Hypoxia inhibits Na and lung fluid reabsorption, which contributes to the formation of pulmonary edema. We tested whether dexamethasone prevents hypoxia-induced inhibition of reabsorption by stimulation of alveolar Na transport. Fluid reabsorption, transport activity, and expression of Na transporters were measured in hypoxia-exposed rats and in primary alveolar type II (ATII) cells. Rats were treated with dexamethasone (DEX; 2 mg/kg) on 3 consecutive days and exposed to 10% O(2) on the 2nd and 3rd day of treatment to measure hypoxia effects on reabsorption of fluid instilled into lungs. ATII cells were treated with DEX (1 muM) for 3 days before exposure to hypoxia (1.5% O(2)). In normoxic rats, DEX induced a twofold increase in alveolar fluid clearance. Hypoxia decreased reabsorption (-30%) by decreasing its amiloride-sensitive component; pretreatment with DEX prevented the hypoxia-induced inhibition. DEX increased short-circuit currents (ISC) of ATII monolayers in normoxia and blunted hypoxic transport inhibition by increasing the capacity of Na(+)-K(+)-ATPase and epithelial Na(+) channels (ENaC) and amiloride-sensitive ISC. DEX slightly increased the mRNA of alpha- and gamma-ENaC in whole rat lung. In ATII cells from DEX-treated rats, mRNA of alpha(1)-Na(+)-K(+)-ATPase and alpha-ENaC increased in normoxia and hypoxia, and gamma-ENaC was increased in normoxia only. DEX stimulated the mRNA expression of alpha(1)-Na(+)-K(+)-ATPase and alpha-, beta-, and gamma-ENaC of A549 cells in normoxia and hypoxia (1.5% O(2)) when DEX treatment was begun before or during hypoxic exposure. These results indicate that DEX prevents inhibition of alveolar reabsorption by hypoxia and stimulates the expression of Na transporters even when it is applied in hypoxia.

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 D 3 (VD3) on renal I/R injury. Thirty male Wistar albino rats were divided into five groups: group 1, control; group 2, right nephrectomy (RN) þ I/R in the contralateral kidney; group 3, melatonin þ RN þ I/R; group 4, VD 3 þ RN þ I/R; and group 5, melatonin þ VD 3 þ RN þ 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.

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 study was designed to evaluate the preventive role of melatonin (Mel) and 1,25-dihydroxyvitamin D3 (VD3) in biochemical and apoptotic events leading to tissue injury and renal dysfunction after ischemia-reperfusion (I/R). Thirty male Wistar rats were divided into five groups: sham-operated, I/R, Mel þ I/R, VD3 þ I/R, and Mel þ VD3 þ I/R. The rats were intraperitoneally administered with Mel (10 mg/kg), VD3 (0.5 μg/kg), or Mel (10 mg/kg) plus VD3 (0.5 μg/kg) each day at 1 week prior to ischemia. Right nephrectomy was initially performed and left renal I/R injury was induced by 45 min of bilateral renal ischemia followed by 45 min of reperfusion. After reperfusion, kidneys and blood were obtained for histopathologic and biochemical evaluation. Mel and VD3 had an ameliorative effect on biochemical parameters such as serum creatinine, blood urea nitrogen, alanine aminotransferase, aspartate aminotransferase, and apoptosis (caspase-3 and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling staining) in the kidneys against renal I/R injury in rats. Additionally, VD3 combined with Mel significantly reduced apoptotic and histological alterations when compared with Mel or VD3 alone. This preventive effect on renal tubular apoptosis was remarkable when Mel was combined with VD3.

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