis are mainly involved processes in intestinal I/R injury. Data regarding the effect of thymosin beta 4 (Tβ4) on intestinal I/R injury are scarce. It was designed to evaluate the potential effects of Tβ4 on intestinal IR injury.Methods: The study was conducted on 3 groups of adult male albino rats: each containing ten rats: group I (I/R group), group II (Sham-operated group), and group III (Tβ4-treated group). After one hour of intestinal ischemia, reperfusion was performed by releasing the clamp. Thirty minutes before reperfusion, the rats in group III received subcutaneous injections of 30 mg Tβ4 per kg and 0.1 ml physiologic saline. Rats in groups I and II received only 0.1 ml physiologic saline. Intestinal histopathologic examination and scoring the degree of injury were done according to chiu's score. Biochemical analyses of malondialdehyde (MDA), super oxide dismutase (SOD) and glutathione peroxidase (Gpx) levels in addition to TNF-α , IL-6 and caspase-3 levels in the rat intestinal tissues were determined. Serum and tissue nitric oxide (NO) levels were also measured.Results: Intestinal I/R injury was confirmed by intestinal histopathologic examination. In the I/R group, tissue MDA, TNF-α , IL-6 and caspase-3 levels were significantly elevated, however, tissue SOD, Gpx, serum and tissue NO levels were significantly declined when compared to the sham group. On receiving Tβ 4, the findings demonstrated significant reductions of tissue MDA, TNF-α, IL-6 and caspase-3 levels and significant elevations of serum and tissue NO, tissue SOD and Gpx levels compared to non-treated one. Further, rats treated with Tβ4 showed amelioration of the degree of intestinal I/R lesions and improvement of intestinal score injury compared to non-treated group.

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