Utility of melatonin in mitigating ionizing radiation-induced testis injury through synergistic interdependence of its biological properties

Abstract

Background Ionizing radiations (IR) have widespread useful applications in our daily life; however, they have unfavorable effects on reproductive health. Maintaining testicular health following IR exposure is an important requirement for reproductive potential. The current study explored the role of melatonin (MLT) in mitigating IR-induced injury in young adult rat testis. Methods Rats were given daily MLT (25 mg/kg) for 3 and 14 days after receiving 4 Gy γ-radiation. Results Serum MLT levels and other antioxidants, including glutathione content, and the activity of glutathione peroxidase and glutathione reductase in the testis of the irradiated rats were remarkably maintained by MLT administration in irradiated rats. Hence, the hydrogen peroxide level declined with remarkably reduced formation of oxidative stress markers, 4-hydroxynonenal, and 8-Hydroxy-2′-deoxyguanosine in the testis of irradiated animals after MLT administration. The redox status improvement caused a remarkable regression of proapoptotic protein (p53, Cyto-c, and caspase-3) in the testis and improved inflammatory cytokines (CRP and IL-6), and anti-inflammatory cytokine (interleukin IL-10) in serum. This is associated with restoration of disturbed sex hormonal balance, androgen receptor upregulation, and testicular cell proliferation activity in irradiated rats, explaining the improvement of sperm parameters (count, motility, viability, and deformation). Consequently, spermatogenic cell depletion and decreased seminiferous tubule diameter and perimeter were attenuated by MLT treatment post irradiation. Moreover, the testis of irradiated-MLT-treated rats showed well-organized histological architecture and normal sperm morphology. Conclusions These results show that radiation-induced testicular injury is mitigated following IR exposure through synergistic interdependence between the antioxidant, anti-inflammatory, anti-apoptotic, and anti-DNA damage actions of MLT.

Melatonin Ameliorates Diquat-Induced Testicular Toxicity via Reducing Oxidative Stress, Inhibiting Apoptosis, and Maintaining the Integrity of Blood-Testis Barrier in Mice

“…Particularly, spermatogonia was most damaged by diquat in an apoptotic manner in vivo and in vitro. In contrast, melatonin treatment reduced TUNEL-positive cells, which agrees with the report that melatonin can protect the testes from external harm via a synergistic interaction of its antioxidant, anti-inflammatory, and anti-apoptotic properties [ 17 ]. This was also confirmed by changes in Cleaved-Caspase3 and Bax/Bcl2 levels induced by melatonin treatment.…”

“…Melatonin modulates testicular functions by regulating testosterone production in Leydig cells [ 12 ], proliferation, and energy metabolism in Sertoli cells [ 13 ], and consequently influences spermatogenesis [ 14 ]. Specifically, melatonin and its metabolites are potent free-radical scavengers that protect the testes against oxidative damage caused by hyperthermia [ 15 ], irradiation [ 16 , 17 ], and environmental toxins [ 18 , 19 ]. However, whether melatonin can alleviate oxidative stress and testicular damage induced by diquat remains to be elucidated.…”

High-fat diet alters the radiation tolerance of female mice and the modulatory effect of melatonin

“…The findings of previous studies led us to hypothesize that MLT might serve as a promising preventative agent that could ameliorate radiation-induced injury. 22,23 To verify this hypothesis, we assessed the regulatory effects of MLT on irradiated HFD-fed mice.…”

“…20,21 Moreover, MLT has also been shown to alleviate ionizing radiation (IR)-induced damage, including intestinal damage and testis injury. 22,23 Furthermore, MLT supplementation can effectively regulate obesity; 24 however, little is known about the effect of MLT on radiation-induced damage in HFD-fed mice.…”

Correction: Utility of melatonin in mitigating ionizing radiation‑induced testis injury through synergistic interdependence of its biological properties

“…Following publication of the original article [ 1 ], the authors identified an error in Figs. 3D and 4.…”