Humanin Ameliorates Late-onset Hypogonadism in Aged Male Rats

Abstract

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.

A novel beneficial role of humanin on intestinal apoptosis and dysmotility in a rat model of ischemia reperfusion injury

“…Moreover, Gottardo et al [ 29 ] demonstrated that HN inhibited apoptosis induced by TNF- α in anterior pituitary cells of male and female rats that had undergone gonadectomies. A further support to our data, El Kattawy et al [ 24 ] proved that HN has anti-aging properties and anti-apoptotic as HN elevated PCNA and BCL2 activity and reduced testicular caspase-3 activity and suppressed pro-apoptotic BAX protein expressions in the aged rats.…”

Evaluation of reproductive capacity in adult male rats exposed to silver nanoparticles and the ameliorative role of lycopene

“…The obtained data were represented as mean ± standard error (SE) using statistical package for social science software (SPSS, Chicago, IL, version 20). The mean difference significance between the studied groups was obtained using one-way analysis of variance (ANOVA test) followed by post hoc test LSD test for pairwise comparison of the means of the different studied groups [60], with significance level set at p˂0.05.…”

Male reproductive ageing: a radical road to ruin

“…Other putative antioxidants such as Korean red ginseng ( Kopalli et al , 2017 ), Cordycepin ( Kopalli et al , 2019 ), Gigantol ( Basque et al , 2021 ), and vitamin C ( Heidari et al , 2023 ) have similar effects. The source of oxidative stress in ageing Leydig cells is thought to be mitochondrial ( Chen et al , 2001 ; Miquel, 2002 ; El Kattawy et al , 2022 ), while the target is thought to be the hormone-sensitive mitochondrial cholesterol transfer step of steroidogenesis ( Diemer et al , 2003 ).…”