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FOR IMMEDIATE RELEASE
December 14, 2007
APS Contact
Donna Krupa
Office:
(301) 634-7253
dkrupa@the-aps.org
www.The-APS.org
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 to create
health or disease. The American Physiological Society (APS;
www.The-APS.org) has been an integral part of the scientific discovery
process since it was established in 1887.
# # #
NOTE TO EDITORS: To schedule an interview with
a member of the research team, please contact Donna Krupa at 301.634.7209
(direct dial) or
DKrupa@the-APS.org.
Key words: alcohol abuse, alcoholic
chronic pancreatitis (ACP), physiology
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