title: Attenuation of bleomycin-induced lung injury and oxidative stress by N-acetylcysteine plus deferoxamine.
abstract: Reactive oxygen species (ROS) play an important role in the pathogenesis of pulmonary injury and antioxidant therapy may be useful with impaired oxidative defense mechanism. This study examines the effect of N-acetylcysteine (NAC) and deferoxamine (DFX) on inflammatory indicators and oxidative stress in the lungs of mice exposed to bleomycin (BLM). The animals received endotracheally a single dose of BLM (2.5 U/kg body weight dissolved in 0.25 ml of 0.9% NaCl) or saline (0.9% NaCl) and were divided into eight groups (n=8): saline; BLM; saline+NAC; BLM+NAC; saline+DFX; BLM+DFX; saline+NAC+DFX; BLM+NAC+DFX. Treatments with NAC (20mg/kg) or DFX (30 mg/kg) were administered for 60 days after BLM exposure. Lactate dehydrogenase (LDH) activity and total cell count, neutrophil and protein concentration were determined in the bronchoalveolar lavage fluid (BALF). Lipid peroxidation thiobarbituric acid-reactive species (TBARS), oxidative protein damage (carbonyl contents), and catalase and superoxide dismutase activities were determined in the lung tissue. BLM administration resulted in lung lesion as determinated lung histology, which is almost completely prevented by NAC plus DFX. The results of total cell counts and neutrophils and LDH increased after BLM exposure and were reduced with NAC. DFX and NAC plus DFX also caused a significant decrease of LDH activity. The increased malondialdehyde equivalents and carbonyl contents in lung tissue produced by BLM were also prevented by NAC plus DFX. However, the isolated use of NAC increased lipid peroxidation. SOD activity increased after BLM exposure only in the group treated with DFX and catalase activity not was altered in the presence of BLM. Data presented here indicates that the isolated use of NAC had limited effects on BLM-induced pulmonary oxidative stress in mice. The use of DFX improves the defense response and in association with NAC may be a good alternative in the treatment or prevention of diseases that have ROS and iron involved in their pathogenesis.
authors: Laboratório de Fisiologia e Bioquímica do Exercício/UNESC, Av. Universitaria, 1105 Bairro Universitario, 88806-000 Criciuma, SC, Brazil.
authors: Kelly C
authors: KC
authors: Teixeira
authors: Fernanda S
authors: FS
authors: Soares
authors: Luís G C
authors: LG
authors: Rocha
authors: Paulo C L
authors: PC
authors: Silveira
authors: Luciano A
authors: LA
authors: Silva
authors: Samuel S
authors: SS
authors: Valença
authors: Felipe
authors: F
authors: Dal Pizzol
authors: Emilio L
authors: EL
authors: Streck
authors: Ricardo A
authors: RA
authors: Pinho
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D001761:Bleomycin / Q000008:administration & dosage / Q000009:adverse effects*; D002374:Catalase / Q000378:metabolism; D003676:Deferoxamine / Q000494:pharmacology / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005355:Fibrosis; D007502:Iron Chelating Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008171:Lung Diseases / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018384:Oxidative Stress / Q000187:drug effects*; D013482:Superoxide Dismutase / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D007502:Iron Chelating Agents; D017392:Thiobarbituric Acid Reactive Substances; D001761:Bleomycin; D007770:L-Lactate Dehydrogenase; D002374:Catalase; D013482:Superoxide Dismutase; D003676:Deferoxamine; D000111:Acetylcysteine