Search PubMed⌕ Search

Biomedical subjects

L S Terada

Publications and source records attributed to L S Terada.

At least 19 recordsLinked to original sources
PubMed1992

Hypoxia injures endothelial cells by increasing endogenous xanthine oxidase activity.

Exposure to decreasing oxygen tensions progressively increased xanthine dehydrogenase (XD) and xanthine oxidase (XO) activities over 48 hr in cultured pulmonary artery endothelial cells (EC) without altering XD/XO ratios. Increases in XD and XO activity in EC induced by hypoxia were associated upon reoxygenation with increased (P less than 0.05) extracellular superoxide anion (O2-.) levels that were inhibited by treatment with XO inhibitors (tungsten, allopurinol) or an anion-channel blocker (4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid). EC monolayers subjected to hypoxia/reoxygenation also leaked more preloaded 51Cr, were more adherent to neutrophils, and permitted greater albumin transit than control monolayers. Treatment with tungsten, allopurinol, and/or superoxide dismutase decreased (P less than 0.05) 51Cr release, neutrophil adherence, and albumin transit in EC monolayers exposed to hypoxia/reoxygenation. We conclude that prolonged hypoxia increases both XO and XD activity in EC and may predispose the endothelium to oxidative and inflammatory damage.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1992

Tungsten treatment prevents tumor necrosis factor-induced injury of brain endothelial cells.

Exposure to recombinant human tumor necrosis factor-alpha (TNF-alpha) or calcium ionophore (A23187) for 4 h increased (P less than 0.05) lactate dehydrogenase (LDH) release from cultured bovine brain endothelial cells (EC). In contrast, treatment with endotoxin or interleukin-1 did not increase (P greater than 0.05). LDH release from brain EC. Pretreatment with tungsten decreased (P less than 0.05) xanthine oxidase activity in brain EC and decreased (P less than 0.05) LDH release from brain EC following exposure to TNF. Our results suggest that TNF-alpha injures brain microvascular EC and that this effect may be mediated by xanthine oxidase.

Animals↗
PubMed1992

Circulating xanthine oxidase mediates lung neutrophil sequestration after intestinal ischemia-reperfusion.

Injury to nonpulmonary organ systems often initiates systemic processes that cause recruitment of neutrophils to the lung. We found that rats subjected to intestinal ischemia-reperfusion (I/R) had increased transvascular leak of 125I-labeled albumin into lungs and decreased lung ATP levels (P less than 0.05). In addition, rats subjected to intestinal I/R had increased plasma xanthine oxidase (XO) activity, plasma leukotactic activity for neutrophils, and lung neutrophil retention (assessed by morphometry and myeloperoxidase activity) compared with sham-treated rats (P less than 0.05). By comparison, after intestinal I/R, rats fed an allopurinol- or tungsten-enriched diet had decreased plasma and intestinal XO activities, decreased plasma leukotacic and lung myeloperoxidase (MPO) activities, decreased lung leak, and increased lung ATP levels compared with rats fed control diets (P less than 0.05). Further studies suggested a more specific role for circulating rather than tissue XO in mediating lung neutrophil accumulation but not lung leak. Plasma XO, plasma leukotactic, and lung MPO activities, but not lung leak, increased in rats administered purified XO intravenously. In addition, plasma XO, plasma leukotactic, and lung MPO activities, but not lung leak, decreased in rats administered antisera against XO and then subjected to intestinal I/R. We conclude that circulating XO increases acutely and may contribute to pulmonary retention of neutrophils after an ischemic intestinal insult.

Allopurinol↗
PubMed1991

Generation of superoxide anion by brain endothelial cell xanthine oxidase.

Bovine brain endothelial cells (EC) that were isolated and propagated in pure culture had increased (greater than 20-fold) levels of xanthine oxidase and xanthine dehydrogenase activity compared to whole brain homogenate. Brain EC also released superoxide anion (O2-) into the extracellular medium. Treatment of EC with tungsten decreased (P less than 0.05) both XO activity and O2- release. XO appears to be highly concentrated in cerebral vascular endothelium and may be an important source of O2-.

Animals↗
PubMed1991

Inactivation of xanthine oxidase by hydrogen peroxide involves site-directed hydroxyl radical formation.

The mechanism of xanthine oxidase (XO) inactivation by hydrogen peroxide (H2O2) and its biologic significance are unclear. We found that addition of increasing concentrations of H2O2 progressively decreased xanthine oxidase activity in the presence but not the absence of xanthine in vitro. Inactivation of XO by H2O2 was also enhanced by anaerobic reduction of XO by xanthine. Inactivation of XO by H2O2 was accompanied by production of hydroxyl radical (.OH), measured as formation of formaldehyde from dimethylsulfoxide (DMSO). In contrast, addition of H2O2 to deflavo XO did not produce .OH. Inactivation of XO by H2O2 was decreased by simultaneous addition of the .OH scavenger, DMSO. However, inactivation of XO by H2O2 and formation of .OH were not decreased following addition of the metal chelator. DETAPAC, and/or the O2 scavenger, superoxide dismutase. The results suggest that inactivation of XO by H2O2 occurs by production of .OH following direct reduction of H2O2 by XO at the flavin site.

Dimethyl Sulfoxide↗
PubMed1991

Existence and participation of xanthine oxidase in reperfusion injury of ischemic rabbit myocardium.

Using a highly specific assay that minimizes enzyme inactivation in vitro, we found that rabbit myocardial tissue contained low levels of xanthine oxidase (XO) and xanthine dehydrogenase (XD) activity that were effectively inhibited by pretreatment of hearts with allopurinol. In parallel, allopurinol treatment also improved ventricular developed pressure, peak systolic pressure, and coronary flow in isolated hearts subjected to 30 min of normothermic global ischemia and 30 min of reperfusion. Although function was protected by allopurinol treatment, creatine kinase (CK) release was not altered by allopurinol. Inhibition of myocardial XO with allopurinol did not increase myocardial ATP or phosphocreatine. In addition, allopurinol did not scavenge superoxide anion or hydrogen peroxide in vitro. The results support the possibility that relatively low amounts of XO activity, similar to levels reported in human myocardium, may contribute to cardiac ischemia-reperfusion injury.

Allopurinol↗
PubMed1991

FNLP injures endotoxin-primed rat lung by neutrophil-dependent and -independent mechanisms.

Bacterial lipopolysaccharide (LPS) and an N-formyl peptide, N-formyl-neoleucyl-leucyl-phenylalanine (FNLP), synergistically promote lung injury in rats as measured by 125I-labeled albumin flux. Concomitantly, neutrophils are sequestered in the lung. We hypothesized that LPS-FNLP-induced lung injury is mediated both by neutrophil-dependent and -independent mechanisms. Rats were depleted of circulating and marginating neutrophils with vinblastine. LPS-FNLP-induced lung protein leak was partially decreased in these neutrophil-depleted animals, although a component of lung injury remained. We hypothesized that LPS-FNLP-induced lung injury was also mediated by xanthine oxidase (XO). Rats were fed a tungsten-enriched diet that inactivates molybdenum-dependent oxidase systems. LPS-FNLP-induced lung leak was partially decreased in these animals as well. When tungsten-fed rats were also neutrophil depleted with vinblastine, no increase in 125I-albumin flux was observed in response to LPS-FNLP. In parallel experiments, lungs from vinblastine-pretreated rats were isolated and perfused. FNLP infusion into the LPS-primed, crystalloid-perfused lungs caused increased 125I-albumin flux, which was prevented by oxidase inhibition. We conclude that LPS-FNLP-induced lung injury is both neutrophil mediated and neutrophil independent. The nonneutrophil component of the LPS-FNLP-induced lung injury appears to be pulmonary XO derived and dependent.

Animals↗
PubMed1991

Hypovolemic shock promotes neutrophil sequestration in lungs by a xanthine oxidase-related mechanism.

Our results suggest that xanthine oxidase (XO) contributes to lung neutrophil sequestration in hypovolemic shock. Catheterized rats subjected to shock by phlebotomy (approximately 30% blood loss) had decreased mean arterial blood pressures (P less than 0.05) and increased (P less than 0.05) lung myeloperoxidase (MPO) activities (indicative of lung neutrophil accumulation) compared with sham-treated normotensive rats. In contrast, rats depleted of lung and plasma XO activity by tungsten diet before phlebotomy had decreased (P less than 0.05) lung MPO activities compared with phlebotomized rats fed regular diets.

Animals↗
PubMed1991

Human serum catalase decreases endothelial cell injury from hydrogen peroxide.

Serum from normal human subjects contained variable amounts of catalase activity, which was inhibitable by heat, azide, trichloroacetic acid (TCA), or aminotriazole treatment. Serum also decreased hydrogen peroxide (H2O2) concentrations in vitro and H2O2-mediated injury to cultured endothelial cells. By comparison, heat-, azide-, TCA-, or aminotriazole-treated serum neither decreased H2O2 concentrations in vitro nor reduced H2O2-mediated damage to endothelial cells. We conclude that serum catalase activity can alter H2O2-dependent reactions. We speculate that variations in serum catalase activity may alter individual susceptibility to oxidant-mediated vascular disease or be a factor when added to test systems in vitro.

Animals↗
PubMed1991

Reperfusion of ischemic skeletal muscle causes erythrocyte hemolysis and decreases subsequent oxidant-mediated lung injury.

A prior transient hindlimb ischemia/reperfusion (I/R) insult decreased acute lung injury in rats subsequently treated with cobra venom factor. I/R-mediated protection was associated with erythrocyte hemolysis, increased plasma catalase activity, and increased plasma hydrogen peroxide scavenging activity. In contrast, hindlimb I/R did not increase lung catalase activity, and large amounts of injected catalase were required to increase lung catalase activity. The results suggest that limited I/R in one organ can induce systemic processes that may decrease a subsequent O2 metabolite-mediated injury in another distant organ. The mechanism may involve release of catalase from hemolyzed erythrocytes at levels that are not sufficient to measurably increase total lung catalase activity.

Animals↗
PubMed1990

Metals inhibit riboflavin-catalyzed generation of superoxide anion in vitro.

We found that addition of cationic metals inhibited flavin-catalyzed superoxide anion (O2-.) production in vitro. Inhibition of O2-. generation by metals appeared to relate to the ability of metal ions to chelate or complex with amine groups, altering their electronegativity. Metal inhibition of O2-. production has important implications for biological systems involving O2-. radical production, as well as for assays requiring the generation of O2-. in vitro.

Catalysis↗
PubMed1990

Interleukin 1 pretreatment decreases ischemia/reperfusion injury.

Hearts isolated from rats treated 36 hr before with interleukin 1 (IL-1) had increased glucose-6-phosphate dehydrogenase (G6PD) activity and decreased hydrogen peroxide levels and injury after global ischemia (I, 20 min)/reperfusion (R, 40 min) compared with hearts from untreated rats. Hearts isolated from rats treated 6 hr earlier with IL-1 also had increased polymorphonuclear leukocytes (PMN), H2O2 levels, and oxidized glutathione (GSSG) contents compared with hearts from untreated rats. Depletion of circulating blood PMN by prior treatment with vinblastine prevented both early (from treatment 6 hr before study) IL-1-induced increases in myocardial PMN accumulation, H2O2 levels, and GSSG contents and late (from treatment 36 hr before study) increases in myocardial G6PD activity and protection against I/R. Our results indicate that IL-1 pretreatment causes an early (6 hr after IL-1 treatment) myocardial PMN accumulation and most likely an H2O2-dependent oxidative stress, which contributes to late (36 hr after IL-1 treatment) increases in myocardial G6PD activity and decreases in I/R injury.

6-Aminonicotinamide↗
PubMed1990

Xanthine oxidase-derived H2O2 contributes to reperfusion injury of ischemic skeletal muscle.

We hypothesized that xanthine oxidase (XO)-derived hydrogen peroxide (H2O2) contributes to ischemic skeletal muscle injury during reperfusion. We found that after ischemia (3 h) and then reperfusion (4 h) rat gastrocnemius muscles had decreased contractile function following direct stimulation. Three lines of investigation suggested that XO-derived H2O2 contributes to reperfusion injury of ischemic skeletal muscle. First, treatment with dimethylthiurea (DMTU), a highly permeant O2 metabolite scavenger, but not urea, just before reperfusion improved muscle function in legs subjected to ischemia and then reperfusion. Second, gastrocnemius muscles from rats fed tungsten or allopurinol had negligible XO activities and increased muscle function after ischemia and reperfusion. Third, as assessed by measurement of skeletal muscle catalase activity in the presence of aminotriazole, H2O2 was measured during reperfusion of ischemic muscles from untreated or urea-treated rats but not during reperfusion of muscles from rats treated with DMTU, tungsten, or allopurinol.

Allopurinol↗
PubMed1990

Neutrophils accumulate and contribute to skeletal muscle dysfunction after ischemia-reperfusion.

Skeletal muscles subjected to ischemia and then reperfusion develop contractile dysfunction for reasons that are unclear. We found that rats pretreated with vinblastine 4 days before study had decreased numbers of blood neutrophils and increased gastrocnemius muscle function after ischemia (3h) and reperfusion (4 h) compared with untreated rats or rats treated 4 days before study with saline. By comparison, rats pretreated with vinblastine or saline 1 day before study had increased blood neutrophils and decreased gastrocnemius muscle contractile function after ischemia-reperfusion compared with untreated rats. In addition, numbers of neutrophils in gastrocnemius muscles paralleled numbers of blood neutrophils and correlated with gastrocnemius muscle edema and contractile function after ischemia and reperfusion. The results indicate that neutrophils accumulate and may play an important role in the genesis of skeletal muscle contractile dysfunction after ischemia-reperfusion.

Animals↗
PubMed1990

Xanthine oxidase is increased and contributes to paraquat-induced acute lung injury.

Two lines of investigation suggested that xanthine oxidase- (XO) derived O2 metabolites contribute to paraquat- (PQ) induced acute lung injury. First, PQ treatment increased lung XO activity and decreased lung xanthine dehydrogenase activity. Second, lung albumin uptake increased compared with control values in untreated XO-replete but not tungsten-treated XO-depleted lungs in rats treated with PQ.

Albumins↗
PubMed1989

Albumin decreases hydrogen peroxide and reperfusion injury in isolated rat hearts.

Perfusion with human serum albumin decreased myocardial hydrogen peroxide (H2O2) levels (as assessed by inactivation of myocardial catalase activities following aminotriazole pretreatment) and increased myocardial ventricular developed pressures (DP), contractility (+dP/dt) but not relaxation rate (-dP/dt) in isolated crystalloid perfused rat hearts subjected to normothermic global ischemia (20 min) and then reperfusion (40 min). Albumin also decreased H2O2 concentrations in vitro. The findings support the possibility that albumin may act as a protective O2 metabolite scavenger in vivo.

Animals↗
PubMed1989

Endotoxin pretreatment increases endogenous myocardial catalase activity and decreases ischemia-reperfusion injury of isolated rat hearts.

Hearts isolated from rats pretreated 24 hr before with endotoxin had increased myocardial catalase activity, but the same superoxide dismutase, glutathione peroxidase, glutathione reductase, and glucose-6-phosphate dehydrogenase activities, as hearts from untreated rats. Hearts isolated from rats pretreated with endotoxin 24 hr before also had increased myocardial function (decreased injury) after ischemia and reperfusion (Langendorff apparatus, 37 degrees C), as assessed by measurement of ventricular developed pressure, contractility (+dP/dt), and relaxation rate (-dP/dt), compared to control hearts. In contrast, hearts isolated from rats pretreated with endotoxin 1 hr before isolation or hearts perfused with endotoxin did not have increased catalase activity or decreased injury following ischemia and reperfusion. Aminotriazole pretreatment prevented increases in myocardial catalase activity and myocardial function after ischemia-reperfusion in hearts from endotoxin-pretreated rats. The results suggest that endotoxin pretreatment decreases cardiac ischemia-reperfusion injury and that increases in endogenous myocardial catalase activity contribute to protection.

Amitrole↗