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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The role exerted by melatonin in human physiology has not been completely ascertained. Melatonin levels have been measured in different physiopathological conditions, but the effects induced by melatonin administration or withdrawal have been tested only recently. Some effects have been clearly documented. Melatonin has hypothermic properties, and its nocturnal secretion generates about 40% of the amplitude of the circadian body temperature rhythm. Melatonin has sleep inducing properties, and exerts important activities in the regulation of circadian rhythms. Melatonin is capable of phase shifting human circadian rhythms, of entraining free-running circadian rhythms, and of antagonizing phase shifts induced by nighttime exposure to light. Its effect on human reproduction is not completely clear, but stimulatory effects on gonadotropin secretion have been reported in the follicular phase of the menstrual cycle. Direct actions on ovarian cells and spermatozoa have been also documented. Beside these, new important actions for melatonin may be proved. Melatonin may exert protective effects on the cardiovascular system, by reducing the risk of atherosclerosis and hypertension, and may influence immune responses. Finally, by acting as an antioxidant, melatonin could be important in slowing the processes of ageing.
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PMID:Melatonin in relation to physiology in adult humans. 898 18

Melatonin has been suggested as a potent antioxidant that may protect against development of atherosclerosis and cancer; however, these effects are unproven and controversial. The antioxidant capacity of melatonin was tested in comparison with alpha-tocopherol, ascorbic acid, and the melatonin precursors tryptophan and serotonin, by measuring inhibition of metal ion-mediated and human macrophage-mediated oxidation of LDL. Melatonin had weak antioxidant activity that was detectable only at concentrations 10000- to 100000-fold higher than physiologic concentrations. These results were comparable with published data showing that the radical scavenging activity of melatonin requires markedly supraphysiologic concentrations. In contrast, alpha-tocopherol was 50- to 100-fold more potent and was efficacious at physiologic concentrations. Ascorbic acid and tryptophan also were active at physiologic concentrations and were significantly more potent than melatonin. In summary, extremely supraphysiologic concentrations of melatonin had only weak antioxidant activity, which was surpassed by alpha-tocopherol, ascorbic acid, and tryptophan.
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PMID:Inhibition of LDL oxidation by melatonin requires supraphysiologic concentrations. 973 79

The pineal hormone, melatonin, was recently found to be a potent free scavenger for hydroxyl and peroxyl radicals. Melatonin also inhibits neuronal and thymocyte damage due to oxidative stress. Atherosclerosis development is mediated by low-density lipoprotein (LDL) oxidation and the endocytosis of oxidized LDL by resident macrophages in the subendothelial vascular wall. Furthermore, the cytotoxic effect of oxidized LDL increases atherogenicity. The goal of this study was to compare the antioxidant activities of melatonin and vitamin E against in vitro LDL oxidation and their cytoprotective actions against oxidized LDL-induced endothelial cell toxicity. An attempt at loading LDL with melatonin by incubating human plasma with an ethanolic melatonin solution gave only low protection against Cu2+-induced LDL oxidation in comparison with vitamin E and gave no detectable incorporation of melatonin into LDL, measured by high-performance liquid chromatography (HPLC) coupled to UV detection. High concentrations of melatonin (10-100 microM) added to the oxidative medium induced a clear inhibition of Cu2+-induced LDL oxidation, characterized as an increase in the lag-phase duration of conjugated diene formation and decreases in the maximal rate of the propagation phase and in the maximal amount of conjugated diene formation. Determination of the median efficacious dose (ED50) of melatonin and vitamin E by their ability to increase lag-phase duration showed that melatonin was less active than vitamin E (ED50, 79 vs. 10 microM, respectively). Melatonin was also less active than vitamin E in limiting the formation of thiobarbituric acid-reactive substances (TBARS) and LDL fluorescence intensity increase in the medium during Cu2+-induced LDL oxidation. Cu2+-induced LDL oxidation in the presence of 100 microM melatonin produced oxidized LDLs that were less recognizable for the scavenger receptors of J774 macrophages than were untreated LDLs. Vitamin E, 10 microM, was more active than 100 microM melatonin in inhibiting LDL oxidation and the resulting lipoprotein alterations leading to binding internalization and degradation by the J774 macrophages. Vitamin E, 100 microM, inhibited the pursuit of the oxidation of oxidized LDL mediated by bovine aortic endothelial cells (BAECs) in a culture medium containing Cu2+, whereas 100 microM melatonin had no antioxidant effect. Melatonin, 100 microM, as well as 100 microM vitamin E inhibited intracellular TBARS formation during the incubation of BAECs with highly oxidized LDL but had no influence on the increase in glutathione (GSH) concentration during this lengthy exposure (16 h) of BAECs to highly oxidized LDL. During this period, the same dose of vitamin E but not of melatonin tended to limit the decrease in adenosine triphosphate (ATP) concentration. Vitamin E, 100 microM, did not significantly reduce cellular lactate dehydrogenase (LDH) release in the culture medium during the incubation of oxidized LDL with BAECs, whereas 100 microM melatonin dramatically increased this release. These data show that melatonin is less active than vitamin E in inhibiting in vitro LDL oxidation and does not inhibit the cytotoxicity of oxidized LDL toward cultured endothelial cells. The concentrations necessary to inhibit LDL oxidation are far beyond those found in human plasma (100 microM vs. 100 pM). Therefore our results indicate that the pineal hormone melatonin per se appears to have little antiatherogenic property in the in vitro oxidation of LDL and the cytoprotective action against the toxicity of oxidized LDL. Nevertheless, in vivo LDL oxidation takes place in the subendothelium of the artery wall, and nothing is known about the concentration of melatonin or its catabolites in this environment.
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PMID:A high concentration of melatonin inhibits in vitro LDL peroxidation but not oxidized LDL toxicity toward cultured endothelial cells. 978 26

We evaluated the antioxidant property of melatonin in countering the vasospastic effect of oxidized low-density lipoprotein (ox-LDL), which has been reported to be the most important risk factor for atherosclerosis and also may be linked to preeclampsia. Helical sections of umbilical arteries were obtained from human placentas at elective cesarean deliveries between 37 and 39 weeks of gestation. Changes in maximal tension induced by potassium chloride were measured in arterial sections with intact endothelium. ox-LDL (200 or 300 microg protein/mL) increased vascular tension by 15.6 +/- 2.3 or 31.9 +/- 4.0%, respectively. In contrast, native LDL only slightly increased vascular tension (2.7 +/- 1.0% for 200 microg protein/mL and 6.0 +/- 1.7% for 300 microg protein/mL). Pretreatment with L-N(G)-monomethyl-arginine (2 x 10(-4) M) significantly reduced the vasospastic effect of ox-LDL, as did pretreatment with mannitol (30 mM). Melatonin (10 microM) significantly reduced the vasospastic effect of ox-LDL. These findings suggest that ox-LDL potentiates vascular tension in the human umbilical artery, possibly by suppressing endothelial synthesis of nitric oxide. Melatonin significantly suppressed the vasospastic effect of ox-LDL, probably because it scavenges hydroxyl radical arising from ox-LDL.
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PMID:Melatonin inhibits vasospastic action of oxidized low-density lipoprotein in human umbilical arteries. 1098 19

Oxidant stress is believed to be enhanced in patients with diabetes mellitus, which may lead to endothelial dysfunction and the development of atherosclerosis. In diabetes, hyperglycemia drives non-enzymatic glycation and oxidation of proteins and lipids which enhances the formation of advanced glycation end products (AGEs), which may be involved in the pathogenesis of diabetic vascular disease. The macrovascular complications of diabetes seem to be due to enhanced cellular oxidant stress by the interaction of AGEs with their receptor. It would be worthwhile to devise methods to reduce this oxidant stress. In alloxan-induced diabetic rats lipid peroxidation products were increased, while levels of nitric oxide glutathione peroxidase and superoxide dismutase were reduced. Melatonin restored these biochemical abnormalities to normalcy independent of hyperglycemia. This model can be used to study the role of oxidant stress in the development of macrovascular complications in diabetes mellitus.
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PMID:Preservation of the antioxidant status in chemically-induced diabetes mellitus by melatonin. 1098 24

Oxidative modification of low density lipoprotein (LDL) induced by free radicals is implicated in the development of atherosclerosis. The aim of the present study was to examine the ability of various pineal indoles in inhibiting LDL oxidation which is accompanied by an increase in mobility in agarose gel electrophoresis and by an augmented generation of thiobarbituric acid-reactive substance induced by Cu2+. It was found that the order of potencies in inhibiting malondialdehyde formation was 5-hydroxytryptamine (serotonin)>5-hydroxytryptophol and 5-hydroxyindole-3-acetic acid when tested at 4 mM. 5-methoxytryptamine was as effective as 5-hydroxytryptophol and 5-hydroxyindole-3-acetic acid when tested at 4 mM but was inactive at 1 mM. 5-methoxytryptophol was marginally active at 4 mM. Melatonin, 5-methoxyindole-3-acetic acid and 6-methoxy-2-benzoxazolinone were inactive even at 4 mM. The ranking of antioxidative potencies as reflected in the shift of mobility in agar gel electrophoresis was 5-hydroxytryptamine>5-methoxytryptamine>5-hydroxyindole-3-acetic acid and 5-methoxytryptophol>5-hydroxytryptophol and melatonin. Another aim of this investigation was to ascertain the action of the aforementioned pineal indoles on the enhanced lipid peroxidation brought about in the mouse kidney and liver by intraperitoneal administrations of carbon tetrachloride. It was found that all pineal indoles tested demonstrated an inhibitory effect in the kidney but not in the liver. 6-methox-2-benzoxazolinone and 5-methoxyindole-3-acetic acid exerted antifungal activity against Mycosphaerella arachidicola, Botrytis cinerea and Physalospora piricola. 6-methoxy-2-benzoxazolinone exhibited antibacterial activity against Proteus vulgaris and 5-methoxytryptamine against Staphylocccus aureus and Bacillus subtilis. Other pineal indoles did not possess antifungal or antibacterial action.
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PMID:Examination of pineal indoles and 6-methoxy-2-benzoxazolinone for antioxidant and antimicrobial effects. 1170 94

Considerable evidence supports the hypothesis that LDL oxidation plays an important role in atherosclerosis. Even though high melatonin doses inhibit LDL oxidation in vitro, the effect of melatonin on atherosclerosis has never been studied. We have demonstrated that the feeding of hypercholesterolemic mice with an atherogenic diet supplemented with melatonin highly increases the surface of atherosclerotic lesions in the proximal aorta. These observations occur without detectable lipidic or glucidic phenotype alteration. Melatonin treatment increased highly the sensitivity of atherogenic lipoprotein to Cu(2+) and gamma-radiolysis generated oxyradical ex vivo oxidation during the fasting period. Moreover, these altered lipoproteins were less recognized by the LDL receptor metabolic pathway of murine fibroblasts while they transferred many more cholesteryl esters to murine macrophages. This study suggests that caution should be taken as regards high melatonin dosage in hypercholesterolemic patients.
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PMID:Daily melatonin supplementation in mice increases atherosclerosis in proximal aorta. 1205 75

Melatonin, the main secretory product of the pineal gland, has been shown to be potentially effective in prevention of numerous types of neurodegenerative disorders in which free radical processes are involved. Homocysteine (Hcy), an independent risk factor for atherosclerosis, undergoes auto-oxidation and generates reactive oxygen species. The purpose of this study was to test whether intracerebroventricular (ICV) injection of Hcy leads to neural lipid peroxidation and also to investigate the protective effects of melatonin on the brain tissue from oxidative stress of Hcy. Adult male Wistar rats under anaesthesia were injected ICV with Hcy at a dose of 143 microg/kg. Melatonin was administered intraperitoneally to a group of rats for three consecutive days before Hcy injection. The rats were decapitated and brain tissues were removed and hippocampus, cortex and cerebellum were dissected. There was a significant development of oxidative stress as indicated by an increase in malondialdehyde in hippocampus, cortex and cerebellum of rats injected with Hcy, whereas melatonin prevented the elevation of lipid peroxidation. Furthermore, melatonin significantly increased glutathione levels and glutathione peroxidase activity in all brain regions. The present study demonstrates that Hcy, in high levels, may be a causal factor in generation of free radicals in the brain and it may be one of the mechanisms which cause neurodegeneration in elderly people. It also shows that melatonin could potentially be beneficial in prevention of neurodegeneration caused by hyperhomocysteinemia.
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PMID:Inhibitory effects of melatonin on neural lipid peroxidation induced by intracerebroventricularly administered homocysteine. 1248 70

Atherosclerosis is currently concerned as a chronic inflammatory process, which is response to an endothelial damage. Therapy of atherosclerosis should influence on various mechanisms. Substances which can prevent and treat this disorder are still being investigated. Melatonin exerts anti-inflammatory and antioxidative properties, which implies that it can be useful in the treatment of atherosclerosis. Melatonin neutralizes ROS (reactive oxygen species), increases antioxidative enzymes activities and glutathione levels, prevents electron leakage from mitochondrial respiratory chain, acts synergistically with vitamins C, E, and glutathione. Melatonin reduces levels of proinflammatory cytokines: IL-6, IL-12, TNF-alpha, IFN-gamma. In vivo studies and experiments on animals melatonin exerts beneficial effect on serum lipids, prevents LDL oxidation, decreases TBARS levels, increases total antioxidant capacity. However, some studies suggest that melatonin can exert atherogenic effects in animals. Clinical studies on patients who are in risk of atherosclerosis development are required.
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PMID:[Melatonin in the treatment of atherosclerosis]. 1804 43

This brief review considers some of the cardiac diseases and conditions where free radicals and related reactants are believed to be causative. The report also describes the beneficial actions of melatonin against oxidative cardiovascular disorders. Based on the data available, melatonin seems to have cardioprotective properties via its direct free radical scavenger and its indirect antioxidant activity. Melatonin efficiently interacts with various reactive oxygen and reactive nitrogen species (receptor independent actions) and it also upregulates antioxidant enzymes and downregulates pro-oxidant enzymes (receptor-dependent actions). Moreover, melatonin enters all cells and subcellular compartments and crosses morphophysiologic barriers. These findings have implications for the protective effects of melatonin against cardiac diseases induced by oxidative stress. Melatonin attenuates molecular and cellular damages resulting from cardiac ischemia/reperfusion in which destructive free radicals are involved. Anti-inflammatory and antioxidative properties of melatonin are also involved in the protection against a chronic vascular disease, atherosclerosis. The administration of melatonin, as a result of its antioxidant features, has been reported to reduce hypertension and cardiotoxicity induced by clinically used drugs. The results described herein help to clarify the beneficial effects of melatonin against these conditions and define the potential clinical applicability of melatonin in cardiovascular diseases.
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PMID:Cardiovascular diseases: protective effects of melatonin. 1807 44


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