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PMID: 16328965 Published · ppublish English Journal Article

Effects of erdosteine on bleomycin-induced lung fibrosis in rats.

Molecular and cellular biochemistry ·Vol. 281 ·No. 1-2 ·2006-01-00 ·Pages 129-37

Boyaci H, Maral H, Turan G, Başyiğit I, Dillioğlugil MO, Yildiz F, Tugay M, Pala A, Erçin C

Abstract

This study was designed to examine the effects of erdosteine on bleomycin (BLM)-induced lung fibrosis in rats. Thirty-three Sprague-Dawley rats were divided randomly into three groups, bleomycin alone (BLM), bleomycin + erdosteine (BLM + ERD), and saline alone (control). The BLM and BLM + ERD groups, were given 2.5 mg/kg BLM intratracheally. The first dose of oral erdosteine (10 mg/kg/day) in the BLM + ERD group was started 2 days before BLM administration and continued until animals were sacrificed. Animals were sacrificed 14 days after intratracheal instillation of BLM. The effect of erdosteine on pulmonary fibrosis was studied by analysis of bronchoalveolar lavage (BAL) fluid, histopathology, and biochemical measurements of lung tissue superoxide dismutase (SOD) and glutathione (GSH) as antioxidants, malondialdehyde (MDA) as an index for lipid peroxidation, and nitrite/nitrate levels. Bleomycin-induced lung fibrosis as determined by lung histology was prevented with erdosteine (grades of fibrosis were 4.9, 2.3, and 0.2 in BLM, BLM + ERD, and control groups, respectively). Erdosteine also prevented bleomycin-induced increase in MDA (MDA levels were 0.50 +/- 0.15, 0.11 +/- 0.02, and 0.087+/- 0.03 nmol/mg protein in BLM, BLM + ERD, and control groups, respectively) and nitrite/nitrate (nitrite/nitrate levels were 0.92 +/- 0.06, 0.60 +/- 0.09, and 0.56+/- 0.1 micromol/mg protein in BLM, BLM + ERD, and control groups respectively) levels. Bleomycin-induced decrease in GSH and SOD levels in the lung tissue also prevented by erdosteine [(GSH levels were 213.5 +/- 12.4, 253.2+/- 25.2, and 287.9+/- 34.4 nmol/mg protein) (SOD levels were 1.42+/- 0.12, 1.75+/- 0.17, and 1.89+/- 0.09 U/mg protein) in BLM, BLM + ERD, and control groups respectively]. Erdosteine prevented bleomycin-induced increases in total cell number and neutrophil content of the BAL fluid. In conclusion, oral erdosteine is effective in prevention of BLM-induced lung fibrosis in rats possibly via the repression of neutrophil accumulation, inhibition of lipid peroxidation, and maintenance of antioxidant and free radical scavenger properties.

MeSH Terms
Acute Lung Injury/chemically induced,drug therapy,pathology Animals Biomarkers Bleomycin/toxicity Bronchoalveolar Lavage Fluid/cytology Male Oxidative Stress/physiology Pulmonary Fibrosis/chemically induced,drug therapy,pathology Rats Rats, Sprague-Dawley Thioglycolates/therapeutic use Thiophenes/therapeutic use
Chemicals
Biomarkers Thioglycolates Thiophenes Bleomycin erdosteine
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Boyaci Haşim
Department of Chest Diseases, Kocaeli University School of Medicine, Kocaeli, Turkey. haboyaci@yahoo.com
Maral Hale
Turan Gupse
Başyiğit Ilknur
Dillioğlugil Meltem O
Yildiz Füsun
Tugay Melih
Pala Ayşe
Erçin Cengiz
References (49)
49 references, click to expand
  1. Idiopathic pulmonary fibrosis: cellular and molecular pathogenesis.
    Am J Med Sci. 1989 Feb;297(2):91-104 PMID: 2919636
  2. Short course dexamethasone treatment following injury inhibits bleomycin induced fibrosis in rats.
    Thorax. 2003 Sep;58(9):765-71 PMID: 12947134
  3. Protective effects of erdosteine against doxorubicin-induced cardiomyopathy in rats.
    J Appl Toxicol. 2003 Jan-Feb;23(1):71-4 PMID: 12518339
  4. A simple method for clinical assay of superoxide dismutase.
    Clin Chem. 1988 Mar;34(3):497-500 PMID: 3349599
  5. Decreasing the oxidant stress from paraquat in isolated perfused rat lung using captopril and niacin.
    Arch Toxicol. 2005 Jun;79(6):341-5 PMID: 15856184
  6. Idiopathic pulmonary fibrosis.
    N Engl J Med. 2001 Aug 16;345(7):517-25 PMID: 11519507
  7. Effects of aminoguanidine and antioxidant erdosteine on bleomycin-induced lung fibrosis in rats.
    Nitric Oxide. 2004 Sep;11(2):156-65 PMID: 15491848
  8. Erdosteine ameliorates neurological outcome and oxidative stress due to ischemia/reperfusion injury in rabbit spinal cord.
    Eur J Vasc Endovasc Surg. 2004 Oct;28(4):379-86 PMID: 15350559
  9. Determination of inorganic nitrate in serum and urine by a kinetic cadmium-reduction method.
    Clin Chem. 1990 Aug;36(8 Pt 1):1440-3 PMID: 2387039
  10. Effects on the reactive oxygen species of erdosteine and its metabolite in vitro.
    Arzneimittelforschung. 2002;52(6):435-40 PMID: 12109043
  11. Inhibitory effects of metabolite I of erdosteine on the generation of nitric oxide and peroxynitrite chemiluminescence by human neutrophils.
    Pharmacology. 2004 Jul;71(3):120-7 PMID: 15161993
  12. The activities of tissue xanthine oxidase and adenosine deaminase and the levels of hydroxyproline and nitric oxide in rat hearts subjected to doxorubicin: protective effect of erdosteine.
    Toxicology. 2003 Sep 30;191(2-3):153-8 PMID: 12965118
  13. Administration of alpha 1-proteinase inhibitor ameliorates bleomycin-induced pulmonary fibrosis in hamsters.
    Am Rev Respir Dis. 1992 Mar;145(3):651-6 PMID: 1372163
  14. Abrogation of bleomycin-induced lung fibrosis by nitric oxide synthase inhibitor, aminoguanidine in mice.
    Nitric Oxide. 2002 Sep;7(2):109-18 PMID: 12223180
  15. Inhibitory effects of a lecithinized superoxide dismutase on bleomycin-induced pulmonary fibrosis in mice.
    Am J Respir Crit Care Med. 2000 Apr;161(4 Pt 1):1279-84 PMID: 10764324
  16. Protein metabolism during bleomycin-induced pulmonary fibrosis in rabbits. In vivo evidence for collagen accumulation because of increased synthesis and decreased degradation of the newly synthesized collagen.
    Am Rev Respir Dis. 1983 Jul;128(1):82-8 PMID: 6191605
  17. Inhibition of nitric oxide synthase reduces Sephadex-induced oedema formation in the rat lung: dependence on intact adrenal function.
    Inflamm Res. 1995 Oct;44(10 ):418-22 PMID: 8564517
  18. Inhibition of bleomycin-induced cell death in rat alveolar macrophages and human lung epithelial cells by ambroxol.
    Biochem Pharmacol. 2003 Oct 1;66(7):1297-306 PMID: 14505809
  19. Oral N-acetylcysteine reduces bleomycin-induced lung damage and mucin Muc5ac expression in rats.
    Eur Respir J. 2003 Dec;22(6):900-5 PMID: 14680076
  20. Erdosteine prevents bleomycin-induced pulmonary fibrosis in rats.
    Eur J Pharmacol. 2004 Jun 28;494(2-3):213-20 PMID: 15212977
  21. Time course of bleomycin-induced lung fibrosis.
    Int J Exp Pathol. 2002 Jun;83(3):111-9 PMID: 12383190
  22. The development of bleomycin-induced pulmonary fibrosis in neutrophil-depleted and complement-depleted rats.
    Am J Pathol. 1981 Oct;105(1):76-81 PMID: 6170232
  23. Protective effect of IL-6 on alveolar epithelial cell death induced by hydrogen peroxide.
    Am J Physiol Lung Cell Mol Physiol. 2005 Feb;288(2):L342-9 PMID: 15475383
  24. Production of superoxide and nitric oxide by alveolar macrophages in the bleomycin-induced interstitial pneumonia mice model.
    Jpn J Pharmacol. 1998 Sep;78(1):69-73 PMID: 9804064
  25. Erdosteine.
    Drugs. 1996 Dec;52(6):875-81; discussion 882 PMID: 8957158
  26. Tissue sulfhydryl groups.
    Arch Biochem Biophys. 1959 May;82(1):70-7 PMID: 13650640
  27. Effects of neutrophil elastase inhibitor on bleomycin-induced pulmonary fibrosis in mice.
    Am J Respir Crit Care Med. 1997 Jul;156(1):260-5 PMID: 9230758
  28. Evidence for in vivo peroxynitrite production in human acute lung injury.
    Am J Respir Crit Care Med. 1995 Apr;151(4):1250-4 PMID: 7697261
  29. In vivo antioxidant treatment protects against bleomycin-induced lung damage in rats.
    Br J Pharmacol. 2003 Mar;138(6):1037-48 PMID: 12684259
  30. Simple method of estimating severity of pulmonary fibrosis on a numerical scale.
    J Clin Pathol. 1988 Apr;41(4):467-70 PMID: 3366935
  31. Peroxynitrite modulates release of inflammatory mediators from guinea pig lung mast cells activated by antigen-antibody reaction.
    Int Arch Allergy Immunol. 2005 Jun;137(2):104-14 PMID: 15855792
  32. Microsomal lipid peroxidation.
    Methods Enzymol. 1978;52:302-10 PMID: 672633
  33. Aerosolized administration of N-acetylcysteine attenuates lung fibrosis induced by bleomycin in mice.
    Am J Respir Crit Care Med. 2000 Jul;162(1):225-31 PMID: 10903246
  34. Attenuation of bleomycin-induced lung fibrosis in rats by mesna.
    Eur J Pharmacol. 2005 Feb 10;509(1):61-70 PMID: 15713430
  35. Nitric oxide. A macrophage product responsible for cytostasis and respiratory inhibition in tumor target cells.
    J Exp Med. 1989 May 1;169(5):1543-55 PMID: 2497225
  36. Attenuation of bleomycin-induced pulmonary fibrosis by a catalytic antioxidant metalloporphyrin.
    Am J Respir Cell Mol Biol. 2001 Aug;25(2):164-9 PMID: 11509325
  37. Bleomycin-induced pneumonitis.
    Chest. 2001 Aug;120(2):617-24 PMID: 11502668
  38. Depressant effects of ambroxol and erdosteine on cytokine synthesis, granule enzyme release, and free radical production in rat alveolar macrophages activated by lipopolysaccharide.
    Pharmacol Toxicol. 2003 Apr;92(4):173-9 PMID: 12753420
  39. Protein measurement with the Folin phenol reagent.
    J Biol Chem. 1951 Nov;193(1):265-75 PMID: 14907713
  40. The SH-metabolite I of erdosteine, a mucolytic drug, enhances the inhibitory effect of salbutamol on the respiratory burst of neutrophils.
    Drugs Exp Clin Res. 2002;28(4):147-54 PMID: 12512232
  41. Role of inflammatory mediators in the pathophysiology of acute respiratory distress syndrome.
    J Pathol. 2004 Feb;202(2):145-56 PMID: 14743496
  42. Pathogenesis of lung fibrosis and potential new therapeutic strategies.
    Exp Nephrol. 1995 Mar-Apr;3(2):96-107 PMID: 7773645
  43. Protection of iron-catalysed the radical damage to DNA and lipids by copper (II) bleomycin.
    Biochem Biophys Res Commun. 1981 Apr 30;99(4):1354-60 PMID: 6167268
  44. Remodeling of the lung in bleomycin-induced pulmonary fibrosis in the rat. An immunohistochemical study of laminin, type IV collagen, and fibronectin.
    Am Rev Respir Dis. 1990 Jul;142(1):206-14 PMID: 1695071
  45. Bleomycin-induced pulmonary toxicity.
    Clin Chest Med. 1990 Mar;11(1):1-20 PMID: 1691067
  46. Reduction of bleomycin induced lung fibrosis by candesartan cilexetil, an angiotensin II type 1 receptor antagonist.
    Thorax. 2004 Jan;59(1):31-8 PMID: 14694243
  47. High levels of peroxynitrite are generated in the lungs of irradiated mice given cyclophosphamide and allogeneic T cells. A potential mechanism of injury after marrow transplantation.
    Am J Respir Cell Mol Biol. 1999 Jun;20(6):1125-35 PMID: 10340931
  48. Oral erdosteine administration attenuates cisplatin-induced renal tubular damage in rats.
    Pharmacol Res. 2003 Feb;47(2):149-56 PMID: 12543063
  49. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) generation by silica in inflammation and fibrosis.
    Free Radic Biol Med. 2003 Jun 15;34(12):1507-16 PMID: 12788471
Article Info
Journal
Molecular and cellular biochemistry
Abbr.
Mol Cell Biochem
ISSN
0300-8177
Published
2006-01-00
Pages
129-37
Language
English
Region
Netherlands
NLM ID
0364456
Subset
IM
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