Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P30044 (antioxidant enzyme)
 8,037 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The protective effect of melatonin on lipopolysaccharide (LPS)-induced oxidative damage in phenobarbital-treated rats was measured using the following parameters: changes in total glutathione (tGSH) concentration, levels of oxidized glutathione (GSSG), the activity of the antioxidant enzyme glutathione peroxidase (GSH-PX) in both brain and liver, and the content of cytochrome P450 reductase in liver. Melatonin was injected intraperitoneally (ip, 4mg/kg BW) every hour for 4 h after LPS administration; control animals received 4 injections of diluent. LPS was given (ip, 4 mg/kg) 6 h before the animals were killed. Prior to the LPS injection, animals were pretreated with phenobarbital (PB), a stimulator of cytochrome P450 reductase, at a dose 80 mg/kg BW ip for 3 consecutive days. One group of animals received LPS together with Nw-nitro-L-arginine methyl ester (L-NAME), a blocker of nitric oxide synthase (NOS) (for 4 days given in drinking water at a concentration of 50 mM). In liver, PB, in all groups, increased significantly both the concentration of tGSH and the activity of GSH-PX. When the animals were injected with LPS the levels of tGSH and GSSG were significantly higher compared with other groups while melatonin and L-NAME significantly enhanced tGSH when compared with that in the LPS-treated rats. Melatonin alone reduced GSSG levels and enhanced the activity of GSH-PX in LPS-treated animals. Additionally, LPS diminished the content of cytochrome P450 reductase with this effect being largely prevented by L-NAME administration. Melatonin did not change the content of P450 either in PB- or LPS-treated animals.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Melatonin administration prevents lipopolysaccharide-induced oxidative damage in phenobarbital-treated animals. 759 65

This study was carried out in order to determine the role of melatonin in preventing lipid peroxidation due to acute ethanol intoxication. Male Wistar Albino rats, 2.5-3 months old, were divided into two groups. Melatonin (in 1% ethanol, 2 mg kg-1 body weight) was given intraperitoneally (i.p.) for 21 days to experimental rats whereas controls received 1% ethanol only. On day 21, 6 g kg-1 body weight ethanol was injected to half of the animals in each group and the remainder were kept as corresponding controls. Animals were killed 5 h after ethanol injection. Malondialdehyde (MDA), reduced glutathione (GSH) and the antioxidant enzyme activities (superoxide dismutase, glutathione peroxidase and catalase) were determined in liver tissue homogenates. MDA levels were increased whereas GSH levels tend to decrease following alcohol injection. Melatonin administration prior to ethanol did not alter MDA and GSH levels of tissue and among antioxidant defence enzymes studied, only CuZn-SOD was found to be increased in animals that received melatonin + ethanol. According to the findings of this study, melatonin did not appear to have any direct effect on alcohol-induced lipid peroxidation.
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PMID:The effect of melatonin administration on ethanol-induced lipid peroxidation in rats. 950 78

Melatonin is a powerful scavenger of oxygen free radicals. In humans, melatonin is rapidly transferred from the maternal to the fetal circulation. To investigate whether or not maternal melatonin administration can protect the fetal rat brain from radical-induced damage by increasing the activities of antioxidant enzymes, we administered melatonin to pregnant rats on day 20 of gestation. Melatonin (10 mg/kg) was injected intraperitoneally at daytime (14:00 hr) and, to remove the fetuses, a laparotomy was performed at 1, 2, or 3 hr after its administration. We measured the melatonin concentration in the maternal serum and in fetal brain homogenates and determined the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in fetal brain homogenates. Melatonin administration markedly increased melatonin concentrations in the maternal serum and fetal brain homogenates, with peak levels achieved 1 hr after melatonin administration (serum: 538.2+/-160.7 pM/mL; brain homogenates: 13.8+/-2.8 pM/mg protein). Between 1 and 3 hr after melatonin administration, GSH-Px activity in fetal brain homogenates increased significantly (P<0.01). Similarly, SOD activity increased significantly between 1 and 2 hr after melatonin administration (P<0.01). These results indicate that melatonin administration to the mother increases antioxidant enzyme activities in the fetal brain and may thereby provide indirect protection against free radical injury. Thus, melatonin may potentially be useful in the treatment of neurodegenerative conditions that may involve excessive free radical production, such as fetal hypoxia and preeclampsia.
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PMID:Melatonin increases activities of glutathione peroxidase and superoxide dismutase in fetal rat brain. 1070 70

The present study investigated the effects of melatonin, an antioxidant, on gentamicin-induced nephrotoxicity in rats. Melatonin (5 mg/kg p.o.) was used 3 days before and 8 days simultaneously with gentamicin (80 mg/kg i.p.) Saline-treated animals served as controls. Determinations of urinary creatinine, N-acetyl-beta-D-glucosaminidase, glucose, protein, blood urea, serum creatinine, plasma and kidney tissue malondialdehyde (MDA), and antioxidant enzyme levels in kidney tissue were done after 8 days of gentamicin treatment. The kidneys were also examined for morphological changes using histological techniques. Gentamicin caused nephrotoxicity as evidenced by marked elevation in blood urea and serum creatinine. Mean blood urea and serum creatinine levels were 289+/-50, and 2.5+/-0.5 mg/dl, respectively, in rats treated with gentamicin. Melatonin significantly protected the rats from gentamicin-induced nephrotoxicity; blood urea and serum creatinine levels were 23+/-2.7 and 0.88+/-0.19 mg/dl, respectively. The creatinine clearance was decreased with gentamicin treatment (0.048+/- 0.007 ml/min) as compared with controls (0.41+/-0.08 ml/h/kg). In rats treated with melatonin plus gentamicin, the creatinine clearance was similar to controls (0.41+/-0.08 ml/h/kg). The product of lipid peroxidation (MDA) was markedly increased in plasma (2.10+/-0.15 nmol) and kidney tissue (8.87+/-3.2 nmol/mg protein) with gentamicin treatment. Melatonin prevented the gentamicin-induced rise in plasma MDA (1.03+/-0.27 nmol) and kidney tissue MDA (2.57+/-0.87 nmol/mg protein). An increased excretion of urinary N-acetyl-beta-D-glucosaminidase, glucose, and protein by gentamicin was also prevented by melatonin. Kidneys from gentamicin-treated rats showed tubular epithelial loss with intense granular degeneration involving more than 50% of renal cortex, while there were findings comparable to controls in melatonin plus gentamicin treated rats. The present study indicates that melatonin significantly protects against gentamicin-induced renal toxicity in Wistar rats.
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PMID:Melatonin, a pineal hormone with antioxidant property, protects against gentamicin-induced nephrotoxicity in rats. 1086 23

In an attempt to define the role of the pineal secretory melatonin and an analogue, 6-hydroxymelatonin (6-OHM), in limiting oxidative stress, the present study investigated the cisplatin (CP)-induced alteration in the renal antioxidant system and nephroprotection with the two indolamines. Melatonin (5 mg/kg), 6-OHM (5 mg/kg), or an equal volume of saline were administered intraperitoneally (i.p.) to male Sprague Dawley rats 30 min prior to an i.p. injection of CP (7 mg/kg). After CP treatment, the animals each received indolamine or saline every day and were sacrificed 3 or 5 days later and plasma as well as kidney were collected. Both plasma creatinine and blood urea nitrogen increased significantly following CP administration alone; these values decreased significantly with melatonin co-treatment of CP-treated rats. In the kidney, CP decreased the levels of GSH (reduced glutathione)/GSSG (oxidized glutathione) ratio, an index directly related to oxidative stress. When animals were treated with melatonin, the reduction in the GSH/GSSG ratio was prevented. Treatment of CP-enhanced lipid peroxidation in the kidney was again prevented in animals treated with melatonin. The activity of the antioxidant enzyme, glutathione peroxidase (GSH-Px), decreased as a result of CP administration, which was restored to control levels with melatonin co-treatment. Upon histological analysis, damage to the proximal tubular cells was seen in the kidneys of CP-treated rats; these changes were prevented by melatonin treatment. 6-OHM has been shown to have some antioxidative capacity, however, the protective effects of 6-OHM against CP-induced nephrotoxicity were less than those of melatonin. The residual platinum concentration in the kidney of melatonin co-treated rats was significantly lower than that of rats treated with CP alone. It is concluded that administration of CP imposes a severe oxidative stress to renal tissue and melatonin confers protection against the oxidative damage associated with CP. This mechanism may be reasonably attributed to its radical scavenging activity, to its GSH-Px activating property, and/or to its regulatory activity for renal function.
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PMID:Melatonin, a pineal secretory product with antioxidant properties, protects against cisplatin-induced nephrotoxicity in rats. 1131 23

Melatonin was recently shown to be a component of the antioxidative defense system of organisms due to its free radical scavenging ability and to its capacity to stimulate several antioxidant enzymes. In this report, we studied the endogenous rhythm of the antioxidant enzyme superoxide dismutase (SOD) in three different tissues (cerebral cortex, liver and lung) of chick (Gallus domesticus) (three weeks, at age and sacrificed every 2 hr). During the study the chicks were under a light:dark cycle of 12:12. Total antioxidant status of the plasma was correlated with physiological blood melatonin concentrations. Superoxide dismutase activity exhibited a marked 24 hr rhythm in cerebral cortex, lung and liver, with peak activity coincident with the melatonin and total antioxidant status peaks. The exposure of chicks to constant light for 7 days eliminated the melatonin rhythm as well as the peaks in superoxide dismutase activity and the total antioxidant status. These findings suggest that the melatonin rhythm may be related to the nighttime increase in the superoxide dismutase activity and to total antioxidant capacity of the blood.
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PMID:Endogenous rhythms of melatonin, total antioxidant status and superoxide dismutase activity in several tissues of chick and their inhibition by light. 1133 12

This study was designed to investigate the effects of melatonin and estradiol (E2) on lipid peroxidation and antioxidant defense enzymes in blood and liver tissue when administered in vivo. Wistar albino rats were divided into three experimental groups and treated with either estradiol (25 mg/kg bw, s.c.), melatonin (i. p.), or melatonin plus E2, whereas control animals had diluent injections only. Melatonin was given 10 mg/kg bw x 2 intraperitoneally 30 min before and 60 min after E2 treatment to the melatonin plus E2 group. Animals were sacrificed three hours after the estradiol injection, and their blood and liver tissues were prepared for biochemical analyses. Tissue malondialdehyde (MDA) levels and antioxidant enzyme activities--superoxide dismutase (SOD) and glutathione peroxidase (GPx)--were determined in the postmitochondrial fraction, and the results were compared. Estradiol injection caused significant increases in both MDA levels and GPx activity in liver. When melatonin was administered in combination with E2, the effect of estradiol on MDA levels was abolished. A significant decrement in SOD activity occurred in melatonin-treated animals. GPx activity in the blood of E2 plus melatonin-injected animals was significantly higher than those in control animals. Melatonin-treated animals exhibited relatively lower levels of SOD activity than those from the control and E2 plus melatonin groups. This indicates that estradiol could exert oxidant action resulting in an increment in tissue malondialdehyde levels. Enhanced activity of GPx in both liver and blood following melatonin injection may indicate the contribution of this neurohormone on the antioxidant defense.
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PMID:Coadministration of melatonin and estradiol in rats: effects on oxidant status. 1160 81

Melatonin was found to be a potent free radical scavenger in 1993. Since then over 800 publications have directly or indirectly confirmed this observation. Melatonin scavenges a variety of reactive oxygen and nitrogen species including hydroxyl radical, hydrogen peroxide, singlet oxygen, nitric oxide and peroxynitrite anion. Based on the analyses of structure-activity relationships, the indole moiety of the melatonin molecule is the reactive center of interaction with oxidants due to its high resonance stability and very low activation energy barrier towards the free radical reactions. However, the methoxy and amide side chains also contribute significantly to melatonin's antioxidant capacity. The N-C=O structure in the C3 amide side chain is the functional group. The carbonyl group in the structure of N-C=O is key for melatonin to scavenge the second reactive species and the nitrogen in the N-C=O structure is necessary for melatonin to form the new five membered ring after melatonin's interaction with a reactive species. The methoxy group in C5 appears to keep melatonin from exhibiting prooxidative activity. If the methoxy group is replaced by a hydroxyl group, under some in vitro conditions, the antioxidant capacity of this molecule may be enhanced. However, the cost of this change are decreased lipophility and increased prooxidative potential. Therefore, in in vivo studies the antioxidant efficacy of melatonin appears to be superior to its hydroxylated counterpart. The mechanisms of melatonin's interaction with reactive species probably involves donation of an electron to form the melatoninyl cation radical or through an radical addition at the site C3. Other possibilities include hydrogen donation from the nitrogen atom or substitution at position C2, C4 and C7 and nitrosation. Melatonin also has the ability to repair damaged biomolecules as shown by the fact that it converts the guanosine radical to guanosine by electron transfer. Unlike the classical antioxidants, melatonin is devoid of prooxidative activity and all known intermediates generated by the interaction of melatonin with reactive species are also free radical scavengers. This phenomenon is defined as the free radical scavenging cascade reaction of the melatonin family. Due to this cascade, one melatonin molecule has the potential to scavenge up to 4 or more reactive species. This makes melatonin very effective as an antioxidant. Under in vivo conditions, melatonin is often several times more potent than vitamin C and E in protecting tissues from oxidative injury when compared at an equivalent dosage (micromol/kg). Future research in the field of melatonin as a free radical scavenger might be focused on: 1), signal transduction and antioxidant enzyme gene expression induced by melatonin and its metabolites, 2), melatonin levels in tissues and in cells, 3), melatonin structure modifications, 4), melatonin and its metabolites in plants and, 5), clinical trials using melatonin to treat free radical related diseases such as Alzheimer's, Parkinson's, stroke and heart disease.
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PMID:Chemical and physical properties and potential mechanisms: melatonin as a broad spectrum antioxidant and free radical scavenger. 1189

Melatonin is a component of the antioxidant defense system since it has radical scavenging and antioxidant activities. In the present study, we aimed to investigate the endogenous rhythm of antioxidant enzyme glutathione peroxidase (GSH-Px) activity, oxidized glutathione (GSSG) and lipid peroxidation levels in tissues of pinealectomized rats (PINX). Rats were sacrificed by decapitation at 4 h intervals. GSH-Px activity, GSSG and lipid peroxidation levels showed a daily rhythm both in controls and in PINX rats. GSH-Px and GSSG exhibited the peak levels after the peak time of melatonin which was determined previously by other groups. Lipid peroxidation levels increased progressively during the night and started to decline before the GSH-Px peak time. These findings suggest that endogenous melatonin is involved in the night time increase of GSH-Px activity and GSSG levels and modulates the daily rhythm pattern of GSH-Px. In conclusion, pinealectomy which eliminates the melatonin rhythm has a supressor effect on GSH-Px activity levels.
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PMID:Daily rhythm of glutathione peroxidase activity, lipid peroxidation and glutathione levels in tissues of pinealectomized rats. 1195 18

We investigated whether long-term melatonin administration in the drinking water influences oxidative modification of lipids and proteins and antioxidative enzyme activity in brain of senescence-accelerated mice (SAM). Cerebral cortex was obtained in the middle of the dark period of the daily light cycle from SAMP8, a strain of mice prone to accelerated senescence, and from SAMR1, a senescence-resistant strain, at 3, 6, and 12 months of age. Thiobarbituric acid-reactive substances (TBARS) and protein carbonyls exhibited significant age-related increases in both strains. Glutathione peroxidase (GPx) activity decreased significantly at 12 months of age in SAMP8. No age effect was found in GPx activity in SAMR1, or in superoxide dismutase (SOD) activity in either strain. Melatonin administration (2 microg/mL) via the drinking fluid beginning at 7 months significantly decreased neural TBARS content (over 30%) in both strains and lowered the protein carbonyl content in the brain of SAMP8 mice. Furthermore, melatonin significantly augmented GPx activity (over 20%) in both strains. Melatonin had no effect on SOD activity. These results suggest an age-related increase in cerebral tissue vulnerability to oxidation in SAM that can be modified by melatonin, most likely through the ability of melatonin to scavenge oxygen free radicals and to stimulate antioxidant enzyme activity.
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PMID:Melatonin reduces oxidative damage of neural lipids and proteins in senescence-accelerated mouse. 1200 13


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