The Protective Effect of Naringin against Bleomycin-Induced Pulmonary Fibrosis in Wistar Rats

The Protective Effect of Naringin against Bleomycin-Induced Pulmonary Fibrosis in Wistar Rats Nergiz H. Turgut,1 Haki Kara,2 Sahende Elagoz,3 Koksal Deveci,4 Huseyin Gungor,2 and Emre Arslanbas2 1Cumhuriyet University School of Pharmacy, Department of Pharmacology, 58140 Sivas, Turkey 2Cumhuriyet University School of Veterinary Medicine, Department of Pharmacology and Toxicology, 58140 Sivas, Turkey 3Cumhuriyet University School of Medicine, Department of Pathology, 58140 Sivas, Turkey 4Cumhuriyet University School of Medicine, Department of Biochemistry, 58140 Sivas, Turkey Received 30 September 2015; Revised 23 December 2015; Accepted 14 January 2016 Academic Editor: Leif Bjermer Copyright © 2016 Nergiz H. Turgut et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract The aim of the current study was to investigate the protective effect of naringin on bleomycin-induced pulmonary fibrosis in rats. Twenty-four Wistar rats randomly divided into four groups (control, bleomycin alone, bleomycin + naringin 40, and bleomycin + naringin 80) were used. Rats were administered a single dose of bleomycin (5 mg/kg; via the tracheal cannula) alone or followed by either naringin 40 mg/kg (orally) or naringin 80 mg/kg (orally) or water (1 mL, orally) for 14 days. Rats and lung tissue were weighed to determine the lung index. TNF-α and IL-1β levels, hydroxyproline content, and malondialdehyde (MDA) levels were assayed. Glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities were determined. Tissue sections were stained with hematoxylin-eosin, Masson’s trichrome, and 0.1% toluidine blue. TNF-α, IL-1β, and MDA levels and hydroxyproline content significantly increased () and GPx and SOD activities significantly decreased in bleomycin group (). Naringin at a dose of 80 mg/kg body weight significantly decreased TNF-α and IL-1β activity, hydroxyproline content, and MDA level () and increased GPx and SOD activities (). Histological evidence supported the results. These results show that naringin has the potential of reducing the toxic effects of bleomycin and may provide supportive therapy for conventional treatment methods for idiopathic pulmonary fibrosis. 1. Introduction Idiopathic pulmonary fibrosis (IPF) is a progressive and devastating lung disease characterized by deposition of extracellular matrix which leads to lung remodeling. The disease is thought to be driven by abnormal and/or dysfunctional alveolar epithelial cells which support fibroblast proliferation, recruitment, and differentiation [1]. Early and accurate diagnosis of the disease is important. From the time of diagnosis, the average survival time is 2.8–4.2 years which is worse than some types of cancer [2]. Idiopathic pulmonary fibrosis mostly occurs after the age of sixty and is more common in men. Pulmonary fibrosis progresses slowly and insidiously for many patients; however, approximately in 10–15% of patients, the course of the disease is much more rapid and the acute exacerbation of the disease is a highly lethal clinical event [3, 4]. Dry cough, chronic exertional dyspnea, bibasilar end-inspiratory crackles, and finger clubbing are clinical features commonly observed with IPF. Medications used in treatment such as steroids and immunosuppressive drugs are insufficient to improve prognosis [5, 6]. Therefore it is necessary to develop new types of drugs. The etiology of idiopathic fibrosis is yet not fully understood. Recent studies have suggested that lung injury can be induced by inflammatory cells through the release of oxidative species, cytokines, proteases, peroxidases, and growth factors [7, 8]. Although inflammation is not the primary mechanism of IPF, it may contribute to the disease pathogenesis by affecting the level of oxidative stress and wound-repair process. Reactive oxygen molecules (ROS) released from active leukocytes contribute to lung damage and inflammation. In some studies carried out recently, it has been suggested that a balance between ROS and antioxidant molecules plays an important role in the pathogenesis of pulmonary fibrosis [9, 10]. Increased levels of ROS have been reported in bronchoalveolar lavage fluid (BALF), obtained from the lung tissue of patients with pulmonary fibrosis and from bleomycin administered animals [11, 12]. It is well known that the accumulated macrophages and neutrophils are capable of inducing oxidant-mediated lung parenchyma cell toxicity [13]. Activated neutrophils can yield myeloperoxidase (MPO) and this enzyme can create toxic hydroxyl radicals by combining with hydrogen peroxide [14]. The supportive therapy provided by agents with both antioxidant and anti-inflammatory properties may be useful to treat IPF and other disorders characterized by excessive inflammation and/or oxidative stress. Bleomyci (...truncated)