Cellular and molecular mechanisms of cigarette smoke-induced lung damage and prevention by vitamin C

Abstract

Background: Cigarette smoke-induced cellular and molecular mechanisms of lung injury are not clear. Cigarette smoke is a complex mixture containing long-lived radicals, including p-benzosemiquinone that causes oxidative damage. Earlier we had reported that oxidative protein damage is an initial event in smoke-induced lung injury. Considering that p-benzosemiquinone may be a causative factor of lung injury, we have isolated p-benzosemiquinone and compared its pathophysiological effects with cigarette smoke. Since vitamin C is a strong antioxidant, we have also determined the modulatory effect of vitamin C for preventing the pathophysiological events.

Crosstalk Between Co-cultured A549 Cells and THP1 Cells Exposed to Cigarette Smoke

“…Monocytes are more resistant to oxidative stress, but activation of THP1 cells by CS may be mediated by nicotine, which is able to activate immune cells (Zhou et al 2013). It has been shown that antioxidants prevent CS toxicity in A549 cells (Banerjee et al 2008) and decrease protein damage, inflammation, apoptosis, and lung injury in smoke-exposed animals (Rahman 2012), supporting the major role of oxidative stress in CS-induced cytotoxicity. Another parameter, which may be related to altered inflammatory signaling and steroid resistance in COPD is acetylated histone H3 (Sundar et al 2013).…”

Activated charcoal filter effectively reduces p-benzosemiquinone from the mainstream cigarette smoke and prevents emphysema

“…Protein damage and DNA fragmentation are hallmarks of emphysema (Tuder et al 2003). We have isolated a major semiquinone from AECS and characterized it as p-benzosemiquinone by various physicochemical analyses, including ultraviolet (UV), mass, nuclear magnetic resonance (NMR) and electron spin resonance (ESR) spectroscopy (Banerjee et al 2008;Chatterjee, US patent 2005;Chatterjee, Japan patent 2008;Chatterjee, Korea patent 2008;Chatterjee, Europe patent 2008).…”

“…Once identifi ed, removal of that chemical entity could effectively reduce smokers' risk. Earlier, it was indicated that long-lived semiquinone radical(s) present in an aqueous extract of CS (AECS) is cytotoxic and causes protein and DNA damage (Pryor et al 1983(Pryor et al , 1986(Pryor et al , 1998Panda et al 1999Panda et al , 2000Panda et al , 2001Chouchane et al 2006;Banerjee et al 2008). Protein damage and DNA fragmentation are hallmarks of emphysema (Tuder et al 2003).…”

“…Using various in vitro and in vivo analyses, we had demonstrated that p-BSQ largely mimics AECS in causing protein modifi cation, apoptosis and emphysematous lung damage (Banerjee et al 2008).…”

A short overview of vitamin C and selected cells of the immune system

“…Finally, it has been shown that ascorbic acid stimulatory mechanism, in different cell types, prevents apoptosis by upregulating the Bcl-2 protein expression level, with resulting change in Bcl-2 and Bax (Bcl-2-associated X protein) protein ratio [72,21]. Intensive oxidative stress sensitizes T-cells to apoptosis, by decreasing the expression of Bcl-2 protein [73], which has been documented in different studies [74][75][76][77][78][79]. Protective role of ascorbic acid in Bcl-2 protein expression increasing and enhancing Bcl-2/Bax protein ratio, may allow T-cells to cope better with the effect of oxidative stress and resulting T-cell toxicity, as was reviewed earlier [80].…”