Melatonin ameliorates restraint stress-induced oxidative stress and apoptosis in testicular cells via NF-κB/iNOS and Nrf2/ HO-1 signaling pathway

Abstract

Decline in semen quality has become a global public health concern. Psychological stress is common in the current modern society and is associated with semen decline. Increasing evidence demonstrated that melatonin has anti-apoptotic and antioxidant functions. Whether melatonin can ameliorate the damage in testes induced by psychological stress has never been investigated. Here, a mouse model of restraint stress demonstrated that melatonin normalized the sperm density decline, testicular cells apoptosis, and testicular oxidative stress in stressed male mice. Melatonin decreased reactive oxygen species (ROS) level, increased superoxide dismutase (SOD) and glutathione (GSH) activities, and downregulated inducible nitric oxide synthase (iNOS) and tumor necrosis factor-α (TNF-α) activities in stressed mice testes. Furthermore, melatonin reduced the stress-induced activation of the NF-κB signaling pathway by decreasing the phosphorylation of nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκBα) and p65 nuclear translocation. In addition, melatonin upregulated the expression of anti-oxidant proteins including nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). Meanwhile, in vitro studies also demonstrated melatonin could reduce oxidative apoptosis of testicular cells. Collectively, melatonin mitigated psychological stress-induced spermatogenic damage, which provides evidence for melatonin as a therapy against sperm impairment associated with psychological stress.

Adrenaline induced disruption of endogenous melatoninergic system, antioxidant and inflammatory responses in the gastrointestinal tissues of male Wistar rat: an in vitro study

“…On the other hand, NF-kB levels were found to be increased following incubation with adrenaline. Possibly, elevation of intracellular oxidative stress upregulates the gene expression of NF-kB as evidenced in an earlier study in rat (53). Notably, intra-cellular calcium and cAMP mediate important functions in the melatonin biosynthesis pathway.…”

Phytochemical profile and protective effect of Ocimum basilicum aqueous extract in doxorubicin/irradiation-induced testicular injury

“…In the direct actions, it presumably scavenges free radicals and reactive intermediates generated. However, in the indirect antioxidant mechanism, it activates the Nrf2‐antioxidant response element (ARE) pathway with subsequent increase in the detoxifying phase‐II enzymes such as NADPH‐quinone dehydrogenase‐1 and hemeoxygenase‐1 . Antioxidants such as polyphenols and flavonoids commonly activate Nrf2, which in turn, mediate the induction of variety of cytoprotective and antioxidant proteins such as catalase, superoxide dismutase and HO‐1 enzymes, thus elevating the cellular TAC against oxidative damage.…”

Tocotrienol-rich fraction supplementation prevents foetal loss in females mated with corticosterone-treated male Sprague-Dawley rats

“…Reduction in the organ weight was probably due to apoptosis secondary to oxidative stress. Oxidative stress is a major factor that induces apoptosis of the testicular cells (Guo et al, ; Maneesh, Jayalekshmi, Dutta, Chakrabarti, & Vasudevan, ). The apoptotic pathway through Bax and Bcl‐2 has been involved in testicular germ cell apoptosis in males subjected to chronic stress (Guo et al, ; Juarez‐Rojas, Garcia‐Lorenzana, Aragon‐Martinez, Gomez‐Quiroz, & Retana‐Marquez Mdel, ).…”

“…Oxidative stress is a major factor that induces apoptosis of the testicular cells (Guo et al, ; Maneesh, Jayalekshmi, Dutta, Chakrabarti, & Vasudevan, ). The apoptotic pathway through Bax and Bcl‐2 has been involved in testicular germ cell apoptosis in males subjected to chronic stress (Guo et al, ; Juarez‐Rojas, Garcia‐Lorenzana, Aragon‐Martinez, Gomez‐Quiroz, & Retana‐Marquez Mdel, ). Degeneration and apoptosis of testicular germ cells and the loss of Leydig cells are associated with lower testosterone levels, which in turn impair steroidogenesis (Juarez‐Rojas et al, ; Juárez‐Rojas, Fahiel, & Socorro, ).…”