Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Melatonin is a ubiquitous molecule and widely distributed in nature, with functional activity occurring in unicellular organisms, plants, fungi, and animals. Several studies have indicated that melatonin synthesis occurs in the retina of most vertebrates, including mammals. The retinal biosynthesis of melatonin and the mechanisms involved in the regulation of this process have been extensively studied. Circadian clocks located in the photoreceptors and retinal neurons regulate melatonin synthesis in the eye. Photoreceptors, dopaminergic amacrine neurons, and horizontal cells of the retina, corneal epithelium, stroma endothelium, and the sclera all have melatonin receptors, indicating a widespread ocular function for melatonin. In addition, melatonin is an effective antioxidant which scavenges free radicals and up-regulates several antioxidant enzymes. It also has a strong antiapoptotic signaling function, an effect that it exerts even during ischemia. Melatonin cytoprotective properties may have practical implications in the treatment of ocular diseases, like glaucoma and age-related macular degeneration.
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PMID:Role of melatonin in the eye and ocular dysfunctions. 1726 77

The pathophysiologic mechanisms leading to acute ischemic renal failure are not completely understood. Melatonin, a compound with well-known antioxidant properties, reduces IR-induced renal injury. The purpose of the present study was to investigate the changes in levels of tumor necrosis factor (TNF)-alpha, IL-beta, and IL-6 in postischemic reperfused renal tissue, and to determine whether the protective effect of melatonin is related the modulation of the production of these inflammatory molecules. Male Wistar albino rats were unilaterally nephrectomized and subjected to 1 hr of renal pedicle occlusion followed by 2 hr or 24 hr of reperfusion. Melatonin (10 mg/kg, i.p.) or vehicle was administrated at 10 min prior to ischemia. After 24 hr of the reperfusion, following decapitation, kidney samples were taken both for histologic examination and for the determination of malondialdehyde (MDA), myeloperoxidase (MPO) activity, total antioxidant capacity (TAC), total oxidative stress (TOS), creatinine, and blood urea nitrogen (BUN). These were measured in serum samples. TNF-alpha, IL-beta, and IL-6 were measured in kidney samples after 2 hr of reperfusion. IR caused a significant increase in renal MDA, MPO, TOS, creatinine, and BUN while decrease TAC without any change in TNF-alpha, IL-beta, and IL-6 levels. Melatonin treatment reduced the biochemical indices without any change in the cytokine levels and ameliorated histopathologic alterations induced by IR. The protective effect of melatonin on IR-induced renal injury is related to its antioxidant properties but not to proinflammatory cytokines.
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PMID:Melatonin protects from ischemia/reperfusion-induced renal injury in rats: this effect is not mediated by proinflammatory cytokines. 1764 95

Reactive oxygen species (ROS) were shown to contribute to the cellular damage induced by ischemia-reperfusion. The purpose of this study was to investigate and compare the efficiency of melatonin and vitamin E in the reduction of injury induced by ROS in a rat model of renal ischemia-reperfusion. Twenty-four Wistar-albino rats were divided into four groups. Rats in the Sham group were given saline 1 mL/kg, intraperitoneally (ip) 72 h, 48 h, 24 h, and 30 min before the sham operation. Rats in ischemia-reperfusion (IR), IR+Melatonin, and IR+Vitamin E groups were given saline (1 mL/kg), melatonin (10 mg/kg), and vitamin E (100 mg/kg) ip, respectively, 72 h, 48 h, 24 h, and 30 min before the ischemia for 60 min, followed by reperfusion for 60 min. The blood samples and kidney tissues of the rats were taken under anesthesia. Ischemia-reperfusion significantly increased urea, creatinine, and malondialdehyde (MDA) levels, and decreased superoxide dismutase (SOD) and catalase (CAT) activities. Histopathological findings of the IR group confirmed that there was renal impairment by cast formation and tubular necrosis in the tubular epithelium. In the IR+Melatonin group, while MDA levels significantly decreased, SOD activities increased. In the IR+Melatonin group, the level of tubular necrosis and cast formation are significantly decreased than those seen in the ischemia-reperfusion group. Melatonin in particular was effective to reverse hot ischemia of kidney by its antioxidant effects. These results may indicate that melatonin pretreatment protects against functional, biochemical, and morphological damage better than vitamin E in renal ischemia-reperfusion injury.
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PMID:The protective effects of melatonin and vitamin E against renal ischemia-reperfusion injury in rats. 1765 14

Acute aortic occlusion with subsequent ischemia-reperfusion of the lower extremities is well known to predispose to lung injury. Melatonin (MEL), a pineal hormone, is a free radical scavenger and an antioxidant. The purpose of this study was to assess the putative protective role of MEL in lung ischemia-reperfusion injury induced by aortic occlusion-reperfusion. Thirty-two rats were randomly allocated to four groups as follows: SHAM (Sham Laparotomy), SHAM+MEL, Aortic Ischemia Reperfusion (AIR) and AIR+MEL. Twenty mg/kg live weight MEL was given intraperitoneally 1 h prior to the experiment. An atraumatic microvascular clamp was placed across the infrarenal abdominal aorta (IAA) just after its origin from the aorta for 30 min. The microvascular clamp on IAA was removed and reperfused for 12 h. Lung tissues were assessed for malondialdehyde (MDA) level and myeloperoxidase (MPO) activity. MDA level and MPO activity, indicating the extent of lipid peroxidation and neutrophil infiltration of lung, respectively, significantly increased in AIR group when compared to SHAM and SHAM+MEL groups (P<0.05). Treating rat with MEL significantly decreased MDA levels as well as MPO activity in AIR+MEL group when compared to AIR group (P<0.05). In this study, exogenously administered MEL reduced lung injury after aortic occlusion reperfusion.
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PMID:The antioxidant effect of melatonin in lung injury after aortic occlusion-reperfusion. 1767 Mar

Melatonin reduces pyramidal neuronal death in the hippocampus and prevents the impairment of place learning and memory in the Morris water maze, otherwise occurring following global cerebral ischemia. The cytoarchitectonic characteristics of the hippocampal CA1 remaining pyramidal neurons in brains of rats submitted 120 days earlier to acute global cerebral ischemia (15-min four vessel occlusion, and melatonin 10mg/(kg h 6h), i.v. or vehicle administration) were compared to those of intact control rats in order to gain information concerning the neural substrate underlying preservation of hippocampal functioning. Hippocampi were processed according to a modification of the Golgi method. Dendritic bifurcations from pyramidal neurons in both the oriens-alveus and the striatum radiatum; as well as spine density and proportions of thin, stubby, mushroom-shaped, wide, ramified, and double spines in a 50 microm length segment of an oblique dendrite branching from the apical dendrite of the hippocampal CA1 remaining pyramidal neurons were evaluated. No impregnated CA1 pyramidal neurons were found in the ischemic-vehicle-treated rats. CA1 pyramidal neurons from ischemic-melatonin-treated rats showed stick-like and less ramified dendrites than those seen in intact control neurons. In addition, lesser density of spines, lower proportional density of thin spines, and higher proportional density of mushroom spines were counted in ischemic-melatonin-treated animals than those in the sinuously branched dendrites of the intact control group. These cytoarchitectural arrangements seem to be compatible with place learning and memory functions long after ischemia and melatonin neuroprotection.
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PMID:Long-term study of dendritic spines from hippocampal CA1 pyramidal cells, after neuroprotective melatonin treatment following global cerebral ischemia in rats. 1770 55

Due to its small size and amphiphilic nature, indoleamine melatonin is able to reach all cell compartments quickly. The highest Melatonin concentrations are to be found in the mitochondria, and cytochrome c (cyt c) represents a Melatonin target, since Melatonin is able to oxidise organic molecules in the presence of physiological amounts of hydrogen peroxide (H(2)O(2)). The mitochondrial cyt c-mediated oxidation of melatonin depends on oxoferrylheme in two one-electron steps. The protective effects of Melatonin against cardiac ischemia/reperfusion (I/R)-induced mitochondrial oxidative damage are well documented as an antioxidant agent which prevents and/or modulates the production of reactive oxygen species (ROS) responsible for the reperfusion injury. On the basis of our previous studies on ischemia/reperfusion (I/R) in human cardiomyocytes it has become clear that severe hypoxic and ischemic stimuli evoke a mitochondrial response in terms of the functional adaptation of cyt c oxidase (COX) to oxygen altered availability. Most, if not all, data are compatible with a mechanism of adaptation, in which nitric oxide (NO) generation is now considered as the major player. The NO-induced COX inhibition represents a key point in ischemia-induced, adaptive changes, since a balanced oxidative metabolism between lower O(2) concentrations and COX catalytic capacity down-regulation is thus obtained. This mechanism is a limiting factor in the cardiac ischemia-induced ROS mitochondrial generation. In the light of this concept and if we consider melatonin to be strongly active in cyt c up-regulation, it is obvious that the use of this molecule in the course of cardiac ischemia could be deleterious. On the contrary, the prompt restoration of the coronary blood flow is inexorably associated with the so-called "reperfusion syndrome" and/or with a condition of myocardial stunning. These phenomena are strictly linked to the aforementioned ischemia-induced cyt c adaptive changes, for the reason that a primary imbalance is induced between the persistent down-regulated enzymatic oxidative capacity and mitochondrial oxygen gradients are rapidly restored. This leads to a massive ROS neo-generation, which evokes well-known cellular disorders. In this scenario the melatonin treatment could play a pivotal role in terms of a cyt c up-regulating agent, crucial for counteracting most, if not all the biochemical and molecular phenomena, on which the clinical symptoms proper of myocardial reperfusion syndrome are based.
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PMID:Melatonin in cardiac ischemia/reperfusion-induced mitochondrial adaptive changes. 1789 56

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

Melatonin is a recognized antioxidant with high potential as a protective agent in many conditions related to oxidative stress such as neurodegenerative diseases, ischemia/reperfusion syndromes, sepsis and aging. These processes may be favorably affected by melatonin through its radical scavenging properties and/or antiapoptotic activity. Also, there is increasing evidence that these effects of melatonin could be relevant in keratinocytes, the main cell population of the skin where it would contribute to protection against damage induced by ultraviolet radiation (UVR). We therefore investigated the kinetics of UVR-induced apoptosis in cultured keratinocytes characterizing the morphological and mitochondrial changes, the caspases-dependent apoptotic pathways and involvement of poly(ADP-ribose) polymerase (PARP) activation as well as the protective effects of melatonin. When irradiated with UVB radiation (50 mJ/cm(2)), melatonin treated, cultured keratinocytes were more confluent, showed less cell blebbing, more uniform shape and less nuclear condensation as compared to irradiated, nonmelatonin-treated controls. Preincubation with melatonin also led to normalization of the decreased UVR-induced mitochondrial membrane potential. These melatonin effects were followed by suppression of the activation of mitochondrial pathway-related initiator caspase 9 (casp-9), but not of death receptor-dependent casp-8 between 24 and 48 hr after UVR exposure. Melatonin down-regulated effector caspases (casp-3/casp-7) at 24-48 hr post-UV irradiation and reduced PARP activation at 24 hr. Thus, melatonin is particularly active in UV-irradiated keratinocytes maintaining the mitochondrial membrane potential, inhibiting the consecutive activation of the intrinsic apoptotic pathway and reducing PARP activation. In conclusion, these data provide detailed evidence for specific antiapoptotic mechanisms of melatonin in UVR-induced damage of human keratinocytes.
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PMID:Melatonin maintains mitochondrial membrane potential and attenuates activation of initiator (casp-9) and effector caspases (casp-3/casp-7) and PARP in UVR-exposed HaCaT keratinocytes. 1808 47

Melatonin and its metabolites are potent antioxidants by virtue of their ability to scavenge both oxygen-based and nitrogen-based radicals and intermediates but also as a consequence of their ability to stimulate the activity of antioxidative enzymes. Melatonin also prevents electron leakage from the mitochondrial electron transport chain thereby diminishing free radical generation; this process is referred to as radical avoidance. The fact that melatonin and its metabolites are all efficient radical scavengers indicates that melatonin is a precursor molecule for a variety of intracellular reducing agents. In specific reference to the brain, melatonin also has an advantage over some other antioxidants given that it readily passes through the blood-brain-barrier. This, coupled with the fact that it and its by-products are particularly efficient detoxifiers of reactive species, make these molecules of major importance in protecting the brain from oxidative/nitrosative abuse. This review summarizes the literature on two brain-related situations, i.e., traumatic brain and spinal cord injury and ischemia/reperfusion, and the neurodegenerative disease, amyotrophic lateral sclerosis, where melatonin has been shown to have efficacy in abating neural damage. These, however, are not the only age-associated neurodegenerative states where melatonin has been found to be protective.
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PMID:Melatonin defeats neurally-derived free radicals and reduces the associated neuromorphological and neurobehavioral damage. 1821 98

Melatonin, the main product of the pineal gland, is also released from the gastrointestinal endocrine-neurocrine (EE) cells. The concentrations of melatonin produced in the gut exceeds that originating from central nervous system. In spite of the presence of melatonin receptors in the pancreatic tissue little is known about the role of this indole in the pancreas. Our experimental studies have shown that exogenous melatonin, as well as this produced endogenously from its precursor; L-tryptophan, strongly stimulates pancreatic amylase secretion when given intraperitoneally, or into the gut lumen. This was accompanied by significant increases of CCK plasma level. Above pancreatostimulatory effects of luminal administration of melatonin, were completely reversed by bilateral vagotomy, capsaicin deactivation of sensory nerves or pretreatment of the rats with CCK1 receptor antagonist; tarazepide as well as serotonin antagonist; ketanserin. Melatonin, as well as its precursor; L-tryptophan, effectively protects the pancreas against the damage induced by caerulein overstimulation or ischemia/reperfusion. The beneficial effects of melatonin or L-tryptophan on acute pancreatitis could be related to the ability of melatonin to scavenge the free radicals, to activate antioxidative enzymes and to modulate the cytokine production.
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PMID:Melatonin as modulator of pancreatic enzyme secretion and pancreatoprotector. 1821 1


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