Abstract
Nicotine, a major component of tobacco and cigarette smoking is an addictive agent and has been characterized as a drug of abuse by the US Surgeon General (1–3). The economic burden due to abuse of this drug is substantial because of the well-documented pathophysiological effects of nicotine on organs in the cardiovascular, respiratory, hepatic, renal, and nervous systems (3). Association of nicotine through cigarette smoking with the increased incidence of pancreatitis and pancreatic cancer has also been reported (4–18). A survey on the association between cigarette smoking and pancreatic cancer showed that cigarette smokers had a significant 70% higher risk of pancreatic cancer in comparison to nonsmokers (8–16). When compared with nonsmokers, subjects who smoke filtered cigarettes had a 50% elevated risk. The proportion of pancreatic cancer attributable to cigarette smoking was 29% in blacks and 26% in whites (10). Most of the data that link cigarette smoke/nicotine to pancreatic diseases were gathered in humans. Recent studies with animals have also shown that nicotine or its metabolites could induce pathological and functional changes in the pancreas (17–25). This review will present and discuss the current understanding of the pathophysiology induced by nicotine in the exocrine pancreas and the possible mechanism of action of nicotine.
Cotinine and nornicotine are natural metabolites of nicotine. About 80%-90% of the dose of nicotine consumed can be accounted for in human urinary metabolites. In rodents, hepatic nicotine metabolism is found to involve cytochrome p450s that catalyze the first step of this pathway (26, 27). It has been demonstrated that pancreatitis could be induced in mice fed a caerulein and choline-deficient ethionine (CDE) supplemented diet (28–33).
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