Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0406810 (NAME)
 13,345 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)
 ...
PMID:Melatonin administration prevents lipopolysaccharide-induced oxidative damage in phenobarbital-treated animals. 759 65

Oxidative damage in various tissues of LPS-treated rats was studied using the following parameters: changes in reduced (GSH) and oxidized glutathione (GSSG) levels in liver, brain and lens; the activity of glutathione peroxidase (GSH-PX) in both liver and brain; the content of cytochrome P450 reductase in liver. Bacterial LPS was injected i.p. (at a dose of 4 mg/kg BW) 6 h before the animals were killed. One group of rats received N omega-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase (NOS) (given for 4 days in the drinking water at a concentration of 50 mM); another group received both L-NAME and LPS. In brain and lens no changes in GSH were observed after either LPS, L-NAME or both. In contrast, GSSG and the GSSG/GSH ratio was significantly higher after LPS. This effect was abolished in the brain by L-NAME treatment. The level of the activity of the antioxidative enzyme GSH-PX in brain was significantly higher after L-NAME in LPS-treated animals. Hepatic GSH-PX activity was enhanced after either LPS, L-NAME or treatment with both substances. Additionally, LPS diminished the level of cytochrome P450 reductase with this effect being largely prevented by L-NAME. The results suggest that GSH, as an endogenous antioxidant, may play a major role in combating toxicity of LPS.
 ...
PMID:Oxidative changes in the liver, brain and lens of lipopolysaccharide-treated rats. 884 34

Many individuals with cardiovascular diseases undergo periodic exercise conditioning with or with out medication. Therefore, this study investigated the interaction of exercise training and chronic nitric oxide synthase (NOS) inhibitor (Nitro-L-Arginine Methyl Ester, L-NAME) treatment on blood pressure and its correlation with aortic nitric oxide (NO), antioxidant defense system and oxidative stress parameters in rats. Fisher 344 rats were divided into four groups: (1) sedentary control, (2) exercise training (ET) for 8 weeks, (3) L-NAME (10 mg/kg, subcutaneous for 8 weeks) and (4) ET + L-NAME. Blood pressure (BP) was monitored weekly for 8 weeks with tail-cuff method. The animals were sacrificed 24 h after last treatments and thoracic aortic rings were isolated and analyzed. Exercise conditioning resulted in a significant increase in respiratory exchange ratio (RER), aortic NO production, NO synthase activity and inducible iNOS protein expression. Training significantly enhanced aortic GSH levels, GSH/GSSG ratio and up-regulation of aortic CuZn-SOD, Mn-SOD, catalase (CAT), glutathione peroxidase (GSH-Px) activity and protein expression and significantly decreased aortic lipid peroxidation. Chronic L-NAME administration resulted in a significant depletion of aortic NO, NOS activity, endothelial (eNOS) and iNOS protein expression, GSH level, GSH/GSSG ratio, down-regulation of aortic antioxidant enzyme activities and protein expressions. Aortic xanthine oxidase (XO) activity significantly increased with increased lipid peroxidation and protein oxidation after L-NAME administration. The biochemical changes were accompanied by increased in BP. Interaction of training and chronic NOS inhibitor treatment resulted in normalization of BP and aortic antioxidant enzyme activity and protein expression, up-regulation of aortic GSH/GSSG ratio, NO levels, Mn-SOD protein expression, depletion of GSSG, protein oxidation and lipid peroxidation. The data suggest that training attenuated the oxidative injury caused by chronic NOS inhibitor treatment by up-regulating the NO and antioxidant systems and lowering the BP in rats.
 ...
PMID:Exercise conditioning attenuates the hypertensive effects of nitric oxide synthase inhibitor in rat. 1195 54

Many individuals with cardiac diseases undergo periodic physical conditioning with or without medication. Therefore, this study investigated the interaction of physical training and chronic nitric oxide synthase (NOS) inhibitor (nitro-L-arginine methyl ester, L-NAME) treatment on blood pressure (BP), heart rate (HR) and cardiac oxidant/antioxidant systems in rats. Fisher 344 rats were divided into four groups and treated as follows: (1) sedentary control (SC), (2) exercise training (ET) for 8 weeks, (3) L-NAME (10 mg/kg, s.c. for 8 weeks) and (4) ET+L-NAME. BP and HR were monitored with tail-cuff method. The animals were sacrificed 24 h after last treatments and hearts were isolated and analyzed. Physical conditioning significantly increased respiratory exchange ratio (RER), cardiac nitric oxide (NO) levels, NOS activity and endothelial (eNOS) and inducible (iNOS) protein expression. Training significantly enhanced cardiac glutathione (GSH) levels, GSH/GSSG ratio and up-regulation of cardiac copper/zinc-superoxide dismutase (CuZn-SOD), manganese (Mn)-SOD, catalase (CAT), glutathione peroxidase (GSH-Px) activity and protein expression. Training also caused depletion of cardiac malondialdehyde (MDA) and protein carbonyls. Chronic L-NAME administration resulted in depletion of cardiac NO level, NOS activity, eNOS, nNOS and iNOS protein expression, GSH/GSSG ratio and down-regulation of cardiac CuZn-SOD, Mn-SOD, CAT, GSH-PX, glutathione-S-transferase (GST) activity and protein expression. Chronic L-NAME administration enhanced cardiac xanthine oxidase (XO) activity, MDA levels and protein carbonyls. These biochemical changes were accompanied by increases in BP and HR after L-NAME administration. Interaction of training and NOS inhibitor treatment resulted in normalization of BP, HR and up-regulation of cardiac antioxidant defense system. The data suggest that physical conditioning attenuated the oxidative injury caused by chronic NOS inhibition by up-regulating the cardiac antioxidant defense system and lowering the BP and HR in rats.
 ...
PMID:Oxidative injury due to chronic nitric oxide synthase inhibition in rat: effect of regular exercise on the heart. 1200 27

The study investigated whether the amelioration of endothelial dysfunction by candesartan (2 mg.kg-1.day-1; 10 wk) in spontaneously hypertensive rats (SHR) was associated with modification of hepatic redox system. Systolic arterial pressure (SAP) was higher (P < 0.05) in SHR than in Wistar-Kyoto rats (WKY) and was reduced (P < 0.05) by candesartan in both strains. Acetylcholine (ACh) relaxations were smaller (P < 0.05) and contractions induced by ACh + NG-nitro-l-arginine methyl ester (l-NAME) were greater (P < 0.05) in SHR than in WKY. Treatment with candesartan enhanced (P < 0.05) ACh relaxations in SHR and reduced (P < 0.05) ACh + l-NAME contractions in both strains. Expression of aortic endothelial nitric oxide synthase (eNOS) mRNA was similar in WKY and SHR, and candesartan increased (P < 0.05) it in both strains. Aortic mRNA expression of the subunit p22phox of NAD(P)H oxidase was higher (P < 0.05) in SHR than in WKY. Treatment with candesartan reduced (P < 0.05) p22phox expression only in SHR. Malonyl dialdehyde (MDA) levels were higher (P < 0.05), and the ratio reduced/oxidized glutathione (GSH/GSSG) as well as glutathione peroxidase activity (GPx) were lower (P < 0.05) in liver homogenates from SHR than from WKY. Candesartan reduced (P < 0.05) MDA and increased (P < 0.05) GSH/GSSG ratio without affecting GPx. Vessel, lumen, and media areas were bigger (P < 0.05) in SHR than in WKY. Candesartan treatment reduced (P < 0.05) media area in SHR without affecting vessel or lumen area. The results suggest that hypertension is not only associated with elevation of vascular superoxide anions but with alterations of the hepatic redox system, where ANG II is clearly involved. The results further support the key role of ANG II via AT1 receptors for the functional and structural vascular alterations produced by hypertension.
 ...
PMID:Effect of AT1 receptor blockade on hepatic redox status in SHR: possible relevance for endothelial function? 1277 56

Many individuals with cardiovascular diseases undergo periodic exercise conditioning with or without medication. Therefore, the purpose of this study was to examine the effect of exercise training on BP and HR under the condition of NOS inhibition and to clarify the mechanism of the effect in regard to oxidative stress, antioxidant enzyme activity, and NO production in the plasma of the rat. Fisher 344 rats were divided into four groups: (1) sedentary control, (2) exercise training for 8 weeks, (3) nitro-L-arginine methyl ester (L-NAME) (10mg/kg, s.c. for 8 weeks) and (4) ET + L-NAME. Blood pressure (BP) and heart rate (HR) were monitored weekly for 8 weeks. The animals were sacrificed 24h after last treatments, plasma isolated and analyzed. The results show that exercise conditioning resulted in enhanced NO production (120% of control), GSH levels (110% of control), GSH/GSSG ratio (124% of control) and the up-regulation of catalase (CAT) (225% of control), glutathione peroxidase (GSH-Px) (161% of control), glutathione reductase (GR) (142% of control) and glutathione-S-transferase (GST) (189% of control) and depression of malondialdehyde (MDA) (90% of control) and lactate (75% of control) in plasma of the rat. These biochemical changes were accompanied by no significant change in BP but slight increase in HR. Chronic L-NAME administration resulted in depression of NO (84% of control), GSH (90% of control), GSH/GSSG ratio (76% of control), the down-regulation of superoxide dismutase (SOD) (67% of control), GST (74% of control), and GR (90% of control). Plasma CAT and GSH-Px activities, MDA and lactate levels were significantly increased in L-NAME treated rats. The biochemical changes were accompanied by increase in blood pressure and heart rate. Interaction of exercise training and chronic NOS inhibitor treatment resulted in normalization of plasma NO levels, GSH/GSSG ratio, SOD and GST activities, and the up-regulation of, CAT, GSH-Px, and GR activities. The interaction resulted in depletion of plasma MDA levels compared to L-NAME treated group. The biochemical changes were accompanied by decrease in BP and HR compared to L-NAME treated group. The data suggest that the exercise training attenuated the oxidative injury caused by NOS inhibitor by increasing the plasma NO levels, GSH/GSSG ratio and up-regulating the antioxidant enzyme and lowering the BP and HR in the rat.
 ...
PMID:Interaction of exercise training and chronic NOS inhibition on blood pressure, heart rate, NO and antioxidants in plasma of rats. 1464 3

Homocysteine (Hcy), an intermediate in methionine metabolism, has been proposed to be involved in hepatic fibrogenesis. Impaired liver function can alter Hcy metabolism. The aim of the present study was to determine plasma Hcy alterations in acute obstructive cholestasis and the subsequent biliary cirrhosis. Cholestasis was induced by bile duct ligation and sham-operated and unoperated rats were used as controls. The animals were studied on the days 7th, 14th, 21st and 28th after the operation. Plasma Hcy, cysteine, methionine, nitric oxide (NO) and liver S-adenosyl-methionine (SAM), S-adenosyl-homocysteine (SAH), SAM to SAH ratio and glutathione were measured. Chronic L-NAME treatment was also included in the study. Plasma Hcy concentrations were transiently elevated by the day 14th after bile duct ligation (P < 0.01) and subsequently returned to control levels. Similar relative fluctuations in plasma Hcy were observed in BDL rats after intraperitoneal methionine overload. Plasma methionine, cysteine and nitrite and nitrate were significantly increased after bile duct ligation. SAM to SAH ratio was diminished by the 1st week of cholestasis and remained significantly decreased throughout the study. These events were accompanied by a decrease in GSH to GSSG ratio in the liver. Chronic L-NAME treatment improved SAM to SAH ratio and prevented the elevation of plasma Hcy and methionine (P < 0.05) while couldn't influence the other parameters. In conclusion, this study demonstrates alterations in plasma Hcy and liver SAM and SAH contents in precirrhotic stages and in secondary biliary cirrhosis, for the first time. In addition, we observed that plasma Hcy concentrations in BDL rats follow a distinct pattern of alteration from what has been previously reported in other models of cirrhosis. NO overproduction may contribute to plasma Hcy elevation and liver SAM depletion after cholestasis.
 ...
PMID:Homocysteine alterations in experimental cholestasis and its subsequent cirrhosis. 1576 80

Depletion of glutathione (GSH), nitrosative stress and chronic intoxication with some neurotoxins have been postulated to play a major role in the pathogenesis of Parkinson's disease. This study aimed to examine the effects of acute and chronic treatments with 1,2,3,4-tetrahydroisoquinoline (TIQ), an endo-/exogenous substance suspected of producing Parkinsonism in human, on the levels of nitric oxide (NO), S-nitrosothiols and glutathione (GSH) in the whole rat brain and in its dopaminergic structures. TIQ administered at a dose of 50 mg/kg i.p. significantly increased the tissue concentrations of NO and GSH in the substantia nigra (SN), striatum (STR) and cortex (CTX) of rats receiving this compound both acutely and chronically. Moreover, it decreased the level of oxidized glutathione (GSSG) and enhanced GSH:GSSG ratio affecting in this way the redox state of brain cells. TIQ also increased the level of S-nitrosothiols when measured in the whole rat brain and CTX, although it markedly decreased their level in the STR after both treatments. Inhibition of the constitutive NO synthase by l-NAME in the presence of TIQ caused decreases in GSH and S-nitrosothiol levels in the brain. The latter effect shows that the TIQ-mediated increases in GSH and S-nitrosothiol concentrations were dependent on the enhanced NO level. The above-described results suggest that TIQ can act as a modulator of GSH, NO and S-nitrosothiol levels but not as a parkinsonism-inducing agent in the rat brain.
 ...
PMID:Treatment with 1,2,3,4-tetrahydroisoquinolone affects the levels of nitric oxide, S-nitrosothiols, glutathione and the enzymatic activity of gamma-glutamyl transpeptidase in the dopaminergic structures of rat brain. 1594 55

Grape seed proanthocyanidin extract (GPSE) at high doses has been shown to exhibit cytotoxicity that is associated with increased apoptotic cell death. Nitric oxide (NO), being a regulator of apoptosis, can be increased in production by the administration of GSPE. In a chick cardiomyocyte study, we demonstrated that high-dose (500 microg/ml) GSPE produces a significantly high level of NO that contributes to increased apoptotic cell death detected by propidium iodide and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining. It is also associated with the depletion of intracellular glutathione (GSH), probably due to increased consumption by NO with the formation of S-nitrosoglutathione. Co-treatment with L-NAME, a NO synthase inhibitor, results in reduction of NO and apoptotic cell death. The decline in reduced GSH/oxidized GSH (GSSG) ratio is also reversed. N-Acetylcysteine, a thiol compound that reacts directly with NO, can reduce the increased NO generation and reverse the decreased GSH/GSSG ratio, thereby attenuating the cytotoxicity induced by high-dose GSPE. Taken together, these results suggest that endogenous NO synthase (NOS) activation and excessive NO production play a key role in the pathogenesis of high-dose GSPE-induced cytotoxicity.
 ...
PMID:Cytotoxicity induced by grape seed proanthocyanidins: role of nitric oxide. 1655 1

We studied lipid metabolism and the antioxidant defense system in plasma and liver of rats fed diets supplemented with L(omega)-nitro-L-arginine methyl ester (L-NAME), isosorbide dinitrate (DIS), L-arginine (Arg), or the associations of these drugs. Liver hydroperoxide and thiobarbituric-acid-reactive substance (TBARS) levels were decreased by Arg and increased by L-NAME or DIS treatments. Oxidized glutathione and conjugated dienes were increased by DIS. Nitrate + nitrite levels and serum calcium ([Ca(++)]) were incremented by Arg or DIS and reduced by L-NAME. Superoxide dismutase and catalase activities decreased under Arg treatment, while L-NAME or DIS caused stimulation. Liver high-density lipoprotein (HDL) cholesterol was increased by DIS or NAME (alone or associated with Arg). Free fatty acids and neutral and polar lipids were increased by Arg, L: -NAME, and DIS. However, predominating phospholipid synthesis increased the neutral/polar ratio. Decreased levels of nitric oxide (NO) (low [Ca(++)]) was directly associated with increased fatty acid synthetase, decreased phospholipase A(2), carnitine-palmitoyl transferase, and fatty acid desaturase activities. Raised NO (high [Ca(++)]) inversely correlated with increased phospholipase-A(2) and acyl-coenzyme A (CoA) synthetase and decreased fatty acid synthetase and beta-oxidation rate. Arg or DIS produced changes that were partially reverted by association with L-NAME. Based on these observations, prolonged therapeutical approaches using drugs that modify NO availability should be carefully considered.
 ...
PMID:Lipid metabolism in rats is modified by nitric oxide availability through a Ca++-dependent mechanism. 1739 27


1 2 3 Next >>