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Caffeic acid phenethyl ester and vitamin E moderates IL-1ß and IL-6 in bleomycin-induced pulmonary fibrosis in rats

Armutcu F. | Çabuk M. | Gurel A. | Atmaca H. | Kart L.

Article | 2007 | Pesticide Biochemistry and Physiology88 ( 2 ) , pp.209 - 212

The aim of this study was to investigate the effects of Caffeic acid phenethyl ester (CAPE), which has been demonstrated to have antiinflammatory, antiproliferative, anticancerogenic, and antioxidant effects, and vitamin E on IL-1ß and IL-6 in bleomycin-induced (BLM-induced) pulmonary fibrosis in rats. Thirty-two Sprague-Dawley rats were divided randomly into four groups as untreated control, bleomycin, bleomycin + CAPE, and bleomycin + vitamin E groups. At the end of the treatment, blood IL-1ß and IL-6 levels were quantified. Bleomycin application to the rats resulted in a significant increase in the cytokine levels as compared to . . .the controls. Administration of CAPE and vitamin E prevented the increase of blood IL-1ß and IL-6 levels compared to the rats treated with bleomycin alone. Data presented here suggest that CAPE and vitamin E play a protective and moderator role against BLM-induced lung injuries by decreasing the primary inflammatory cytokines, such as IL-1ß and IL-6. © 2006 Elsevier Inc. All rights reserved Daha fazlası Daha az

The effect of melatonin on bleomycin-induced pulmonary fibrosis in rats

Arslan S.O. | Zerin M. | Vural H. | Coskun A.

Article | 2002 | Journal of Pineal Research32 ( 1 ) , pp.21 - 25

The present investigation was designed to determine the protective effects of melatonin against bleomycin (BLM)-induced oxidant lung toxicity. Wistar-albino rats were divided into four groups: saline (SA, 0.4 mL/animal), 1% ethanol-saline (ALC, 0.4 mL/animal), bleomycin sulphate (BLM, 10 mg/kg), or bleomycin sulphate + melatonin (BLM, 10 mg/kg + MLT, 10 mg/kg). All injections were given intraperitoneally (i.p.), twice weekly for a period of 3 wk (a total of seven injections for each group). Twenty-five days after BLM treatment, pulmonary fibrosis was assessed as hydroxyproline content in lung homogenates. Findings show that BLM-indu . . .ced pulmonary injury resulted in increases in bronchoalveolar lavage fluid (BALF) biomarkers including total protein, lactate dehydrogenase (LDH), glutathione-peroxidase (GSH-Px), superoxide dismutase (SOD), and catalase (CAT). Additionally, the levels of thiobarbituric acid reactive substances (TBARS), an index of lipid peroxidation (LPO), were also increased in BALF. Conversely, the level of glutathione (GSH) was reduced in BALF of BLM-treated rats. Melatonin provided protection against BLM-induced pulmonary fibrosis by suppressing oxidative stress. It abolished BLM-stimulated LPO and reversed the imbalance between oxidants and antioxidants in the BALFs. Results thus indicate that melatonin inhibits BLM-induced lung toxicity associated with oxidative damage Daha fazlası Daha az

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

Oxidant and antioxidant status of plasma and erythrocyte in the bleomycin-administered rats: The protective role of erdosteine and vitamin E

Armutçu F. | Sögüt S. | Gürel A. | Kart L. | Coşkun Ö.

Article | 2004 | THOD - Turk Hematoloji-Onkoloji Dergisi14 ( 4 ) , pp.205 - 213

Bleomycin (BLM) toxicity is associated with lipid peroxidation, which is an autocatalytic mechanism leading to oxidative destruction of cellular membranes, and their destruction can lead to the production of toxic, reactive metabolites and cell death. Therefore, we investigated reactive oxygen species production, antioxidant enzyme activities and protective effect of vitamin E and erdosteine in BLM-administrated rats. Thirty-five Sprague-Dawley rats were divided randomly into four groups as untreated control, BLM, BLM+erdosteine and BLM+vitamin E groups. At the end of the treatment, plasma and erythrocytes were obtained and the leve . . .ls of thiobarbituric acid reactive substances (TEARS) and nitric oxide (NO) as well as the activities of superoxide dismutase (SOD), catalase (CAT) and glutathion peroxidase (GSH-Px) were measured. Bleomycin administration resulted in the generation of reactive oxygen species in the blood of rats by decreasing the activities of enzymes SOD, CAT and GSH-Px, while increasing the levels of NO and TEARS, an indicative of lipid peroxidation. Erdosteine and vitamin E treatment prevented the increase in the lipid peroxidation. Erdosteine alone significantly prevented the decrease in SOD, CAT and GSH-Px activities in the erythrocyte and plasma. We suggest that erdosteine is more effective on the prevention of BLM-induced hematotoxicity via antioxidant and free radical scavenger properties than vitamin E at the doses used in the present study. However, further studies at different doses of erdosteine are needed to determine most appropriate doses and to clarify the issue Daha fazlası Daha az

Inhibitory effect of caffeic acid phenethyl ester on bleomycine-induced lung fibrosis in rats

Özyurt H. | Sögüt S. | Yildirim Z. | Kart L. | Iraz M. | Armutçu F. | Temel I.

Conference Object | 2004 | Clinica Chimica Acta339 ( 01.Feb ) , pp.65 - 75

Background: Pulmonary fibrosis (PF) induced by anticancerogenic bleomycin (BLM) is one of the more common side effects encountered during cancer treatment. It has been suggested in the last decades that the main responsible agent in PF is reactive oxygen species which were generated also in normal physiological conditions in the human body. In this experimental study, we investigated the preventive or attenuating effects of caffeic acid phenethyl ester (CAPE) that has been demonstrated to have anti-inflammatory, cytocytatic, anticancerogenic, antiprolipherative and antioxidant effects on BLM-induced PF. Methods: Thirty-six Sprague-D . . .awley rats were divided randomly into four groups as sham operation, BLM, BLM+vitamin E (vit E), and BLM+CAPE groups. BLM (7.5 mg/kg, single dose) was applied intratracheally, and CAPE and vit E intraperitoneally in the appropriate groups. At the end of the fibrosis processes, lung tissues were removed and the levels of tissues hydroxyproline (OH-proline), malondialdehyde (MDA) and NO as well as the activities of superoxide dismutase (SOD), catalase (CAT) and myeloperoxidase (MPO) were determined. Also, the weights of the rats were recorded at 7th and 14th days of the experiments. Results: BLM application to the rats resulted in a significant increase in the OH-proline level as compared to the controls. Administration of CAPE and vit E led to the remarkable reduction of total lung OH-proline levels compared to the rats treated with BLM alone ( 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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