20 - Oxidant(s) in tobacco smoke is the key etiopathogenic factor for cigarette-smoke induced pulmonary emphysema and vascular remodeling: prevention by vitamin C

• Published in: Free radical biology & medicine Vol. 112; p. 29
• Main Authors: Ganguly, Souradipta, Gupta, Indranil, Stuehr, Dennis J, Panda, Koustubh
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.11.2017
• ISSN: 0891-5849; 1873-4596
• DOI: 10.1016/j.freeradbiomed.2017.10.033

Cigarette smoking can cause fatal pulmonary injury involving extensive structural and functional damage of the lung through a disease called emphysema followed by extensive vascular remodeling, that restricts pulmonary circulation to cause pulmonary hypertension and right ventricular dystrophy of the heart. We demonstrate that oxidant(s) present in tobacco smoke not only inflict direct oxidative damage to lung tissues to predispose them to increased proteolysis through endogenous proteases like matrix-metalloproteinase-9 (MMP-9), but are also responsible for triggering the extensive pulmonary vascular remodeling that is causally associated with pulmonary hypertension. Our present work also reveals that tobacco-smoke oxidants elicit such degenerative lung injury and lung remodeling in two different cellular environments in the lung by activating diverse classes of inflammatory cytokines. Overexpression of two key enzymes in the lung, inducible Nitric-Oxide Synthase (iNOS) and Arginase (Arginase I) also seem to play a determining role in predisposing lung tissues to emphysema and pulmonary hypertension respectively. The versatile dietary antioxidant, ascorbate or vitamin C, was found to comprehensively prevent emphysematous lung damage by inhibiting both tobacco-smoke induced direct lung protein oxidation as well as inflammatory cytokine-mediated oxido-nitrosative modification of lung proteins, that otherwise leads to increased proteolysis of such oxidized or nitrated proteins by endogenous lung proteases during emphysema. Vitamin C also restricts the upregulation of MMP-9, the major lung protease involved in the proteolysis of such modified lung proteins during tobacco-smoke induced emphysema. Interestingly, it also prevents the cytokines involved in triggering the subsequent peri-vascular collagen deposition and medial thickening characterizing vascular remodeling and pulmonary hypertension as well as the overexpression of the enzyme, Arginase I involved in this process. Overall, our findings implicate tobacco-smoke oxidant(s) as the key etiopathogenic factor behind both the degenerative breakdown (emphysema) and vascular remodeling (pulmonary hypertension) of the lung during smoking. It also reveals the inexpensive prospects of holistic prevention of both these major forms of tobacco-smoke induced lung damage by vitamin C particularly in those inveterate smokers who fail to bail themselves out from the addictive influence of smoking.