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A T Demiryürek

Publications and source records attributed to A T Demiryürek.

At least 19 recordsLinked to original sources
PubMed2005

Effects of whole-body hypoxic preconditioning on hypoxia/reoxygenation-induced intestinal injury in newborn rats.

PURPOSE: The precise cause of necrotizing enterocolitis (NEC) is elusive. Ischemia and reperfusion injury of the intestine has been considered to be a major contributing factor for NEC. Ischemic preconditioning is defined as one or more brief periods of ischemia with intermittent reperfusion that protects tissues against a sustained period of subsequent ischemia. Contribution of preconditioning to hypoxia/reoxygenation-induced intestinal injury in newborn rats has not been evaluated previously. METHODS: The study was carried out on 1-day-old Wistar albino rat pups. Whole-body hypoxia and reoxygenation (H/R) was achieved by 10 min hypoxia using 95 % N (2) + 5 % CO (2) followed by 10 min reoxygenation with 100 % oxygen. Whole body hypoxic preconditioning (HP) cycles were performed with 3 min hypoxia and 5 min reoxygenation. Thirty-three pups were randomly allocated into 4 groups. Group 1 served as untreated controls. The pups in group 2 were subjected to H/R only. In groups 3 and 4, 1 cycle and 3 cycles of HP were performed prior to H/R, respectively. Animals were killed at the end of the protocols. Intestine specimens were obtained to determine the histological changes, as well as to measure the tissue malondialdehyde (MDA) and nitric oxide (NO) levels, and xanthine oxidase (XO) and myeloperoxidase (MPO) activities. RESULTS: The microscopic lesions in H/R rat pups were virtually the same as those seen in neonatal NEC, with severe destruction of villi and crypts, in some cases extending to the muscularis. In both HP groups, the lesions were found to be milder. H/R resulted in a marked elevation in MDA and NO levels, and XO and MPO activities compared to the untreated controls. Both 1 cycle and 3 cycles of HP prior to H/R resulted in an obvious decrease in all biochemical parameters. Differences of the biochemical results between both HP groups were not statistically significant. CONCLUSION: This study revealed that whole-body hypoxic preconditioning is beneficial for hypoxia/reoxygenation-induced intestinal injury in newborn rats.

Analysis of Variance↗
PubMed2005

Cardiotoxicity of digitalis glycosides: roles of autonomic pathways, autacoids and ion channels.

1 Cardiac glycosides have been used for centuries as therapeutic agents for the treatment of heart diseases. In patients with heart failure, digoxin and the other glycosides exert their positive inotropic effect by inhibiting Na(+)-K(+)-ATPase, thereby increasing intracellular sodium, which, in turn, inhibits the Na(+)/Ca(2+) exchanger and increases intracellular calcium levels. As the therapeutic index of digitalis is narrow, arrhythmias are common problems in clinical practice. The mechanisms and mediators of these arrhythmias, however, are not completely understood. 2 The involvement of the sympathetic and parasympathetic nervous system in digitalis cardiac toxicity is reviewed. 3 Receptors, channels, exchange systems or other cellular components involved in digitalis-induced cardiotoxicity are also reviewed. 4 Possible mediators of digitalis-induced cardiac toxicity are discussed. 5 Management of digitalis toxicity in patients is summarized. 6 The determination of the possible mediators of digitalis-induced cardiac toxicity will enhance our knowledge and lead to the development of new therapeutic strategies to treat these lethal arrhythmias.

Animals↗
PubMed2001

Contribution of peroxynitrite to the beneficial effects of preconditioning on ischaemia-induced arrhythmias in rat isolated hearts.

We studied the effects of urate, a peroxynitrite scavenger, on ischaemia- and peroxynitrite-induced preconditioning in rat isolated hearts. Isolated hearts perfused with Krebs-Henseleit solution were preconditioned either by 3 min of coronary artery occlusion or by peroxynitrite administration (1 microM) for 3 min, followed by 10 min of reperfusion and 30 min of coronary artery occlusion. Both ischaemia and peroxynitrite produced a marked reduction in arrhythmias. Urate (1 mM) added to the perfusate 10 min prior to ischaemic preconditioning or peroxynitrite infusion and maintained until coronary artery occlusion, markedly reversed the beneficial effects in the ischaemic and peroxynitrite-treated groups. Urate administration in the peroxynitrite-treated group increased the incidence of ventricular tachycardia from 57% (n = 11) to 100% (n = 6) and total ventricular fibrillation from 0% (n=0) to 44% (n=4). Similarly, urate augmented the incidence of ventricular tachycardia from 47% (n=8) to 85% (n = 6) in the ischaemic preconditioning group. On its own, urate did not affect the severity of cardiac arrhythmias. Peroxynitrite infusion caused a marked increase in the effluent nitrate levels, from 0.05 +/- 0.1 microM (n = 5) to 0.4 +/- 0.2 microM (n = 6), and urate significantly decreased these levels to 0.08 +/- 0.03 microM (n = 9). These results suggest that peroxynitrite at low concentrations contributes to the beneficial effects of preconditioning on ischaemia-induced arrhythmias in rat isolated hearts.

Animals↗
PubMed2001

Effects of prilocaine and articaine on human leucocytes and reactive oxygen species in vitro.

BACKGROUND: The aim of this study was to investigate the ability of local anaesthetics to inhibit reactive oxygen and nitrogen species generated by either stimulated human leucocytes or cell-free systems using luminol chemiluminescence (CL). METHODS: Free radical generation was stimulated in leucocyte assay by formyl-methionyl-leucyl-phenylalanine (FMLP, 2 microM). In cell-free experiments, hydrogen peroxide (H2O2) 3.5 mM, sodium hypochloride 5 microM, ferrous sulphate (FeSO4) 40 nM, peroxynitrite 50 nM and xanthine 0.1 mmol l(-1) plus xanthine oxidase 0.25 U ml(-1) were used to produce H2O2, hypochlorous acid (HOCl), hydroxyl radical, peroxynitrite and superoxide-induced CL, respectively. RESULTS: Prilocaine inhibited FMLP-induced CL in leucocytes (94+/-1%, at 1 mM), whereas articaine showed an activation (59+/-7%) at high concentration (1 mM) and inhibition (13+/-6%) at low concentration (0.1 mM). In cell-free experiments, prilocaine (22+/-6%, at 1 mM) and articaine (85+/-1%, at 1 mM) caused concentration-dependent inhibition in xanthine-xanthine oxidase-induced CL. Although articaine had no effect on H2O2-induced CL, prilocaine significantly attenuated the H2O2 signal (97+/-0.3%, at 1 mM). Prilocaine (99+/-0.04%, 1 mM) and articaine (70+/-6%, 1 mM) markedly inhibited HOCl-induced CL, whereas these drugs had no effect on FeSO4-induced CL. Articaine inhibited peroxynitrite CL (63+/-6%, 1 mM), but prilocaine did not produce any depression on this signal. CONCLUSION: Prilocaine interacted with superoxide, HOCl and H2O2, whereas articaine reacted with superoxide, HOCl, and peroxynitrite. The direct scavenging properties of these drugs might be involved in the inhibition observed in leucocyte assay and could provide experimental support for investigating the potential benefit of using these local anaesthetics in patients presenting pathologies associated with free radical reactions.

Adult↗
PubMed2000

Hypochlorous acid-induced responses in sheep isolated pulmonary artery rings.

The formation of reactive oxygen species (ROS) appears to play a significant role in many pathological states including cystic fibrosis and asthma. Although stimulated inflammatory cells represent a major source of oxygen metabolites and these cells are able to generate the potent oxidant hypochlorous acid (HOCl) effects of HOCl on arteries are not known. HOCl at low concentrations (10(-7)to 10(-4)m) did not affect the resting force or have an action in precontracted sheep pulmonary arteries. HOCl at 10(-4) m concentration reduced histamine-induced relaxations in endothelium intact preparations. However, at high concentrations (10(-2) to 1 m) HOCl led to constriction under resting conditions and caused vasodilation in endothelium intact and denuded serotonin (10 microm) precontracted arteries. These effects of HOCl were significantly reduced by pretreatment of l -arginine (10(-3)m), sodium nitroprusside (SNP, 10(-5) m) and N -acetyl-l-cysteine (NAC, 10(-4) m). The effects of SNP and NAC on HOCl-induced responses were due to direct interaction since only these compounds markedly diminished the HOCl-induced luminol chemiluminescence (CL). Lack of contraction with KCl after high concentrations of HOCl showed that HOCl causes irreversible tissue damage. These results suggest that HOCl produce vasoconstriction under resting force and cause vasodilation when the pulmonary arteries precontracted. HOCl may interact with endothelium-derived mediators and contribute to tissue injury and vascular dysfunction seen in disease states.

Animals↗
PubMed2000

Effects of lidocaine on rabbit isolated thoracic aorta.

Lidocaine has been demonstrated to modify both contraction and relaxation of the vascular smooth muscle. Although lidocaine has been shown to inhibit endothelium-independent relaxations, the effects of lidocaine on arterial relaxation induced by peroxynitrite, a reaction product of superoxide and nitric oxide, have not been studied. The current study was designed to evaluate the effects of lidocaine on endothelium-dependent and -independent relaxations in isolated rabbit thoracic aorta. Rings of the rabbit thoracic aorta with or without endothelium were mounted for isometric force recording. Concentration-response curves to calcium ionophore A23187 ( 10(-9)to 3 x 10(-6)m), acetylcholine ( 10(-9)to 10(-3)m), sodium nitroprusside (SNP, 10(-9)to 10(-3)m), and peroxynitrite ( 10(-9)to 10(-3)m) were obtained in a cumulative manner. Lidocaine ( 10(-6)to 10(-4)m) was applied 15 min before addition of phenylephrine. Under resting force, lidocaine produced contractions at high concentrations ( 10(-5)to 10(-2)m) in endothelium-intact and -denuded arteries but removal of the endothelium did not significantly affect contractile activity. In phenylephrine-precontracted arteries, lidocaine caused concentration-dependent relaxations in both endothelium-intact and -denuded arteries. Inhibition of nitric oxide synthase or removal of endothelium did not affect the relaxations to lidocaine. Lidocaine suppressed the endothelium-independent relaxations of peroxynitrite, also poly (ADP-ribose) synthetase (PARS) enzyme activator, and SNP at high concentrations. Concentration-dependent vascular relaxations to A23187 and acetylcholine were significantly inhibited by lidocaine. These results suggest that lidocaine can depress vascular relaxations by a complex mechanism including inhibition of PARS enzyme activity.

Animals↗
PubMed2000

Accumulation of nitrotyrosine correlates with endothelial NO synthase in pulmonary resistance arteries during chronic hypoxia in the rat.

Nitrotyrosine and eNOS were detected immunocytochemically using specific antibodies in paraffin sections of lung from rats subjected to hypoxia for 2, 7, or 14 days. The staining intensity for eNOS was enhanced in the endothelium of both resistance and conduit pulmonary arteries at 2 days. Staining intensity for eNOS remained elevated at 7 and 14 days in conduit arteries, whereas it progressively increased further in resistance arteries. Nitrotyrosine staining was elevated to a similar degree in endothelium and adjacent vascular smooth muscle. In resistance pulmonary arteries, there was a progressive increase in nitrotyrosine, which matched the increase in eNOS. In conduit pulmonary arteries, nitrotyrosine increased only after 14 days of hypoxia. The results suggest that in chronic hypoxia the up-regulation of eNOS leads to the formation of peroxynitrite which has access to both endothelium and vascular smooth muscle.

Actins↗
PubMed2000

Evidence for the involvement of peroxynitrite in ischaemic preconditioning in rat isolated hearts.

1. The aim of this study was to investigate the involvement of peroxynitrite, reactive metabolite originating from nitric oxide and superoxide, in preconditioning of the ischaemic myocardium in rat isolated hearts. 2. Isolated hearts perfused with Krebs-Henseleit solution were preconditioned either by 3 min of coronary artery occlusion (CAO) or by peroxynitrite administration at three different concentrations (0.1, 1, 10 microM) for 3 min, followed by 10 min reperfusion and 30 min of CAO. Peroxynitrite, at 1 microM concentration, decreased the incidence of VT from 100% (n=14) to 62% (n=13) and abolished the occurrence of VF (50% in the control group). 3. N-2-mercaptopropionylglycine (MPG, 1 microM - 10 mM) produced a concentration-dependent inhibition of peroxynitrite signals in luminol chemiluminescence and 67+/-1% inhibition was observed at 100 microM (n=7). MPG (at 300 microM, n=7) added to the perfusate 10 min prior to ischaemic preconditioning or peroxynitrite infusion and maintained until CAO, significantly reversed the beneficial effects of the ischaemic and peroxynitrite-treated groups. MPG administration in the peroxynitrite-treated group increased the incidence of VT from 62% (n=13) to 100% (n=10) and total VF from 0% (n=0) to 67% (n=10). Similarly, MPG elevated the incidence of VT from 50% (n=10) to 100% (n=8) in the ischaemic preconditioned group. On its own, MPG did not affect the severity of cardiac arrhythmias. 4. These results suggest that endogenously produced peroxynitrite plays a significant role in the antiarrhythmic effect of ischaemic preconditioning in the rat isolated hearts.

Animals↗
PubMed1999

The beneficial effects of peroxynitrite on ischaemia-reperfusion arrhythmias in rat isolated hearts.

The simultaneous production of nitric oxide (NO) and superoxide leads to the formation of a potent toxic metabolite peroxynitrite (ONOO(-)). However, ONOO(-) at low concentrations has been found to exert cardioprotective effects. The purpose of the present study was to investigate the effects of exogenous ONOO(-) on ischaemia-reperfusion arrhythmias. We studied the concentration-response effects of ONOO(-) (0.4, 4, 40 microM ml(-1) min(-1) for 20 min) in rat isolated hearts perfused with Krebs-Henseleit solution. The 0.4 microM concentration of ONOO(-) was selected for further experiments since it did not affect the sinus rhythm. In the hearts subjected to 10 min of ischaemia followed by 10 min of reperfusion during 0.4 microM ml(-1) min(-1) ONOO(-) infusion, the incidence of ventricular fibrillation was decreased significantly from 93% to 38% (n=8) and none of the hearts had an irreversible ventricular fibrillation. Urate, a ONOO(-) scavenger (at 1 mM, n=7), added to the perfusate 5 min prior to the coronary artery occlusion and maintained throughout the experimental period, did not significantly modify the beneficial effects of ONOO(-). Although L-N(G)-nitroarginine methylester (L-NAME) (100 microM, n=8) had no effect, superoxide dismutase (10 U ml(-1))+catalase (100 U ml(-1)) increased the number of ventricular ectopic beats from 91+/-32 to 286+/-83 (n=5) and augmented the incidence of irreversible ventricular fibrillation from 0% to 60%. There were no marked changes in the time of onset of the first arrhythmias in any group. These results suggest that ONOO(-) at a low concentration may exert beneficial effects on ischaemia-reperfusion-induced arrhythmias in rat isolated hearts.

Animals↗
PubMed1999

Superoxide in the pulmonary circulation.

Superoxide formation in pulmonary tissue is modulated by cytokines, PO2, shear force, and disease states, and can be stimulated by drugs. Superoxide has diverse actions on pulmonary cells, including smooth muscle contraction, interaction with redox enzymes, cell proliferation, and gene transcription. In the lungs, there is an impressive array of specific defence mechanisms that destroy superoxide, especially superoxide dismutase (SOD) and metallothionein. Superoxide formation is increased in hyperoxia (e.g., oxygen therapy); however, superoxide-forming enzymes also can be up-regulated in hypoxia. Superoxide has been implicated in acute respiratory distress syndrome, lung ischaemia-reperfusion injury, and lung transplantation. Novel approaches to therapy have been explored, including SOD gene therapy and SOD targeting to the lung. In the future, new drugs interacting with superoxide may provide significant advances in the treatment of lung diseases.

Animals↗
PubMed1999

The role of nitric oxide in digoxin-induced arrhythmias in guinea-pigs.

We have investigated the effects of nitric oxide synthase inhibitor (L-NAME), nitric oxide precursor (L-arginine) and nitric oxide donor (sodium nitroprusside) on digoxin-induced arrhythmias both in guinea-pig isolated hearts and in anaesthetised animals. Sodium nitroprusside (0.1 mumol kg-1 min.-1 for 70 min.) caused a marked inhibition in mortality and arrhythmia score but L-NAME (10 mg kg-1) and L-arginine (30 mg kg-1 intravenous bolus followed by 10 mg kg-1 min.-1 for 60 min.) treatments were ineffective in anaesthetised guinea-pigs. None of the drugs markedly affected the time of onset of first arrhythmias or ventricular fibrillation incidence. In isolated heart experiments, nitric oxide generated by either L-arginine (1 mM) or sodium nitroprusside (1 mM) significantly reduced the arrhythmia score whereas L-NAME (1 mM) had no effect. Ventricular fibrillation incidence was totally abolished by sodium nitroprusside and none of the hearts treated with L-arginine had an irreversible ventricular fibrillation. L-NAME decreased ventricular tachycardia duration but increased ventricular fibrillation duration. There were no marked changes in the time of onset of first arrhythmias with these drugs in in vitro experiments. These results suggest that nitric oxide may play a modulatory role in the digoxin-induced arrhythmias in guinea-pigs.

Animals↗
PubMed1998

The role of tyrosine kinase in hypoxic constriction of sheep pulmonary artery rings.

Complex and incompletely understood mechanisms underline the vascular responses to hypoxia. Recent studies showed that the tyrosine kinase pathway is involved in vasoconstriction of vascular smooth muscle. Therefore, the aim of this study was to determine the tyrosine kinase pathway for the hypoxic contraction in large-diameter sheep pulmonary artery rings in vitro by studying the effects of selective inhibitors of tyrosine kinase and of a protein tyrosine kinase inhibitor. Lowering the pO2 from 96 to 5 mm Hg caused a contraction in arteries precontracted with 5-hydroxytryptamine (5-HT) but not under resting force. Preincubation of arteries with the tyrosine kinase inhibitors, genistein and tyrphostin, abolished the hypoxic contraction without affecting 5-HT contractions. Inhibition of tyrosine phosphatase activity by sodium orthovanadate increased the hypoxic vasoconstriction in 5-HT-precontracted arteries. These results suggest that the tyrosine kinase pathway is involved in hypoxic pulmonary vasoconstriction in sheep isolated pulmonary artery rings.

Animals↗
PubMed1998

Effects of free radical production and scavengers on occlusion-reperfusion induced arrhythmias.

Ventricular arrhythmias were studied in rat isolated hearts subjected to coronary artery occlusion and reperfusion. Free radicals in the perfusate were detected by continuous flow luminol-enhanced chemiluminescence. Administration of purine (2.3 mM) and xanthine oxidase (0.12 U ml-1 min-1) did not significantly modify the severity of reperfusion-induced arrhythmias but did generate free radicals. No free radical generation was detected during the period of coronary artery occlusion or reperfusion. Superoxide dismutase (SOD) 20-80 U ml-1 did not alter the severity of reperfusion arrhythmias but, in the presence of 80 U ml-1 SOD, occlusion-induced arrhythmias were augmented. SOD did not produce any effect on haemodynamics at the concentrations tested. Ventricular arrhythmias and cardiac haemodynamics were also not significantly changed by the combination of scavengers, SOD (10 U ml-1), catalase (100 U ml-1) and mannitol (20 mM). These data suggest that the superoxide free radical is unlikely to be the primary cause of reperfusion induced arrhythmias in rat isolated hearts subjected to regional ischaemia.

Animals↗
PubMed1998

Ferrous iron-induced luminol chemiluminescence: a method for hydroxyl radical study.

We have investigated the chemiluminescence signal of the ferrous iron in the presence of the luminol and lucigenin. Ferrous, but not ferric, iron produced a transient signal in the presence of luminol, but not lucigenin. Ferrous iron-induced luminol chemiluminescence was significantly inhibited in a concentration-dependent manner by superoxide dismutase (SOD) and catalase. Specific hydroxyl radical scavengers, mannitol and dimethyl sulfoxide (DMSO), also markedly attenuated the ferrous iron-induced chemiluminescence. Additionally, antioxidants, urate, ascorbate, and methionine produced concentration-dependent significant inhibitions in this chemiluminescence. These results show that the hydroxyl radical generation is dependent on simultaneous formation of superoxide and hydrogen peroxide (H2O2). Ferrous iron does not generate a chemiluminescence signal in the presence of lucigenin suggesting that the formation of a hydroxyl radical is responsible for the luminol chemiluminescence. Thus, the present study has established a simple and inexpensive cell-free screening method for monitoring the scavenging effects of drugs on the hydroxyl radical.

Catalase↗
PubMed1998

Comparison of antioxidant activities of aminoguanidine, methylguanidine and guanidine by luminol-enhanced chemiluminescence.

1. The objective of this study was to investigate the ability of aminoguanidine, methylguanidine and guanidine to inhibit free radicals or metabolites generated by either stimulated human leucocytes or cell-free systems using luminol-enhanced chemiluminescence (CL). 2. Aminoguanidine (0.1 microM-10 mM), methylguanidine (10 microM-10 mM) and guanidine (10 microM-10 mM) produced concentration-dependent inhibition (96+/-0.1%, n=7, 59+/-1.3%, n=6, and 62+/-3%, n=6, P<0.05 at 10 mM, respectively) in FMLP-stimulated leucocytes CL. 3. In cell-free experiments, hydrogen peroxide (H2O2), hypochlorous acid (HOCl), hydroxyl radical and peroxynitrite-induced CL responses were initiated by hydrogen peroxide (3.5 mM), NaOCl (50 microM), FeSO4 (40 nM) and peroxynitrite (20 nM), respectively. Aminoguanidine, methylguanidine and guanidine produced concentration-dependent inhibition in H2O2-(69+/-0.7%, n=7, 26+/-1%, n=6, and 15+/-0.5%, n=6, at 1 mM, respectively) and HOCl-(84+/-0.3%, n=6, 50+/-1%, n=6, and 29+/-1%, n=7, at 1 mM, respectively) induced luminol CL. Peroxynitrite-induced CL was markedly attenuated in a concentration-dependent manner by aminoguanidine (99+/-0.1%, n=6, at 10 mM), methylguanidine (5+/-0.2%, n=6, at 10 mM) and guanidine (27+/-0.4%, n=7, at 10 mM). However, inhibition with aminoguanidine was found to be more marked than with methylguanidine and guanidine. Aminoguanidine (95+/-0.5%, n=6, at 1 mM) and methylguanidine (25+/-1%, n=6, at 1 mM), but not guanidine (2+/-1%, n=6, at 1 mM), significantly decreased ferrous iron-induced CL. 4. Collectively, these data suggest that aminoguanidine and a high concentration (> or = 0.1 mM) of methylguanidine have direct scavenging activities against H2O2, HOCl, hydroxyl radical and peroxynitrite. Guanidine, at a high concentration (> or = 0.1 mM), scavenges H2O2, HOCl and peroxynitrite, but not the hydroxyl radical. These direct scavenging properties may contribute to inhibitory effects of these compounds on human leucocyte CL.

Antioxidants↗
PubMed1998

Propofol and intralipid interact with reactive oxygen species: a chemiluminescence study.

We have studied the ability of propofol and Intralipid to inhibit reactive oxygen species generated either by stimulated human leucocytes or cell-free systems using luminol chemiluminescence. Human leucocytes were stimulated by a chemotactic peptide, FMLP 1 mumol litre-1, or by a phorbol ester, PMA (protein kinase C activator) 0.1 mumol litre-1. In cell-free experiments, superoxide-hydrogen peroxide, hypochlorous acid or hydroxyl radical-induced chemiluminescence responses were initiated by xanthine 0.1 mmol litre-1 with xanthine oxidase 10 mu. ml-1, NaOCl 70 mumol litre-1 and FeSO4 3 mumol litre-1, respectively. Propofol with Intralipid, and to a lesser degree Intralipid alone, produced a concentration-dependent reduction in chemiluminescence from stimulated leucocytes. Similar attenuations were also observed using propofol with Intralipid on xanthine with xanthine oxidase-, HOCl- and ferrous iron-induced chemiluminescence. However, Intralipid produced a reduction only at high concentrations. Intralipid produced marked decreases in ferrous iron-induced chemiluminescence. This study suggests that propofol had a direct scavenging activity against HOCl, superoxide-hydrogen peroxide and hydroxyl radical in the concentrations used. These direct scavenging effects may contribute to the effect of propofol on human leucocyte chemiluminescence.

Anesthetics, Intravenous↗
PubMed1998

Peroxynitrite: a putative cytotoxin.

In recent years it has become apparent that peroxynitrite, which is one of the toxic metabolites originating from the reaction of nitric oxide and superoxide presents a number of pathologic states in which free radicals are thought to be involved. Peroxynitrite is capable of oxidizing a wide variety of biomolecules including plasma, proteins, lipids, carbohydrates and nucleic acids. Peroxynitrite is involved in the hydroxylation of aromatic compounds and acts as a nitrating agent. It modifies free or protein-associated tyrosine residues to give nitrotyrosines, leaving a marker detectable in vivo. Peroxynitrite has been implicated in the pathophysiology of a variety of diseases including inflammation, atherosclerosis, arthritis, endotoxemia, ischaemia-reperfusion injury, or acute respiratory distress syndrome. Development of specific peroxynitrite scavengers may provide new approaches for the effective treatment of these disease states.

Animals↗