Synergistic Effects of Erythromycin and N-Acetyl-cysteine on Amelioration of Cigarette Smoke-Induced Chronic Obstructive Pulmonary Disease in Adult Male Rats

Background: Chronic obstructive pulmonary disease (COPD) affects various structural and functional domains in the lungs. It is characterized by damage of small airways due to an inflammatory process, oxidative stress and imbalance of proteolytic and anti-proteolytic activities. The aim of this work is to investigate the mechanisms involved in COPD and the role of erythromycin and/or N-acetyl cysteine in amelioration of these mechanisms by their role in the extracellular matrix remodeling together with their anti-inflammatory and antioxidant effects. Methods: In this study a total of 50 male albino rats were divided into five groups (10 rats/group); control group, COPD group, COPD group treated by erythromycin, COPD group treated by N-acetyl-cysteine and COPD group treated by both erythromycin and N-acetyl-cysteine. In lung tissue, levels of interleukin-6 (IL-6) and tumor necrosis factorα (TNF-α ) were measured using ELISA techniques, glutathione (GSH), catalase, myeloperoxidase activity (MPO) and malondialdehyde (MDA) were measured by specific chemical methods, together with gene expression of Interleukin-8 (IL-8), matrix metalloproteinase-9 (MMP-9) and tissue inhibitors of matrix metalloproteinase-1 (TIMP-1) by RT-PCR, histo-pathological examination of lung tissues to detect the damage level was also done. Results: When compared with the control group, COPD group showed significant increase of IL-8, IL-6, TNFα , MPO activity, MDA and MMP-9 with significant decrease of GSH, catalase and TIMP-1 together with tissue damage shown by the histo-pathological examination. The use of erythromycin or N_acetyl-cysteine lead to significant decrease of IL-8, IL6, TNF-α , MPO activity, MDA and MMP-9 with significant increase of GSH, catalase and TIMP-1and improvement of histo-pathological damages, but the use of erythromycin affected significantly the inflammatory aspect of COPD ( IL8, IL-6, TNF-α , MPO activity, MDA and MMP-9 and TIMP1 balance), while N-acetyl-cysteine affect significantly oxidative stress in COPD (TNFα , MPO activity, MDA, GSH and catalase). However, treatment of COPD by both erythroCorrespondence to: Dr. Heba M. Shawky, The Department of Physiology, Faculty of Medicine, Cairo University mycin and N-acetyl-cysteine lead to improvement of inflammation, alveolar structure destruction (emphysema) and oxidative stress in COPD. Conclusion: Administration of erythromycin or N-acetylcysteine can ameliorate the changes that occur in COPD by their anti-inflammatory, antioxidant effects and their role in regain the balance between extracellular matrix degradation and deposition, while treatment of COPD using combination of the two drugs resulted in better improvement.