Possible Effects Of Melatonin Research Articles

Melatonin Mitigates Cisplatin-Induced Submandibular Gland Damage by Inhibiting Oxidative Stress, Inflammation, Apoptosis, and Fibrosis.

The study aims to examine the possible effect of melatonin against cisplatin-induced submandibular degeneration in experimental rats exploring its ameliorative mechanisms. Rats were classified into four experimental groups; control group; melatonin group; cisplatin group; and cisplatin+melatonin group. Submandibular tissues were collected. Biochemical, histopathological, and immunohistopathological examination and quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis were performed. The results indicate that intraperitoneal administration of melatonin (30 mg/kg body weight) alongsidecisplatin significantly elevated submandibular glands (SMG) and reduced glutathione (GSH) and superoxide dismutase (SOD) levels (p < 0.001), while it reducedmalondialdehyde (MDA) levels, NF-κB gene expression, the protein level of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-1 beta (IL-1β), immunoexpression of low-dose cyclooxygenase-2 (Cox-2), and CD68. Moreover, melatonin reduced immune and gene expression of alpha-smooth muscle actin (α-SMA), immunoexpression of caspase-3, and gene expression of Bax in comparison to the cisplatin group. Melatonin attenuated cisplatin-induced submandibular destruction alleviating SMG oxidative stress, inflammation, and fibrosis in addition to halting cellular apoptosis, sheds light on its usage in clinical application.

Exogenously applied melatonin enhanced chromium tolerance in pepper by up-regulating the photosynthetic apparatus and antioxidant machinery

Chromium (Cr) is widely recognized as a highly toxic metal pollutant that adversely affects the agricultural productivity and poses considerable risks to human health. The regulatory role of melatonin (MEL) in Cr stress is well recognized, however, the potential role of MEL in enhancing Cr stress tolerance in pepper is rarely investigated. This study examined the possible effect of MEL in alleviating the adverse effects of Cr toxicity in pepper seedlings. When pepper seedlings were exposed to Cr toxicity, they showed a significant reduction in growth traits, photosynthetic efficiency, root morphological characteristics, and biochemical attributes. Cr treatment greatly caused oxidative damage that was directly related to increased EL, H2O2, O2•−, and MDA production. Conversely, MEL supplementation significantly mitigated the phytotoxic effects of Cr on root morphology, gas exchange elements, and leaf photosynthetic capacity, and restored the growth of pepper seedlings. MEL application stimulated the plant's defense system by enhancing the modulation of antioxidant enzymes, AsA-GSH pools, maintaining the glyoxalase enzymes activity, and reducing oxidative damage. Notably, MEL supplementation significantly reduced Cr accumulation from root to shoot. Hence, MEL supplementation might be regarded as a successful approach for reducing Cr accumulation and its adverse effects in pepper seedlings cultivated in contaminated soils. The research may also provide novel perspectives on the potential application of MEL in mitigating heavy metal toxicity in pepper seedlings.

Pre-treatment of melatonin enhances the seed germination responses and physiological mechanisms of soybean (Glycine max L.) under abiotic stresses.

The germination of soybean (Glycine max L.) seeds is critically affected by abiotic stresses which resulting in decreasing crop growth and yield. However; little is known about the physiological mechanisms of germination and the potential role of melatonin on soybean seed germination under drought, salt, cold, and heat stresses. Therefore, the current study investigated the possible effects of melatonin to enhance germination indices and other physiological attributes by alleviating the harmful impacts of these stresses during germination. Seeds of soybean were pre-treated (seed priming) with melatonin at MT1 (20 μmol L-1), MT2 (50 μmol L-1), MT3 (100 μmol L-1), MT4 (200 μmol L-1), and MT5 (300 μmol L-1) and exposed to the four stresses (drought at PEG 15%, salt at 150mM, cold at 10 °C, and heat at 30 °C) . It was noted that MT1 (20 μmol L-1), MT2 (50 μmol L-1), and MT3 (100 μmol L-1) remarkably improved the germination potential, germination rate, radical length, and biomass under given stresses. Furthermore, MT1, MT2, and MT3 progressively increased the proline to minimize the impact of drought, salt, cold, and heat stresses. In addition, all stresses significantly induced oxidative damage however, salt (150 mM NaCl) and heat (30 °C) stresses highly increased the malondialdehyde content (MDA) and hydrogen peroxide (H2O2) as compared to drought (PEG 15%) and cold (10 °C) stresses. Moreover, MT2 and MT3 significantly enhanced the activities of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), and ascorbate peroxidase (APX) to reduce the oxidative damage in soybean seeds during the germination. Overall, melatonin at 50 μmol L-1 and 100 μmol L-1 considerably mitigated the harmful impacts of drought, salt, cold, and heat stress by enhancing germination and other physiological mechanisms of soybean. This study could provide bases to enhance the melatonin-mediated tolerance of soybean and other related crops at early growth stages when exposed to abiotic stresses.

Pinealectomy and melatonin administration in rats: their effects on pulmonary edema induced by α-naphthylthiourea

We aimed to observe the possible effects of melatonin (MLT) deprivation (pinealectomy) and exogenous MLT administration on pulmonary edema induced by alpha-naphthylthiourea (ANTU), a toxic chemical agent, in rats. Seventy animals were assigned to seven groups: control, sham pinealectomy (PINX), PINX, ANTU (10 mg/kg intraperitoneal on day 30), ANTU + MLT (10 mg/kg/day i.p. for 30 days), ANTU + PINX, and ANTU + PINX + MLT. In this study, pleural effusion (PE) formation, lung weight/body weight (LW/BW) and PE/BW ratios (fluid accumulation and weight values in the lungs) increase detected. Pre-ANTU MLT administration led to significant decreases in PE, LW/BW, and PE/BW levels. The inhibited glutathione (GSH) and superoxide dismutase (SOD) levels and high malondialdehyde (MDA) levels that ANTU increase lipid peroxidation in the study. MLT administration eliminated oxidative stress by reducing MDA and ameliorating GSH and SOD levels. Pre-ANTU MLT administration led to a significant decrease in interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) levels in the lung when compared to the ANTU group without MLT administration. Post-pinealectomy ANTU administration significantly increased IL-1β and TNF-α levels when compared to ANTU and MLT administration without pinealectomy. Diffused inflammatory cell infiltration, interstitial pulmonary edema, and histopathological congestion were observed after the administration of ANTU. Severity of the damage was elevated in the ANTU + PINX group. MLT treatment regressed pulmonary effusion and edema and improves lung structure. In brief, the findings suggested that MLT inhibited proinflammatory mediators and could serve as a therapeutic agent to prevent inflammatory disorders.

Possible effects of melatonin on reperfusion injury following coronary artery bypass graft surgery.

Although coronary artery bypass graft (CABG) surgery has been reported to be one of the most effective internentions in terms of myocardial salvage, reperfusion itself can cause additional damage to the myocardium. Since there is strong evidence that free radicals are the principal offender in ischemia-reperfusion (I/R) injury, it has been suggested that treatment with antioxidant agents can be protective. Investigations have shown that melatonin secretion is partially disturbed in CABG patients. The aim of this study was to evaluate the protective effect of melatonin as an antioxidant agent on I/R injury. 164 elective CABG candidates participated in this randomized clinical trial during the preoperative period. The candidates were randomized to receive 3 mg of melatonin tablets (physiologic dose) from 3 days before surgery until the day of discharge. Cardiac biomarkers [troponin and creatine kinase myocardial band (CKMB)] were assessed once before surgery (24 hours before surgery), and 8 and 24 hours after surgery. Finally, 130 patients, 65 (50%) patients in the melatonin group and 65 (50%) in the control arm finished our study. Mean age of melatonin and control groups was 59.90 ± 9.59 and 60.80 ± 8.00 years, respectively; moreover, 47 (72.30%) in melatonin and 45 (69.23%) in control group were men. No significant difference was seen in baseline cardiac biomarkers between two groups (P > 0.05). In both groups, cardiac biomarkers (CKMB and troponin) elevated after surgery in comparison to their preoperative values. There was no statistically significant difference between the control and melatonin groups regarding the 8-hour and 24-hour troponin and CKMB when adjusted for interacting factors (P > 0.05). Although physiological concentration of melatonin is protective against I/R injury, substitution of endogenous melatonin with the oral supplement which creates physiologic concentration may not prevent I/R injury. In order to have antioxidant effect, pharmacologic doses of melatonin should be employed.

Putative effect of melatonin on cardiomyocyte senescence in mice with type 1 diabetes mellitus.

To date, many investigators have tried to clarify the molecular mechanism of cardiovascular injuries after T1D. In present study, we evaluated the possible effects of melatonin on the levels of aging-related factors in the heart tissue of streptozotocin-induced diabetic mice. 40 male mice were enrolled in this study and randomly allocated into 4 groups (n = 10) as follows: Control group (C), Control group + melatonin (CM), Diabetic group (D), Diabetic + melatonin (DM) group. Single Streptozotocin (50mg/kbW) was applied for the induction of T1D. 3mg/kg melatonin was injected intraperitoneally twice a week for consequent four weeks. After the completion of this period, the animals were sacrificed and their heart tissue was obtained for histological examination (IHC analysis of vWF and α-SMA cells), aging and inflammation-related gene analysis. Hematoxylin and Eosin staining indicated cardiomyocyte toxicity in T1D mice. IHC analysis of vascular tissue showed the detachment of vWF and α-SMA cells and disintegration into the vascular lumen. Additionally, real-time PCR assay showed the up-regulation of β-galactosidase and suppression of SOX2, Klotho, and Telomerase genes in T1D mice compared to the control group (p < 0.05). We noted that melatonin administration can revert these condition and closed near-to-control levels. Along with these conditions, the levels of IL-1β were also decreased after melatonin treatment. In general, one can hypothesizethat modulation of different effectors associatedwith aging is beneficial to alleviate cardiac injuries under hypergylcemic condition. Melatonin can exert its therapeutic effects, in part, through anti-aging capacity.

Melatonin protects against PM2.5-induced lung injury by inhibiting ferroptosis of lung epithelial cells in a Nrf2-dependent manner

PM2.5 refers to ambient air particulate matter with aerodynamic diameters ≤ 2.5 µm, which has been a global environmental problem threatening public health in recent years. Melatonin serving as one of the predominant hormones secreted by the pineal gland displays multiple pharmacological properties in various diseases. However, little is known about the possible effects of melatonin in the development of lung injury induced by PM2.5. This study was designed to explore the potential roles of melatonin as well as its possible mechanisms in PM2.5-induced lung injury. In the present study, mice were intratracheally instilled with PM2.5 dissolved in sterile water to induce lung injury with or without intragastric administration of melatonin. The results showed that melatonin treatment significantly alleviated lung pathological injury and edema, apart from inhibiting inflammatory cell infiltration. Meantime, melatonin also decreased the makers of ferroptosis and lipid peroxidation products in lung tissues challenged with PM2.5. Additionally, melatonin promoted the nuclear translocation and expression of Nrf2 and the protein degradation of Keap1. However, the pulmonary protection and anti-ferroptosis effect of melatonin were counteracted in Nrf2-deficiency mice. In vitro experiments further demonstrated that Nrf2 knockdown could offset anti-ferroptosis effect of melatonin in MLE-12 lung epithelial cells. Taken together, our study disclosed that melatonin could relieve PM2.5-induced lung injury via inhibiting ferroptosis of lung epithelial cells by activating Nrf2. Hence, melatonin may be a promising candidate against lung injury associated with air particulate matter.

FLUCTUATIONS IN MELATONIN CONTENT AND ITS EFFECTS ON THE AGEING PROCESS OF LETTUCE SEEDS DURING STORAGE

This research was carried out to determine the changes in melatonin and tryptophan contents and the possible effects of melatonin on the ageing process of lettuce seeds stored for two years. For this purpose, seeds were treated with melatonin (0 or 250 µM) for one day after which they were stored for up to two years at two temperature (4°C or 25°C) regimes. The results showed that seed melatonin content varied significantly during storage reaching its peaks in October-December and lowest levels in August while tryptophan levels displayed an opposite trend with a strong peak in August and low levels in October. Similar seasonal changes were observed in seeds stored under both temperature conditions suggesting that endogenous melatonin could play a crucial role in seasonal rhythms independent of environmental conditions. Lettuce seed quality deteriorated fast when stored at 25°C but pre-treatment with melatonin reduced seed deterioration significantly by increasing the activities of antioxidant enzymes and restoring membrane properties indicating that melatonin could be used to slow the ageing process in seeds.

Effects of melatonin and resveratrol on recognition memory and passive avoidance performance in a mouse model of Alzheimer’s disease

Alzheimer’s disease (AD) is the foremost cause of dementia among other neurodegenerative diseases, leading to memory loss and cognitive deficits. AD has gained extensive attention in research for exploring possible interventions. One promising field is natural substances and compounds that could provide a wide range of neuroprotection against AD. This study aimed to investigate the possible effects of melatonin (MEL) and resveratrol (RES) in improving memory deficits in a sporadic mouse model of AD. Memory deficit was induced using AlCl3 and d-galactose for generating an AD mouse model. Mice were randomly distributed into five groups (n = 13): control, AD, AD + MEL (AD mice treated with 80 mg/kg of MEL), AD + RES (AD mice treated with 40 mg/kg of RES), and AD + Combination)AD mice that received 80 mg/kg MEL and 40 mg/kg RES). A novel object recognition task (NORT) and passive avoidance task (PAT) were used for assessing memory. Moreover, acetylcholinesterase (AChE) level, brain-derived neurotrophic factor (BDNF), and cAMP-response element binding (CREB) protein expression were measured in the prefrontal cortex tissue. Our results showed that MEL significantly improved memory deficits in both the NORT and PAT of the AD model, while RES improved the PAT only in the AD model. Co-treatment with MEL and RES exerted beneficial additive effects on recognition memory impairment in the AD mouse model. Moreover, our results demonstrated that both MEL and RES enhanced the cholinergic system and BDNF and CREB signaling pathways in the prefrontal cortex in an AD mouse model.

Treatment with melatonin induces a reduction of Toxoplasma gondii development in LLC-MK2 cells.

It is known that the current treatment for toxoplasmosis causes side effects. Thus, it is essential to develop new therapies with reduced adverse effects while concurrently maintaining broad coverage and prophylactic therapy. Melatonin is a hormone that participates in the circadian cycle in vertebrates and has antioxidant, immunomodulatory, and antitumoral functions. In addition, it has been shown that melatonin can modulate immune responses and parasitic development during infection by Trypanosoma cruzi and Leishmania spp. Furthermore, studies indicate that melatonin increases the number of lymphocytes in rats infected by Toxoplasma gondii. However, there is no information on the possible effects of melatonin in T. gondii-infected host cells in vitro. This study analyzed the effects of melatonin treatment in the monkey kidney cell epithelial cell line, LLC-MK2, after infection with T. gondii. LLC-MK2 cells were infected and treated/not treated with melatonin, and the infection index was then quantified. Melatonin treatment did not alter host cell viability and was able to reduce parasite proliferation in LLC-MK2 cells at 24 and 48h and at 6days. Analysis by scanning electron microscopy confirmed reduction of parasite proliferation and alterations of tachyzoite shapes. Transmission electron microscopy images showed parasites with ruptured plasma membranes and cytoplasmic leakage. After treatment, parasites showed positive staining for apoptotic-like cell death. These results suggest that the use of melatonin as the lead compound for the synthesis of new compounds may constitute an alternative treatment for toxoplasmosis.

Melatonin ameliorates ketoconazole-induced increase in thyroid function

Background&#x0D; The antithyroid effect of ketoconazole has been reported. The secretion and action of melatonin in the thyroid gland are also known. However, the possible effect of melatonin on ketoconazole-induced antithyroid effect is unknown.&#x0D; Objective&#x0D; We sought to investigate the modulatory effect of ketoconazole and/or melatonin on thyroid function in female rats.&#x0D; Methods&#x0D; Groups 1-4 of female rats respectively underwent 14-day treatment with normal saline, 25 mg/kg ketoconazole, 4 mg/kg melatonin and 10 mg/kg melatonin. Groups 5 and 6 both received 14-day treatment with ketoconazole and were respectively treated with 4 mg/kg melatonin and 10 mg/kg melatonin simultaneously. Groups 7 and 8 respectively underwent 14-day pretreatment with 4 mg/kg melatonin and 10 mg/kg melatonin, followed by 14-day administration of ketoconazole to both groups. Groups 9 and 10 were both treated with ketoconazole for 14 days, followed by respective 14-day administration of 4 mg/kg melatonin and 10 mg/kg melatonin.&#x0D; Results&#x0D; TSH, T3, T4, and iodine concentrations were increased by separate administration of ketoconazole and either dose of melatonin when compared to control. However, pre-treatment or post-treatment of ketoconazole-treated rats with melatonin abolished the ketoconazole-induced increase in TSH, T3, T4, and iodine while co-administration of ketoconazole with melatonin caused no improvement in the ketoconazole-induced increase in TSH, T3, and T4 except iodine concentration.&#x0D; Conclusion&#x0D; Ketoconazole increased thyroid function, which was ameliorated by pre- or post-treatment with melatonin, possibly via modulation of the iodination process.&#x0D; Keywords: Iodine; Ketoconazole; Melatonin; Thyroid function; Toxicity

Melatonin-related mitochondrial respiration responses are associated with growth promotion and cold tolerance in plants

Melatonin has the ability to improve plant growth and strengthened plant tolerance to environmental stresses; however, the effects of melatonin on mitochondrial respiration in plants and the underlying biochemical and molecular mechanisms are still unclear. The objective of the study is to determine possible effects of melatonin on mitochondrial respiration and energy efficiency in maize leaves grown under optimum temperature and cold stress and to reveal the relationship between melatonin-induced possible alterations in mitochondrial respiration and cold tolerance. Melatonin and cold stress, alone and in combination, caused significant increases in activities and gene expressions of pyruvate dehydrogenase, citrate synthase, and malate dehydrogenase, indicating an acceleration in the rate of tricarboxylic acid cycle. Total mitochondrial respiration rate, cytochrome pathway rate, and alternative respiration rate were increased by the application of melatonin and/or cold stress. Similarly, gene expression and protein levels of cytochrome oxidase and alternative oxidase were also enhanced by melatonin and/or cold stress. The highest values for all these parameters were obtained from the seedlings treated with the combined application of melatonin and cold stress. The activity and gene expression of ATP synthase and ATP concentration were augmented by melatonin under control and cold stress. On the other hand, cold stress reduced markedly plant growth parameters, including root length, plant height, leaf surface area, and chlorophyll content and increased the content of reactive oxygen species (ROS), including superoxide anion and hydrogen peroxide and oxidative damage, including malondialdehyde content and electrolyte leakage level; however, melatonin significantly promoted the plant growth parameters and reduced ROS content and oxidative damage under control and cold stress. These data revealed that melatonin-induced growth promotion and cold tolerance in maize is associated with its modulating effect on mitochondrial respiration.

Integration of Melatonin Related Redox Homeostasis, Aging, and Circadian Rhythm.

Circadian rhythms (CRs) are intrinsic clocks organizing the behavior and physiology of organisms. These clocks are thought to have coevolved with cellular redox regulation. Metabolism, redox homeostasis, circadian clock, and diet offer insights into aging. Mitochondria play a pivotal role in redox homeostasis, CR, and aging. Melatonin is synthesized in mitochondria, is the key regulator of CRs, and shows substantial antioxidative effects. Melatonin levels tend to decrease significantly with advancing age. Recent reports showed that disruptions of CRs may render aging populations even more susceptible to age-related disorders. Recent and high-quality articles investigating CR, redox homeostasis, aging, and their relationship during aging process were included. Putting special emphasis on the possible effects of melatonin on redox homeostasis and mitochondrial dynamics, recent clinical evidence highlighting the importance of circadian mechanisms was utilized. A deeper understanding of the role of altered mitochondrial redox homeostasis in the pathogenesis of age-related disorders and its relationship with CR could offer novel therapeutic interventions. Chronotherapy, a therapeutic approach considering CR of organisms and best therapeutic times, could potentially reduce side effects and improve therapeutic efficiency. Redox homeostasis, energy metabolism, and CR are all intertwined.

Exogenous Melatonin Mitigates Acid Rain Stress to Tomato Plants through Modulation of Leaf Ultrastructure, Photosynthesis and Antioxidant Potential.

Acid rain (AR) is a serious global environmental issue causing physio-morphological changes in plants. Melatonin, as an indoleamine molecule, has been known to mediate many physiological processes in plants under different kinds of environmental stress. However, the role of melatonin in acid rain stress tolerance remains inexpressible. This study investigated the possible role of melatonin on different physiological responses involving reactive oxygen species (ROS) metabolism in tomato plants under simulated acid rain (SAR) stress. SAR stress caused the inhibition of growth, damaged the grana lamella of the chloroplast, photosynthesis, and increased accumulation of ROS and lipid peroxidation in tomato plants. To cope the detrimental effect of SAR stress, plants under SAR condition had increased both enzymatic and nonenzymatic antioxidant substances compared with control plants. But such an increase in the antioxidant activities were incapable of inhibiting the destructive effect of SAR stress. Meanwhile, melatonin treatment increased SAR-stress tolerance by repairing the grana lamella of the chloroplast, improving photosynthesis and antioxidant activities compared with those in SAR-stressed plants. However, these possible effects of melatonin are dependent on concentration. Moreover, our study suggests that 100-μM melatonin treatment improved the SAR-stress tolerance by increasing photosynthesis and ROS scavenging antioxidant activities in tomato plants.

Bisfenol A'nın Tuba Uterina'da Neonatal Dönemde Oluşturduğu Değişikliklere Karşı Melatonin'in Olası Etkisi

Bisfenol A'nın Tuba Uterina'da Neonatal Dönemde Oluşturduğu Değişikliklere Karşı Melatonin'in Olası Etkisi

Possible effects of melatonin against rat uterus exposure to bisphenol A during neonatal period.

The aim of this study was to investigate the possible effects of melatonin on rat uterine tissue against exposure with bisphenol A (BPA) in the neonatal period. Twenty-four female rats were divided into four groups, (n=6) per group. Group I was used as a control (sesame oil + ethanol), group II was injected daily with (100mg/kg) BPA by subcutaneously (sc) daily postnatal days (PND 0-10), group III was injected daily with (10mg/kg) melatonin by sc for 10days (PND 20-30), and group IV was injected daily with (100mg/kg) BPA (PND 0-10) and (10mg/kg) melatonin (PND 20-30). All rats were sacrificed in the same day of metestrus cycle, approximately PND 70. Histological analyses, immunostaining of B cell lymphoma 2 (Bcl-2), and cytochrome c and TUNEL assays were performed. According to our results, neonatal exposure to BPA accelerates onset of puberty, causes degenerative and morphometric changes on rat uterus, and increases apoptotic reaction rates. The immunoreactivity of Bcl-2 was decreased after BPA administration. In addition, immunoreactivity of Bcl-2 showed an increase after melatonin treatment. However, cytochrome c immunoreactivity was decreased after melatonin administration. Our results suggest that melatonin may have positive effects against BPA-induced degenerative changes on rat uterus.

Oncostatic-Cytoprotective Effect of Melatonin and Other Bioactive Molecules: A Common Target in Mitochondrial Respiration.

For several years, oncostatic and antiproliferative properties, as well as thoses of cell death induction through 5-methoxy-N-acetiltryptamine or melatonin treatment, have been known. Paradoxically, its remarkable scavenger, cytoprotective and anti-apoptotic characteristics in neurodegeneration models, such as Alzheimer’s disease and Parkinson’s disease are known too. Analogous results have been confirmed by a large literature to be associated to the use of many other bioactive molecules such as resveratrol, tocopherol derivatives or vitamin E and others. It is interesting to note that the two opposite situations, namely the neoplastic pathology and the neurodegeneration, are characterized by deep alterations of the metabolome, of mitochondrial function and of oxygen consumption, so that the oncostatic and cytoprotective action can find a potential rationalization because of the different metabolic and mitochondrial situations, and in the effect that these molecules exercise on the mitochondrial function. In this review we discuss historical and general aspects of melatonin, relations between cancers and the metabolome and between neurodegeneration and the metabolome, and the possible effects of melatonin and of other bioactive molecules on metabolic and mitochondrial dynamics. Finally, we suggest a common general mechanism as responsible for the oncostatic/cytoprotective effect of melatonin and of other molecules examined.

Can Melatonin Act as an Antioxidant in Hydrogen Peroxide-Induced Oxidative Stress Model in Human Peripheral Blood Mononuclear Cells?

Purpose. We aimed to investigate the possible effects of melatonin on gene expressions and activities of MnSOD and catalase under conditions of oxidative stress induced by hydrogen peroxide (H2O2) in peripheral blood mononuclear cells (PBMCs). Materials and Methods. PBMCs were isolated from healthy subjects and treated as follows: (1) control (only with 0.1% DMSO for 12 h); (2) melatonin (1 mM) for 12 h; (3) H2O2 (250 μM) for 2 h; (4) H2O2 (250 μM) for 2 h following 10 h pretreatment with melatonin (1 mM). The gene expression was evaluated by real-time PCR. MnSOD and catalase activities in PBMCs were determined by colorimetric assays. Results. Pretreatment of PBMCs with melatonin significantly augmented expression and activity of MnSOD which were diminished by H2O2. Melatonin treatment of PBMCs caused a significant upregulation of catalase by almost 2-fold in comparison with untreated cells. However, activity and expression of catalase increased by 1.5-fold in PBMCs under H2O2-induced oxidative stress compared with untreated cell. Moreover, pretreatment of PBMCs with melatonin resulted in a significant 1.8-fold increase in catalase expression compared to PBMCs treated only with H2O2. Conclusion. It seems that melatonin could prevent from undesirable impacts of H2O2-induced oxidative stress on MnSOD downregulation. Moreover, melatonin could promote inductive effect of H2O2 on catalase mRNA expression.

Melatonin affects voltage-dependent calcium and potassium currents in MCF-7 cell line cultured either in growth or differentiation medium

Big efforts have been dedicated up to now to identify novel targets for cancer treatment. The peculiar biophysical profile and the atypical ionic channels activity shown by diverse types of human cancers suggest that ion channels may be possible targets in cancer therapy. Earlier studies have shown that melatonin exerts an oncostatic action on different tumors. In particular, it was shown that melatonin was able to inhibit growth/viability and proliferation, to reduce the invasiveness and metastatic properties of human estrogen-sensitive breast adenocarcinoma MCF-7 cell line cultured in growth medium, with substantial impairments of epidermal growth factor (EGF) and Notch-1-mediated signaling. The purpose of this work was to evaluate on MCF-7 cells the possible effects of melatonin on the biophysical features known to have a role in proliferation and differentiation, by using the patch-clamp technique. Our results show that in cells cultured in growth as well as in differentiation medium melatonin caused a hyperpolarization of resting membrane potential paralleled by significant changes of the inward Ca2+ currents (T- and L-type), outward delayed rectifier K+ currents and cell capacitance. All these effects are involved in MCF-7 growth and differentiation. These findings strongly suggest that melatonin, acting as a modulator of different voltage-dependent ion channels, might be considered a new promising tool for specifically disrupting cell viability and differentiation pathways in tumour cells with possible beneficial effects on cancer therapy.

Effects of melatonin on the serum levels of pro-inflammatory cytokines and tissue injury after renal ischemia reperfusion in rats

We investigated the changes in the serum levels of tumor necrosis factor (TNF)-α and interleukin (IL)-6, the pro-inflammatory cytokines, and the possible effect of melatonin on the modulation of these inflammatory molecules after renal ischemia reperfusion (IR). The study was carried out in the laboratory of Department of Pharmacology. Forty-six male Wistar albino rats were divided into five groups as control (n = 6), positive control (n = 4), sham (n = 12), renal IR (n = 12), and renal IR melatonin (n = 12). After 1 h renal pedicle occlusion, the blood samples were taken for the measurement of cytokine levels at second hour of the reperfusion. The rats were sacrificed after 24 h of reperfusion for histopathological evaluation. Melatonin or vehicle was administrated to IR rats. Lipopolysaccharide (LPS) was administered to the positive control group and the blood was taken at fourth hour. Serum TNF-α levels increased significantly in renal IR and LPS groups. Serum IL-6 levels were not different from control except the LPS group. There was no significant correlation between the serum TNF-α levels and the histopathological score after renal IR. Melatonin treatment reversed the increase of serum TNF-α levels and histopathological injury in renal tissue after renal IR. Melatonin may have a protective effect by reducing the serum level of TNF-α in renal IR.