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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We assessed the effects of melatonin, a powerful scavenger of oxygen free radicals, on ischemia/reperfusion-induced oxidative damage to mitochondria in the rat placenta. In Wistar rats at day 19 of pregnancy, feto-placental ischemia was induced by occluding both utero-ovarian arteries for 20 min. Reperfusion was achieved by releasing the occlusion and restoring circulation for 30 min. Melatonin solution or the vehicle alone was injected intraperitoneally at dose of 10 mg/kg 1 hr before occlusion. Sham-ischemic animals were treated with vehicle. Each group consisted of 10 pregnant rats. We measured placental mitochondrial respiratory control index (RCI; a marker of mitochondrial respiratory activity), the ratio of the added adenosine 5-diphosphate (ADP) concentration to consumption of oxygen during state 3 respiration (ADP/O), and the concentration of thiobarbituric acid reactive substances (TBARS) in each group. RCI and ADP/O were significantly decreased by ischemia/reperfusion, while TBARS were increased. Melatonin prevented these changes. These results indicate that exogenous melatonin protects against ischemia/reperfusion-induced oxidative damage to mitochondria in rat placenta. Melatonin could be useful in treating preeclampsia and possibly other clinical states involving excess free radical production, such as fetal growth restriction and fetal hypoxia.
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PMID:Melatonin protects against oxidative mitochondrial damage induced in rat placenta by ischemia and reperfusion. 1155 74

Free radicals have been implicated in neuronal injury during ischemia reperfusion in stroke. Therefore, in the present study, melatonin, a potent antioxidant, was studied in male Wistar rats subjected to 2 h of transient middle cerebral artery occlusion. Melatonin (10, 20 and 40 mg/kg i.p.) was administered four times in an animal at the time of middle cerebral artery occlusion, 1 h after middle cerebral artery occlusion, at the time of reperfusion and 1 h after reperfusion. Two hours after reperfusion, rats were euthanized for estimation of oxidative stress markers (malondialdehyde and reduced glutathione). The doses of 20 and 40 mg/kg of melatonin significantly attenuated the raised level of malondialdehyde (287+/-28, 279+/-52 nmol/g wet tissue, respectively) as compared to the levels (420+/-61 nmol/g wet tissue) in vehicle-treated middle cerebral artery-occluded rats. There was an insignificant change in levels of reduced glutathione at these doses (95+/-42, 88.7+/-36 microg/g wet tissue, respectively) as compared to those in the vehicle-treated middle cerebral artery-occluded rats (108.21+/-21 microg/g wet tissue). However, there was an insignificant difference between 20 and 40 mg/kg treated rats. Therefore, the dose of 20 mg/kg i.p. was used to evaluate the neuroprotective effect by using diffusion-weighted imaging (30 min after reperfusion), assessing the neurological deficit (24 h after middle cerebral artery occlusion) and estimating oxidative stress markers (72 h after middle cerebral artery occlusion). In the 20 mg/kg melatonin-treated group, percent ischemic lesion volume on diffusion-weighted imaging was significantly attenuated (9.8+/-3.9) as compared to that in the vehicle-treated group (21.4+/-4.7). The neurological deficit was significantly improved in the melatonin group (1.8+/-0.06) as compared to that in the vehicle-treated (2.9+/-0.38) group. The level of malondialdehyde (321.4+/-31 nmol/g wet tissue) and reduced glutathione (142.6+/-13 microg/g wet tissue) in the melatonin-treated group was also significantly decreased as compared to the level of malondialdehyde (623+/-22 nmol/g wet tissue) and reduced glutathione (226.6+/-19 microg/wet tissue) in the vehicle-treated group. The present study indicates that melatonin has a neuroprotective action in focal ischemia, which may be attributed to its antioxidant property.
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PMID:Effect of melatonin on ischemia reperfusion injury induced by middle cerebral artery occlusion in rats. 1167 35

Effects of melatonin on various manifestations of ischemia/reperfusion injury of the isolated perfused rat heart were examined. Ischemia- and reperfusion-induced ventricular arrhythmias were studied under constant flow in hearts subjected to 10, 15 or 25 min of regional ischemia (induced by LAD coronary artery occlusion) and 10-min reperfusion. Melatonin was added to the perfusion medium 5 min before ischemia at concentrations of 10 micromol/l or 10 nmol/l and was present throughout the experiment. Recovery of the contractile function was evaluated under constant perfusion pressure after 20-min global ischemia followed by 40-min reperfusion. Hearts were treated with melatonin at a high concentration (10 micromol/l) either 5 min before ischemia only (M1) or 5 min before ischemia and during reperfusion (M2) or only during reperfusion (M3). At the high concentration, melatonin significantly reduced the incidence of reperfusion-induced ventricular fibrillation and decreased arrhythmia score (10% and 2.2+/-0.3, respectively) as compared with the corresponding untreated group (62% and 4.1+/-0.3, respectively); the low concentration had no effect. This substance did not affect the incidence and severity of ischemic arrhythmias. Melatonin (M2, M3) significantly improved the recovery of the contractile function as compared with the untreated group; this protection did not appear if melatonin was absent in the medium during reperfusion (Ml). Our results show that melatonin, in accordance with its potent antioxidant properties, effectively protects the rat heart against injury associated with reperfusion. It appears unlikely that melatonin is cardioprotective at physiological concentrations.
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PMID:Effects of melatonin on ischemia and reperfusion injury of the rat heart. 1208 78

Endogenously produced metabolites of ground state oxygen are highly reactive and destructive to intracellular and extracellular molecules. The resulting damage, referred to as oxidative stress, leads to molecular and cellular dysfunction. The destruction of essential macromolecules by oxygen-based reactants is the basis of some diseases and is believed to be involved in the processes of aging. Free radical scavengers and antioxidants neutralize and/or metabolically remove reactive species from cells before they carry out their destructive activities. Melatonin is a highly ubiquitous direct free radical scavenger and indirect antioxidant. This brief report summarizes the interactions of melatonin with reactive species and identifies the resulting products. The paper also defines the melatonin antioxidant cascade wherein not only melatonin but at least one of the products, i.e., N(1)-acetyl-N(2)-formyl-5-methoxykynuramine, formed as a result of melatonin scavenging hydrogen peroxide is also a potent scavenger. The review summarizes the data which shows that melatonin is not only a pharmacologically useful free radical scavenger but that it functions in this capacity at physiological concentrations as well. Finally, this report identifies high oxidative stress situations in humans where melatonin has proven effective in reducing the severity of the disease state. In the last decade there have been hundreds of publications documenting melatonin's protective actions against a vast array of conditions, e.g., ischemia/reperfusion injury, toxin exposure, lipopolysaccharide exposure, etc., where free radical damage is a component of the condition.
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PMID:Melatonin: reducing molecular pathology and dysfunction due to free radicals and associated reactants. 1201 43

Oxygen free radicals are considered to be important components involved in the pathophysiological tissue alterations observed during ischemia-reperfusion (I/R). In this study, we investigated the putative protective effects of melatonin treatment on renal I/R injury. Wistar albino rats were unilaterally nephrectomized and subjected to 45 min of renal pedicle occlusion followed by 1, 3, 6, 24, 48 hr or 1 wk of reperfusion. Melatonin (10 mg/kg, s.c.) or vehicle was administered twice, 15 min prior to ischemia and immediately before the reperfusion period. At the end of the reperfusion periods, rats were decapitated. Kidney samples were taken for histological examination or the determination of renal malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity and protein oxidation (PO). Serum creatinine and blood urea nitrogen (BUN) concentrations were measured for the evaluation of renal function. The results revealed that I/R induced nephrotoxicity, as evidenced by increases in BUN and creatinine levels at each time point, was reversed by melatonin treatment. The decrease in GSH and increases in MDA, MPO and PO induced by I/R indicated that renal injury involves free radical formation. As melatonin administration reversed these oxidant responses, improved renal function and microscopic damage, it seems likely that melatonin protects kidney tissue against oxidative damage.
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PMID:The protective effect of melatonin on renal ischemia-reperfusion injury in the rat. 1207 69

Cardiac arrhythmias during ischemia-reperfusion (I/R) are believed to be related to free radicals generated in the heart especially during the period of reperfusion. The pineal secretory product, melatonin, is known to be a potent free radical scavenger and its pharmacological concentrations have been shown to reduce the I/R-induced arrhythmias in isolated rat hearts. However, the physiological role of melatonin in the prevention of these arrhythmias is unknown. Rats were pinealectomized (Px) or sham-operated (non-Px) (control) 2 months before the I/R studies. To produce arrhythmias, left main coronary artery was occluded for 7 min, followed by 7 min reperfusion, in anesthetized rats. The incidence of mortality resulted from irreversible ventricular fibrillation (VF) was found significantly higher in the Px rats (63%) than in the control group (25%). Melatonin administration (0.4 mg/kg, either before ischemia or reperfusion) to Px rats significantly reduced the incidence of total (irreversible plus reversible) and irreversible VF and returned them to control values. On the other hand, melatonin administration (0.4 and 4 mg/kg) to non-Px rats failed to attenuate the I/R arrhythmias, significantly. These results suggest that physiological melatonin concentrations are important to reduce the I/R-induced VF and mortality, while pharmacological concentrations of melatonin did not increase its beneficial effect on these arrhythmias. As melatonin levels have been reported to decrease with age, melatonin replacement therapy may attenuate the incidence of sudden cardiac death especially in older patients.
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PMID:Effects of physiological and pharmacological concentrations of melatonin on ischemia-reperfusion arrhythmias in rats: can the incidence of sudden cardiac death be reduced? 1207 4

In the present study, double fluorescence staining combined with confocal laser scanning microscopy analysis were used to examine the effects of melatonin on ischemia-induced neuronal DNA strand breaks and its possible mechanisms in a transient middle cerebral artery (MCA) occlusion model. Results showed that melatonin dose-dependently reduced infarct areas and decreased both DNA double and single strand breaks (DSB and SSB) and enhanced cell viability in the peri-ischemic brain regions. Furthermore, Bcl-2 induction in the ischemic brain was further enhanced by melatonin treatment. Double staining analysis indicated that the cells costained for Bcl-2 and TdT-mediated-deoxyuridine triphosphate (dUTP) nick-end labeling (TUNEL), a DSB marker, displayed a relative regular morphology compared with the cells only stained with TUNEL. Transient ischemia induced an expression of excision repair cross-complementing factor 6 (ERCC6) mRNA, a gene essential for the preferential repair of nuclear excision repair, in the injured neurons. Double labeling showed that ERCC6 only co-localized with proliferating cell nuclear antigen (PCNA), a member of the nuclear excision repair complex, but not with TUNEL. Melatonin further and statistical significantly up-regulated ERCC6 mRNA expression in the peri-ischemic region of rat brains. The results suggest that neuroprotection by melatonin against ischemic injury may be related to modulation of apoptosis and DNA repair capacity.
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PMID:Neuroprotection by melatonin against ischemic neuronal injury associated with modulation of DNA damage and repair in the rat following a transient cerebral ischemia. 1212 85

The production of oxygen free radicals has been strongly implicated as an important pathophysiological mechanism mediating myocardial ischemia/reperfusion (I/R) injury. Various antioxidants have cardioprotective effects. Melatonin, an indoleamine synthesized by the pineal gland, is a potent antioxidant and a direct free radical scavenger. This is the first in vivo study to evaluate the effect of melatonin (0.5, 1.0, and 5.0 mg/kg, i.v. bolus) on myocardial I/R injury in anesthetized Sprague-Dawley rats. Results demonstrate that pretreatment with intermediate or high doses of melatonin (1.0 and 5.0 mg/kg) at 10 min before left coronary artery occlusion markedly suppressed ventricular tachycardia (VT) and ventricular fibrillation (VF), while reducing the total number of premature ventricular contractions and total duration of VT and VF that occurred during the 45-min ischemic period. Pretreatment with melatonin dramatically improved survival rate of rats when compared with the I/R-only group. After 1-hr reperfusion, melatonin caused a significant reduction in infarct size when compared with I/R-only group. Meanwhile, pretreatment with melatonin (1.0 mg/kg) significantly reduced superoxide anion production and myeloperoxidase activity; the latter is an index of neutrophil infiltration in the ischemic myocardium. Additionally, pretreatment with melatonin (1.0 and 5.0 mg/kg) significantly attenuated ventricular arrhythmias and mortality elicited by reperfusion following 5-min ischemia. In conclusion, melatonin suppresses ischemia- and reperfusion-induced ventricular arrhythmias and reduces infarct size resulting from I/R injury. The pronounced cardioprotective activity of melatonin may be mediated by its antioxidant activity and by its capacity for neutrophil inhibition in myocardial I/R.
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PMID:Protective effects of melatonin on myocardial ischemia/reperfusion injury in vivo. 1215 40

Myocardial ischemia-reperfusion (I/R) represents a clinically relevant problem associated with thrombolysis, angioplasty and coronary bypass surgery. I/R injury is believed to be a consequence of free radical generation in the heart especially during the period of reperfusion. The pineal secretory product, melatonin, is known to be a potent free radical scavenger and pharmacological concentrations have been shown to reduce the I/R-induced cardiac damage in isolated rat hearts. However, the physiological role of melatonin in the prevention of this damage is unknown. Rats were pinealectomized or sham-operated (control) 2 months before the I/R studies. To produce cardiac damage, the left main coronary artery was occluded for 30 min, followed by 120 min reperfusion, in anesthetized rats. Infarct size, expressed as the percentage of the risk zone, was found significantly higher in pinealectomized rats (49+/-3.4%) than in the control group (34+/-3.6%). Melatonin administration (4 mg/kg, either before ischemia or reperfusion) to pinealectomized rats significantly reduced the infarct size values and returned them to the control values. On the other hand, melatonin administration (4 mg/kg) to sham-operated rats failed to attenuate significantly the I/R-induced infarct size. These results suggest that physiological melatonin concentrations are important in reducing the I/R-induced myocyte damage, while pharmacological concentrations of melatonin did not add to the beneficial effect. As melatonin levels have been reported to decrease with age, melatonin replacement therapy may attenuate I/R-induced myocardial injury, especially in older patients.
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PMID:Myocardial ischemia-reperfusion in rats: reduction of infarct size by either supplemental physiological or pharmacological doses of melatonin. 1239 May 6

Reduction of cerebral edema, an early symptom of ischemia, is one of the most important remedies for reducing subsequent chronic neural damage in stroke. Melatonin, a metabolite of tryptophan released from the pineal gland, has been found to be effective against neurotoxicity in vitro. The present study was aimed to demonstrate the effectiveness of melatonin in vivo in reducing ischemia-induced edema using magnetic resonance imaging (MRI). Rats were subjected to middle cerebral artery (MCA) occlusion/reperfusion surgery. Melatonin was administered twice (6.0 mg/kg, p.o.): just prior to 1 h MCA occlusion and 1 day after the surgery. T2-weighted multislice spin-echo images were acquired 1 day after the surgery. Increases in T2-weighted signals in ischemic sites of the brain were clearly observed after MCA occlusion. The signal increase was found mainly in the striatum and in the cerebral cortex in saline-treated control rats. In the melatonin-treated group, the total volume of cerebral edema was reduced by 45.3% compared to control group (P < 0.01). The protective effect of melatonin against cerebral edema was more clearly observed in the cerebral cortex (reduced by 56.1%, P < 0.01), while the reduction of edema volume in the striatum was weak (reduced by 23.0%). The present MRI study clearly demonstrated that melatonin is effective in reducing edema formation in ischemic animals in vivo, especially in the cerebral cortex. Melatonin may be highly useful in preventing cortical dysfunctions such as motor, sensory, memory, and psychological impairments.
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PMID:Melatonin reduces cerebral edema formation caused by transient forebrain ischemia in rats. 1246 99


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