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Introduction and aim

EFFECTS OF ERDOSTEINE ON INFLAMMATION AND FIBROSIS IN RATS WITH PULMONARY FIBROSIS INDUCED BY BLEOMYCIN. Ersin Şükrü Erden 1 , Gamze Kırkıl 2 , Figen Deveci 2 , Nevin İlhan 3 , Bengü Çobanoğlu 4 , Teyfik Turgut 2 , Mehmet Hamdi Muz 2 Erciş State Hospital, Van 1

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Introduction and aim

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  1. EFFECTS OF ERDOSTEINE ON INFLAMMATION AND FIBROSIS IN RATS WITH PULMONARY FIBROSIS INDUCED BY BLEOMYCIN Ersin Şükrü Erden1, Gamze Kırkıl2, Figen Deveci2, Nevin İlhan3, Bengü Çobanoğlu4, Teyfik Turgut2, Mehmet Hamdi Muz2 Erciş State Hospital, Van1 Firat University, Faculty of Medicine, Department of Chest Disease2, Elazig Firat University, Faculty of Medicine, Department of Biochemistry3,Elazig Firat University, Faculty of Medicine, Department of Pathology4 ,Elazig

  2. Introduction and aim • Idiopathic pulmonary fibrosis (IPF) is an interstitial pulmonary disease that has a poor prognosis with current treatment modalities

  3. There are 2 phases in the pathophysiology of experimental lung fibrosis induced by BLM, an antineoplastic agent, Early inflammatory phase; infiltration of macrophage, neutrophil, and lymphocytes in interstitium and alveolus Second phase; fibrosis

  4. It is shown that erdostein, one of mucolytic agent, Supressed the inactivation of 1-antitrypsin in human induced by smoking, and increased the airway secretions of mice and rabbits.

  5. Aims 1. To obtain the data that can contribute to clarify the pathogenesis of IPF in the experimental lung fibrosis model induced by BLM 2. To determine the effect of erdosteine on acute inflammatory changes and fibrosis, contribution of antioxidant therapy to IPF treatment

  6. Material and method • 45 Wistar male rats classified into 3 groups • 5 of them on 0th day • 5 of them on 14th ay • 5 of them on 29th day were sacrificed

  7. Group 1 (n=15) NaHCO3 (10 mg/kg/d, 1x1, po) it 0.2 mg PBS -2th day 0th day 14th day 29th day Group 2 (n=15) NaHCO3 (10 mg/kg/d, 1x1, po) it BLM 7.5u/kg -2th day 0th day 14th day 29th day Group 3 (n=15) Erdostein (10 mg/kg/gd1x1, po) it BLM 7.5u/kg -2th day 0th day 14th day 29th day

  8. Performing BAL • BAL was performed by flushing the airways with 1 ml PBS through the tracheal cannula five times. Approximately 4.5 ml (90%) aliquot was withdrawn MDA, MIP-1α, MIP-2 levels were measured in BALF

  9. Cell classification of BALF • After cytospin procedure, the cell smear was stained with May-Grünwald-Giemsa • White cell count and NG were measured by counting 200 cells under light microscopy.

  10. Histopathologic Analysis of the Lung • After performing BAL, left lung were fixed in 10% of formaldehyde, and the tissues were cut • Right lung was used to measure the hydroxyproline levels

  11. Statistical Analysis • To compare the data of more than two groups,the non-parametric Kruskal-Wallis test was used. • Comparisons between groups were performed using the Mann-Whitney U test

  12. RESULTS

  13. BAL cell classification on day O BAL cell (%) control Bleomycin Erdostein neutrophil lymphocyte

  14. BAL cell classification on day 14th BAL cell (%) Neutrophil CxBLM p=0.008 CxE p=0.007 BLMxE p=0.008 Lymphocyte CxBLM p=0.009 control Bleomycin Erdostein neutrophil lymphocyte

  15. BAL cell classification on day 29th BAL cell (%) Neutrophil CxBLM p=0.009 CxE p=0.012 BLMxE p=0.009 Lymphocyte CxBLM p=0.027 control Bleomycin Erdostein neutrophil lymphocyte

  16. BALMIP-1 levels of all groups on days 0, 14th and 29th 14th day CxBLM p=0.009 CxE p=0.009 BLMxE p=0.016 29th day CxBLM p=0.009 BLMxE p=0.009 BAL MIP-1(pg/ml) control Bleomycin Erdostein Oth day 14th day 29th day

  17. BAL MIP-2 levels of all groups at 0th,14 th,29 th days 14th day CxBLM p=0.009 BLMxE p=0.009 29th day CxBLM p=0.009 BLMxE p=0.016 control Bleomycin Erdostein Oth day 14th day 29th day

  18. BAL MDA levels of all groups at 0th,14th,29th days 14th day CxBLM p=0.009 CxE p=0.016 BLMxE p=0.009 29th day CxBLM p=0.012 BLMxE p=0.009 control Bleomycin Erdostein Oth day 14th day 29th day

  19. Tissue levels of OH-P and fibrosis scores of all groups

  20. The histopathological views of lung tissues of control group (A), BLM group (B), and erdostein group (C) A) B) (C) Grade 3 fibrosis Decrease in fibrosis

  21. The inflammatory cell infiltration in BALF of control group (A), BLM group (B), and Erdostein group (C) A) B) (C)

  22. In conclusion • Erdostein may prevent the acute lung inflammation and fibrosis induced by BLM in rats • This protective effect of erdostein may be due to supression the accumulation of neutrophils, inhibition of lipid peroxydation, chemokine production, and release.

  23. Our results may suggest that erdostein can be a new pharmacological agent for IPF therapy, • Erdostein can be used as a proflactic agent during the use of antineoplastic agents especially in early phases

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