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The aim of this review is to summarize current studies on the relationship between melatonin and aging. Nowadays, age-related diseases come into prominence, and identifying age-related changes and developing proper therapeutic approaches are counted as some of the major issues regarding community health. Melatonin is the main hormone of the pineal gland. Melatonin is known to influence many biological processes in the body, including circadian rhythms, the immune system, and neuroendocrine and cardiovascular functions.Melatoninrhythms also reflect the biological process of aging. Aging is an extremely complex and multifactorial process. Melatonin levels decline considerably with aging and its decline is associated with several age-related diseases. Aging is closely associated with oxidative damage and mitochondrial dysfunction. Free radical reactions initiated by the mitochondria constitute the inherent aging process. Melatonin plays a pivotal role in preventing age-related oxidative stress. Coronavirus disease 2019 (COVID-19) fatality rates increase with chronic diseases and age, where melatonin levels decrease. For this reason, melatonin supplementation in elderly could be beneficial in COVID-19 treatment. Therefore, studies on the usage of melatonin in COVID-19 treatment are needed., (This work is licensed under a Creative Commons Attribution 4.0 International License.)

Ischemia-reperfusion (I/R) injury induces the generation of reactive oxygen species (ROS) which affect many organs. This study was designed to investigate the roles of melatonin and 1,25-dihydroxyvitamin D3 (VD3) on renal I/R injury. Thirty male Wistar albino rats were divided into five groups: group 1, control; group 2, right nephrectomy (RN) +  I/R in the contralateral kidney; group 3, melatonin + RN + I/R; group 4, VD3 + RN + I/R; and group 5, melatonin + VD3 + RN + I/R. Melatonin (10 mg/kg), VD3 (0.5 μg/kg), and melatonin plus VD3 were injected intraperitoneally for 7 days before renal I/R. After 7 days, right nephrectomy was initially performed and left renal artery was clamped for 45 min. After 45-min reperfusion, the serum and kidney tissue samples were obtained for assays. Melatonin and VD3 had an ameliorative effect on biochemical parameters such as serum creatinine (SCr) and blood urea nitrogen (BUN). Renal tissue malondialdehyde (MDA), glutathione (GSH), nitric oxide (NO) levels, and superoxide dismutase (SOD) activity were determined. Renal I/R decreased the kidney tissue GSH levels and SOD activity and increased the NO levels as compared with control group. However, melatonin and VD3 and melatonin plus VD3 treatment significantly increased the tissue GSH levels and SOD activity and decreased the NO levels compared with those of I/R group. Meanwhile, MDA levels were not different between the control and I/R groups. But, MDA levels decreased in all treated groups compared to I/R and control groups. These data support that melatonin and VD3 have beneficial effects on renal injury.

Objective: To compare the efficacy of ozone with melatonin, shown as the most powerful antioxidant in attenuation of testicular ischemia/reperfusion injury, in an experimental rat model of testicular torsion/detorsion., Methods: Twenty-four male Wistar rats were divided into 4 groups: sham-operated, torsion/detorsion, torsion/detorsion plus melatonin, and torsion/detorsion plus ozone. Melatonin (10 mg/kg) and ozone (4 mg/kg) were intraperitoneally injected daily beginning 15 minutes before detorsion for the following 7 days. At the seventh day, blood and tissue samples were obtained. Johnsen score, malondialdehyde, inhibin B, glutathione plasma total sulfhydryl group (RSH) levels, and total nitric oxide were studied., Results: Torsion/detorsion caused increase in tissue malondialdehyde and total nitric oxide along with a decrease in Johnsen score, tissue and plasma inhibin B, RSH, and glutathione levels. Melatonin prevented the rise in malondialdehyde and total nitric oxide levels and improved Johnsen score, tissue and plasma inhibin B, and tissue glutathione levels, along with a decrease in plasma RSH level. Ozone showed similar results except for the total nitric oxide level. Concomitantly, in contralateral testis, melatonin and ozone induced similar changes for Johnsen score, malondialdehyde, and inhibin B (not significant) and in glutathione (significant). Melatonin decreased the total nitric oxide level in both testes and ozone increased the same parameter., Conclusion: On different pathways, ozone was comparable with melatonin in the amelioration of ischemia/reperfusion injury. Protective effects of ozone were associated with nitrous oxide. The potential for ozone as a treatment for torsion/detorsion therefore deserves to be further elucidated., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Oxidative stress is an important factor for aging. The antioxidative enzymes glutathione peroxidase (GPx), glutathione reductase (GRd) and superoxide dismutase (SOD) play a crucial role protecting the organism against the age-dependent oxidative stress. Glutathione (GSH) is present in nearly all living cells. GSH is one of the main antioxidants in the cell and it serves several physiological functions. Our purpose was to evaluate the age-related changes in mitochondrial GPx, GRd and SOD activities, and mitochondrial GSH pool in the brains of young (3 months) and aged rats (24 months). We also investigated whether melatonin administration influences these brain mitochondrial enzyme activities and GSH levels in young and aged rats. The results showed that GPx activity increased with age, whereas melatonin treatment decreased GPx activity in the aged rats at levels similar to those in young and young+melatonin groups. The activities of GRd and SOD, however, did not change with age. But, melatonin treatment increased SOD activity in the aged rats. GSH levels, which also increased with age, were not modified by melatonin treatment. The reduction in the SOD/GPx and GR/GPx ratios with age was prevented by melatonin administration. Together, our results suggest that the age-related oxidative stress in rat brain mitochondria is more apparent when the antioxidant enzyme ratios are analyzed instead of their absolute values. The antioxidative effects of melatonin were also supported by the recovery of the enzyme ratios during aging., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: To determine the effects of pinealectomy on endometrial explants in rats and evaluate the activity of superoxide dismutase (SOD) and catalase (CAT) and the levels of malondialdehyde (MDA) in the rat endometriosis model., Study Design: Rats with experimentally induced endometriosis were randomly divided into three groups after second-look laparotomies. Group 1 (pinealectomy, n = 8) and Group 2 (pinealectomy+melatonin, n = 8) underwent pinealectomies after the second-look laparotomies. Group 3 was presented as control group (vehicle solution+without pinealectomy (n = 6)). Melatonin was administered intraperitoneally for 4 weeks in Group 2, whereas an equal volume of vehicle solution was given to Groups 1 and 3. Evaluation of the volume of the endometrial explants, histopathological examination and preservation of explant epitheliums according to the scoring system were undertaken., Results: There was a statistically significant increase in spherical explant volumes of Group 1 compared to Groups 2 and 3. In Group 1, the level of MDA was significantly higher and SOD and CAT activity was significantly lower compared to Groups 2 and 3. A statistically significant increase in the epithelial lining scores of explants was noted in Group 1 compared to Groups 2 and 3., Conclusion: The effects of pinealectomy on the progression of endometriosis explants were reversed by melatonin., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Background/purpose: The hormone melatonin affects cellular immunity in particular and the immune system in general both directly and indirectly. We report our evaluation of the effects of decreasing and increasing serum melatonin levels on hepatocyte damage in rats with experimental acute pancreatitis., Methods: Wistar Albino rats with experimentally induced acute pancreatitis were divided into three groups of ten rats each: (1) control (induced acute pancreatitis only); (2) rats with induced acute pancreatitis plus surgical pinealectomy (no melatonin injections); (3) rats with induced acute pancreatitis plus injections of exogenous melatonin. The effects of melatonin levels were evaluated using biochemical and histopathological parameters., Results: Rats undergoing the pinealectomy had increased amylase and lactate dehydrogenase (LDH) levels, while those receiving injections of exogenous melatonin had decreased amylase, aspartate transaminase, LDH, and bilirubin levels but increased levels of alanine transferase levels., Conclusion: Melatonin may have a therapeutic or protective effect on acute pancreatitis and obstructive jaundice.

Melatonin (MEL) is synthesized mainly in the pineal gland and derived from 5-hydroxytryptophan (5-HTP). Zinc (Zn) is one of the most important trace elements in the body. Zn and MEL levels are changed with aging. The aim of this study was to investigate the age-related changes of tissue and plasma Zn levels and effect of MEL administration on these parameters. Male wistar rats received for 3 weeks subcutaneous injection of MEL (10 mg/kg). Kidney and pancreas Zn levels in old rats were significantly lower than middle-aged group. Spleen, small intestine, and plasma Zn levels were not different in middle-aged and old rats. On the other hand, MEL treatment increased Zn levels of small intestine and plasma in middle-aged rats. However, kidney, spleen, and pancreas Zn levels were unaffected by MEL treatment.