Ameliorative Effect Of Melatonin Research Articles

Ameliorative effects of melatonin on dark-induced leaf senescence in gardenia (Gardenia jasminoides Ellis): leaf morphology, anatomy, physiology and transcriptome

Cut gardenia (Gardenia jasminoides Ellis) foliage is widely used as a vase material or flower bouquet indoors; however, insufficient indoor light accelerates its senescence, which shortens its viewing time. In this study, applying melatonin to delay gardenia leaf senescence when exposed to extremely low light condition (darkness), and the results showed that 1.0 mM was the effective concentration. At this concentration, chlorophyll contents and chlorophyll fluorescence parameters (Fv/Fm, Fv/F0 and Y(II)) increased, while the carotenoid and flavonoid contents decreased. Meanwhile, stress physiological indices decreased in response to exogenous melatonin application, whereas an increase in glutamine synthetase activity, water and soluble protein contents was observed. Moreover, exogenous melatonin application also reduced leaf programmed cell death under darkness, increased the endogenous melatonin level, expression levels of tryptophan decarboxylase gene, superoxide dismutase and catalase activities and the ascorbate–glutathione cycle, and maintained more intact anatomical structures. Furthermore, transcriptome sequencing revealed that various biological processes responded to exogenous melatonin application, including carbohydrate metabolism, amino acid metabolism, lipid metabolism, plant hormone signal transduction and pigment biosynthesis. Consequently, dark-induced leaf senescence in gardenia was significantly delayed. These results provided a better understanding for improving the ornamental value of cut gardenia foliage using melatonin.

Low dose of melatonin ameliorates cryptorchidism-induced spermatotoxicity in rats

IntroductionCryptorchidism has been associated with spermatotoxicity and oxidative stress while melatonin is a well-known anti-oxidant. This study investigated the possible ameliorative effect of melatonin on cryptorchidism-induced spermatotoxicity and oxidative stress. MethodsThirty six male Wistar rats were randomised into sham-operated (n=18) and bilaterally cryptorchid (n=18) groups, each of which were subdivided into 3 oral treatment groups (n=6 rats each) that received normal saline, low dose (4mg/kg) and high dose (10mg/kg) melatonin. ResultsCryptorchidism reduced sperm parameters, oestradiol, luteinising hormone, follicle stimulating hormone and glutathione peroxidase activity, but increased testosterone and lactate dehydrogenase activity. The cryptorchidism-induced spermatotoxicity and oxidative stress were ameliorated by low dose of melatonin but exacerbated by its high dose. DiscussionMelatonin’s effect on cryptorchidism-induced spermatotoxicity is dose-dependent.

Subchronic Chlorpyrifos and Cypermethrin-induced Sensorimotor Changes in Male Wistar Rats: Ameliorative Effects of Melatonin

Subchronic Chlorpyrifos and Cypermethrin-induced Sensorimotor Changes in Male Wistar Rats: Ameliorative Effects of Melatonin

The effect of melatonin on adrenal gland and pancreas function in alloxan – induced diabetes in adult female rabbits

The present study was carried out to investigate the ameliorative effect of melatonin on pancreatic and adrenal dysfunction induced by alloxan in adult female rabbits. Twenty four adult female rabbits were randomly divided into four equal groups treated for 42 days as follows: control group received 2 ml of distal water intraperitoneally, animals of the second group received single dose of 150 mg /kg of alloxan (group T1), while the third group received single dose of 150 mg/kg of alloxan and after 7 days received 10mg/kg I/P of melatonin for 42 days of experiment (T2 group). The fourth group received 10 mg/kg I/P of melatonin for 42 days .After the 7 days of alloxan injection the blood is collected from (T1) and (T2) animals, to investigate of diabetes induction in these groups. Also blood samples were collected at zero time, 14, 28 and 42 days of the experiment for measuring the serum concentration of glucose, total protein, total cholesterol, reduce glutathione and hormones concentration (insulin and cortisol). The result of present study indicated that melatonin administration is not affected in body weight in rabbits to T2 and T3 as compared with control group, while (T1) group showed significant decrease in these parameters as compared with other groups. The adrenal gland weight to body weight ratio showed significant increase in adrenal weight in (T1) as compared with all other group while T2 and T3 groups showed significant decrease as compared with T1 groups. While the pancreas gland weight to body weight ratio showed significant increase in pancreas weight in (T3) group as compared with other groups. Animals T1 and T2 groups showed significant decrease as compared with T3 and control groups. Animals T1 group showed significant elevation in serum glucose, total cholesterol and serum cortisol concentration as compared with control, T2 and T3 groups. The results also showed a significant decrease in total serum protein, serum insulin and reduce glutathione concentrations in alloxan treated group (T1) as compared with control, T2 and T3 animals. Inferred from the result of this experiment is treatment of diabetic female rabbits with melatonin (10 mg /kg .B.W) for 42 days lead to improve the function of adrenal gland and pancreas gland. Also it showed the possibility of reducing oxidative stress triggered by alloxan through the use of melatonin.

Ameliorative effect of melatonin against increased intestinal permeability in diabetic rats: possible involvement of MLCK-dependent MLC phosphorylation.

The increased intestinal permeability and functional impairment play an important role in type 2 diabetes (T2D), and melatonin may possess enteroprotection properties. Therefore, we used streptozotocin-induced diabetic rat model to investigate the regulation of intestinal permeability by melatonin. Rats were randomly divided into three groups, including control, diabetes mellitus (DM), and DM rats treated with melatonin. Melatonin was administered (10mg/kg/day) by gavage for 24weeks. The DM rats significantly increased the serum fasting blood glucose and lipid levels, which were alleviated by melatonin treatment. Importantly, the intestinal epithelial permeability was significantly increased in DM rats but was ameliorated following treatment with melatonin. These findings also indicated the expression of myosin light chain kinase (MLCK) and phosphorylation of MLC targeting subunit (MYPT) induced myosin light chain (MLC) phosphorylation level was markedly elevated in hyperglycemic and hyperlipidemic status. They were partly associated with down-regulated membrane type 1 and 2 (MT1 and MT2) expression, and up-regulated Rho-associated protein kinase (ROCK) expression and increased extracellular signal-regulated kinase (ERK) phosphorylation. However, the changes in target protein expression were reversed by melatonin. In conclusion, our results show melatonin beneficial effects on impaired intestinal epithelial permeability in T2D by suppressing ERK/MLCK- and ROCK/MCLP-dependent MLC phosphorylation.

Ameliorative effects of melatonin on the liver of pregnant albino rats and their offspring induced by monosodium glutamate

Ameliorative effects of melatonin on the liver of pregnant albino rats and their offspring induced by monosodium glutamate

Melatonin ameliorates metabolic risk factors, modulates apoptotic proteins, and protects the rat heart against diabetes-induced apoptosis

The present study investigated the ability of melatonin in reducing metabolic risk factors and cardiac apoptosis induced by diabetes. Streptozotocin (60mg/kg, i.p.) was injected into male rats, and after diabetic induction melatonin (10mg/kg i.g.) was administered orally for 21 days. Diabetic hearts showed increased number of apoptotic cells with downregulation of Bcl-2 and activation of p53 and CD95 as well as the caspases 9, 8 and 3. In addition, there was a significant decrease in insulin level, hyperglycemia, elevated HOMA-IR, glycosylated hemoglobin (HbA1c), total lipids, triglycerides, total cholesterol, low and very low-density lipoprotein and decreased high-density lipoprotein. These changes were coupled with a significant increase in the activities of creatin kinase-MB (CK-MB) and lactate dehydrogenase (LDH) in the serum of the diabetic rats indicating myocardium injury. Oral administration of melatonin for 3 weeks after diabetes induction ameliorated the levels of hyperglycemia, insulin, HbA1c, lipids profile and HOMA-IR. The oral melatonin treatment of diabetic rats significantly decreased the number of apoptotic cells in the heart compared to diabetic rats. It enhanced Bcl-2 expression and blocked the activation of CD95 as well as caspases 9, 8 and 3. These changes were accompanied with significant improvement of CK-MB and LDH in the serum indicating the ameliorative effect of melatonin on myocardium injury. Melatonin effectively ameliorated diabetic myocardium injury, apoptosis, reduced the metabolic risk factors and modulated important steps in both extrinsic and intrinsic pathways of apoptosis. Thus, melatonin may be a promising pharmacological agent for ameliorating potential cardiomyopathy associated with diabetes.

Melatonin improves adriamycin-induced hepatic oxidative damage in rats

The present study investigated the possible ameliorative effects of melatonin (MLT) against adriamycin (ADR)-induced hepatotoxicity and oxidative stress in rats. The following four experimental groups were evaluated: (1) vehicle control, (2) MLT (15 mg/kg/day), (3) ADR (10 mg/kg), and (4) ADR&MLT. ADR caused severe hepatotoxicity as evidenced by an elevation of serum aspartate aminotransferase and alanine aminotransferase activities, increased total bilirubin concentration, and decreased albumin and total protein concentration, indicating hepatic function abnormalities. Histopathological examination revealed various structural changes in liver, characterized by hepatocyte degeneration/necrosis, congestion, sinusoidal dilatation, vacuolation, and inflammatory cell infiltration. The significant decrease in reduced glutathione (GSH) content, catalase, superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione reductase (GR) activities and the significant increase in malondialdehyde (MDA) content indicated that ADR-induced hepatotoxicity was mediated through oxidative stress. In contrast, MLT treatment significantly improved ADR-induced serum biochemical and histo-pathological alterations reflecting hepatic dysfunction. Moreover, MDA concentration and GSH content, GR, GPx, and SOD activities were not affected when MLT was administered in conjunction with ADR. These results indicated that MLT improved the oxidative damage induced by ADR in rat liver, presumably due to its ability to inhibit lipid peroxidation, and restore both enzymatic and nonenzymatic antioxidant activities.

The Possible Ameliorative Effect of Melatonin on Oxidative Stress and Delayed Apoptosis in Rat's Brain Exposed to Deltamethrin

Deltamethrin is a broad spectrum, non- cumulative, fast acting neurotoxic synthetic pyrethroid. The aim of this study was to analyze the neurotoxicity induced by deltamethrin which caused neuro-oxidative stress, histopathological & immunohistochemical changes in adult male Wistar rats and to evaluate the possible ameliorative effect of melatonin. Melatonin (10mg/Kg, once daily), ethanol 99% (1 ml/kg, once daily), corn oil (0.005ml/Kg, once daily), deltamethrin (12.5mg/Kg, once daily), and melatonin (10mg/Kg) + deltamethrin (12.5mg/Kg) combination were given to rats I.P for 8 weeks. By the end of 8th week, rats given deltamethrin alone had significantly higher MDA (malondialdehyde), lower reduced glutathione and catalase levels in the hippocampus and lower ACTH (adrenocortocotrophic hormone) & cortisol hormone levels than the control group. Co- treatment of deltamethrin with melatonin had an ameliorative effect on the previous parameters. Light microscopic investigations revealed that deltamethrin caused marked degenerative changes in the hippocampus & pituitary gland of rats. Mild degenerative changes were observed in rats received deltamethrin + melatonin combination. Immunohistochemical studies revealed that deltamethrin caused marked expression of P-53 (a marker for apoptosis) in the hippocampus & pituitary gland. Mild expression of P-53 was observed in rats received deltamethrin & melatonin combination. Thus, deltamethrin can induce oxidative damage in rat brain & melatonin has an ameliorative effect against this damage.

Protective role of melatonin supplementation against nicotine-induced liver damage in mouse

The present study was carried out to determine histopathological effects of nicotine, one of the most significant components of tobacco, on mouse liver and ameliorative effect of melatonin on liver damage. A total of 140 mature Swiss Albino mice (Mus musculus) were divided into four experimental groups: control group, nicotine group, melatonin group and nicotine + melatonin group. Each group was further subdivided into seven groups (five mice each) according to the time of killing (12 h and days 1, 3, 5, 7, 14 and 21 after drug administration). In nicotine and nicotine + melatonin groups, 3 mg/kg of nicotine was injected intraperitoneally every day until killing. The nicotine + melatonin group was additionally injected with 10 mg/kg of melatonin after 30 min of nicotine injection. The melatonin group was injected only with 10 mg/kg of melatonin every day until killing. All the treatments were given 2 h before sunset, when melatonin receptors were active. After the last injection, five mice from each group were killed at 12th hour and on days 1, 3, 5, 7, 14 and 21; the livers were removed for histopathological processing by light microscopy. The histopathological results revealed time-dependent degeneration in the livers of mice in nicotine group. Regenerative changes in the nicotine and melatonin groups were observed when compared with nicotine groups.

Ameliorative effect of melatonin on meristematic cells of chilled and re-warmed Vigna radiata roots

Changes in ultrastructure of meristematic cells as well as growth and lipid peroxidation in roots of 3-d-old seedlings obtained from control (C), hydroprimed (H) and hydroprimed with melatonin (H-MEL) seeds after 2 d of incubation at 25 or 5 °C and 2 d of re-warming after chilling were investigated. Under 25 °C hydropriming (H and H-MEL) inhibited root growth, but after chilling and re-warming a positive MEL effect on root elongation was observed. The results show decreased lipid peroxidation in H-MEL roots already after chilling, but the significant extent of MEL impact was seen after re-warming. Similarly at the ultrastructural level, the protective effect of MEL at chilling was also visible, especially in plastids, and this effect maintained also after re-warming.

Ameliorative Effects of Melatonin against Hydrogen Peroxide‐Induced Oxidative Stress on Boar Sperm Characteristics and Subsequent In Vitro Embryo Development

Melatonin, the major secretory product of the pineal gland, scavenges a variety of reactive oxygen and nitrogen species in vivo and in vitro, indicating that melatonin is a potent function as an antioxidant. The objective of this study was to investigate the effect of melatonin in the presence or absence of hydrogen peroxide (H(2)O(2)) on sperm characteristics (motility, viability, survival rate, membrane integrity, lipid peroxidation (LPO) and mitochondria activity) and also to examine the developmental rates to the blastocysts stage of porcine oocytes fertilized in vitro with semen treated with or without melatonin (100 nM) in the presence or absence of H(2)O(2) (250 μM). The sperm were treated with melatonin in the presence or absence of H(2)O(2) for 3, 6, 9 and 12 h at 37°C and then analysed for the sperm characteristics. The porcine embryos were produced by in vitro maturation and in vitro fertilization (IVM/IVF) using semen treated with or without melatonin (100 nM) in the presence or absence of H(2)O(2) (250 μM) for 6 h. The semen characteristics, including motility, viability, survival rate, membrane integrity and mitochondria activity, were higher in the groups that were treated with melatonin in comparison to other groups, irrespective of incubation periods. Malondialdehyde levels in control, melatonin and melatonin + H(2)O(2) groups were lower than H(2)O(2) only group. A positive correlation was shown among motility, viability, survival rate and membrane integrity, but a negative correlation was observed between LPO and the other evaluation methods. The developmental rates to blastocysts of IVM/IVF porcine oocytes fertilized by semen treated with melatonin were significantly increased compared with any other groups, with the cell number of blastocysts shown to have a similar trend to the developmental rates. These results demonstrate that melatonin can improve the semen characteristics during in vitro storage and support the developmental ability of IVM/IVF embryos in pigs.

Ameliorative effect of melatonin against gamma-irradiation-induced oxidative stress and tissue injury

While radiation hazards, due to free radical generation, present an enormous challenge for biological and medical safety, melatonin is a potent scavenger of a variety of free radicals. The aim of this study was to investigate the radioprotective effect of melatonin against oxidative stress and tissue injury induced by gamma radiation. Rats were subjected to two doses of 2 and 4 Gy from cesium-137 source. Four days prior to irradiation, animals received melatonin daily (10 mg/kg body weight i.p.). In the irradiated animals, the oxidative stress markers malondialdehyde (MDA) and protein carbonyl were significantly increased in the liver, while a marked decrease in hepatic contents of DNA, RNA, and glutathione (GSH) as well as activity of glutathione- S-transferase (GST) was demonstrated. In addition, catalase (CAT) activity was increased in the liver 5 days after irradiation. The levels of total lipids, cholesterol, triglyceride (TG), low-density lipoprotein (LDL), urea, and creatinine, as well as activities of aspartate aminotransferase (AST), alkaline phosphatase (ALP), and gamma-glutamyltransferase (GGT), were significantly increased in sera of the irradiated rats. This is coupled with decreased serum levels of high-density lipoprotein (HDL), total protein and albumin, and total globulins by irradiation. The administration of melatonin alone daily for 4 days caused significant decreases in MDA and protein carbonyl content and produced significant elevations of GSH content and GST activity in the liver. Moreover, significant decreases in total lipids, cholesterol, and TG without change in LDL or HDL levels in serum were demonstrated. Treatment with melatonin for 4 days before acute irradiation significantly abolished radiation-induced elevations in MDA and protein carbonyl levels in the liver and significantly maintained hepatic GSH content, GST, and CAT activities close to the control values. Preirradiation treatment with melatonin showed significantly higher hepatic DNA and RNA contents than irradiated rats. The levels of total lipids, cholesterol, TG, HDL, LDL, total proteins, albumin, total globulins, creatinine, and urea, as well as the activities of AST, ALT, and GGT in serum were significantly ameliorated when melatonin was injected before irradiation. In conclusion, the increase in oxidative stress markers and the concomitant change in antioxidant levels indicate the role of oxidative stress in radiation-induced tissue damage. Moreover, melatonin shows a radioprotective impact against ionizing-radiation-induced oxidative stress and organ injury.

Histopathologic changes in liver and renal tissues induced by Ochratoxin A and melatonin in rats.

Nephrotoxicity and hepatotoxicity induced by Ochratoxin A (OTA) and ameliorating effects of melatonin were investigated in rats exposed to OTA. Experimental groups were as follows: control; OTA-treated; and OTA plus melatonin (MEL)-treated (OTA+MEL). The rats in the control group were administered with only a daily oral administration of 0.5 M NaHCO3. OTA was administered with a dose of 289 microg/kg in the same way. OTA and MEL were administered orally with OTA (289 microg/kg) and melatonin (10 mg/kg) in two different periods of time during the same day. The histopathologic changes in the liver and kidney tissues of control, OTA and OTA+MEL-treated rats were examined. There were no significant changes in the kidney and liver tissues of the control rats. Significant histopathologic changes were found in the kidney and liver tissue of rats treated with OTA. These were granular or vacuolated degeneration and necrosis of the liver cells, sinusoidal and central vein dilatation, bile duct proliferation, enlargement of periportal areas with mononuclear cell inflammatory infiltration and mild degree fibrous tissue proliferation, tubular epithelial cells degeneration, necrosis, proliferation and karyomegaly in the epithelial cells nuclei and peritubular and periglomerular lymphocyte infiltration, stromal fibrous tissue proliferation, hyperemic vessels. The severity of the lesions was significantly reduced by administration of melatonin. These results revealed that OTA induced significant histopathologic changes in liver and kidney tissue advocating OTA toxicity (P < 0.001), and administration of MEL+OTA significantly reduced the toxic effect of OTA on kidney and liver tissue of rats (P > 0.05).

Ameliorative effect of melatonin against contrast media induced renal tubular cell injury

Reactive oxygen species (ROS) is a mediator of renal damage. Melatonin is a potent-free radical scavenger. Our objective was to test whether melatonin would protect against the nephrotoxicity of contrast media. In an experimental study 40 adult male Wistar rats were randomly divided into four equal groups including: 1) Control group (No drug), 2) Contrast media group (10 ml/kg iodixanol i.v. single dose), 3) Contrast media and melatonin (first 10 ml/kg iodixanol then 10 ml/kg/day melatonin by i.p. injection on days 3, 4 and 5) and 4) Contrast media and melatonin pretreatment group (melatonin 10 ml/ kg/day by i.p. injection on 1, 2 and 3 days, then 10 ml/kg iodixanol by i.v. injection on third day. The blood creatinine and BUN as well as the histological changes were evaluated for severity of renal injury (degeneration, vacuolization of tubular renal cells, dilatation of tubular lumen and presence of debris in the lumens), by scoring from one to four. Contrast media significantly increased the creatinine and BUN and renal injury (p<0.05). Melatonin prevented and reversed the injury induced by contrast media (P<0.05). Pretreatment with melatonin reduced the renal injury induced by contrast media (P<0.05). Melatonin is an effective drug to prevent contrast-induced renal injury. Therefore its usage (especially pretreatment) might be beneficial in patients who are planning to use contrast media agents.