RESEARCH PAPER
An Exploratory Study on the Development of an Animal Model of Acute Pancreatitis Following Nicotine Exposure
P Chowdhury 1  
 
 
More details
Hide details
1
Department of Physiology & Biophysics, University of Arkansas for Medical Sciences
CORRESPONDING AUTHOR
P Chowdhury   

Department of Physiology & Biophysics, Slot #505, University of Arkansas for Medical Sciences, 4301West Markham Street, Little Rock, AR 72205
Publish date: 2003-09-15
 
Tobacco Induced Diseases 2003;1(September):213
KEYWORDS
ABSTRACT
Cigarette smoking is known to be a major risk factor for pancreatic cancer and pancreatitis is believed to be a predisposed condition for pancreatic cancer. As of this date, there is no established experimental animal model to conduct detailed studies on these two deadly diseases. Our aim is to establish a rodent model by which we can systematically study the pathogenesis of pancreatitis and pancreatic cancer.

Methods:
Adult Male Sprague Dawley rats were exposed to graded doses of nicotine by various routes for periods of three to 16 weeks. Blood samples were measured for hormonal and metabolic parameters. The pancreas was evaluated for histopathological changes and its function was assessed in isolated pancreatic acini upon stimulation with cholecystokinin (CCK) or carbachol (Cch). The pancreatic tissue was evaluated further for oncogene expression.

Results:
Body weight, food and fluid intakes, plasma glucose and insulin levels were significantly reduced in animals with nicotine exposure when compared to control. However, CCK and gastrin levels in the blood were significantly elevated. Pancreatic function was decreased significantly with no alteration in CCK receptor binding. Pancreatic histology revealed vacuolation, swelling, cellular pyknosis and karyorrhexis. Mutant oncogene, H-ras, was overexpressed in nicotinetreated pancreatic tissue

Summary and conclusion:
The results suggest that alterations in metabolic, hormonal and pathologic parameters following nicotine-treatment appear consistent with diagnostic criteria of human pancreatitis. It is proposed that rats could be considered as a potential animal model to study the pathogenesis of pancreatitis.

 
REFERENCES (30)
1.
Bergen AW, Caparoso N: Cigarette Smoking. J Natl Cancer Inst. 1999, 91: 1365-75. 10.1093/jnci/91.16.1365.
 
2.
American Cancer Society: Facts and Figures. 1996, San Francisco: American Cancer Society.
 
3.
Shopland DR, Eyre HJ, Pechacek TF: Smoking attributable cancer mortality in 1991: is lung cancer now the leading cause of death among smokers in the United States?. J Natl Cancer Inst. 1991, 83: 1142-48. 10.1093/jnci/83.16.1142.
 
4.
Rossing MA: Genetic influences on smoking: candidate genes. Environ Health Perspect. 1998, 106: 231-238. 10.2307/3434009.
 
5.
Sellers EM: Pharmacogenetics and ethnoracial differences in smoking. JAMA. 1998, 280: 179-180. 10.1001/jama.280.2.179.
 
6.
Chowdhury P, MacLeod S, Udupa KB, Rayford PL: Pathophysiological effects of nicotine on the pancreas: an update. Exp Biol Med. 2002, 445-54.
 
7.
Weibel ER: Stereological Methods. Practical Methods for Biological Morphometry. 1979, New York, Academic Press, 1: 63-161.
 
8.
Watanabe O, Baccino FM, Steer ML, Meldolesi J: Supramaximal caerulein stimulation and ultrastructure of rat pancreatic acinar cell; early morphological alterations during development of experimental pancreatitis. Am J Physiol. 1984, 246: G457-G467.
 
9.
Lombardi B, Estes LW, Longnecker DS: Acute hemorrhagic pancreatitis (massive necrosis) with fat necrosis induced in mice by DL-ethionine with a choline-deficient diet. Am J Pathol. 1975, 79: 464-480.
 
10.
Niderau C, Ferrell LD, Grendall JH: Caerulein induced acute necrotizing pancreatitis in mice: protective effects of proglumide, benzotript, and secretin. Gastroenterology. 1985, 88: 1192-1204.
 
11.
Niderau C, Niderau M, Luthen R, Strohmeyer G, Ferrell LD, Grendell JH: Pancreatic exocrine secretion in acute experimental pancreatitis. Gastroenterology. 1990, 99: 1120-1127.
 
12.
Williams JA, Korc M, Dormer RL: Action of secretagogues on a new preparation of functionally intact, isolated pancreatic acini. Am J Physiol. 1978, 235: E517-E52.
 
13.
Hosotani R, Chowdhury P, McKay D, Rayford PL: Effects of L-364,718 a new CCK antagonist on amylase secretion in isolated rat pancreatic acini. Pancreas. 1988, 3: 95-98. 10.1097/00006676-198802000-00016.
 
14.
Baba N, Suzuki T, Tobe T, Inoue K, Chowdhury P, Chang LW, Rayford PL: Influence of obstructive jaundice on pancreatic growth and on basal plasma levels of cholecystokinin and gastrin in rats. Dig Dis & Sci. 1986, 1233-1241. 10.1007/BF01296526.
 
15.
Chowdhury P, Hosotani R, Rayford PL: Weight loss and circulating GI peptides in rats exposed chronically to nicotine. Pharmacol Biochem & Behav. 1989, 33: 591-594. 10.1016/0091-3057(89)90393-6.
 
16.
Cooper GR, McDaniel V: Standard Methods of Clinical Chemistry. The Determination of Glucose by Ortho-Toluidine Method. 1959, Academic Press, New York, 6.
 
17.
Jung DH: Preparation and application of procion yellow starch for amylase assay. Clin Chim Acta. 1980, 3: 95-98.
 
18.
Bradford MA: A rapid and sensitive method for determination of microgram quantities of protein utilizing the principle of protein dye binding. Anal Biochem. 1976, 72: 248-254. 10.1016/0003-2697(76)90527-3.
 
19.
Steigerwalt RW, Williams JA: Characterization of cholecystokinin receptors on rat pancreatic membranes. Endocrinology. 1988, 109: 1756-1753.
 
20.
Munson PJ, Rodbard D: Ligand: A versatile computerized approach for characterization of ligand-binding systems. Anal Biochem. 1980, 107: 220-239. 10.1016/0003-2697(80)90515-1.
 
21.
McPherson GA: Analysis of radioligand binding experiments: A collection of computer programs for the IBM PC. J Pharmacol Methods. 1985, 14: 213-228. 10.1016/0160-5402(85)90034-8.
 
22.
Innis MA, Gelford DH, Snisky J, White TJ, (editors): PCR protocols: A guide to methods and applications. Cetus Corporation. 1992, Academic Press, Emeryville.
 
23.
Newsholme EA: A possible metabolic basis for the control of body weight. N Eng J Med. 1980, 302: 400-404.
 
24.
Dalloso HM, James WT: The role of smoking in regulation of energy balance. Int J Obes. 1983, 8: 365-75.
 
25.
Baile GA, McLaughlin CL, Della-Ferra MA: Role of cholecystokinin and opioid in control of food intake. Physiol Rev. 1986, 66: 172-234.
 
26.
Tada M, Omata M, Kawai S, Saisho H, Ohto M, Saiki R, Sniski JJ: Detection of ras gene mutations in pancreatic juice and peripheral blood of patients with pancreatic adenocarcinoma. Cancer res. 1993, 53: 2472-74.
 
27.
Almoguera C, Shibata D, Firrester K, Matin J, Armhein N, Perucho M: Most human carcinomas of the exocrine pancreas contain mutant K-ras genes. Cell. 1988, 53: 549-54. 10.1016/0092-8674(88)90571-5.
 
28.
Tada M, Omata M, Ohto M: Clinical application of ras gene mutation for diagnosis of pancreatic adenocarcinoma. Gastroenterology. 1991, 100: 233-238.
 
29.
Lemoine N, Jain S, Hughes C: Ki-ras oncogene activation in preinvasive pancreatic cancer. Gastroenterology. 1992, 102: 230-236.
 
30.
Kubrusly MS, Cunha JEM, Bacchella T, Abodo EE, Jukemura J, Penteado S, Morioka CY, de Souza LJ, Machedo MCC: Detection of K-ras point mutation at codon 12 in pancreatic diseases: a study in a Brazilian Casuistic. J Pancreas. 2002, 3: 144-151.
 
 
CITATIONS (10):
1.
A cell-based approach to study changes in the pancreas following nicotine exposure in an animal model of injury
Parimal Chowdhury, Azida Walker
Langenbeck's Archives of Surgery
 
2.
Pancreatic damage induced by cigarette smoke: the specific pathological effects of cigarette smoke in the rat model
Senay Topsakal, Ozlem Ozmen, Rahime Aslankoc, Demet Hancer Aydemir
Toxicology Research
 
3.
Tobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone initiates and enhances pancreatitis responses
M. Alexandre, A. K. Uduman, S. Minervini, A. Raoof, C. A. Shugrue, E. O. Akinbiyi, V. Patel, M. Shitia, T. R. Kolodecik, R. Patton, F. S. Gorelick, E. C. Thrower
American Journal of Physiology-Gastrointestinal and Liver Physiology
 
4.
Smoking and Pancreatic Disease
Mouad Edderkaoui, Edwin Thrower
Journal of Cancer Therapy
 
5.
Pathologic Cellular Events in Smoking-Related Pancreatitis
Edwin Thrower
Cancers
 
6.
Epidemiologic and Mechanistic Associations Between Smoking and Pancreatitis
Julia B. Greer, Edwin Thrower, Dhiraj Yadav
Current Treatment Options in Gastroenterology
 
7.
How does cigarette smoking cause acute pancreatitis?
Savio G. Barreto
Pancreatology
 
8.
The Emerging Role of Smoking in the Development of Pancreatitis
Martine Alexandre, Stephen J. Pandol, Fred S. Gorelick, Edwin C. Thrower
Pancreatology
 
9.
Pathophysiological Events Associated With Pancreatitis in Response to Tobacco
María Luaces-Regueira, Margarita Castiñeira-Alvariño, María Castro-Manzanares, Manuel Campos-Toimil, J. Enrique Domínguez-Muñoz
Pancreas
 
10.
New Insights into Cellular Mechanisms in Smoking-Related Acute Pancreatitis
Wilson R Catapani
Gastroenterology & Hepatology : Open Accessg
 
eISSN:1617-9625