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1.
The oxidant/antioxidant network: role of melatonin   总被引:13,自引:0,他引:13  
Melatonin is now known to be a multifaceted free radical scavenger and antioxidant. It detoxifies a variety of free radicals and reactive oxygen intermediates including the hydroxyl radical, peroxynitrite anion, singlet oxygen and nitric oxide. Additionally, it reportedly stimulates several antioxidative enzymes including glutathione peroxidase, glutathione reductase, glucose-6-phosphate dehydrogenase and superoxide dismutase; conversely, it inhibits a prooxidative enzyme, nitric oxide synthase. Melatonin also crosses all morphophysiological barriers, e.g., the blood-brain barrier, placenta, and distributes throughout the cell; these features increase the efficacy of melatonin as an antioxidant. Melatonin has been shown to markedly protect both membrane lipids and nuclear DNA from oxidative damage. In every experimental model in which melatonin has been tested, it has been found to resist macromolecular damage and the associated dysfunction associated with free radicals.  相似文献   

2.
Melatonin oxidative stress and neurodegenerative diseases   总被引:3,自引:0,他引:3  
Oxidative Stress is implicated as one of the primary factors that contribute to the development of neurodegenerative diseases like Alzheimer's Disease, Parkinsonism and neurological conditions like epileptic seizures, stroke, brain damage, neurotrauma etc. The increased formation and release of oxygen free radicals coupled with the rather low antioxidative potential of the central nervous system are the major reasons that account for the enhanced oxidative stress seen in neuronal cells. In addition to this, brain is also enriched with polyunsaturated fatty acids that render neuronal cells easily vulnerable to oxidative attack. The fact that there is increased incidence of neurodegenerative disorders in aged individuals, has prompted many investigators to search for a common factor whose progressive decline with increase in age could account for increased oxidative stress resulting in senescence and age associated degenerative diseases. Since melatonin, the hormone secreted from the pineal gland has a remarkable anti-oxidant property and whose rate of production declines with increase in age, has prompted many to suggest that this hormone plays a crucial role in the genesis of neurodegenerative diseases. Melatonin cannot only scavenges oxygen free radicals like super oxide radical (O2-), hydroxyl radical (*OH), peroxyl radical (LOO*) and peroxynitrite anion (ONOO-), but can also enhance the antioxidative potential of the cell by stimulating the synthesis of antioxidative enzymes like super oxide dismutase (SOD), glutathione peroxidase (GPX), and also the enzymes that are involved in the synthesis of glutathione. In many instances, melatonin increases the expression of m RNA's of the antioxidative enzymes. Melatonin administration has been shown to be effective in counteracting the neurodegenerative conditions both in experimental models of neurodegenerative diseases and in patients suffering from such diseases. A disturbance of melatonin rhythm and secretion also has been noted in patients suffering from certain neurodegenerative diseases. From all these, it is evident that melatonin has a neuroprotective role.  相似文献   

3.
Melatonin is a potent endogenous free radical scavenger, actions that are independent of its many receptor-mediated effects. In the last several years, hundreds of publications have confirmed that melatonin is a broad-spectrum antioxidant. Melatonin has been reported to scavenge hydrogen peroxide (H(2)O(2)), hydroxyl radical (HO(.)), nitric oxide (NO(.)), peroxynitrite anion (ONOO(-)), hypochlorous acid (HOCl), singlet oxygen ((1)O(2)), superoxide anion (O(2)(-).) and peroxyl radical (LOO(.)), although the validity of its ability to scavenge O(2)(-). and LOO(.) is debatable. Regardless of the radicals scavenged, melatonin prevents oxidative damage at the level of cells, tissues, organs and organisms. The antioxidative mechanisms of melatonin seem different from classical antioxidants such as vitamin C, vitamin E and glutathione. As electron donors, classical antioxidants undergo redox cycling; thus, they have the potential to promote oxidation as well as prevent it. Melatonin, as an electron-rich molecule, may interact with free radicals via an additive reaction to form several stable end-products which are excreted in the urine. Melatonin does not undergo redox cycling and, thus, does not promote oxidation as shown under a variety of experimental conditions. From this point of view, melatonin can be considered a suicidal or terminal antioxidant which distinguishes it from the opportunistic antioxidants. Interestingly, the ability of melatonin to scavenge free radicals is not in a ratio of mole to mole. Indeed, one melatonin molecule scavenges two HO. Also, its secondary and tertiary metabolites, for example, N(1)-acetyl-N(2)-formyl-5-methoxykynuramine, N-acetyl-5-methoxykynuramine and 6-hydroxymelatonin, which are believed to be generated when melatonin interacts with free radicals, are also regarded as effective free radical scavengers. The continuous free radical scavenging potential of the original molecule (melatonin) and its metabolites may be defined as a scavenging cascade reaction. Melatonin also synergizes with vitamin C, vitamin E and glutathione in the scavenging of free radicals. Melatonin has been detected in vegetables, fruits and a variety of herbs. In some plants, especially in flowers and seeds (the reproductive organs which are most vulnerable to oxidative insults), melatonin concentrations are several orders of magnitude higher than measured in the blood of vertebrates. Melatonin in plants not only provides an alternative exogenous source of melatonin for herbivores but also suggests that melatonin may be an important antioxidant in plants which protects them from a hostile environment that includes extreme heat, cold and pollution, all of which generate free radicals.  相似文献   

4.
Melatonin plays several important physiological functions in mammals, such as immune enhancement and regulation of dark-light signal transduction. Melatonin is also known to be an endogenous free radical scavenger and an efficient antioxidant. It detoxifies a variety of free radicals and reactive oxygen intermediates, including the hydroxyl radical, singlet oxygen and nitric oxide. These radicals participate in many diseases, for example diabetes. This study determined the effect of melatonin on the antioxidant enzymes: superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), and the level of glutathione (GSH) in human diabetic (C2 line) skin fibroblasts. Confluent monolayers of control (S2 line) and diabetic (C2 line) skin fibroblasts were incubated with different concentrations of melatonin: 10, 50, 100 and 1000 micromol/l at 37 degrees C for 24 h. Next, the GSH level and SOD, CAT and GPx activities were measured colorimetrically. The activities of the antioxidant enzymes and the GSH level were lower in diabetic skin fibroblasts than in the control S2 line. Concentrations of melatonin of 100 and 1000 micromol/l caused a significant increase in the enzymes' activities and GSH level.  相似文献   

5.
Melatonin secreted by the pineal gland acts as a free radical scavenger besides its role as a hormonal signaling agent. It detoxifies a variety of free radicals and reactive oxygen intermediates including hydroxyl radical, peroxynitrite anion and singlet oxygen. Ascorbic acid (Vitamin C), a water soluble vitamin, is a naturally occurring antioxidant and cofactor in various enzymes. Protein carbonyls are formed as a consequence of the oxidative modification of proteins by reactive oxygen species. Oxidative modification alters the function of protein and is thought to play an important role in the decline of cellular functions during aging. In the present study, the effect of melatonin and ascorbic acid on age-related carbonyl content of cerebral hemispheres in mice was investigated. Protein carbonyls of cerebral hemispheres have been found to be significantly higher in 18-month-old mice as compared to 1-month old mice. Administration of a single dose of melatonin (10 mg/kg body weight) and ascorbic acid (10 mg/kg body weight) intraperitoneally for three consecutive days decreases the carbonyl content in 1- and 18-month-old mice significantly. The present study thus suggests that the formation of protein carbonyls in the cerebral hemispheres of the aging mice can be prevented by the antioxidative effects of melatonin and ascorbic acid that could in turn be beneficial in having health benefits from age-related neurodegenerative diseases.  相似文献   

6.
This brief resume enumerates the multiple actions of melatonin as an antioxidant. This indoleamine is produced in the vertebrate pineal gland, the retina and possibly some other organs. Additionally, however, it is found in invertebrates, bacteria, unicellular organisms as well as in plants, all of which do not have a pineal gland. Melatonin's functions as an antioxidant include: a), direct free radical scavenging, b), stimulation of antioxidative enzymes, c), increasing the efficiency of mitochondrial oxidative phosphorylation and reducing electron leakage (thereby lowering free radical generation), and 3), augmenting the efficiency of other antioxidants. There may be other functions of melatonin, yet undiscovered, which enhance its ability to protect against molecular damage by oxygen and nitrogen-based toxic reactants. Numerous in vitro and in vivo studies have documented the ability of both physiological and pharmacological concentrations to melatonin to protect against free radical destruction. Furthermore, clinical tests utilizing melatonin have proven highly successful; because of the positive outcomes of these studies, melatonin's use in disease states and processes where free radical damage is involved should be increased.  相似文献   

7.
Melatonin has been shown to play a role in antioxidative defence. We therefore studied its effect on oxidative damage to the rat cerebral cortex evoked by painful stimulation and immobilization-induced stress. Moreover, the effect of melatonin on chronic pain perception was examined. Rats were injected with either a high dose of melatonin (100 mg/kg i.p.) or a vehicle for five days and were subjected to painful stimulation or immobilization stress 30 min after the treatment. To determine the degree of oxidative stress, the levels of free radicals, thiobarbituric acid reactive substances (TBARS) as indicators of lipid peroxidation and glutathione peroxidase (GSHPx) were estimated in somatosensory cortex. Pain perception was measured by the tail-flick and plantar test. Melatonin reduced the level of TBARS previously increased by painful stimulation. Melatonin also exhibited a slight analgesic effect in those animals exposed to painful stimulation but its role in free radical scavenging did not contribute to this effect.  相似文献   

8.
An enormous amount of data has been published in recent years demonstrating melatonin's defensive role against toxic free radicals. In the present study, we examined the role of melatonin as an antioxidant against the effect of continuous light exposure. Rats were divided into three groups. Control rats (group A) were kept under natural conditions whereas other group of rats (group B and C) were exposed to constant light for inhibition of melatonin secretion by the pineal gland. Group C rats also received melatonin via s.c. injection (1 mg x kg(- 1) body weight x day(- 1)). At the end of experiment, all animals were sacrificied by decapitation, serum and tissue samples were removed for determination of malondialdehyde (MDA), a product of lipid peroxidation, conjugated dienes levels and glutathione peroxidase (GSH-Px) activity levels. It was found that lipid peroxidation was increased in the rats which were exposed to constant light. Melatonin injection caused a decrease in lipid peroxidation, especially in the brain. In addition, melatonin application resulted in increased GSH-Px activity, which has an antioxidant effect. Thus, melatonin is not only a direct scavenger of toxic radicals, but also stimulates the antioxidative enzyme GSH-Px activity to detoxify hydroxyl radical produced by constant light exposure.  相似文献   

9.
The fact that the full extent of the function of the pineal gland has not yet been elucidated, has stimulated melatonin research worldwide. This review introduces melatonin’s mechanism of action, direct and indirect antioxidant actions as well as the antioxidant properties of its metabolites, 6-hydroxymelatonin (6-OHM) and N-acetyl-N-formyl-5-methoxykynurenamine (AFMK). At present the mechanism of action is proposed to be receptor-, protein- and nonprotein-mediated. From its popular role in the treatment of jetlag, melatonin is now implicated in the reduction of oxidative stess, both as a free radical scavenger and antioxidant. Melatonin’s direct scavenging action in respect of the following will be discussed: superoxide anions, hydrogen peroxide, hydroxyl radicals, singlet oxygen, peroxy radicals and nitric oxide/peroxy nitrite anions. In addition melatonin also possesses indirect antioxidant activity and the role of its metabolites, AFMK and 6-OHM will be presented. It is these free radical scavenging and antioxidant properties of melatonin that has shifted the focus from that of merely strengthening circadian rhythms to that of neuroprotectant: a new place in therapy.  相似文献   

10.
The concentrations of ROS were measured in samples of the sensorimotor brain cortex and in the rat blood. We measured the following parameters: The six lines spectra, nitroxide radical, free hydroxyl radical and singleton oxygen. Their concentration was measured under physiological conditions, after the nociceptive stimulation and after the application of melatonin, both in normal and stimulated animals. In the brain cortex only the singleton oxygen decreased after the nociceptive stimulation, whereas the nitroxide radicals and six lines spectra increased. The free hydroxyl radicals did not change significantly. In the blood serum the six lines spectra and nitroxide radical increased, the concentration of the free hydroxyl radicals did not change. Melatonin increased both the hydroxyl and nitroxide radicals. There was a non-significant decrease in the six lines spectra. The estimation of ROS can be used as a tool for detecting metabolic changes and the consequences of different environmental influences, in our case the influence of nociception and melatonin.  相似文献   

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