Abstract
OBJECTIVE: Despite a strong epidemiological association between cigarette smoking and pancreatic diseases, such as pancreatic cancer and chronic pancreatitis, the effects of long-term cigarette smoke inhalation on the pancreas have not been clearly determined. In the present study, we investigated the effect of cigarette smoke inhalation on the pancreas. METHODS: Thirty-six female Sprague Dawley rats were exposed to two different doses of environmental tobacco smoke averaging 100 mg or 160 mg/m3 total suspended particulate matter (TSP) per m3 for 70 min twice a day for 12 wk. The animals were sacrificed and examined for the effects of tobacco smoke exposure on pancreatic morphology and function. RESULTS: In 58% (7/12) of the animals, exposure to 160 mg/m3 TSP cigarette smoke induced a chronic pancreatic inflammatory process with fibrosis and scarring of pancreatic acinar structures. Animals with fibrotic alterations showed an induction of pancreatic pro-collagen 1 gene expression, and the infiltration of immune cells was accompanied by the expression of the inflammatory mediators MIP-1α, IL-1β, and TGF-β in 33% (4/12) of the animals. Acinar cell stress was manifested by a significant up-regulation of pancreatitis-associated protein expression (PAP) in smoke-exposed animals (smoke-exposed 6,932 ± 1,236 vs control 3,608 ± 305, p <0.05). Possibly contributing to the morphological damage to the exocrine pancreas, the inhalation of cigarette smoke induced trypsinogen and chymotrypsinogen gene expression and, furthermore, reduced pancreatic enzyme content. CONCLUSIONS: This study provides experimental evidence of morphological pancreatic damage induced by the inhalation of cigarette smoke, which is likely to be mediated by alterations of acinar cell function.