Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.15.1 (ACE)
18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present study was carried out to examine whether nitrofurantoin-induced pulmonary toxicity in normal rats was mediated via oxidant stress mechanisms. The relative importance of the cellular antioxidant enzymes in nitrofurantoin toxicity was also assessed. For this, the pulmonary toxicity induced by nitrofurantoin in rats was evaluated at various time intervals after a single subcutaneous injection. Data from this study showed that nitrofurantoin (200 mg/kg, s.c.) resulted in transient but measurable lung damage as evidenced by the increases in wet lung weight/body weight ratio and decreases in lung angiotensin converting enzyme activity. A transient decrease in GSH concentrations with a concurrent increase in GSSG concentrations as well as an increase in lipid peroxidation levels (measured by the formation of diene conjugates and thiobarbituric acid reactants) were also evident in lungs of nitrofurantoin-treated rats. In addition, nitrofurantoin did not alter the pulmonary superoxide dismutase and glutathione peroxidase activities, but it did produce transient decreases in catalase and glutathione reductase activities. These data indicate that impairment of the ability of the lung to detoxify reactive oxygen species may play an important role in the development of nitrofurantoin-induced pulmonary toxicity. The results of the present study suggest that nitrofurantoin can damage the lungs of rats, probably through oxidative stress-mediated mechanisms. Also, our data have provided in vivo evidence for substantiating lipid peroxidation as a possible cause of lung damage.
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PMID:Nitrofurantoin-induced pulmonary toxicity. In vivo evidence for oxidative stress-mediated mechanisms. 131 37

In order to clarify the preventive action of Dai-Saiko-to (Da-Chai-Hu-Tang) extract (TJ-8) on the progression of acute liver injury in rats intoxicated with carbon tetrachloride (CCl4), we examined the effect of post-oral TJ-8 administration on hepatic active oxygen metabolism following the progression of this liver damage. When TJ-8 (1.0 g/kg body weight) was administered orally to male Wistar rats aged five weeks 2 hrs after i.p. injection of CCl4 (1.0 ml/kg body weight), an apparent liver injury occurred. Significant prevention against the progression of liver injury was found at 24 hrs after injection, judging from the activities of serum transaminases, indexes of liver cell damage. Liver cytosolic superoxide dismutase (SOD) activity decreased 2 and 24 hrs after CCl4 injection, while liver cytosolic catalase and glutathione reductase (GSSG-R) activities decreased 24 hrs after the injection. At 2 and 24 hrs after CCl4 treatment, liver cytosolic Se-containing glutathione peroxidase (GSH-px) activity did not change and liver cytosolic glucose-6-phosphate dehydrogenase (G-6-PDH) activity increased. Post-oral TJ-8 administration significantly ameliorated decreases in liver SOD, catalase, and GSSG-R activities at 24 hrs after CCl4 injection, but did not affect liver Se-GSH-px and increased liver G-6-PDH activities at 24 hrs after the injection. Although increased liver lipid peroxide level and decreased liver reduced glutathione and ascorbic acid levels were observed 2 and 24 hrs after CCl4 injection, post-oral TJ-8 administration significantly prevented these changes found at 24 hrs after injection. These results indicate that post-oral TJ-8 administration can prevent the progression of acute liver injury in CCl4-injected rats by inhibiting enhanced lipid peroxidation and by improving disrupted active oxygen metabolism in the injured liver.
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PMID:Preventive effect of dai-saiko-to (da-chai-hu-tang) extract on disrupted hepatic active oxygen metabolism in rats with carbon tetrachloride-induced liver injury. 759 92

In the liver of male ddY mice intoxicated once with carbon tetrachloride (CCl4), the change in lipid peroxide (LPO) level with the development of damage over a 24 hr period after i.p. treatment of the toxicant (1.0 mL/kg) was compared with the changes in reduced glutathione (GSH) and oxidized glutathione (GSSG) levels, GSSG/GSH ratio, and activities of the glutathione redox cycle-related enzymes such as Se-dependent glutathione peroxidase (Se-GSH-px), glutathione reductase (GSSG reductase), and glucose-6-phosphate dehydrogenase (G-6-PDH) and of Se-independent glutathione peroxidase (non-Se-GSH-px) with the development of damage during the same period. An apparent liver injury was observed 0.5 hr after CCl4 treatment and the injury progressed rapidly later than 8 hr, judging from the activities of serum transaminases, marker enzymes of liver cell damage. Hepatic LPO level slightly increased once during the first 4 hr after CCl4 treatment and a marked increase in the level occurred later than 12 h, while serum LPO level increased later than 12 h. Hepatic GSH level decreased rapidly during the first 4 hr after CCl4 treatment and the decreased level recovered slowly thereafter, although the recovered level did not reach the control level. Hepatic GSSG level rapidly increased once during the first 1 hr after CCl4 treatment and an increase in the level occurred again later than 12 h. Hepatic GSSG/GSH increased during the first 1 hr and later than 8 hr after CCl4 treatment, although the ratio was maintained above the control level later than 0.5 h. Hepatic Se-GSH-px activity increased during the first 2 hr after CCl4 treatment and later than 8 h, while hepatic non-Se-GSH-px activity increased during the first 1 hr but decreased below the control level at 8 and 12 h. Hepatic GSSG reductase activity decreased during the first 2 hr after CCl4 treatment but the decrease activity returned up to the control level at 8 h. Hepatic G-6-PDH activity increased rapidly during the first 2 hr after CCl4 treatment and the increase proceeded slowly thereafter. These results indicate that although hepatic lipid peroxidation is enhanced at early and progressed stages of liver injury in mice intoxicated once with CCl4, endogenous GSH through hepatic glutathione redox cycle can respond well to enhanced hepatic lipid peroxidation at an early stage of liver injury but not enough to enhanced hepatic lipid peroxidation at a progressed stage of liver injury.
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PMID:Response of endogenous reduced glutathione through hepatic glutathione redox cycle to enhancement of hepatic lipid peroxidation with the development of acute liver injury in mice intoxicated with carbon tetrachloride. 888 91

Redox stress during post-ischemic reperfusion may be the prime signal for processes leading to myocardial remodelling and hypertrophy. Nitric oxide (NO) is antioxidative, antiadhesive for neutrophils (PMN) and antiproliferative. Thus, enhancing endothelial production of NO, e.g. by inhibiting breakdown of endogenous bradykinin via angiotensin converting enzyme (ACE), could be beneficial. The effect of cilazaprilat (CILA, 10 micro M), an ACE inhibitor, on redox status, expression of the adhesion molecule P-selectin, and PMN adhesion under conditions of oxidative stress was investigated in cultured human umbilical vein endothelial cells (HUVECs). Incubation of the cells with H2O2 (0.1 and 1 mm) for 15 min served as oxidative stimulus. The intra- and extracellular concentrations of reduced and oxidized glutathione (GSH and GSSG) were measured by HPLC as indicators of endothelial redox status. Expression of P-selectin was measured by flow cytometry. Furthermore, firm leukocyte adhesion to HUVECs was assessed. In controls, the intracellular ratio GSH/GSSG averaged 47 and dropped to 30 after incubation with 0.1 mm H2O2. The ratio declined to 6.5 with 1 mm H2O2. CILA blocked the effects of 0.1 mm H2O2, but was ineffective against 1 mm peroxide. The extracellular ratio did not discriminate between 0.1 and 1 mm H2O2, falling from 18 to 1 in both situations. P-selectin expression rose from 100% (control) to 146% after 1 mm H2O2 without CILA, but only to 114% in the presence of CILA. PMN adhesion was enhanced from about 1600 PMN per microwell (control) to 4300/well by 1 mm H2O2. CILA had no significant effect on adhesion (3900 PMN/well). Exposure of HUVECs to 0.1 mm H2O2 affected neither P-selectin expression nor PMN adhesion. Consequently, ACE inhibition can mitigate mild (0.1 mm H2O2) but not more severe redox stress in HUVECs. Irrespectively, CILA reduced the upregulation of P-selectin at the higher H2O2 concentration, indicating that this process is regulated independently of the cellular redox status. The firm adhesion of PMN to HUVECs was independent of P-selectin expression.
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PMID:Effects of ACE-inhibition on redox status and expression of P-selectin of endothelial cells subjected to oxidative stress. 940 70

We have developed a rapid and precise method for glutathione quantitation by capillary electrophoresis, that allows a low amount of both redox forms to be measured. Small fragments of rat heart or liver tissues (20 mg wet weight) and the corresponding mitochondria (1 mg protein) were homogenized in 1% perchloric acid and the acid-soluble phase ultrafiltered by centrifugation with a microconcentrator (Mr cut-off 3000 Da). The analysis was performed at a constant temperature (28 degrees C) using a Beckman P/ACE System 2100, equipped with a UV absorbance detector set to 200 nm. The limit of quantitation in heart tissue was 1.8 microM for GSH and 1.2 microM for GSSG. Myocardial concentrations of GSH and GSSG were 8.1 +/- 2.6 and 0.45 +/- 0.15 (nmol/mg protein +/- S.D.), respectively. The ratio of GSH to GSSG was 17.8 +/- 1.3 for heart tissue, whereas it was much higher (>100) in the mitochondria. An oxidative stress decreased the myocardial tissue GSH/GSSG ratio, indicating that the CE analysis of both glutathione forms is also a useful method to study biological redox modification.
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PMID:Simultaneous detection of reduced and oxidized glutathione in tissues and mitochondria by capillary electrophoresis. 961 63

The effect of enalapril and captopril on total glutathione content (GSSG + GSH) and selenium-dependent glutathione peroxidase (Se-GPx) and glutathione reductase (GSSG-Rd) activities was investigated in mouse tissues. CF-1 mice (4-mo-old females) received water containing enalapril (20 mg/l) or captopril (50 mg/l) for 11 wk. Enalapril increased GSSG + GSH content (P < 0.05) in erythrocytes (147%), brain (112%), and lung (67%), and captopril increased GSSG + GSH content in erythrocytes (190%) and brain (132%). Enalapril enhanced Se-GPx activity in kidney cortex (42%) and kidney medulla (23%) and captopril in kidney cortex (30%). GSSG-Rd activity was enhanced by enalapril in erythrocytes (21%), brain (21%), liver (18%), and kidney cortex (53%) and by captopril in erythrocytes (25%), brain (19%), and liver (34%). In vitro erythrocyte oxidant stress was evaluated by thiobarbituric acid-reactive substances (TBARS) production (control 365 +/- 11, enalapril 221 +/- 26, captopril 206 +/- 17 nmol TBARS x g Hb(-1) x h(-1); both P < 0.05 vs. control) and phenylhydrazine-induced methemoglobin (MetHb) formation (control 66.5 +/- 3.5, enalapril 52.9 +/- 0.4, captopril: 56.4 +/- 2.9 micromol MetHb/g Hb; both P < 0.05 vs. control). Both angiotensin-converting enzyme inhibitor treatments were associated with increased nitric oxide production, as assessed by plasma NO-(3) + NO-(2) level determination (control 9.22 +/- 0.64, enalapril 13.7 +/- 1.9, captopril 17.3 +/- 3.0 micromol NO-(3) + NO-(2)/l plasma; both P < 0.05 vs. control). These findings support our previous reports on the enalapril- and captopril-induced enhancement of endogenous antioxidant defenses and include new data on glutathione-dependent defenses, thus furthering current knowledge on the association of ACE inhibition and antioxidants.
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PMID:Enalapril and captopril enhance glutathione-dependent antioxidant defenses in mouse tissues. 1071 74

We have reported that melatonin protects against alpha-naphthylisothiocyanate (ANIT)-induced acute liver injury in rats by preventing enhanced lipid peroxidation. Herein, we examine the effect of melatonin on hepatic antioxidant enzyme activities in rats with a single i.p. injection of ANIT (75 mg/kg body weight) in order to clarify the protective mechanism of the indoleamine against ANIT-induced acute liver injury. Rats received a single oral administration of melatonin (10 or 100 mg/kg body weight) at 12 hr after ANIT treatment. Hepatic Cu,Zn-superoxide dismutase (Cu,Zn-SOD), Mn-superoxide dismutase (Mn-SOD), catalase (CAT), Se-glutathione peroxidase (Se-GSH-Px), glutathione reductase (GSSG-R), and glucose-6-phosphate dehydrogenase (G-6-PDH) activities and reduced glutathione (GSH) concentration were determined 12 and 24 hr after ANIT treatment. ANIT-treated rats showed decreases in hepatic Cu,Zn-SOD and GSSG-R activities at 24 hr after treatment, transient increases in hepatic CAT and Se-GSH-Px activities at 12 hr, and no changes in hepatic Mn-SOD and G-6-PDH activities at 12 or 24 hr. Only the high dose of melatonin attenuated the decrease in hepatic Cu,Zn-SOD activity, while both doses of the indoleamine almost completely attenuated the decrease in hepatic GSSG-R activity. Neither dose of melatonin affected hepatic CAT, Se-GSH-Px, and G-6-PDH activities. ANIT-treated rats showed an increase in hepatic GSH concentration at 24 hr after treatment. Neither dose of melatonin affected the increase in hepatic GSH concentration. These results indicate that orally administered melatonin prevents decreases in Cu,Zn-SOD and GSSG-R activities in the liver of ANIT-treated rats, and suggest that the indoleamine may protect against ANIT-induced acute liver injury by attenuating the disruption of hepatic antioxidant defense systems.
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PMID:Effect of melatonin on changes in hepatic antioxidant enzyme activities in rats treated with alpha-naphthylisothiocyanate. 1170 68

Five commercial peptides, namely, reduced glutathione (GSH), oxidized glutathione (GSSG), carnosine, homocarnosine, and anserine, were used to test angiotensin converting enzyme inhibitory (ACEI) activities using N-[3-(2-furyl)acryloyl]-Phe-Gly-Gly (FAPGG) as a substrate. All of these peptides showed dose-dependent ACEI activities. Using 50% inhibition (IC(50)) of captopril as 0.00781 microM for the reference, the IC(50) values of GSH, carnosine, homocarnosine, and anserine were determined to be 32.4 microM, 5.216 mM, 6.147 mM, and 6.967 mM, respectively. GSH or carnosine showed mixed noncompetitive inhibition against ACE. When 0.0164 mM GSH or 0.4098 mM carnosine was added, the apparent inhibition constant (K(i)) was 49.7 microM or 3.899 mM, respectively. Commercial glutathione-Sepharose 4 fast flow, GSH-coupled CNBr-activated and GSH-coupled EAH-activated Sepharose gels were used for ACE purification. Commercial ACE could be adsorbed only by EAH-coupled GSH gels and eluted off the gels by increasing salt concentrations. These EAH-coupled GSH gels might be developed as affinity aids for ACE purification.
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PMID:Antioxidant peptides with Angiotensin converting enzyme inhibitory activities and applications for Angiotensin converting enzyme purification. 1261 9

We reported that melatonin prevents the progression of carbon tetrachloride (CCl4)-induced acute liver injury in rats possibly by attenuating enhanced lipid peroxidation and reduced glutathione depletion. Herein, we examined the effect of melatonin on the changes in hepatic reactive oxygen species (ROS) metabolism in rats with a single intraperitoneal injection of CCl4 (1.6 g/kg body weight); the intent was to clarify the therapeutic mechanism of the indoleamine on CCl4-induced acute liver injury. Rats with and without CCl4 treatment received a single oral dose of melatonin (10, 50 or 100 mg/kg body weight) 6 hr after CCl4 treatment. Hepatic concentrations of ascorbic acid (ASC) and vitamin E (VE) and hepatic activities of superoxide dismutase (SOD), catalase (CAT), Se-glutathione peroxidase (Se-GSH-Px), glutathione reductase (GSSG-R), glucose-6-phosphate dehydrogenase (G-6-PDH), and xanthine oxidase (XO) were determined 6 and 24 hr after CCl4 treatment. The liver of CCl4-treated rats showed reductions in ASC concentrations, and SOD activity and an increase in G-6-PDH activity at 6 hr after treatment and further decreases in ACS concentrations and SOD activity and also further increase in G-6-PDH activity in addition to decreases in CAT and GSSG-R activities and increases in VE concentrations and XO activity at 24 hr after treatment. Melatonin attenuated the reductions in hepatic ASC concentrations and SOD, CAT and GSSG-R activities and the increase in hepatic XO activity in a dose-dependent manner without affecting either hepatic Se-GSH-Px activity or the increased hepatic VE concentration and G-6-PDH activity at 24 hr after CCl4 treatment. No dose of melatonin influenced hepatic ACS and VE concentrations and SOD, CAT, Se-GSH-Px, G-6-PDH, and XO activities in CCl4-untreated rats. These results indicate that melatonin postadministered at pharmacological doses prevents the disruption of hepatic ROS metabolism associated with ASC, SOD, CAT, GSSG-R, and XO, in addition to reduced glutathione, in CCl4-treated rats.
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PMID:Melatonin prevents disruption of hepatic reactive oxygen species metabolism in rats treated with carbon tetrachloride. 1467 25

We previously demonstrated a high susceptibility of neonatal red blood cells (RBC) to oxidative stress at birth. The aim of this study was to compare the RBC antioxidant capacity and redox cycle enzyme activities as well as glutathione (GSH) recycling in full-term and preterm infants at birth and in normal adults. GSH and GSH disulfide (GSSG) concentrations, GSH/GSSG ratio, and the activities of glucose-6-phosphate dehydrogenase (G-6-PDH), GSH peroxidase, GSH reductase (GR), catalase (CAT), superoxide dismutase (SOD), and hexokinase (HK) were measured in RBC of 25 healthy adults and 56 newborns (23 term, 33 preterm) at birth. The GSH recycling was measured in adult and newborn RBC exposed to oxidative stress (1 mM tert-butylhydroperoxide). The RBC of term and preterm babies showed higher GSH, GSSG, G-6-PDH, GR, and HK levels/activities and lower GSH/GSSG ratios and higher GSH-recycling rates than those of adults. In preterm babies significant correlations were found between G-6-PDH and CAT, GSH, GSH/GSSG ratio, and GSSG (r = -0.67, r = 0.71, r = -0.66, p < 0.01; r = 0.71, p < 0.05, respectively). In term newborns, statistically significant correlations were observed between G-6-PDH and CAT, SOD, and GSH (r = -0.65, r = -0.65, r = -0.69, p < 0.01, respectively). The results indicate the central role of the G-6-PDH activity in antioxidant defenses. We speculate that preterm babies have prompter involvement of antioxidant defenses than term babies.
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PMID:Glutathione recycling and antioxidant enzyme activities in erythrocytes of term and preterm newborns at birth. 1470 31


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