Effects of erdosteine on bleomycin-induced lung fibrosis in rats

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.

The bleomycin animal model: A useful tool to investigate treatment options for idiopathic pulmonary fibrosis?

“…J. Wang, Giri, Hyde, Nakashima, & Javadi, 1990), Taurin (Blaisdell & Giri, 1995;Gurujeyalakshmi, Hollinger, & Giri, 1998;Gurujeyalakshmi, Iyer, Hollinger, & Giri, 1996;Gurujeyalakshmi, Wang, & Giri, 2000;Q. J. Wang, Giri, Hyde, & Nakashima, 1989), N-Acetylcysteine (Cortijo et al, 2001;Hagiwara, Ishii, & Kitamura, 2000;Mata et al, 2003;Serrano-Mollar et al, 2003;Shahzeidi, Sarnstrand, Jeffery, McAnulty, & Laurent, 1991;Yildirim et al, 2005), Vitamin E (Kilinc et al, 1993), Curcumin (Punithavathi, Venkatesan, & Babu, 2000), Aminoguanidine (X. L. Chen, Huang, Li, Wang, & Wang, 2001; X. L. Chen, Li, Zhou, Ai, & Huang, 2003;de Rezende, Martinez, Capelozzi, Simoes, & Beppu, 2000;Giri, Biring, Nguyen, Wang, & Hyde, 2002;Hu, Xu, & Li, 1999;Yildirim et al, 2004), Melatonin (Arslan, Zerin, Vural, & Coskun, 2002;Genovese, Di Paola et al, 2005;Yildirim et al, 2006), Bilirubin (H. D. , CAPE = caffeic acid phenethyl ester , Erdosteine (Boyaci et al, 2006;Sogut et al, 2004;Yildirim et al, 2005;Yildirim et al, 2004) etc. ), Angiotensin converting enzyme inhibitors (Captopril (R. Wang, Ibarra-Sunga, Verlinski, Pick, & Uhal, 2000), Ramipril (Marshall et al, 2004) etc.…”

“…Compound Name Application Reference 1 Pirfenidone analogues early (Ammar et al, 2006) (Azuma et al, 1998) 8 14-MRMLs early (Azuma et al, 2001) 9 IFN-beta early (Azuma, Li et al, 2005) 10 Taurine and Niacin early (Blaisdell & Giri, 1995) 11 EC-SOD early (Bowler, Nicks, Warnick, & Crapo, 2002) 12 Erdosteine early (Boyaci et al, 2006) 13 CME early (Breuer et al, 1995) 14 Tetrathiomolybdate early (Brewer, Ullenbruch, Dick, Olivarez, & Phan, 2003) …”

Effects Of Erdosteine On Oxidative-Antioxidative Equilibrium And On Cataract Formation In Rat Pups With Selenite-Induced Cataract

“…It is a potent antioxidant and mucolytic pharmacological agent (24,25). Erdosteine inhibits lipid peroxidation (25).…”

“…It is a potent antioxidant and mucolytic pharmacological agent (24,25). Erdosteine inhibits lipid peroxidation (25). The pharmacological agent, therefore, decreases malondialdehyde (MDA), which is the end product of lipid peroxidation (24).…”

Deneysel Sepsis Modelinde Glutatyon, Myeloperoksidaz, Plazma Ve Doku Mda Düzeylerine N-Asetilsistein Ve Erdostein’in Etkilerinin Karşılaştırılması

“…ratlarda Bleomisine ba¤l› akci¤er fibrozisinde Erdostein'in etkilerini araflt›rd›klar› çal›flmada, Erdostein'in BAL s›v›s›nda nötrofil içeri¤i ve total hücre say›s›nda art›fllar› önledi¤i bulundu. Ayr›ca antioksidan özelli¤i ile nötrofil toplanmas›n› engelledi¤i görüldü (20) . Çal›flmam›z lökosit de¤erleri aç›s›ndan de¤erlendirildi¤inde; sepsis grubunda sepsisin kötü prognoz göstergesi olan lökopeni saptand›.…”