Protective Effect Of Melatonin Research Articles

Melatonin alleviates lead-induced fatty liver in the common carps (Cyprinus carpio) via gut-liver axis

As a widespread aquatic environmental contaminant, Lead (Pb) can provoke hepatic injury in various animals. Melatonin (MT) plays a crucial role in the regulation of inflammatory response. Accumulating evidence elucidates exogenous toxins can elicit hepatic lipid metabolic disorders by influencing the gut microbiome. Nevertheless, the effects of Pb on gut microbiota and hepatic lipid metabolism of the common carps, and whether MT can prevent and cure Pb-induced toxicity via regulating microbiome remains unknown. Here, metagenomic and transcriptomic analysis were subsequently implemented to identify the Pb exposure-triggered prominent alternation of gut-liver signal. In the present study the severe intestinal injury and fatty liver formation caused by Pb in common carp were preliminarily determined. Metagenomic analysis confirmed that the gut microbiome dominant phyla, family and genus of the common carps were Fusobacteria, Fusobacteriaceae and Cetobacterium. Meanwhile, lipopolysaccharide (LPS) biosynthesis pathway was regarded as one of the main responsible for Pb exposure. Subsequently, LPS was demonstrated as the Pb-triggered microbial-derived signal of the common carps by ELISA analysis, and involves in the hepatic metabolic disorders via deteriorating the intestinal barrier. Additionally, it confirmed that hepatocytes ferroptosis associated with Pb-evoked fatty liver of the common carps, and the aggravation of lysosomal dyshomeostasis as well as inhibition of AMPK phosphorylation were referred to lipid metabolic disorders. The results of the present study demonstrated microbial-derived signal induced by aquatic Pb contaminant cause fatty liver formation in the common carps, and the protective effects of MT on Pb toxicity were performed by receding LPS over-synthesis, restraining microbiota-sourced LPS transport, along with attenuation of hepatocytes ferroptosis.

Melatonin protects against body weight gain induced by sleep deprivation in mice

Sleep deprivation is an epidemic phenomenon in modern society. Lack of sleep has been shown to result in metabolic and endocrine disorders that predispose to obesity and other chronic metabolic diseases. Melatonin is a sleep-related neurohormone and affected by the circadian rhythm and light/dark cycles. Melatonin has recently been used to ameliorate diet-induced or night light-induced energy metabolic imbalance. However, the effect of melatonin on sleep deprivation-induced obesity has been poorly characterized. This study focuses on the protective effects of melatonin on lipid metabolism and body weight homeostasis in sleep-deprived mice. Mice subjected to sleep deprivation had significantly decreased plasma melatonin content and increased food intake and body weight gain compared to that of control. Meanwhile, the transcription factor PPARγ protein in liver increased, but there were no significant changes in hepatic circadian proteins BMAL1 and REV-ERBα after 10 consecutive days of sleep deprivation. Moreover, melatonin supplementation increased liver AMPKα/PPARα signaling pathway activity, which leads to lipid catabolism and reduced fat accumulation. These findings suggested that melatonin may be a potential agent for protecting against sleep deprivation-induced obesity.

Melatonin prevents diabetes-induced nephropathy by modulating the AMPK/SIRT1 axis: Focus on autophagy and mitochondrial dysfunction.

Impaired nutrient sensing mechanisms such as AMPK/silent information regulator type 1 (SIRT1) axis and autophagy in renal cells upon chronic diabetic condition accelerate renal injury and upregulating these mechanisms has been reported to prevent renal damage. Melatonin, a neuroendocrine agent, also possess antioxidant and AMPK modulatory effect. In the current study, the protective effect of melatonin against diabetic renal injury was assessed in streptozotocin-induced diabetic nephropathy model and in in vitro model of high-glucose-induced tubular injury. Melatonin (3 and 10 mg/kg) was administered for 28 days after 4 weeks of diabetes induction in Sprague-Dawley rats. For in vitro model, the NRK-52E cells were co-incubated with high glucose and melatonin (25 and 50 μM). Melatonin supplementation abrogated the diabetes-induced renal injury and improved renal function in diabetic rats. Immunoblot analysis of renal tissue lysates revealed improved expression of AMPK, as well as upregulated the expression of nuclear factor erythroid 2-related factor 2, SIRT1, PGC-1α, TFAM and enhanced autophagy upon melatonin treatment in diabetic rats. Likewise, melatonin treatment in high glucose exposed NRK-52E cells improved expression of AMPK, enhanced mitochondrial biogenesis and positively modulated autophagy. However, these effects were repressed upon inhibition of AMPK activity in NRK-52E cells by treatment of Compound-C, suggesting that the protective effects of melatonin were mainly mediated through activation of AMPK. These results suggest that melatonin might mediate the renoprotective effect by upregulating the AMPK/SIRT1 axis, enhancing the autophagy and mitochondrial health in DIabetic Nephropathy.

Crosstalk among apoptosis, inflammation, and autophagy in relation to melatonin protective effect against contrast-induced nephropathy in rats.

Contrast medium (CM) is a chemical substance that is used for imaging anatomical boundaries and to explore normal and abnormal physiological findings; the use of CM was associated with kidney injury and acute renal failure. Melatonin (M) possesses antioxidant, anti-inflammatory, and antiapoptotic effects in addition to autophagy modulation. This study aimed to investigate the protective effect of M against contrast-induced nephropathy (CIN) and its impact on the crosstalk between inflammasome, apoptosis, and autophagy in CIN. Male albino rats received M (10, 20, and 40 mg/kg/day, intraperitoneally) for 3 days. One hour after the last administration, rats were subjected to CIN induction (10mg/kg indomethacin, double doses of l-NAME 10mg/kg, i.v., and meglumine diatrizoate 60% 6mL/kg, i.v.). CIN-induced kidney damage was evidenced through elevated kidney function biomarkers and induced renal histopathological changes. Pretreatment with M caused a significant decrease in nephrotoxicity biomarkers and histopathological alterations. Moreover, CIN-induced oxidative stress, NLRP3 inflammasome, and apoptosis were attenuated by M. Furthermore, M modulates autophagy in CIN rats. M inhibits CIN-induced NLRP3-inflammasome activation and apoptosis as well as enhances autophagy.

Melatonin Ameliorates the Progression of Alzheimer's Disease by Inducing TFEB Nuclear Translocation, Promoting Mitophagy, and Regulating NLRP3 Inflammasome Activity.

Background The NLRP3 inflammasome is overactivated in the brains of APP/PS1 transgenic mice and AD patients, and mitophagy has an obvious negative regulatory role on NLRP3 inflammasome activation. The protective effect of melatonin in AD may be related to the regulation of mitophagy and NLRP3 inflammasome activity. TFEB plays a critical role in maintaining autophagy/mitophagy. Studies have found that TFEB plays a protective role in AD. Methods APP/PS1 transgenic mice were given melatonin in their drinking water for 3 months. Compared with mice without melatonin treatment, the mice given melatonin showed changes in the following features: (1) cognitive function, (2) mitophagy-related proteins in the brain, (3) ROS, (4) NLRP3 inflammasome and related proteins and the concentrations of inflammatory cytokines, and (5) Aβ deposition. In in vitro experiments, effects of melatonin on mitophagy, NLRP3 inflammasome activity, and TFEB in SH-SY5Y cells with Aβ25-35 were observed. TFEB knockdown was implemented in combination with Aβ25-35 and melatonin treatment, and the expressions of TFEB, Parkin, p62, IL-1β, caspase-1, ROS, and IL-18 were explored. Results Melatonin improved cognitive function in APP/PS1 transgenic mice and decreased ROS and senile plaques. Melatonin promoted mitophagy in SH-SY5Y cells with Aβ25-35 and APP/PS1 transgenic mice. NLRP3 inflammasome activity was inhibited, and the concentrations of IL-18 and IL-1βwere clearly reduced. Compared with C57/BL6J mice, the amount of TFEB in the brain nucleus of APP/PS1 transgenic mice was decreased. Melatonin treatment increased the nuclear translocation of TFEB in SH-SY5Y cells. TFEB knockout was implemented in combination with Aβ25-35 and MT treatment; the expressions of Parkin, p62, caspase-1, IL-1β, IL-18, and ROS were accelerated. Conclusions Melatonin promotes mitophagy by inducing TFEB nuclear translocation, downregulates NLRP3 inflammasome activation, and exerts protective effects in SH-SY5Y cells and APP/PS1 transgenic mice.

Protective Effects of Melatonin and Its Supplements on the Arterial Mechanics

Melatonin (5-methoxy-N-acetyltryptamine), a neurohormone, is synthesized from tryptophan taken up by the pineal gland cells. It affects several cardiovascular functions such as arterial blood pressure, heart rate, cardiac rhythms, and mechanical properties of the large arteries and aorta. Melatonin and its supplements, generally made in a laboratory, can improve several cardiovascular functions such as arterial blood pressure and arterial mechanics.

Protective Effects of Melatonin on Prenatal Restraint Stress-Induced Memory Impairment in Offspring Rats

Protective Effects of Melatonin on Prenatal Restraint Stress-Induced Memory Impairment in Offspring Rats

Protective effect of melatonin and carnosine against radiation induced kidney injury

Protective effect of melatonin and carnosine against radiation induced kidney injury

Protective effect of melatonin on alleviating early oxidative stress induced by DOX in mice spermatogenesis and sperm quality maintaining

Doxorubicin (DOX) is an effective chemotherapy drug, but its clinical use has adverse effects on male reproduction. However, there are few studies about the specific biological processes related to male reproduction or strategies for improving fertility protection. In this paper, we examined the effects of DOX on spermatogenesis and sperm function, and tested the possible protective role of melatonin (MLT) against DOX’s reproductive toxicity. DOX-treated mice showed signs of significantly impaired spermatogenesis, including vacuolated epithelial cells, decreased testis weights, and lowered sperm counts and motility. DOX also reduced germ cell proliferation (PCNA) and meiosis-related proteins (SYCP3), but this effect could be partially improved with MLT administration. HSPA2 expression was maintained, which indicated that although MLT did not improve sperm motility, it did have a significant protective effect on elongated sperm. IVF results showed that MLT could partially promote two-cell and blastocyte development that was restricted by DOX. MLT reversed DOX-driven changes in the testes, including the antioxidant indices of SOD1, CAT and PRDX6, and the apoptotic indices of BAX and Caspase3. These results suggest that MLT effectively prevents DOX-induced early reproductive toxicity, and increase our understanding of the molecular mechanisms underlying DOX’s effects on male reproduction and the protective mechanism of MLT.

Melatonin Alters the miRNA Transcriptome of Inflammasome Activation in Murine Microglial Cells.

Systemic inflammation can have devastating effects on the central nervous system via its resident immune cells, the microglia. One of the primary mediators of this inflammation is inflammasomes, multiprotein complexes that trigger a release of inflammatory proteins when activated. Melatonin, a hormone with anti-inflammatory effects, is an attractive candidate for suppressing such inflammation. In this study, we have investigated how melatonin alters the microRNA (miRNA) transcriptome of microglial cells. For that purpose, we have performed RNA sequencing on a lipopolysaccharide and adenosine triphosphate (LPS + ATP) induced NLR family pyrin domain containing 3 (NLRP3) inflammasome activation model in the N9 mouse microglial cell line, with and without melatonin pre-treatment. We have identified 136 differentially expressed miRNAs in cells exposed to LPS + ATP compared to controls and 10 differentially expressed miRNAs in melatonin pre-treated cells compared to the inflammasome group. We have identified miR-155-3p as a miRNA that is upregulated with inflammasome activation and downregulated with melatonin treatment. We further confirmed this pattern of miR-155-3p expression in the brains of mice injected intraperitoneally with LPS. Moreover, an overexpression study with miRNA-155-3p mimic supported the idea that the protective effects of melatonin in NLRP3 inflammasome activation are partly associated with miRNA-155-3p inhibition.

Melatonin Ameliorates 2,4-Dichlorophenoxyacetic Acid Induced Testicular Steroidogenesis Upset in Mice: An <i>In Vivo</i> and <i>In Silico</i> Study

2,4-Dichlorophenoxyacetic acid (2,4-D) is used as a selective herbicide and associated with a variety of toxicities in mammals. In contrast, melatonin is an antioxidant that promotes the elimination of free radicals. In the present study, the protective effects of melatonin (10 mg/kg body weight) against 2,4- D (low, mid, and high dose-16.5, 33.0, and 66.0 mg/kg body weight) induced testicular steroidogenesis alteration were examined using in vivo and in silico models. Doses of 2,4-D and melatonin were administered orally for 28 days. The evaluated parameters were body weight, total protein, markers for male reproductive function, and steroidogenesis i.e. testis weight, total lipid, cholesterol, testosterone, 3 beta-hydroxysteroid dehydrogenase, 17 betahydroxysteroid dehydrogenase, total sperm count, sperm motility, and sperm viability along with the histopathology of the testis. The statistical significant value was considered at p<0.05. Molecular docking study was performed for interaction of 2,4-D and melatonin with steroid binding proteins. In vivo results revealed that 2,4-D treatment showed a significant dose-dependent alteration in above all studied parameters. No significant auto-recovery was observed in the withdrawal study, on the contrarily, the altered parameters were normalized and comparable to control when melatonin was given alone and in combination with 2,4-D. In silico results also demonstrated that the binding affinity of melatonin with steroid binding proteins is higher than 2,4-D. Collectively, these in vivo and in silico findings indicated that 2,4-D induced testicular toxicity accompanied by steroidogenesis upset and can be reduced by melatonin significantly by interacting directly and strongly with studied molecular markers.

Activating Parkin-dependent mitophagy alleviates oxidative stress, apoptosis, and promotes random-pattern skin flaps survival

The random-pattern skin flap is a crucial technique in reconstructive surgery and flap necrosis caused by ischemia/reperfusion injury is a major postoperative complication. Herein, we investigated the mechanism of mitophagy induced by Melatonin (ML) and its effect on the survival of skin flaps. Our results demonstrated that ML could activate mitophagy, ameliorate oxidative stress and alleviate apoptosis in Tert-Butyl hydroperoxide solution (TBHP)-stimulated human umbilical vein endothelial cells in vitro. Inhibiting ML-induced mitophagy considerably abolished its protective effects. Moreover, knockdown of Parkin by siRNA inhibited ML-induced mitophagy, and subsequently exacerbated oxidative stress and apoptosis. Further study demonstrated that inhibition of AMPK reversed these protective effects of ML and downregulated the expression of TFEB. In the vivo study, ML effectively promoted flap survival by activating mitophagy and subsequently ameliorating oxidative stress and mitigating apoptosis. These results established that ML is a potent agent capable for increasing random-pattern skin flap survival by activating Parkin-dependent mitophagy through the AMPK-TFEB signaling pathway.

Effect ofmelatonin onthe gastric antioxidant defence inexperimental burn trauma.

Severe burn trauma triggers oxidative gastric mucosal injury. The purpose ofthis study was toinvestigate the antioxidant defence mechanisms and protective effect ofmelatonin inthe gastric mucosa after burn injury. Inorder toinvestigate the mechanisms involved inthe gastric antioxidant defence inarat burn model, quantitative real-time PCR and immunohistochemistry techniques were applied. Ananalysis ofglutathione peroxidase4 (GPx4), glutathione reductase (GR), and catalase (Cat) gene expression was performed along with the evaluation ofthe gastric Cu/Zn superoxide dismutase (Cu/Zn SOD) activity. Melatonin was applied immediately and 12h after 30% oftotal body surface area burns. The burn injury significantly increased the Gpx4 mRNA (P<0.0001) and Gsr mRNA (P<0.0001) expression. Italso had aslight positive effect onthe Cat mRNA expression and Cu/Zn SOD activity. Melatonin, inturn, markedly augmented the burn-induced Cu/Zn SOD (P<0.0001) activity, reversed the Gpx4 mRNA (P<0.0001) and Gsr mRNA (P<0.0001) expression, and inhibited the Cat mRNA level. Inconclusion, the present study suggests that aburn injury adaptively increases the Cu/Zn SOD activity and enhances the Gpx4 and Gsr gene expression inthe gastric mucosa. Melatonin effectively modulates the expression ofthe cellular antioxidant enzymes, and improves the antioxidant defence byaugmenting the Cu/Zn SOD activity.

New insights into the reverse of chromium-induced reprotoxicity of pregnant mice by melatonin

Hexavalent chromium Cr(VI) is a well-known environmental toxic metal that causes reprotoxicity in pregnant females. There are currently no appropriate interventions or treatments for Cr(VI) exposure during pregnancy. Herein, the protective effect of melatonin (MLT) against Cr(VI)-induced reprotoxicity is investigated by administrating MLT to pregnant mice exposed to Cr(VI). The results indicate that MLT effectively alleviates Cr(VI)-induced adverse pregnancy outcomes, restoring the decreased fetal weight and increased fetal resorption and malformation caused by Cr(VI) exposure to normal levels. MLT reduces the negative effects of Cr(VI) on follicular atresia and the development of primordial follicle in the maternal ovarian, thereby mitigating the decline in the reserve of primordial follicles. MLT alleviates Cr(VI)-induced oxidative stress, hence reducing the excessive accumulation of malondialdehyde in the maternal ovary. MLT inhibits Cr(VI)-induced apoptosis of ovarian granulosa cells and the expression of cleaved caspase-3 in the ovary. MLT reduces the increase in serum follicle-stimulating hormone caused by Cr(VI) exposure, while elevating anti-Mullerian hormone levels. We demonstrate that MLT reverses Cr(VI)-induced reprotoxicity in pregnant mice, opening up a new avenue for treating reproductive defects caused by environmental stress.

Melatonin Alleviates Venous Dysfunction in a Mouse Model of Iliac Vein Occlusion.

The iliac vein can be severely stenosed and occluded due to thrombosis, tumor compression, or an anatomical abnormality. Such occlusion could result in limb swelling, venous claudication, and persistent leg ulcers. Its devastating sequelae heavily impact patients lifestyles and the social economy. Due to a lack of a stable and easy-to-operate iliac vein occlusion (IVO) model, its underlying molecular mechanism and pathophysiological process has not been completely understood. Melatonin (MLT) plays a critical role in anti-inflammation, but the potential protective effect of melatonin on venous dysfunction induced by IVO has not been revealed. In this study, a mouse model of IVO was established to study the effects of MLT on injured veins. The results of laser speckle images and Evans blue showed that MLT inhibited venous permeability in an IVO mouse model. Furthermore, MLT suppressed inflammation of surrounding tissues close to the affected vein by inhibiting the mRNA levels of TNF-α, IL-1α, and MCP-1. In addition, endothelial injury was inhibited by MLT using zonula occludens protein-1 (ZO-1) staining. Taken together, we elucidated the therapeutic effect of MLT on vascular dysfunction induced by IVO, mainly by inhibiting the TNF-α, IL-1α, and MCP-1 mRNA levels, improving endothelial function, and inhibiting vascular leakage.

Evaluation of the protective effect of melatonin on histological changes in the liver of adult male rats treated with gemcitabine

Melatonin is an endocrine hormone, produced by the pineal gland from the amino acid tryptophan. Melatonin level in the body according to a predetermined cycle and are affected by light received. Gemcitabine is an anti-cancer drug. The mechanism of action of gemcitabine affects the properties of the cellular phase and mainly destroys the cells that are making DNA (phase-s). Nephrotoxic side effects of gemcitabine have been reported in patients receiving this drug medication. Melatonin is a potent free radical scavenger and antioxidant and has protective effects against ischemic damage. The aim of the present study was to investigate the protective effect of melatonin on histological changes in the liver of adult male rats treated with gemcitabine and to evaluate the effects of different doses of melatonin on the protection of adult liver cells treated with gemcitabine. This experimental study was performed on male Wistar rats weighing approximately 250±20g and aged 8 weeks. Mice were randomly divided into 3 main groups. The first group (G1); the control group, received only normal saline. The second group (G2); the treated groups, divided into 2 subgroups T1 and T2, This group received melatonin at doses of 10 and 20 mg/kg and intraperitoneal (IP) with gemcitabine at a dose of 50 mg/kg, respectively. The third group (G3); negative control group, divided into 3 subgroups T3, T4 and T5. Subgroup T3, gemcitabine at 50 mg/kg, and T4 and T5, they received melatonin at doses of 10 and 20 mg/kg, intraperitoneally (IP) respectively. The number of mice in each group was 6 mice. The results obtained from the injection of gemcitabine in groups clearly showed the side and cytotoxic effects in the liver tissue that the most lesions were observed in the subgroup (T3). In the groups receiving melatonin, the amount of these lesions was significantly reduced and the reduction of injuries was directly related to the dose of melatonin. The results of this study show that melatonin is effective in reducing the side effects of gemcitabine.

Tunneling nanotubes and mesenchymal stem cells: New insights into the role of melatonin in neuronal recovery

Efficient cell‐to‐cell communication is essential for tissue development, homeostasis, and the maintenance of cellular functions after injury. Tunneling nanotubes (TNTs) have emerged as a new important method of cell‐to‐cell communication. TNTs are primarily established between stressed and unstressed cells and can transport a variety of cellular components. Mitochondria are important trafficked entities through TNTs. Transcellular mitochondria transfer permits the incorporation of healthy mitochondria into the endogenous network of recipient cells, changing the bioenergetic profile and other functional properties of the recipient and may allow the recipient cells to recuperate from apoptotic processes and return to a normal operating state. Mesenchymal cells (MSCs) can form TNTs and transfer mitochondria and other constituents to target cells. This occurs under both physiological and pathological conditions, leading to changes in cellular energy metabolism and functions. This review summarizes the newly described capacity of melatonin to improve mitochondrial fusion/fission dynamics and promote TNT formation. This new evidence suggests that melatonin's protective effects could be attributed to its ability to prevent mitochondrial damage in injured cells, reduce senescence, and promote anastasis, a natural cell recovery phenomenon that rescues cells from the brink of death. The modulation of these new routes of intercellular communication by melatonin could play a key role in increasing the therapeutic potential of MSCs.

Anti-Inflammatory Effects of Melatonin in Rats with Induced Type 2 Diabetes Mellitus.

Introduction: Insulin resistance is associated with a pro-inflammatory state increasing the risk for complications in patients with type 2 diabetes mellitus (T2DM). In addition to its chronobiotic effects, the pineal hormone melatonin is known to exert anti-inflammatory and antioxidant effects. Melatonin was also suggested to affect insulin secretion. The aim of this study was therefore to investigate the effect of melatonin on inflammation in diabetic rats and to study the possible involvement of the melatonin receptor, MT2. Materials and Methods: Male Sprague Dawley rats were randomly divided into four experimental groups (n = 10 per group): (1) control, (2) streptozotocin/nicotinamide induced diabetes type 2 (T2DM), (3) T2DM treated with melatonin (500 µg/kg/day), and (4) T2DM treated with melatonin (500 µg/kg/day for 6 weeks) and the selective MT2 receptor antagonist luzindole (0.25 g/kg/day for 6 weeks). Blood samples were taken for biochemical parameters and various tissue samples (liver, adipose tissue, brain) were removed for immunohistochemistry (IHC), Western blot (WB), and Q-PCR analyses, respectively. Results: Melatonin significantly reduced increased blood levels of liver transaminases (AST, ALT), blood urea nitrogen (BUN), triglyceride, very low-density lipoprotein (VLDL), and cholesterol in diabetic rats with luzindole treatment partly reversing this effect regarding the lipids. Furthermore, the liver and adipose tissues of T2DM rats treated with melatonin showed lower expression of the inflammatory markers IL-1β, IL-6, TNF-α, and NF-κB as compared to the T2DM group without melatonin. The results also showed that the MT2 receptor is at least partly involved in the protective effects of melatonin. Conclusions: Our results suggest that melatonin exerts relevant anti-inflammatory effects on various tissues in type 2 diabetic rats.

Effect of low concentration of melatonin on the quality of stored red blood cells &lt;em&gt;in vitro&lt;/em&gt;

Introduction. Oxidative stress is one of the important causes of red blood cells (RBCs) storage lesion. As a hormone, melatonin (MT) is also an effective antioxidant, however the pro- and antioxidative properties of MT depend on the cell type, redox state, as well as experimental conditions.Aim of this study — to investigate the protective effects of low concentration of MT on the stored RBCs in vitro.Materials and methods. Leukofi ltered RBCs were incubated in MAP RBC additive solution with or without 150 pg/mL of MT for 42 days under blood bank conditions. The morphology, aggregation index, methemoglobin (MetHb), m alondialdehyde (MDA), glucose, lactic acid and ATP of RBCs were detected on days 0, 7, 14, 21, 28, 35 and 42 to observe the protective effects of MT during the storage of RBCs.Results. During RBCs s torage, the number of deformed RBCs, relative hemolysis rate, aggregation index, MDA and MetHb were signifi cantly affected by both storage time (p &lt; 0.0001) and melatonin (p &lt; 0.01), and they had interaction only on the number of deformed RBCs (p &lt; 0.0001). The concentration of glucose, lactic acid and ATP were affected by storage time (p &lt; 0.0001), but not by MT concentration (p &gt; 0.05). The number of deformed RBCs, relative hemolysis rate, MDA and MetHb in MT group were signifi cantly lower than that in control group at the end of storage stage (p &lt; 0.05).Conclusion. Our study showed low hypnotic drug concentration of MT is speculated to have protective effects on the quality of stored RBCs through antioxidative mechanism.

Melatonin attenuates cisplatin-induced acute kidney injury in mice: Involvement of PPARα and fatty acid oxidation

The present study focused on the protective effects of melatonin against cisplatin-induced acute kidney injury in mice and its possible mechanism of action in relation to the major regulator of fatty acid oxidation (FAO), peroxidase proliferative receptor α (PPARα). The experiment consisted of the following four groups: vehicle control, cisplatin (15 mg/kg), cisplatin & melatonin (20 mg/kg/day), and melatonin (20 mg/kg/day). Concomitant administration of melatonin significantly ameliorated cisplatin-induced acute kidney injury in mice by decreasing serum levels of triglyceride, blood urea nitrogen and creatinine, reducing the number and size of lipid droplets in tubular epithelial cells, and decreasing the incidence of histopathological changes including tubular cell apoptosis. Moreover, melatonin administration protected kidney tissue by significantly upregulating the levels of PPARα reduced by cisplatin injection, resulting in increased FAO pathway-associated genes (PGC-1a, Acadm, Acat1, Acsm2, Acsm3, Bdh2, Echs and Pecr) as well as reducing protein levels of caspase-3, -9 and Bax. Melatonin not only partially modulated FAO via PPARα signaling, but also decreased cisplatin-induced apoptosis by inhibiting the caspase-3, -9 and Bax pathways. Our findings suggest that melatonin prevents cisplatin-induced acute kidney injury in mice, possibly by upregulating the expression of PPARα, resulting in enhanced FAO and anti-apoptotic properties.