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New Research Model Opens Way To Better Understanding Of Alcohol’s Role In Developing Alcoholic Chronic Pancreatitis

BETHESDA, MD – Chronic, excessive alcohol consumption is a major risk factor for developing chronic pancreatitis (pancreatic inflammation). It is therefore surprising that alcoholic chronic pancreatitis (ACP) develops in only a small percentage of heavy drinkers. Research findings suggest that liquor per se may not cause ACP, but rather sensitizes the pancreas to genetic and/or environmental factors that predispose the organ to the disease.  A critical obstacle to testing this (and other) assumptions about ACP has been the lack of animal models to study it.

A team of California researchers has now developed a rat model that reproduces three key responses in human ACP. The results of their new study conclude that (1) alcohol impairs the ability to recover from acute pancreatitis, and (2) alcohol may sensitize the pancreas to chronic injury. 

The study, “A Rat Model Reproducing Key Pathologic Responses of Alcoholic Chronic Pancreatitis,” was conducted by Ilya Gukovsky, Aurelia Lugea, Mohammad Shahsahebi, Jason H. Cheng, Peggy P. Hong, Yoon J. Jung, and Stephen J. Pandol of the University of California at Los Angeles and the VA Greater Los Angeles Healthcare System, Los Angeles, CA; and Quing-gao Deng, Barbara A. French, William Lungo, Samuel W. French and Hidekazu Tsukamoto of the University of Southern California - University of California at Los Angeles (USC-UCLA) Research Center for Alcoholic Liver and Pancreatic Diseases.  Their study appears in the online edition of the American Journal of Physiology – Gastrointestinal and Liver Physiology (doi:10.1152/ajpgi.00006.2007).

First Available Model for Testing ACP 

The researchers induced chronic pancreatic changes in rats by pair feeding them either an ethanol (E; alcohol) or control (C) diets for eight weeks. During the last two weeks, the rodents received cyclosporin A (CsA; a medication designed to stop the rejection of a transplanted organ) or a placebo. After one week on CsA, one episode of acute pancreatitis was induced through injections of cerulein (Cer; an analogue of cholecystokinin, high doses of which are used to excessively stimulate digestive secretion and thus induce acute experimental pancreatitis). The controls received saline injections. One week after the episode of acute pancreatitis, the rats’ pancreas was analyzed.   

Results – Key Findings

In their model, termed “the CsA model of ACP,” the researchers found that:

  • ethanol (E) feeding greatly sensitizes the pancreas to pathologic responses of chronic pancreatitis. As a result, there was a massive loss of the main type of exocrine pancreatic (acinar) cells, sustained inflammation and widespread fibrosis in the rats who were fed alcohol
  • the pancreas of rats treated with E+CsA+Cer lost approximately 86 percent of acinar tissue, indicating massive acinar cell death. By comparison, the corresponding control-fed C+CsA+Cer rat group was almost equal to the group that had not been treated 
  • the model was able to reproduce the key responses of human alcohol chronic pancreatitis 
  • neither CsA nor Cer treatments alone led to pancreatic injury in either the control- or ethanol-fed rats.

Next Steps

The researchers have developed a model of alcohol mediated post-acute pancreatitis that reproduces the three key responses of human ACP: loss of parenchyma, sustained inflammation, and fibrosis. These findings will allow researchers to investigate the ways in which ethanol consumption sensitizes the pancreas to chronic injury. Ilya Gukovsky, Ph.D., lead author of the study said, “The results of this study are a significant step forward in our better understanding ACP, and helping those who suffer from it.” 

Physiology is the study of how molecules, cells, tissues and organs function in health and disease. Established in 1887, the American Physiological Society (APS) was the first U.S. society in the biomedical sciences field. The Society represents more than 10,500 members and publishes 15 peer-reviewed journals with a worldwide readership.