Koji Yoshinaga*, Masataka Washizuka and Yoshihide Segawa
Central Research Laboratories, Zeria Pharmaceutical Co., Ltd., 2512-1
Oshikiri, Kohnan-machi, Ohsato-gun, Saitama 360-0111, Japan
*Corresponding author.ﾊﾊFAX:+81-48-539-1072
E-mail: ken-yakuri@zeria.co.jp
Abstract: We examined the effects of fasting and non-fasting on gallstone-related
acute pancreatitis by the occlusion of the common bile duct (OCD). We prepared
a rat OCD-induced pancreatitis model under both fasting and non-fasting
conditions, and we measured amylase activity in ascites as well as production
of inflammatory cytokines and chemokines. We also examined the pathology
of the pancreas, myeloperoxidase (MPO) activity in some tissues and mortality
rates. In the fasted OCD group, ascites containing a large amount of amylase,
interleukinﾊ1b (IL-1b),
interleukinﾊ6 (IL-6), and cytokine-induced neutrophil chemoattractant-1
(CINC-1) as well as marked hemorrhage and necrosis of the pancreatic acinar
cells were observed. Pulmonary MPO activity increased 3.4-fold compared
to the control group. In the non-fasted OCD group, there was no development
of ascites. Slight necrosis of acinar cells and slight increases in pulmonary
MPO activity were observed. In addition, in the fasted OCD group, the cumulative
mortality rate was 50% 6ﾊdays after ligation. However, in the non-fasted
OCD group, none of the animals died. These results suggest that gallstone-related
severe pancreatitis depends on fasting-related structural and/or functional
changes in the pancreas. Moreover, increased production of inflammatory
cytokines and chemokines in ascites under fasting condition may be involved
in multiple organ failure resulting from severe acute pancreatitis.
Keywords: Occlusion of the common bile duct (OCD), Severe acute pancreatitis,
Cytokine, Myeloperoxidase
Copyrightｩ The Japanese Pharmacological Society 2000
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