Superoxide and hydroxyl radicals along with hydrogen peroxide (H 2 O 2 ) are commonly termed as reactive oxygen species (ROS). The main source of generation of ROS in cells are various metabolic reactions including the incomplete reduction of oxygen in mitochondrial electron transport chain during respiration.1,2) If superoxide radicals are not neutralized, they in turn generate hydroxyl radicals by reacting with H 2 O 2 in the presence of free iron by classical Fenton reaction.2,3) Thus generated ROS, if not quickly disposed from cellular environment, can drive the cell to a prooxidant state, referred as oxidative stress, by attacking almost all major biological molecules including membrane lipids.
2)Thwarting the damage inflicted by free radicals and reactive species is the function of a complex antioxidative defense system. This system includes enzymes such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) and some of the most commonly used and experimentally studied nonenzymatic antioxidants such as vitamin E, vitamin C, carotenoids and glutathione. 4,5) Under some pathological conditions where ROS are formed in excess, the antioxidant systems of cells cannot withstand the oxidative stress and eventually results in damage of cells and tissues.
6)The lung, as the organ exposed to the highest oxygen concentration, is particularly at risk to the toxic effects of oxygen.7) Several lung diseases have been associated with oxidative stress and linked to oxidant insults. 8) Therefore the lungs and tissues of the respiratory tract require a specific defense system against oxidants and free radicals. Pulmonary fibrosis is a pathological state that is characterized by superfluous synthesis and deposition of extracellular matrix (ECM) in the distal airspace, and is probably initiated by acute or chronic lung injury.9,10) The current treatment to pulmonary fibrosis involves corticosteroids, antifibrotic and immunosuppressive agents, with very less achievement.11,12) Therefore, treating pulmonary fibrosis successfully remains an uphill task, and development of drug regimens for the same remains an imperative challenge.Bleomycin is an antibiotic used as an anti-cancer drug that has shown efficacy in an array of tumors both in humans and animals.13) The therapeutic utility of the drug has, however, been precluded by severe toxicities especially of the lung.
14)Pulmonary fibrosis is the major side effect that is elicited by bleomycin and depends upon the duration and the dosage of the anti-neoplastic drug. Although the exact mechanism of development of pulmonary fibrosis is not yet fully explored, it is believed that bleomycin generates ROS and initiates inflammatory and fibroproliferative changes via a concerted action of various cytokines leading to collagen accumulation in the lung. 15,16) Bleomycin induction also results in depletion of endogenous antioxidant defenses thereby increasing the risk of oxidant mediated tissue injury. 17,18) Bleomycin induced pulmonary fibrosis in rodents is popul...