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Erdosteine prevents bleomycin-induced pulmonary fibrosis in rats

Sogut S. | Ozyurt H. | Armutcu F. | Kart L. | Iraz M. | Akyol O. | Ozen S.

Article | 2004 | European Journal of Pharmacology494 ( 02.Mar ) , pp.213 - 220

Oxidative stress plays an important role in the pathogenesis of idiopathic pulmonary fibrosis. Therefore, erdosteine, an antioxidant, is expected to have an inhibitor potential against the disease. Rats were given one dose of bleomycin in pulmonary fibrosis groups and saline in controls. The first dose of oral erdosteine (10 mg/kg/day) was given 2 days before the bleomycin injection to achieve the plateau level in blood and continued until killing. At day 14, fibrotic changes were evaluated, using Aschoft's criteria and lung hydroxyproline content. Bleomycin produced a fivefold increase in fibrosis score that was decreased by 87% by . . . erdosteine (P>0.001) and almost twofold increases in hydroxyproline content which were completely prevented by erdosteine. Myeloperoxidase activities and MDA levels, which were significantly higher in the bleomycin group, were then significantly attenuated by erdosteine. These results revealed that oral erdosteine may prevent the development of acute pulmonary inflammation caused by bleomycin injection via the repression of neutrophil accumulation and lipid peroxidation, resulting in the inhibition of subsequent lung fibrosis. © 2004 Elsevier B.V. All rights reserved Daha fazlası Daha az

Attenuation of bleomycin-induced lung fibrosis by oral sulfhydryl containing antioxidants in rats: Erdosteine and N-acetylcysteine

Yildirim Z. | Kotuk M. | Iraz M. | Kuku I. | Ulu R. | Armutcu F. | Ozen S.

Article | 2005 | Pulmonary Pharmacology and Therapeutics18 ( 5 ) , pp.367 - 373

Antioxidant therapy may be useful in diseases with impaired oxidant antioxidant balance such as lung fibrosis. The effects of sulfhydryl-containing antioxidant agents N-acetylcysteine (NAC) and erdosteine on the bleomycin-induced lung fibrosis were compared in rats. The animals were divided into four groups: Vehicle+vehicle, vehicle+bleomycin (2.5 U/kg), bleomycin+erdosteine (10 mg/kg), and bleomycin+NAC (3 mmol/kg). Bleomycin administration resulted in prominent lung fibrosis as measured by lung hydroxyproline content and lung histology which is almost completely prevented by erdosteine and NAC. Hydroxyproline content was 18.7±3.5 . . .and 11.2±0.6 mg/g dried tissue in bleomycin and saline treated rats, respectively ( Daha fazlası Daha az

Effects of aminoguanidine and antioxidant erdosteine on bleomycin-induced lung fibrosis in rats

Yildirim Z. | Turkoz Y. | Kotuk M. | Armutcu F. | Gurel A. | Iraz M. | Ozen S.

Article | 2004 | Nitric Oxide - Biology and Chemistry11 ( 2 ) , pp.156 - 165

Reactive oxygen and nitrogen species have been implicated in the pathogenesis of bleomycin-induced lung fibrosis. The effects of aminoguanidine and erdosteine on the bleomycin-induced lung fibrosis were evaluated in rats. The animals were placed into five groups: Vehicle + vehicle, vehicle + bleomycin (2.5 U/kg), bleomycin + aminoguanidine (200 mg/kg), bleomycin + erdosteine (10 mg/kg), and bleomycin + erdosteine + aminoguanidine. Bleomycin administration resulted in prominent lung fibrosis as measured by lung hydroxyproline content and lung histology, which is completely prevented by erdosteine and aminoguanidine. A strong staining . . . for nitro tyrosine antibody in lung tissue and increased levels of lung NO were found in bleomycin group, that were significantly reduced by aminoguanidine and erdosteine. Aminoguanidine and erdosteine significantly prevented depletion of superoxide dismutase and glutathione peroxidase and elevated myeloperoxidase activities, malondialdehyde level in lung tissue produced by bleomycin. Data presented here indicate that aminoguanidine and erdosteine prevented bleomycin-induced lung fibrosis and that nitric oxide mediated tyrosine nitration of proteins plays a significant role in the pathogenesis of bleomycin-induced lung fibrosis. Also our data suggest that antifibrotic affect of antioxidants may be due to their inhibitory effect on nitric oxide generation in this model. © 2004 Elsevier Inc. All rights reserved Daha fazlası Daha az

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