Search

Objective: The β-glucans are long-chain polymers of glucose, which comprise the fungal cell wall, stimulate cells of the innate immune system, enhance disturbed epithelization, and have antioxidant effects. Oxidative stress has been implicated in the pathogenesis of bleomycin-induced lung fibrosis and various antioxidant agents have been studied for prevention and treatment of the disease. In this experimental animal study, we assessed effects of β-glucan, extracted from barley, on the bleomycin-induced lung fibrosis, and evaluated differences of starting before and after bleomycin instillation., Materials and Methods: Male Spraque-Dawley rats were given a single dose of bleomycin in pulmonary fibrosis groups. First dose of β-glucan and NAC was given three days before the bleomycin injection, and at one of the other group β-glucan was started 12 hours after bleomycin and continued until 14th day. Fibrotic changes in lung were estimated by using Aschoft's criteria and measuring lung hydroxyproline content., Results: Bleomycin induced severe pulmonary fibrosis with marked increase in hydroxyproline content of lung tissue and typical lung fibrosis, which was prevented by β-glucan. Hydroxyproline level was significantly higher in bleomycin treated rats than the other groups, and its level was decreased in the therapeutic groups, especially in the β-glucan post-bleomycin group fibrosis score, hydroxyproline and MDA levels returned to the control levels. On the other hand, reduced glutathione level elevated in the same group., Conclusions: The data suggest that β-glucans have protective and early therapeutic effects against bleomycin-induced lung fibrosis in rats.

Bleomycin is an anti-neoplastic agent and its clinical usage is limited by its toxicity, which is mostly induced by oxygen radicals. The aim of this study was to investigate the effect of Ginkgo biloba on plasma indices of oxidants induced by bleomycin in rats. Male Sprague-Dawley rats were divided into five groups: none medicated or 0.9% NaCl injected or only Ginkgo biloba (orally, 100 mg/kg per day for 14 days) or only a single dose of bleomycin (intratracheal, 2.5 U/kg) or Gingko biloba and bleomycin-treated groups. After 14 days, blood was taken before the rats were sacrificed. The plasma was removed and stored at -85 degrees C until the study day. Plasma superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and xanthine oxidase (XO) enzyme activities with malondialdehyde and nitric oxide (NO) levels were studied. The levels of malondialdehyde and NO with activity of XO were higher in plasma of bleomycin group than the other groups (P <0.05). The activities of SOD and GSH-Px were increased in the bleomycin plus Gingko biloba group in comparison with the bleomycin group (P <0.05). There was a positive correlation between malondialdehyde and NO levels in the bleomycin group (r =0.859, P <0.05). There were positive correlations between SOD and GSH-Px activities (r =0.760, P <0.05) and between XO activity and malondialdehyde level (r =0.822, P <0.05) in the bleomycin plus Gingko biloba group. In conclusion, it was thought that bleomycin induced oxidative stress can be prevented by Gingko biloba treatment via high anti-oxidant enzyme activity together with decreased radical production from XO.

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 + (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 (P < 0.001), and this level was 11.3 +/- 1.2 and 13.8 +/- 1.2 mg/g dried tissue in erdosteine and NAC pretreated, respectively. Erdosteine and NAC significantly reduced depletion of glutathione peroxidase, and prevented increases in myeloperoxidase activities, nitric oxide, and malondialdehyde levels in lung tissue produced by bleomycin. Data presented here indicate that erdosteine and NAC similarly prevented bleomycin-induced lung fibrosis and their antioxidant effects were also similar in this experiment.

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.

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.

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-Dawley 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 (p < 0.0001). There were a decreases in antioxidant enzyme (SOD and CAT) activities while an increase in MPO activity in BLM group was found vs. the control group (p < 0.0001). CAPE had a regulator effect on these parameters: the increase in CAT and SOD activities and the decrease in MPO activity were seen after CAPE application. NO, MDA and OH-proline levels were increased in BLM group vs. the control group. CAPE was more effective in decreasing the tissue levels of NO, MDA and OH-proline than vit E. MPO activity, as a good marker of neutrophil sequestration to the tissues, in the BLM group was decreased by CAPE approximately to the control group., Conclusion: We suggest that CAPE is more effective on the prevention of BLM-induced fibrosis via antioxidant and free radical scavenger properties than vit E at the doses used in the present study. CAPE has some attenuating effects on BLM-induced PF affecting both oxidant and antioxidant systems as well as neutrophils sequestration.