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

Oxygen free radicals generated by leukocytes may contribute to tissue injury after central nervous system (CNS) focal ischemia or trauma. Inhibiting oxygen free radicals has improved outcome in experimental models of these conditions and antioxidant therapy appears promising. We evaluated the ability of a novel antioxidant, OPC-14117, to reduce hydrogen peroxide (H2O2) production by stimulated human polymorphonuclear (PMN) leukocytes and monocytes. Stimulated PMN and monocytes were incubated with several concentrations of OPC-14117 for 20 min and H2O2 production, nmol/1 x 10(6) cells/30 min, was measured. OPC-14117 significantly reduced PMN H2O2 production (P less than 0.001) and monocyte H2O2 production (P less than 0.05). A dose response relationship was observed for both leukocytes, as the 100 microM drug concentration was significantly (P less than 0.05) more effective than the 10 microM concentration. These results demonstrate that OPC-14117 inhibits H2O2 generation by stimulated human leukocytes and support further studies of its effects in disorders such as CNS focal ischemia and trauma, conditions where antioxidant therapy may be beneficial.
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PMID:Inhibition of stimulated human leukocyte hydrogen peroxide generation by a novel antioxidant, OPC-14117. 151 59

During the procedure of coronary artery bypass graft surgery (CABG), the release of free oxygen radicals as a result of ischemia and reperfusion which plants the seeds of post-operative low cardiac output and arrhythmias has grave consequence on the reestablishment of cardiac function. A variety of chemical agents such as mannitol, allopurinol, catalase (Q-10) and superoxide dismutase (SOD) has proved to be considerably effective to improve the myocardial necrosis following ischemia and reperfusion. In this study we chose mannitol (0.2 gm/kg) as the free oxygen radicals scavenger and utilized mass spectrophotometric method to detect the variation of concentration of [H2O2], a by-product of free oxygen radical, in an attempt to evaluate the efficacy of mannitol in this regard in patients undergoing CABG. Patients were divided into experimental group (n = 19) and control group (n = 20). In the experimental group the concentration of [H2O2] changed from 61 +/- 24 microM/L pre-operatively to 77 +/- 18 microM/L post-operatively as against 75 +/- 31 microM/L and 99 +/- 31 microM/L respectively in the control group. In comparison, only the change in experimental group was statistically significant (p less than 0.05). We confirmed that mannitol functions considerably as a free oxygen radical scavenger since it reduces the production of [H2O2] in patients undergoing CABG.
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PMID:[Mannitol reduces plasma hydrogen peroxide free radical in patients undergoing coronary artery bypass graft surgery]. 152 1

The potassium channel activator nicorandil, under evaluation for antianginal management, has been shown to decrease neutrophil respiratory burst. Since our laboratory has demonstrated that reactive oxygen species (ROS) increase tumor necrosis factor (TNF) production, we hypothesized that nicorandil might decrease TNF production from a lipopolysaccharide (LPS) challenge via reduction of respiratory burst. Macrophage viability and TNF production were determined after an 18-hr exposure to 5.0 micrograms/ml LPS and varying concentrations of nicorandil. Nicorandil was not toxic to macrophages below 12 mM (94 +/- 3% viability versus control) and decreased ROS and TNF production. Intracellular superoxide production decreased from 164 +/- 24 OD550 to 99 +/- 6 OD550 with 10 mM nicorandil and extracellular superoxide decreased from 3108 +/- 111 to 1760 +/- 210 nM. Hydrogen peroxide production was also decreased by 10 mM nicorandil. TNF production in response to 5 micrograms/ml LPS decreased from 6.8 +/- 0.6 to 2.7 +/- 0.4 ng/ml with 10 mM nicorandil. Northern and slot blot analyses demonstrate that nicorandil acts at a post-transcriptional site. These data imply that nicorandil decreases macrophage TNF production from an LPS challenge, possibly through a reduction in respiratory burst. Such compounds may prove useful in the treatment of conditions thought to be associated with free radical-lymphokine interactions such as ischemia-reperfusion injury, oxygen toxicity, adult respiratory distress syndrome, and septic shock.
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PMID:Alterations in macrophage free radical and tumor necrosis factor production by a potassium channel activator. 153 87

Mesenteric ischemia reflexly activates the cardiovascular system. In addition, mesenteric ischemia and reperfusion generate reactive oxygen species. However, the ability of these short-lived reactive oxygen species to generate cardiovascular reflexes is unknown. We therefore investigated cardiovascular reflexes induced by serosal application of hydrogen peroxide (H2O2) to the gallbladder, stomach, or duodenum in anesthetized cats. Serosal application of hydrogen peroxide (44 mumols) to the gallbladder (n = 14) significantly (p less than 0.05) increased mean arterial blood pressure (MAP) by 37 +/- 6 mm Hg, left ventricular dP/dt by 1,893 +/- 416 mm Hg/sec, heart rate by 6 +/- 1 beats per minute, and systemic vascular resistance from 0.34 +/- 0.01 to 0.42 +/- 0.04 peripheral resistance units. The cardiovascular effects were dose-dependent over a range of 0.4 pmol to 132 mumols H2O2. Celiac and superior mesenteric ganglionectomy abolished H2O2-induced cardiovascular effects. Dimethylthiourea (10 mg/kg), a reactive oxygen species scavenger, significantly (p less than 0.05) attenuated 44 mumols H2O2-induced increases in MAP from 36 +/- 3 to 2 +/- 2 mm Hg. Deferoxamine (10 mg/kg) also significantly attenuated 44 mumols H2O2-induced increases in MAP from 40 +/- 7 to 19 +/- 10 mm Hg, but iron-loaded deferoxamine did not. Aspirin (50 mg/kg) did not attenuate H2O2-induced excitation of the cardiovascular system. These data suggest that H2O2 activates abdominal visceral afferents to reflexly stimulate the cardiovascular system by a mechanism involving hydroxyl radicals. Thus, reactive oxygen species could modulate systemic vascular tone by stimulating abdominal visceral afferents during mesenteric ischemia and reperfusion.
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PMID:Hydrogen peroxide-induced cardiovascular reflexes. Role of hydroxyl radicals. 162 88

Although reactive oxygen species are believed to participate in postischemic renal injury, the actual chemical species involved and the role of endogenous scavenging systems in protecting against injury requires additional study. Hydrogen peroxide, which derives from superoxide radical, is toxic and also yields toxic hydroxyl radical. 3-amino-1,2,4-triazole reacts with catalase to form irreversibly inactivated catalase only in the presence of hydrogen peroxide. We made use of this chemical reaction both to determine whether inhibition of the hydrogen peroxide-scavenging enzyme catalase would influence ischemic renal injury and to measure hydrogen peroxide production rates after ischemia. Sprague-Dawley rats were given aminotriazole (100 mg/kg) one hour before 40 min of renal ischemia. Twenty-four h after ischemia GFR had decreased to 300 microL/min in control animals and to 50 microL/min in aminotriazole-treated animals. Histologic evidence of injury was also worse in catalase-inhibited animals. To measure hydrogen peroxide production rates aminotriazole was given 60 min before measurement of renal catalase activity. In control animals, aminotriazole caused a 53.4% decrease in catalase activity. In animals subjected to 40 min of ischemia plus either 10 or 60 min of reflow catalase activity decreased by 33.9 and 49.5% (not significantly different from control). Thus, when measured by this method total renal hydrogen peroxide production was considerable but was not increased by ischemia. However, in isolated proximal tubule segments 60 min of anoxia and 30 min of reoxygenation caused a 42% increase in H2O2 released into the incubation medium. In summary, inhibition of catalase before ischemia led to exacerbation of ischemic injury.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hydrogen peroxide and ischemic renal injury: effect of catalase inhibition. 164 49

The following species; superoxide (O2-.), hydrogen peroxide (H2O2), hydroxyl radical (.OH) and singlet oxygen (1O2), are generally called as reactive oxygen species (ROS). These species have been suggested to play important roles in various diseases caused by oxygen toxicity such as ischemia, carcinogenesis, inflammation, diabetes and aging. During the past two decades, considerable interests have been focused on chemical and biological research of ROS. We have also reported about the research results on ROS, which can be classified as following below; 1) chemical reactivities of O2-., 2) formation and toxicity of 1O2, 3) chemical reactivities of .OH, 4) enzyme mechanism of xanthine oxidase, 5) development of the compounds which induce the formation of O2-. and H2O2 in living cells and 6) development of superoxide dismutase mimics. These studies are reviewed from the standpoint of both chemical and biological interests.
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PMID:[Chemical and biochemical studies on reactivities, formations and toxicities of reactive oxygen species]. 164 54

Tissue oxidases, especially xanthine oxidase, have been proposed as primary sources of toxic oxygen radicals in many experimental models of disease states. Among these, ischemia-reperfusion injury may be of the greatest clinical interest. In this paper we propose the use of methylene blue as a means of suppressing the production of superoxide radicals O2- by acting as an alternative electron acceptor for xanthine oxidase. Previous work has indicated that methylene blue accepts electrons from xanthine oxidase at the iron-sulfur center. Initial experiments in our laboratory demonstrated that (1) pairs of electrons from each enzymatic oxidation are transferred to methylene blue, (2) the reduction of methylene blue can be achieved by model iron-sulfur centers, similar to the iron-sulfur center of xanthine oxidase, (3) reduced methylene blue auto-oxidizes to produce H2O2 directly, rather than O2-, and (4) methylene blue is effective at non-toxic levels (2-5 mg/kg) in preventing free radical damage to liver and kidney tissues in an in vitro model of ischemia and reoxygenation. Accordingly, we propose that methylene blue may represent a new class of antioxidant drugs that competitively inhibit reduction of molecular oxygen to superoxide by acting as alternative electron acceptors for tissue oxidases. We have termed these agents "parasitic" electron acceptors.
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PMID:Methylene blue as an inhibitor of superoxide generation by xanthine oxidase. A potential new drug for the attenuation of ischemia/reperfusion injury. 165 Feb 13

The accumulation of polymorphonuclear leucocytes (PMN) may play an important role in liver injury by toxins and ischemia/reperfusion. Upon activation these cells generate hypochlorous acid (HOCl) and long-lived oxidants such as monochloramine (NH2Cl) and taurinechloramine (TauNHCl) which could contribute to organ injury when PMN accumulate in the liver. Therefore, the effects of HOCl, NH2Cl and TauNHCl on hepatic function were investigated in the perfused rat liver. HOCl at a concentration of 2.7 microM resulted in a marked increase in the perfusion pressure and the release of LDH associated with a decrease in bile flow. These effects were abolished by increasing the concentration of extracellular glutathione in the perfusate to physiological levels. NH2Cl (15 microM) and TauNHCl (65 microM) increased the perfusion pressure only slightly, but resulted in significant increases in the biliary excretion of glutathione disulfide, indicating that chloramines are reduced intracellularly by glutathione. The increment in biliary glutathione disulfide depended on the amount of chloramine taken up by the liver. The extraction of NH2Cl averaged 98% compared to 13% for TauNHCl. The present data indicates that intra- and extracellular glutathione plays an important role not only in the detoxification of O2-. and H2O2 generated by activated PMN but also in the protection against the cytotoxic effects of products of myeloperoxidase released by PMN upon activation.
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PMID:Effects of hypochlorous acid and chloramines on vascular resistance, cell integrity, and biliary glutathione disulfide in the perfused rat liver: modulation by glutathione. 165 71

Hypertonic saline with dextran (HSD) has been recently introduced for prehospital resuscitation of hemorrhagic shock, and is currently undergoing clinical investigation. To determine the effect of clinically relevant amounts of hypertonic saline (7.5% NaCl) and/or 6% dextran 70 on non-ischemic and post-ischemic hearts, we infused rat hearts (Langendorff, 20 minutes global ischemia, 37 degrees, 40 minutes' reperfusion) with: 1) 0.9% NaCl (control); 2) 7.5% NaCl/dextran; 3) 7.5% NaCl; or 4) dextran. We found that 7.5% NaCl alone or with dextran depressed ventricular function (developed pressure, DP; contractility, +dP/dt; and relaxation rate, -dP/dt) in non-ischemic hearts. In contrast, equimolar (2,400 mOsm) sucrose increased myocardial contractility (+dP/dt) of non-ischemic hearts. Coronary flow was unchanged by the addition of 7.5% NaCl, dextran, or sucrose. Treatment of ischemic hearts with 7.5% NaCl/dextran, dextran alone, or sucrose improved recovery of ventricular function compared to 0.9% or 7.5% NaCl. Furthermore, dextran (but not sucrose) with or without 7.5% NaCl reduced myocardial hydrogen peroxide (H2O2) levels during ischemia and reperfusion. We conclude that when given in clinically relevant amounts in the isolated rat heart: 1) 7.5% NaCl directly depresses myocardial function; 2) 7.5% NaCl alone does not improve post-ischemic ventricular function; 3) 7.5% NaCl with dextran or dextran alone improves post-ischemic ventricular function in part by reducing myocardial H2O2; and 4) sucrose equimolar to 7.5% HSD increases ventricular function in non-ischemic and post-ischemic hearts. This investigation suggests that the post-shock benefit of HSD is unrelated to direct myocardial effects of saline but is due in part to toxic oxygen metabolite scavenging by dextran.
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PMID:Hypertonic saline and dextran: impact on cardiac function in the isolated rat heart. 169 95

Hydrogen peroxide produces marked antigonadotropic and lytic actions in luteal cells, but the effects of superoxide, the archetypal oxygen radical, are unknown. Xanthine oxidase generates superoxide, and the activity of this enzyme, and purine substrate, are increased under ischemia, such as that seen at luteal regression. We therefore examined the actions of xanthine oxidase on luteal cells to assess the effects of this enzyme and the superoxide anion on luteal function. Xanthine oxidase, in the presence of hypoxanthine (50 microM), produced marked inhibition of LH-sensitive cAMP and progesterone production with complete inhibition at 25 mU/ml and half-maximal inhibition at about 5 mU/ml. These antigonadotropic actions of xanthine oxidase were rapid with maximal effects within 5 min, followed several minutes later by substantial depletion of ATP. Heat, superoxide dismutase, and catalase or catalase alone abolished the actions of xanthine oxidase. While depletion of ATP by xanthine oxidase was prevented by 3-amino-benzamide, an inhibitor of DNA repair, inhibition of cAMP and progesterone production was still evident. Xanthine oxidase also inhibited progesterone synthesis stimulated by 8-bromo-cAMP. Isobutylmethylxanthine, a cAMP phosphodiesterase inhibitor, did not reverse the inhibition of cAMP accumulation by xanthine oxidase, and the enzyme had no effect on LH receptor binding activity. Since catalase reversed the effects of xanthine oxidase, we conclude that superoxide was rapidly dismuted to hydrogen peroxide and mediated the antigonadotropic and antisteroidogenic actions of xanthine oxidase in luteal cells. The sensitivity of luteal cells to xanthine oxidase raises the possibility that this enzyme may serve as a significant source of hydrogen peroxide in the corpus luteum.
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PMID:Inhibition of gonadotropin action and progesterone synthesis by xanthine oxidase in rat luteal cells. 170 32


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