Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P47989 (xanthine oxidase)
 8,633 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The intrapulmonary instillation into rat lung of enzymes that generate oxygen metabolites results in acute lung injury. The injection of xanthine oxidase and xanthine produces acute lung injury that, in the presence of superoxide dismutase, but not in the presence of catalase, can be significantly diminished, suggesting that O2- has the capacity to injure the lung. Instillation of a generator of H2O2, namely glucose oxidase, will, in sufficient quantities, produce acute injury that is not neutrophil-dependent. When either a low dose of glucose oxidase alone or lactoperoxidase alone is employed, little lung injury occurs. However, instilling the combination of the two enzymes produces severe, acute injury that can be blocked in a dose-dependent manner by catalase, but not by superoxide dismutase. Purified human leukocytic myeloperoxidase, but not horseradish peroxidase, will substitute for lactoperoxidase in the model of lung injury. The lung damaging effects of these enzymes cannot be attributed to the presence of contaminating proteases. Acute lung injury produced by the instillation of glucose oxidase and lactoperioxidase progresses to interstitial fibrosis. These studies represent a direct application of generators of oxygen metabolites to the in vivo induction of lung injury. The data suggest that rat lung is susceptible to injury by a variety of oxygen metabolites, including O2-, H2O2 and its lactoperoxidase or myeloperoxidase-produced derivatives. The studies also indicate that lung injury produced by oxygen metabolites can result in interstitial pulmonary fibrosis.
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PMID:In vivo damage of rat lungs by oxygen metabolites. 689 54

Fibroproliferative response of rat heart and lung fibroblasts to the lanthanide cerium was examined, as the element has been implicated in the causation of cardiac and pulmonary fibrosis. Fibroblasts from both of the organs were morphologically identical, and the response to fetal bovine serum, a nonspecific mitogen, was also comparable. The oxygen radical generator (hypoxanthine + xanthine oxidase [Hyp. + XO]) induced a proliferative response that was neutralized in both cardiac and lung fibroblasts by free-radical scavengers. Superoxide dismutase was more effective than catalase in reducing the mitogenic effect of Hyp. + XO. The free-radical scavenger N-acetyl-L-cysteine neutralized the free-radical-mediated changes in pulmonary fibroblasts but had a negative effect in cardiac fibroblasts, indicating a tissue-dependent variation. Reactive oxygen species are known to act as biological mediators of tissue fibrosis induced by metallic compounds. Exposure to low levels of cerium (0.5 microM) stimulated a mitogenic response in cardiac fibroblasts, but the pulmonary fibroblasts were not sensitized by the element. Tissue-dependent variation in proliferative response to cerium shows a positive association with intracellular generation of reactive oxygen species. Fibrotic changes in cerium pneumoconiosis may either be replacement fibrosis following tissue damage or mediated by nonfibroblastic cells. The study confirms that cardiac and pulmonary fibroblasts are dissimilar cellular subtypes.
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PMID:Variation in mitogenic response of cardiac and pulmonary fibroblasts to cerium. 1297 91

Pirfenidone is a newly developed antifibrotic drug that has been reported to retard the progression of pulmonary fibrosis induced by bleomycin and cyclophosphamide in animal models of lung fibrosis. The present in vitro studies using noncellular and cellular systems evaluated the antioxidant and cytotoxic properties of this drug. The Fenton reaction [Fe(II) + H2O2 --> Fe(III) + *OH + OH-] and the xanthine/xanthine oxidase system were used as sources of hydroxyl (*OH) and superoxide anion (O2*-) radicals, respectively. Electron spin resonance spin trapping was used for free radical detection and measurement. The reaction rate of pirfenidone with *OH was found to be 1.63 x 10(10) M(-1) s(-1), which is comparable to several well-established antioxidants, such as ascorbate, glutathione, cysteine, azide, and lipoic acid. Compared to *OH radicals, the O2*- scavenging was less efficient 42.36 M(-1) s(-1) with pirfenidone. Pirfenidone was also effective in inhibiting zymosan-stimulated chemiluminescence. In a noncellular model of lipid peroxidation, pirfenidone inhibited crystalline silica-induced lipid peroxidation. The inhibition of crystalline silica-induced cytotoxic reactions and lipid peroxidation combined with the efficient antioxidant properties of pirfenidone indicate that this agent may express its antifibrotic effects partly through its ability to scavenge reactive oxygen species.
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PMID:Effects of pirfenidone on the generation of reactive oxygen species in vitro. 1528 Dec 29

The present study aimed to examine the antioxidant properties of Houttuynia cordata (HC) and its protective effect on bleomycin-induced pulmonary fibrosis in rats. Results showed that aqueous extract of HC exhibited a different magnitude of antioxidant activities in all model systems tested. Although HC showed weaker free radical scavenging and xanthine oxidase inhibitory activity than vitamin E, its anti-lipid peroxidation activity in rat liver homogenate was close to that of vitamin E. In animal studies, HC significantly decreased the levels of superoxide dismutase, malondialdehyde, hydroxyproline, interferon-gamma, and tumor necrosis factor-alpha. However, an increase in the concentration of catalase was noted in the bronchoalveolar lavage fluid. HC also remarkably improved the morphological appearance of the lung of bleomycin-treated rats. These results suggest that HC possesses a protective effect against bleomycin-induced pulmonary fibrosis. Interestingly, this protective effect was more pronounced than that of vitamin E. In conclusion, the protective effect of HC on pulmonary fibrosis could be partly associated with the reduction of oxidative damage caused by bleomycin.
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PMID:Protective effect of Houttuynia cordata extract on bleomycin-induced pulmonary fibrosis in rats. 1759 5

Reactive oxygen species (ROS) have been implicated in the pathogenesis of fibrosis. However, it remains unclear which ROS is the major cause. We hypothesize that superoxide elicits specific toxicity to human lung fibroblasts and plays an important role in the development of pulmonary fibrosis. In this study, superoxide generated from xanthine and xanthine oxidase activated lung fibroblasts by increasing the release of TGF-beta1 and collagen. This was associated with increased levels of intracellular superoxide. SOD and tempol, by scavenging respectively extracellular and intracellular superoxide, prevented the activation of fibroblasts induced by exposure to exogenous superoxide, whereas catalase did not. Moreover, hydrogen peroxide did not activate fibroblasts. Apparently, superoxide rather than hydrogen peroxide is involved in the regulation of TGF-beta1 and collagen release in lung fibroblasts. The chloride channel blocker, DIDS, inhibited the increase of intracellular superoxide levels induced by exogenous superoxide and consequently prevented the activation of fibroblasts. This suggests that the cellular influx of superoxide through chloride channels is essential for superoxide-induced activation of fibroblasts. ERK1/2 and p38 MAPKs are involved in the intracellular pathway leading to superoxide-induced fibroblasts activation. Superoxide possesses until now undiscovered specific pro-fibrotic properties in human lung fibroblasts. This takes place via the cellular influx of superoxide through chloride channels rather than via the formation of hydrogen peroxide.
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PMID:Superoxide radicals increase transforming growth factor-beta1 and collagen release from human lung fibroblasts via cellular influx through chloride channels. 1926 87

Bleomycin causes pulmonary fibrosis by increasing free oxygen radicals. Cigarette smoke is a strong oxidant which adversely affects pulmonary tissue. We evaluated the effects of cigarette smoke administered with intratracheal bleomycin on pulmonary tissue. We studied 3 groups of rats (n=10): one group received intratracheal saline and served as a control; one received intratracheal bleomycin (IT) (0.5 U/100 g body weight, single dose on the first day), and one group received intratracheal bleomycin (single dose on first day) and tobacco smoke (two times per day) (IT-S). After 4 weeks, the levels of malondialdehyde (MDA) and nitric oxide (NO) and the activities of superoxide dismutase (SOD) and xanthine oxidase (XO) were assayed in the homogenate of the lung tissue samples. The severity of interstitial fibrosis was assessed using the grading system described by Ashcroft. There was more intensive fibrosis in the IT and IT-S than in the control samples (P<0.001). The levels of MDA, NO and activity of XO were significantly increased (P<0.001, <0.002 and <0.002, respectively), and SOD activity (P<0.001) was significantly decreased in the IT group when compared to these values in the control group. The concentration of NO was significantly decreased (P<0.002), and SOD activity was significantly increased (P<0.05) in the lung tissue samples of the IT-S group. Theoretically, the combination of cigarette smoke and bleomycin may have a synergistic effect on oxidative lung injury. In conclusion, we showed that inhalation of cigarette smoke provides protection against oxidative stress in the lung tissue of rats with bleomycin-induced pulmonary fibrosis.
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PMID:Cigarette smoke and bleomycin-induced pulmonary oxidative stress in rats. 2306 Sep 34