Mitogenic and functional responses by nicotine and hydrogen peroxide in AR42J cells: a comparative study

Nicotine, one of the main chemicals in tobacco, has been known as a primary psychoactive ingredient that is responsible for the reinforced behavior in smokers. Each year in the United States, 435,000, or 1 in every 5 deaths, are attributed to cigarette smoking [1]. About half of the young adult smokers today who continue to smoke throughout their life will die of a smoke related diseases [2]. Further, it has been shown that smoking is an independent risk factor in the development of chronic pancreatitis and pancreatic cancer [3,4]. In animal studies it has been shown that nicotine plays a role in the induction of pathophysiology of pancreas [5,6].Evidence shows that lipid peroxidation occurs in pancreatic tissues when exposed to nicotine [7] and that the mitochondrial respiratory chain is affected by nicotine leading to an increased generation of superoxide anions and hydrogen peroxide [8]. Clinical studies have indicated that patients with acute pancreatitis have a higher plasma levels of lipid peroxide than that observed in patients with mild pancreatitis [9]. This suggests that multiple etiological factors other than the release of enzymes may be responsible in this mechanism. As of to-date, however, there have been no reported studies investigating the role of oxyradicals induced by nicotine in the pancreas, and to determine whether oxyradical formation by nicotine contribute to the pathophysiological mechanisms associated with pancreatic injury encountered in smokers We have shown earlier that nicotine induces functional alterations and MAP kinase signaling pathways in pancreatic acinar cells [10,11]; however, the underlying mechanisms responsible for these observed effects by nicotine are still not completely understood. We surmise in this study that nicotine induces the oxidative stress in pancreatic acinar cells and thus contributes to this mechanism.Oxidative stress arises when there is an imbalance between the formation of reactive oxygen species (ROS) and