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

Waintrub, Mauricio; Terada, Lance S.; Beehler, Connie J.; Anderson, Benjamin O.; Leff, Jonathan A.; Repine, John E.

doi:10.1152/jappl.1990.68.4.1755

Cited by 17 publications

(6 citation statements)

References 9 publications

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“…One of the plausible explanations for an increased UA level in human PQ poisoning is upregulation of XO activity. Studies have confirmed that PQ treatment significantly induces XO activity and increases hypoxanthine-dependent superoxide production 13 14 18 , which would then result in increased UA as it is the other main product of XO activity. Similarly, we previously reported significantly higher serum XO activity in a PQ poisoning group vs healthy controls 15 .…”

Section: Discussionmentioning

confidence: 95%

“…Uric acid (UA) is the major end product of purine metabolism and is formed from hypoxanthine and xanthine by the rate-limiting enzymatic action of xanthine oxidoreductase (XO) 11 12 . It has been reported that PQ treatment increases XO activity and stimulates hypoxanthine-dependent superoxide production in the cytosol of rat lungs 13 14 . Our previous study indicated increased XO activity accompanied by lipid peroxidation and reduced total antioxidant capacity in subjects with acute PQ poisoning 15 .…”

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confidence: 99%

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The significance of serum uric acid level in humans with acute paraquatpoisoning

Zhang

Zhao

Bai

et al. 2015

Sci Rep

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Hyperuricemia is a strong and independent predictor of all-cause mortality in cardiovascular disease and has been found to play a role in diseases exacerbated by oxidative stress and inflammation. This study aimed to evaluate whether serum uric acid (UA) level is an indicator of outcome in patients with acute paraquat poisoning. A total of 205 subjects who had attempted suicide by oral ingestion of paraquat were admitted to the emergency room between January 2009 and June 2014. Initial serum UA level and other laboratory parameters were measured. A total of 66 patients died during the 30 days after admission, corresponding to a 32.2% cumulative incidence of mortality. UA levels were higher in non-survivors than survivors (P < 0.001) and 30-day mortality increased with increasing baseline serum UA level (P < 0.001). In a prediction analysis for 30-day mortality, the serum UA level had a cut-off concentration of 284 µmol/L in female patients and 352 µmol/L in male patients. Multivariate Cox proportional hazards regression analyses showed that white blood cell counts and UA were independent prognostic factors. In conclusion, we showed that serum UA may be an independent predictor of 30-day mortality in patients with paraquat poisoning.

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Section: Discussionmentioning

confidence: 95%

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confidence: 99%

The significance of serum uric acid level in humans with acute paraquatpoisoning

Zhang

Zhao

Bai

et al. 2015

Sci Rep

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“…Lipoperoxidation is the oxidation of unsaturated lipids and cholesterol in membranes as well as in lipoproteins, which is promoted by ROS [14]. This lipid oxidation process is considered the most widespread and deleterious consequence of IR in different organs and tissues [41][42][43][44][45][46].…”

Section: Marker Of Os -Lipoperoxidation Levels (Tbars)mentioning

confidence: 99%

“…It is worth to stress out that measurements of lipoperoxidatin as TBARS, as well as other markers of oxidative insult, are often used for the evaluation of tissue lesion associated to IR injury [5,19,26,[44][45][46]. Furthermore, in the spectrophotometric TBARS assay, malondialdehyde (MDA) is the major (approximately 90%) among other toxic dialdehydes produced by lipid oxidation especially on cell membranes [14].…”

Section: Marker Of Os -Lipoperoxidation Levels (Tbars)mentioning

confidence: 99%

Focusing lung transplant: physiological and antioxidant responses and effect of allopurinol to ischemia-reperfusion oxidative stress under different inspired oxygen concentrations

Fm¹,

Rj²,

Jj³

et al. 2018

Trends in Transplant

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“…Additionally, the effect of paraquat on the lipid peroxidation is independent of paraquat radical formation mediated by NADPH-cytochrome P450 reductase (Hara et al 1991). Alternatively, xanthine oxidase, as well as NADPH-cytochrome P450 reductase, has been also suggested as the intracellular source of reactive oxygen species in paraquat-induced lung injury (Waintrub et al 1990;Kitazawa et al 1991). The toxicity of paraquat to pulmonary artery endothelial cells is at least partly attributed to reactive oxygen species generated by xanthine oxidase, because paraquat toxicity is reduced by xanthine oxidase inhibitors, such as allopurinol and tungsten (Sakai et al 1995).…”

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confidence: 99%

Paraquat‐Induced Membrane Dysfunction in Pulmonary Microvascular Endothelial Cells

Tsukamoto

Tampo

Sawada

et al. 2000

Pharmacology & Toxicology

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Membrane dysfunction monitored by lactate dehydrogenase release from cultured pulmonary microvascular endothelial cells of pigs, which were exposed to paraquat at different concentrations (0.1-2 mM), was examined. Paraquat caused a time-dependent increase in lactate dehydrogenase release. Lactate dehydrogenase releases after 72 hr, 32, 58, and 84% by 0.1, 0.5, and 2 mM paraquat, respectively, were well correlated with cell viability measured by cell adherence. In contrast, reductions of two tetrazolium compounds were depleted profoundly by 72 hr after exposure to 0.5 mM paraquat, suggesting depletion of intracellular reductive substances. Extracellular hydrogen peroxide began to significantly increase 56 hr or 32 hr after exposure to 0.5 mM or 1.5 mM paraquat, respectively, preceding the initial increase of lactate dehydrogenase release (64 hr by 0.5 mM or 48 hr by 1.5 mM). Lactate dehydrogenase release 72 hr after exposure to 0.5 mM paraquat was prevented strongly by catalase (1000 units/ml), but weakly by superoxide dismutase (1000 units/ml). These enzymes failed to restore the reduced acid phosphatase activity. Also, 0.1 mM desferal or a,aø-dipyridyl protected lactate dehydrogenase release. Similarly, 1 mM thiourea or dimethylthiourea, and 0.5 mM a-tocopherol or trolox, were effective, but diethylenetriaminepentaacetic acid (0.1 mM) and probucol (5 or 10 mM) were ineffective. Exposure of 0.5 or 1.5 mM paraquat suppressed levels of lipid peroxidation. These results indicate that membrane dysfunction by paraquat is ascribed to an iron-catalyzed reaction of extracellularly increased hydrogen peroxide. A deleterious species for the membrane dysfunction is discussed.

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

Cited by 17 publications

References 9 publications

The significance of serum uric acid level in humans with acute paraquatpoisoning

The significance of serum uric acid level in humans with acute paraquatpoisoning

Focusing lung transplant: physiological and antioxidant responses and effect of allopurinol to ischemia-reperfusion oxidative stress under different inspired oxygen concentrations

Paraquat‐Induced Membrane Dysfunction in Pulmonary Microvascular Endothelial Cells

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