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 present study demonstrates that manganese superoxide dismutase (MnSOD) (Escherichia coli), binds nitric oxide (*NO) and stimulates its decay under both anaerobic and aerobic conditions. The results indicate that previously observed MnSOD-catalyzed *NO disproportionation (dismutation) into nitrosonium (NO+) and nitroxyl (NO-) species under anaerobic conditions is also operative in the presence of molecular oxygen. Upon sustained aerobic exposure to *NO, MnSOD-derived NO- species initiate the formation of peroxynitrite (ONOO-) leading to enzyme tyrosine nitration, oxidation and (partial) inactivation. The results suggest that both ONOO- decomposition and ONOO(-)-dependent tyrosine residue nitration and oxidation are enhanced by metal centre-mediated catalysis. We show that the generation of ONOO- is accompanied by the formation of substantial amounts of H2O2. MnSOD is a critical mitochondrial antioxidant enzyme, which has been found to undergo tyrosine nitration and inactivation in various pathologies associated with the overproduction of *NO. The results of the present study can account for the molecular specificity of MnSOD nitration in vivo. The interaction of *NO with MnSOD may represent a novel mechanism by which MnSOD protects the cell from deleterious effects associated with overproduction of *NO.
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PMID:Consequences of MnSOD interactions with nitric oxide: nitric oxide dismutation and the generation of peroxynitrite and hydrogen peroxide. 1716 79

We evaluated the effects of caffeic acid phenethyl ester (CAPE) on antioxidant enzyme levels and histopathologic changes in dizocilpine (MK-801) induced schizophrenic rat testis. A total of 30 adult male Wistar-Albino rats were divided into three groups. Group-I was used as control. Rats in the Group-II were intraperitoneally injected with MK-801, whereas those in Group-III were intraperitoneally injected with CAPE in addition to MK-801. The testes were collected for biochemical and histopathological examinations. Antioxidant enzyme activities, malondialdehyde, protein carbonyl and nitric oxide levels in testicular tissues were analyzed with spectrophotometric methods. Induction of schizophrenia resulted in a significant oxidative stress by increasing the levels of antioxidant enzymes. Tissue malondialdehyde and protein carbonyl levels were also increased. Treatment with CAPE led to significant decrease in oxidative injury. Administration of CAPE reduced the detrimental histopathologic changes caused by MK-801. The results showed that experimentally induced schizophrenia caused oxidative stress in testes of rats and treatment with CAPE reduced these harmful effects.
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PMID:A preliminary study of the levels of testis oxidative stress parameters after MK-801-induced experimental psychosis model: protective effects of CAPE. 1716 78

Adriamycin (ADR), a potent anti-tumor agent, produces reactive oxygen species (ROS) in cardiac tissue. Treatment with ADR is dose-limited by cardiotoxicity. However, the effect of ADR in the other tissues, including the brain, is unclear because ADR does not pass the blood-brain barrier. Some cancer patients receiving ADR treatment develop a transient memory loss, inability to handle complex tasks etc., often referred to by patients as chemobrain. We previously demonstrated that ADR causes CNS toxicity, in part, via systemic release of cytokines and subsequent generation of reactive oxygen and nitrogen species (RONS) in the brain. Here, we demonstrate that treatment with ADR led to an increased circulating level of tumor necrosis factor-alpha in wild-type mice and in mice deficient in the inducible form of nitric oxide (iNOSKO). However, the decline in mitochondrial respiration and mitochondrial protein nitration after ADR treatment was observed only in wild-type mice, not in the iNOSKO mice. Importantly, the activity of a major mitochondrial antioxidant enzyme, manganese superoxide dismutase (MnSOD), was reduced and the protein was nitrated. Together, these results suggest that NO is an important mediator, coupling the effect of ADR with cytokine production and subsequent activation of iNOS expression. We also identified the mitochondrion as an important target of ADR-induced NO-mediated CNS injury.
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PMID:Adriamycin-mediated nitration of manganese superoxide dismutase in the central nervous system: insight into the mechanism of chemobrain. 1722 39

Erdosteine was introduced in the market as a mucolytic agent for chronic pulmonary diseases more than 10 years ago. The drug contains two blocked sulphydryl groups one of which, after hepatic metabolization and opening of the thiolactone ring, becomes available both for the mucolytic and free radical scavenging and antioxidant activity too. There are several experimental evidences which support the protective effect of erdosteine in acute injury induced by a variety of pharmacological or noxious agents, mediated by products of oxidative stress. Experimental data in animal assigned to receive the noxious agent evidence that co-treatment with erdosteine increases the tissue antioxidant enzyme activities such as superoxide dismutase, catalase and glutathione peroxidase, compared with the toxic agent alone; meanwhile erdosteine decreases the tissue level of nitric oxide, xanthine oxidase, which catalyze oxygen-free radical production. In summary, erdosteine prevents the accumulation of free oxygen radicals when their production is accelerated and increases antioxidant cellular protective mechanisms. The final result is a protective effect on tissues which reduces lipid peroxidation, neutrophil infiltration or cell apoptosis mediated by noxious agents. Recent positive clinical trials in humans seem to fulfill the impressive promises that theory and experimental research have put forward.
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PMID:An overview of erdosteine antioxidant activity in experimental research. 1726 40

Hepatic Encephalopathy (HE) is one of the most common complications of acute liver diseases and is known to have profound influence on the brain. Most of the studies, available from the literature are pertaining to whole brain homogenates or mitochondria. Since brain is highly heterogeneous with functions localized in specific areas, the present study was aimed to assess the oxidative stress in different regions of brain-cerebral cortex, cerebellum and pons medulla during acute HE. Acute liver failure was induced in 3-month old adult male Wistar rats by intraperitoneal injection of thioacetamide (300 mg/kg body weight for two days), a well known hepatotoxin. Oxidative stress conditions were assessed by free radical production, lipid peroxidation, nitric oxide levels, GSH/GSSG ratio and antioxidant enzyme machinery in three distinct structures of rat braincerebral cortex, cerebellum and pons medulla. Results of the present study indicate a significant increase in malondialdehyde (MDA) levels, reactive oxygen species (ROS), total nitric oxide levels [(NO) estimated by measuring (nitrites + nitrates)] and a decrease in GSH/GSSG ratio in all the regions of brain. There was also a marked decrease in the activity of the antioxidant enzymes-glutathione peroxidase, glutathione reductase and catalase while the super oxide dismutase activity (SOD) increased. However, the present study also revealed that pons medulla and cerebral cortex were more susceptible to oxidative stress than cerebellum. The increased vulnerability to oxidative stress in pons medulla could be due to the increased NO levels and increased activity of SOD and decreased glutathione peroxidase and glutathione reductase activities. In summary, the present study revealed that oxidative stress prevails in different cerebral regions analyzed during thioacetamide-induced acute liver failure with more pronounced effects on pons medulla and cerebral cortex.
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PMID:Fulminant hepatic failure in rats induces oxidative stress differentially in cerebral cortex, cerebellum and pons medulla. 1726 43

Lenses from mice lacking the antioxidant enzyme copper-zinc superoxide dismutase (SOD1) show elevated levels of superoxide radicals and are prone to developing cataract when exposed to high levels of glucose in vitro. As superoxide may react further with nitric oxide, generating cytotoxic reactive nitrogen species, we attempted to evaluate the involvement of nitric oxide in glucose-induced cataract. Lenses from SOD1-null and wild-type mice were incubated with high or normal levels of glucose (55.6 and 5.56 mM). A nitric oxide synthase inhibitor (L-NAME) or a nitric oxide donor (DETA/NO) was added to the culture medium. Cataract development was assessed using digital image analysis of lens photographs and cell damage by analyzing the leakage of lactate dehydrogenase. The levels of superoxide radicals in the lenses were also measured. L-NAME was found to reduce cataract development and cell damage in the SOD1-null lenses exposed to high glucose. On the other hand, DETA/NO accelerated cataract development, especially in the SOD1-null lenses. These lenses also showed a higher leakage of lactate dehydrogenase than wild-type controls. We conclude that a combination of high glucose and absence of SOD1 increases the formation of cataract and that nitric oxide probably contributes to this process.
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PMID:Glucose-induced cataract in CuZn-SOD null lenses: an effect of nitric oxide? 1734 36

This study was performed to evaluate the effect of melatonin on methanol-induced liver injury. We evaluated the levels of malondialdehyde (MDA), protein carbonylation (PC), myeloperoxidase (MPO) activities and to assess lipid peroxidation, protein oxidation, neutrophil accumulation and nitrite which is a stable end product of nitric oxide respectively. We also studied superoxide dismutase, catalase, and glutathione peroxidase activities of liver tissue to evaluate the changes in the antioxidant status. Histopathological alterations were also determined. The experiment was performed on Wistar rats, which received intragastric 3 g/kg methanol as a 50% solution in isotonic saline once. After 6 and 24 hr all the drug received and intoxicated rats were killed under anesthesia. Pretreatment with melatonin (10 mg/kg) decreased the MDA levels significantly, restored the PC levels to the control, prevented the increase of nitrite level and MPO activity significantly and reversed to the control levels, prevented the reduction in all of the antioxidant enzyme activities. Additionally in melatonin treated group piecemeal necrosis, lobular lytic necrosis, and portal inflammation returned to normal histologic appearances when compared with methanol administration. In conclusion, melatonin has protective effects against methanol-induced hepatic injury.
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PMID:Melatonin improves methanol intoxication-induced oxidative liver injury in rats. 1761 34

Mildly elevated homocysteine levels (Hcy) increase the risk for atherothrombotic vascular disease in the coronary, cerebrovascular, and peripheral arterial circulations. The molecular mechanisms responsible for decreased bioavailability of endothelium-derived nitric oxide (NO) by Hcy involve an increase of vascular oxidant stress and inhibition of important antioxidant capacity. Glutathione peroxidase-1 (GPx-1), a selenocysteine-containing antioxidant enzyme, may be a key target of Hcy's deleterious actions, and several experimental and clinical studies have demonstrated a complex relationship between plasma total homocysteine (tHcy), GPx-1, and endothelial dysfunction. Hcy may promote endothelial dysfunction, in part by decreasing GPx-1 expression; however, there is evidence to suggest that overexpression of GPx-1 can compensate for these effects. This review summarizes the current knowledge of the metabolism of Hcy, the effects of hyperhomocysteinemia observed in in vitro and in vivo models that lead to endothelial dysfunction and the possible mechanisms for these actions, and the role of GPx-1 in the pathogenesis of Hcy-induced cardiovascular disease (CVD).
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PMID:Homocysteine and glutathione peroxidase-1. 1782 68

Cadmium (Cd) exposure has been recognized to result in a wide variety of cellular responses, including oxidative stress and body weight loss. The aim of the present study was to examine the effect of lycopene supplementation on the antioxidant defense system, lipid peroxidation (LPO) level, nitric oxide (NO), tumor necrosis factor alpha (TNF-alpha) production, and body weight in Cd-exposed rats. Animals were divided into four groups (n = 7): control, Cd-treated, Cd plus lycopene-treated, and lycopene-treated. Cadmium (as CdCl2) was administrated orally for 20 days (6.6 mg kg(-1) day(-1)), and lycopene (10 mg kg(-1) day(-1)) was similarly administered. Lycopene administration significantly suppressed Cd-induced LPO in plasma and kidney homogenates. Lycopene also reversed Cd-decreased body weight compared to the control. Cadmium treatment had diverse effects on the antioxidant enzyme activities. Although antioxidant superoxide dismutase activity was unchanged, glutathione peroxidase activity was decreased, and catalase activity was elevated in kidney homogenates of Cd-administrated group. However, lycopene treatment reversed Cd-changed enzyme activities to the control level. Xanthine oxidase activity and TNF-alpha concentration were not altered by Cd administration, indicating that superoxide anion production and inflammation were not stimulated. Cadmium did not change NO levels in kidney homogenates but decreased those in plasma, and this effect was not prevented by lycopene supplementation. The result suggests that consumption of adequate levels of lycopene may be useful to prevent heavy-metal-induced LPO and body weight loss.
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PMID:Oral administration of lycopene reverses cadmium-suppressed body weight loss and lipid peroxidation in rats. 1787 60

The aim of this study was to evaluate the role of antioxidant enzyme activity and nitric oxide levels induced by 28 day biliary obstruction in the rat. A total of 21 young Swiss albino rats were divided in to 3 groups. Bile duct ligations, bile duct ligations plus resveratrol, sham operated. Bile duct ligations plus resveratrol group received 10 mg/kg dose of resveratrol intraperitonealy once daily throughout for 28 days. Liver damage and cholestasis were determined by biochemical examination. SOD, CAT and GSH-PX activity decreased in BDL group compared with shame opareted groups (p < 0.001). NO levels increased in BDL groups compared with shame opareted groups (p < 0.001). SOD, CAT and GSH-PX activity was found higher in BDL+resveratrol treated groups than BDL groups (p < 0.001). In addition this NO levels decreased in BDL+resveratrol treated groups than BDL groups (p < 0.001). In conclusion, it is thought that resveratrol may be used as a protective agent in biliary obstructions; however, further clinical and experimental studies are needed to verify its antioxidative and hepatoprotective effects.
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PMID:Changing of antioxidant enzyme activity on the biliary obstructed rats treated with resveratrol. 1792 75


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