Cholelithiasis, oxidative stress and melatonin.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
D X Tan
Publications and source records attributed to D X Tan.
Free radical-mediated molecular damage. Mechanisms for the protective actions of melatonin in the central nervous system.
This review briefly summarizes the multiple actions by which melatonin reduces the damaging effects of free radicals and reactive oxygen and nitrogen species. It is well documented that melatonin protects macromolecules from oxidative damage in all subcellular compartments. This is consistent with the protection by melatonin of lipids and proteins, as well as both nuclear and mitochondrial DNA. Melatonin achieves this widespread protection by means of its ubiquitous actions as a direct free radical scavenger and an indirect antioxidant. Thus, melatonin directly scavenges a variety of free radicals and reactive species including the hydroxyl radical, hydrogen peroxide, singlet oxygen, nitric oxide, peroxynitrite anion, and peroxynitrous acid. Furthermore, melatonin stimulates a number of antioxidative enzymes including superoxide dismutase, glutathione peroxidase, glutathione reductase, and catalase. Additionally, melatonin experimentally enhances intracellular glutathione (another important antioxidant) levels by stimulating the rate-limiting enzyme in its synthesis, gamma-glutamylcysteine synthase. Melatonin also inhibits the proxidative enzymes nitric oxide synthase and lipoxygenase. Finally, there is evidence that melatonin stabilizes cellular membranes, thereby probably helping them resist oxidative damage. Most recently, melatonin has been shown to increase the efficiency of the electron transport chain and, as a consequence, to reduce election leakage and the generation of free radicals. These multiple actions make melatonin a potentially useful agent in the treatment of neurological disorders that have oxidative damage as part of their etiological basis.
Animals↗
High levels of melatonin in the seeds of edible plants: possible function in germ tissue protection.
The seeds of plants represent the anlage of the next generation and are vital to their existence. Melatonin has been identified in the leaves and flowers of plants but not in seeds. In this study, we examined the seeds of 15 edible plants for the presence of melatonin which was extracted using cold ethanol. Melatonin was initially identified by radioimmunoassay and subsequently quantified and confirmed using high performance liquid chromatography. The physiological concentrations of melatonin in the 15 seeds studied ranged from 2 to 200 ng/g dry weight. The highest concentrations of melatonin were observed in white and black mustard seeds. This level of melatonin is much higher than the known physiological concentrations in the blood of many vertebrates. Since the seed, particularly its germ tissue, is highly vulnerable to oxidative stress and damage, we surmise that melatonin, a free radical scavenger, might be present as an important component of its antioxidant defense system. Thus, melatonin in seeds may be essential in protecting germ and reproductive tissues of plants from oxidative damage due to ultraviolet light, drought, extremes in temperature, and environmental chemical pollutants.
Chromatography, High Pressure Liquid↗
Melatonin reduces rat hepatic macromolecular damage due to oxidative stress caused by delta-aminolevulinic acid.
Delta-aminolevulinic acid, precursor of heme, accumulates in a number of organs, especially in the liver, of patients with acute intermittent porphyria. The potential protective effect of melatonin against oxidative damage to nuclear DNA and microsomal and mitochondrial membranes in rat liver, caused by delta-aminolevulinic acid, was examined. Changes in 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels, an index of DNA damage, and alterations in membrane fluidity (the inverse of membrane rigidity) and lipid peroxidation in microsomal and mitochondrial membranes, as indices of damage to lipid and protein molecules in membranes, were estimated. Measurements were made in rat liver after a 2 week treatment with delta-aminolevulinic acid (40 mg/kg b.w., every other day). To test the potential protective effects of melatonin, the indole was injected (i.p. 10 mg/kg b.w.) 3 times daily for 2 weeks. 8-OHdG levels and lipid peroxidation in microsomal membranes increased significantly whereas microsomal and mitochondrial membrane fluidity decreased as a consequence of delta-aminolevulinic acid treatment. Melatonin completely counteracted the effects of delta-aminolevulinic acid. Melatonin was highly effective in protecting against oxidative damage to DNA as well as to microsomal and mitochondrial membranes in rat liver and it may be useful as a cotreatment in patients with acute intermittent porphyria.
8-Hydroxy-2'-Deoxyguanosine↗
Melatonin reduces the oxidation of nuclear DNA and membrane lipids induced by the carcinogen delta-aminolevulinic acid.
Well known are the anti-oxidant, free radical-scavenging and anti-tumorigenic properties of melatonin. delta-Aminolevulinic acid (ALA) is a precursor of heme synthesis. When over-produced and accumulated in tissues, ALA is a potential carcinogen, such as in the course of acute intermittent porphyria, hereditary tyrosinemia and lead poisoning. Our aim was to examine the potential protective effect of melatonin against oxidative damage to nuclear DNA and membrane lipids in rat lung and spleen caused by ALA. Changes in 8-hydroxy-2;-deoxyguanosine (8-OHdG) levels, an index of DNA damage, and the level of malondialdehyde + 4-hydroxyalkenals, an index of lipid peroxidation, were measured. Rats were injected with ALA (i.p., 40 mg/kg body weight, every other day) and/or with melatonin (i.p., 10 mg/kg body weight, 3 times daily) for 2 weeks. Both 8-OHdG and lipid peroxidation levels increased significantly in lung and spleen due to ALA treatment. Co-treatment with melatonin completely counteracted the effects of ALA. In conclusion, melatonin effectively protects nuclear DNA and lipids in rat lung and spleen against oxidative damage caused by the carcinogen ALA, and the indole may be of value as a supplement in patients suffering from molecular damage related to ALA accumulation.
8-Hydroxy-2'-Deoxyguanosine↗
Melatonin reduces oxidative neurotoxicity due to quinolinic acid: in vitro and in vivo findings.
The in vivo and in vitro effects of melatonin on quinolinic acid-induced oxidative damage in rat brain were determined. The concentrations of malonaldehyde and 4-hydroxyalkenals were assayed as an index of oxidatively damaged lipid. In in vitro experiments, the increase in malonaldehyde and 4-hydroxyalkenals concentrations induced by quinolinic acid were concentration-dependent and time-dependent. The accumulation of products of lipid peroxidation induced by quinolinic acid were very significantly reduced by melatonin in a concentration-dependent manner. Additionally, at the highest concentrations of melatonin used in quinolinic acid treated homogenates, it reduced the levels of oxidatively damaged lipid products below those measured in control homogenates (no quinolinic acid or melatonin). When quinolinic acid (200 mg/kg) was intraperitonally injected into 11-day-old rats, lipid peroxidation in the brain was significantly increased 24 hours later compared to levels in control rats. When melatonin (10 mg/kg) was injected i.p. 30 min before and 4 and 20 hours after the administration of quinolinic acid, the increased lipid peroxidation induced by quinolinic acid was significantly reduced. Likewise, neurobehavioral signs associated with quinolinate administration were attenuated by melatonin. These results show that both in vitro and in vivo pharmacological levels of melatonin confer protection against quinolinic acid-induced oxidative toxicity in the brain. The findings also indicate that melatonin may be pharmacologically useful in combatting quinolinic neurotoxicity which is associated with several acute and chronic neurodegenerative neurological diseases.
Animals↗
5-methoxytryptophol preserves hepatic microsomal membrane fluidity during oxidative stress.
Lipid peroxidation is a degenerative chain reaction in biological membranes that may be initiated by exposure to free radicals. This process is associated with changes in the membrane fluidity and loss of several cell membrane-dependent functions. 5-methoxytryptophol (ML) is an indole isolated from the mammalian pineal gland. The purpose of this study was to investigate the effects of ML (0. 01mM-10mM) on membrane fluidity modulated by lipid peroxidation. Hepatic microsomes obtained from rats were incubated with or without ML (0.01-10 mM). Then lipid peroxidation was induced by FeCl(3), ADP, and NADPH. Membrane fluidity was determined using fluorescence spectroscopy. Malonaldehyde (MDA) +4-hydroxyalkenals (4-HDA) concentrations were estimated as an indicator of the degree of lipid peroxidation. With oxidative stress, membrane fluidity decreased and MDA+4-HDA levels increased. ML (0.01-3 mM) reduced membrane rigidity and the rise in MDA+4-HDA formation in a concentration-dependent manner. 10 mM ML protected against lipid peroxidation but failed to prevent the membrane rigidity. In the absence of oxidative reagents, ML (0.3-10 mM) decreased membrane fluidity whereas MDA+4-HDA levels remained unchanged. This indicates that ML may interact with membrane lipids. The results presented here suggest that ML may be another pineal indoleamine (in addition to melatonin) that resists membrane rigidity due to lipid peroxidation.
Aldehydes↗
Melatonin directly scavenges hydrogen peroxide: a potentially new metabolic pathway of melatonin biotransformation.
A potential new metabolic pathway of melatonin biotransformation is described in this investigation. Melatonin was found to directly scavenge hydrogen peroxide (H(2)O(2)) to form N(1)-acetyl-N(2)-formyl-5-methoxykynuramine and, thereafter this compound could be enzymatically converted to N(1)-acetyl-5-methoxykynuramine by catalase. The structures of these kynuramines were identified using proton nuclear magnetic resonance, carbon nuclear magnetic resonance, and mass spectrometry. This is the first report to reveal a possible physiological association between melatonin, H(2)O(2), catalase, and kynuramines. Melatonin scavenges H(2)O(2) in a concentration-dependent manner. This reaction appears to exhibit two distinguishable phases. In the rapid reaction phase, the interaction between melatonin and H(2)O(2) reaches equilibrium rapidly (within 5 s). The rate constant for this phase was calculated to be 2.3 x 10(6) M(-1)s(-1). Thereafter, the relative equilibrium of melatonin and H(2)O(2) was sustained for roughly 1 h, at which time the content of H(2)O(2) decreased gradually over a several hour period, identified as the slow reaction phase. These observations suggest that melatonin, a ubiquitously distributed small nonenzymatic molecule, might serve to directly detoxify H(2)O(2) in living organisms. H(2)O(2) and melatonin are present in all subcellular compartments; thus, presumably, one important function of melatonin may be complementary in function to catalase and glutathione peroxidase in keeping intracellular H(2)O(2) concentrations at steady-state levels.
Catalase↗
Protective effects of melatonin against oxidation of guanine bases in DNA and decreased microsomal membrane fluidity in rat liver induced by whole body ionizing radiation.
The aim of the study was to examine the potential protective effect of melatonin against whole body ionizing radiation (800 cGy). Changes in 8-hydroxy-2'-deoxyguanosine (8-OH-dG) levels, an index of DNA damage, and alterations in membrane fluidity (the inverse of membrane rigidity) and lipid peroxidation in microsomal membranes, as indices of damage to lipid and protein molecules in membranes, were estimated. Measurements were made in rat liver, 12 h after their exposure to radiation. To test the potential protective effects of melatonin, the indole was injected (i.p. 50 mg/kg b.w.) at 120, 90, 60 and 30 min prior to radiation exposure. Both 8-OH-dG levels and microsomal membrane rigidity increased significantly 12 h after radiation exposure. Melatonin completely counteracted the effects of ionizing radiation. Changes in 8-OH-dG levels and membrane fluidity are early sensitive parameters of DNA and microsomal membrane damage, respectively, induced by ionizing radiation and our findings document the protective effects of melatonin against ionizing radiation.
8-Hydroxy-2'-Deoxyguanosine↗
Increased levels of oxidatively damaged DNA induced by chromium(III) and H2O2: protection by melatonin and related molecules.
Chromium (Cr) compounds are known occupational and environmental carcinogens. This trace element is found in the workplace primarily in the valence forms Cr(III) and Cr(VI). Cr(III), which was thought originally to be relatively nontoxic, was recently found to be more reactive toward purified DNA than was chromium(VI). Herein, we examined the ability of Cr(III) to induce oxidative DNA damage by measuring the formation of 8-hydroxydeoxyguanosine (8-OH-dG) in purified calf thymus DNA incubated with CrCl3 plus H2O2. In this system we observed that the Cr(III)-induced formation of 8-OH-dG in isolated DNA was both dose- and time-dependent. When melatonin and related molecules, including 6-methoxy-1,2,3,4-tetrahydro-beta-carboline (pinoline), N-acetylserotonin, 6-hydroxymelatonin and indole-3-propionic acid, were co-incubated with CrCl3 plus H2O2, the accumulations of 8-OH-dG in DNA samples were markedly inhibited in a concentration-dependent manner. The concentrations of each indole required to reduce DNA damage by 50%, i.e. the IC50 values, were 0.48, 0.51, 0.88, 1.00 and 3.08 microM for pinoline, melatonin, N-acetylserotonin, 6-hydroxymelatonin and indole-3-propionic acid, respectively. These results suggest that one of the mechanisms by which Cr(III) may induce cancer is via Fenton-type reactions which generate the hydroxyl radical (*OH). The findings also indicate that the protective effects of melatonin and related molecules against Cr(III)-induced carcinogenesis relate to their direct *OH scavenging ability which thereby reduces the formation of the damaged DNA product, 8-OH-dG.
8-Hydroxy-2'-Deoxyguanosine↗
Melatonin and its relation to the immune system and inflammation.
Melatonin (N-acetyl-5-methoxytryptamine) was initially thought to be produced exclusively in the pineal gland. Subsequently its synthesis was demonstrated in other organs, for example, the retinas, and very high concentrations of melatonin are found at other sites, for example, bone marrow cells and bile. The origin of the high level of melatonin in these locations has not been definitively established, but it is likely not exclusively of pineal origin. Melatonin has been shown to possess anti-inflammatory effects, among a number of actions. Melatonin reduces tissue destruction during inflammatory reactions by a number of means. Thus melatonin, by virtue of its ability to directly scavenge toxic free radicals, reduces macromolecular damage in all organs. The free radicals and reactive oxygen and nitrogen species known to be scavenged by melatonin include the highly toxic hydroxyl radical (.OH), peroxynitrite anion (ONOO-), and hypochlorous acid (HOCl), among others. These agents all contribute to the inflammatory response and associated tissue destruction. Additionally, melatonin has other means to lower the damage resulting from inflammation. Thus, it prevents the translocation of nuclear factor-kappa B (NF-kappa B) to the nucleus and its binding to DNA, thereby reducing the upregulation of a variety of proinflammatory cytokines, for example, interleukins and tumor neurosis factor-alpha. Finally, there is indirect evidence that melatonin inhibits the production of adhesion molecules that promote the sticking of leukocytes to endothelial cells. By this means melatonin attenuates transendothelial cell migration and edema, which contribute to tissue damage.
Animals↗
Circadian rhythm abnormalities of melatonin in Smith-Magenis syndrome.
BACKGROUND: Smith-Magenis syndrome (SMS) is a multiple congenital anomalies/mental retardation syndrome associated with a hemizygous deletion of chromosome 17, band p11.2. Characteristic features include neurobehavioural abnormalities such as aggressive and self-injurious behaviour and significant sleep disturbances. The majority of patients have a common deletion characterised at the molecular level. Physical mapping studies indicate that all patients with the common deletion are haploinsufficient for subunit 3 of the COP9 signalosome (COPS3), which is conserved from plants to humans, and in the plant Arabidopis thaliana regulates gene transcription in response to light. Haploinsufficiency of this gene is hypothesised to be potentially involved in the sleep disturbances seen in these patients. Melatonin is a hormone secreted by the pineal gland. SMS patients are reported to have fewer sleep disturbances when given a night time dose of this sleep inducing hormone. METHODS: Urinary excretion of 6-sulphatoxymelatonin (aMT6s), the major hepatic metabolite of melatonin, in 19 SMS patients were measured in conjunction with 24 hour sleep studies in 28 SMS patients. Five of the 28 patients did not have the common SMS deletion. To investigate a potential correlation of COPS3 haploinsufficiency and disturbed melatonin excretion, we performed fluorescence in situ hybridisation (FISH) using two BACs containing coding exons of COPS3. RESULTS: All SMS patients show significant sleep disturbances when assessed by objective criteria. Abnormalities in the circadian rhythm of aMT6s were observed in all but one SMS patient. Interestingly this patient did not have the common deletion. All patients studied, including the one patient with a normal melatonin rhythm, were haploinsufficient for COPS3. CONCLUSIONS: Our data indicate a disturbed circadian rhythm in melatonin and document the disturbed sleep pattern in Smith-Magenis syndrome. Our findings suggest that the abnormalities in the circadian rhythm of melatonin and altered sleep patterns could be secondary to aberrations in the production, secretion, distribution, or metabolism of melatonin; however, a direct role for COPS3 could not be established.
Abnormalities, Multiple↗
Chromium(III)-induced 8-hydroxydeoxyguanosine in DNA and its reduction by antioxidants: comparative effects of melatonin, ascorbate, and vitamin E.
Chromium compounds are well documented carcinogens. Cr(III) is more reactive than Cr(VI) toward DNA under in vitro conditions. In the present study, we investigated the ability of Cr(III) to induce oxidative DNA damage by examining the formation of 8-hydroxydeoxyguanosine (8-OH-dG) in calf thymus DNA incubated with CrCl(3) plus H(2)O(2). We measured 8-OH-dG using HPLC with electrochemical detection. In the presence of H(2)O(2), we observed that Cr(III)-induced formation of 8-OH-dG in isolated DNA was dose and time dependent. Melatonin, ascorbate, and vitamin E (Trolox), all of which are free radical scavengers, markedly inhibited the formation of 8-OH-dG in a concentration-dependent manner. The concentration that reduced DNA damage by 50% was 0.51, 30.4, and 36.2 microM for melatonin, ascorbate, and Trolox, respectively. The results show that melatonin is 60- and 70-fold more effective than ascorbate or vitamin E, respectively, in reducing oxidative DNA damage in this in vitro model. These findings also are consistent with the conclusion that the carcinogenic mechanism of Cr(III) is possibly due to Cr(III)-mediated Fenton-type reactions and that melatonin's highly protective effects against Cr(III) relate, at least in part, to its direct hydroxyl radical scavenging ability.
8-Hydroxy-2'-Deoxyguanosine↗
Changes in lipid peroxidation during pregnancy and after delivery in rats: effect of pinealectomy.
Pregnancy is a physiological state accompanied by a high energy demand of many bodily functions and an increased oxygen requirement. Because of the increased intake and utilization of oxygen, increased levels of oxidative stress would be expected. In the present study, the degree of lipid peroxidation was examined in different tissues from non-pregnant and pregnant rats after the delivery of their young. Melatonin and other indole metabolites are known to be direct free radical scavengers and indirect antioxidants. Thus the effect of pinealectomy at 1 month before pregnancy on the accumulation of lipid damage was investigated in non-pregnant and pregnant rats after the delivery of their young. Malonaldehyde and 4-hydroxyalkenal concentrations were measured in the lung, uterus, liver, brain, kidney, thymus and spleen from intact and pinealectomized pregnant rats soon after birth of their young and at 14 and 21 days after delivery. The same parameters were also evaluated in intact and pinealectomized non-pregnant rats. Shortly after delivery, lipid oxidative damage was increased in lung, uterus, brain, kidney and thymus of the mothers. No differences were detected in liver and spleen. Pinealectomy enhanced this effect in the uterus and lung. It is concluded that during pregnancy high levels of oxidative stress induce an increase in oxidative damage to lipids, which in some cases is inhibited by the antioxidative actions of pineal indoles.
Analysis of Variance↗
Inhibitory effects of melatonin on ferric nitrilotriacetate-induced lipid peroxidation and oxidative DNA damage in the rat kidney.
Ferric nitrilotriacetate (Fe-NTA) is a known complete renal carcinogen which induces lipid peroxidation and oxidative DNA damage in rat kidney. In this study, the in vivo and in vitro effects of melatonin on Fe-NTA-induced lipid and oxidative DNA damage were determined. The levels of malondialdehyde (MDA) and 4-hydroxyalkenals (4-HDA) were assayed as an index of lipid peroxidation and the levels of 8-hydroxydeoxyguanosine (8-OH-dG) as an endpoint of oxidative DNA damage. In in vitro studies, the increased levels of MDA and 4-HDA induced by Fe-NTA were observed to be dose-dependent and time-dependent. The increase in lipid peroxidation was inhibited by melatonin in a concentration-dependent manner. When Fe-NTA(15 mg Fe/kg body weight) was intraperitoneally injected into rats, the levels of MDA + 4-HDA and 8-OH-dG in the rat kidney were increased 1 h after its administration as compared to levels of these constituents in the control group. Pretreatment with melatonin (25 mg/kg or 50 mg/kg) 30 min before the Fe-NTA injection resulted in a significant reduction in the levels of lipid peroxidation and 8-OH-dG induced by Fe-NTA in the rat kidney. These results are consistent with the conclusion that the toxicity of Fe-NTA is due to the generation of reactive oxygen species and that melatonin's protective effects relate to its direct radical scavenging ability and due to other antioxidative processes induced by the indole.
8-Hydroxy-2'-Deoxyguanosine↗
Identification of highly elevated levels of melatonin in bone marrow: its origin and significance.
Bone marrow is an important tissue in generation of immunocompetent and peripheral blood cells. The progenitors of hematopoietic cells in bone marrow exhibit continuous proliferation and differentiation and they are highly vulnerable to acute or chronic oxidative stress. In this investigation, highly elevated levels of the antioxidant melatonin were identified in rat bone marrow using immunocytochemistry, radioimmunoassay, high performance liquid chromatography with electrochemical detection and mass spectrometry. Night-time melatonin concentrations (expressed as pg melatonin/mg protein) in the bone marrow of rats were roughly two orders of magnitude higher than those in peripheral blood. Measurement of the activities of the two enzymes (N-acetyltransferase (NAT) and hydroxyindole-O-methoxyltransferase (HIOMT)) which synthesize melatonin from serotonin showed that bone marrow cells have measurable NAT activity, but they have very low levels of HIOMT activity (at the one time they were measured). From these studies we could not definitively determine whether melatonin was produced in bone marrow cells or elsewhere. To investigate the potential pineal origin of bone marrow melatonin, long-term (8-month) pinealectomized rats were used to ascertain if the pineal gland is the primary source of this antioxidant. The bone marrow of pinealectomized rats, however, still exhibited high levels of melatonin. These results indicate that a major portion of the bone marrow's melatonin is of extrapineal origin. Immunocytochemistry clearly showed a positive melatonin reaction intracellularly in bone marrow cells. A melatonin concentrating mechanism in these cells is suggested by these findings and this may involve a specific melatonin binding protein. Since melatonin is an endogenous free radical scavenger and an immune-enhancing agent, the high levels of melatonin in bone marrow cells may provide on-site protection to reduce oxidative damage to these highly vulnerable hematopoietic cells and may enhance the immune capacity of cells such as lymphocytes.
Acetylserotonin O-Methyltransferase↗
Melatonin and tryptophan derivatives as free radical scavengers and antioxidants.
Several tryptophan derivatives function as free radical scavengers and antioxidants. The molecule that has been most widely investigated in this regard is N-acetyl-5-methoxytryptamine (melatonin); however, pinoline (6-methoxy-1,2,3,4-tetrahydro-beta-carboline) and N-acetylserotonin also possess free radical scavenging activity. Experimental studies have shown that melatonin directly scavenges the hydroxy radical, peroxyl radical, peroxynitrite anion, and singlet oxygen. Furthermore, this tryptophan derivative stimulates a number of antioxidative enzymes and stabilizes cell membranes; this latter action helps membranes to resist free radical damage. While the antioxidative actions of most molecules are limited by their specific intracellular distribution, e.g., vitamin E in lipid-rich membranes, melatonin's antioxidative actions include the protection of lipids in the cell membrane, proteins in the cytosol, and DNA in the nucleus. Furthermore, melatonin crosses all morphophysiological barriers and enters equally well all cells in the organism.
Animals↗
Melatonin reduces lipid peroxidation and tissue edema in cerulein-induced acute pancreatitis in rats.
Since oxygen free radicals and lipid peroxidation have been implicated in the pathogenesis of an early stage of acute pancreatitis, we examined whether melatonin, a recently discovered free-radical scavenger, could attenuate pancreatic injury in Sprague-Dawley rats with cerulein-induced pancreatitis. Acute pancreatitis was induced by four intraperitoneal injections of cerulein (50 microg/kg body wt) given at 1-hr intervals. Thirty minutes after the last cerulein injection, the rats were killed and the degree of pancreatic edema, the level of lipid peroxidation in the pancreas, and serum amylase activity were increased significantly. Pretreatment with melatonin (10 or 50 mg/kg body wt) 30 min before each cerulein injection resulted in a significant reduction in pancreatic edema and the levels of lipid peroxidation. Serum amylase activity, however, was not significantly influenced by either dose of melatonin. Moreover, we found that cerulein administration was associated with stomach edema as well as high levels of lipid peroxidation in the stomach and small intestine, which were also reduced by melatonin. Melatonin's protective effects in cerulein-treated rats presumably relate to its radical scavenging ability and to other antioxidative processes induced by melatonin.
Acute Disease↗