International Journal of Animal and Veterinary Advances 3(5): 330-336, 2011 ISSN: 2041-2908 © Maxwell Scientific Organization, 2011 Submitted: July 28, 2011 Accepted: September 25, 2011 Published: October 15, 2011 Corresponding Author: Peyman Mikaili, Department of Pharmacology, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran 330 Evaluation of the Effects of Nicotinamide on the Bleomycin-induced Pulmonary Fibrosis in Rat 1 Peyman Mikaili, 2 Ali Asghar Hemmati, 2 Mohammad Javad Khodayar, 3 Mehri Ghafurian and 4 Iran Rashidi 1 Department of Pharmacology, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran 2 Department of Pharmacology and Toxicology, School of Pharmacy, Jondishapour University of Medical Sciences, Ahwaz, Iran 3 Department of Immonology, 4 Department of Pathology, Jondishapour University of Medical Sciences, Ahwaz, Iran Abstract: Fibrosis is the abnormal production of collagen fibers following tissue damage. This accounts for the formation of scar tissue. Lung fibrosis is one of the typical ways in which the lung reacts to damaging stimuli. In this study we tried to investigate the involving phenomena during the process of bleomycin-induced fibrosis in murine lung. We have evaluated this process at three levels, namely, at (1) cellular level (cells with contraction activity of pulmonary tissue), (2) intercellular signaling agents (e.g., IL-8, TNF-", TGF-$), tissue index factors (collagen, hydroxyproline) and some inorganic elements which may hypothetically be engaged as efficient enzymatic cofactors (e.g., copper), (3) pathophysiological or exaggerated physiological processes (inflammation and fibrosis). The pharmacological agent which have been selected for evaluating in this study is Nicotinamide, which their selection rationale will be discussed in detail separately in the discussion section. Bleomycin-induced pulmonary fibrosis is a widely used animal model for lung injury and fibrosis. After single dose instillation of intratracheal bleomycin, the fibrotic responses were studied by biochemical measurement of collagen deposition and analysis of pathological lung changes in different treatment groups. The results of this study showed that administrated agents in different doses, had satisfactorily healing effects on fibrosis process, ranging from good to moderate, through significant decreasing in lung collagen content (p<0.05). Key words: Bleomycin, L- Hydroxyproline, nicotinamide, pulmonary fibrosis, rat INTRODUCTION From man's earliest attempts to manufacture tools and cloths and construct buildings, he has faced health risks from inhalable substances or dusts in the workplace. With sophistication of life and creation of villages, cities and societies, such risks became more serious. The earliest recorded acknowledgement of this problem comes from the time of Hippocrates, (377-460 B.C), the father of medicine. He knew that inhaled dust could affect the health and stated: "The metal miner is a man who breathes with difficulty". Georgius Agricola, in his book, 'De Re Metalica' (1556), wrote about dusts and suggested that they ulcerate the lung and cause consumption. He described several methods for ventilation of mines to reduce the risk of lung disease (Holt, 1987). Fibrosis is the abnormal production of collagen fibers following tissue damage. This accounts for the formation of scar tissue. Lung fibrosis is one of the typical ways in which the lung reacts to damaging stimuli. Historically, idiopathic pulmonary fibrosis was thought to be a deleterious consequence of persistent lung inflammation that followed an unknown insult. However, the growing recognition that foci of proliferating fibroblasts are more prominent than evidence of inflammation in lung tissue (Kuhn, 1989), as well as the lack of efficacy of anti- inflammatory drugs in the majority of affected patients, has led to a focus on the fibrotic pathway itself (Selman et al., 2001). At first blush, the article by Kolb et al. (2001) in this issue of the JCI (Kolb et al., 2001) might suggest that we may have discounted inflammation too hastily. The authors show that treatment of rats with a single dose of a recombinant adenovirus encoding the cytokine IL-1$, a central regulator of acute inflammation (Dinarello, 1996) leads to a progressive form of pulmonary fibrosis that continues over at least 60 days. Importantly, this progression is not due to any persistent effects of IL-1$ itself, since, as expected with adenovirus infection, IL-1ß expression is only increased transiently, returning to near base-line values by 14 days after infection. In contrast, pulmonary fibrosis (as determined by increases in lung hydroxyproline content) is not