Effect of carboxamide derivative IS-741 on rat spontaneous chronic pancreatitis

This study aimed to analyze the therapeutic effects of the carboxamide derivative IS-741 on spontaneous chronic pancreatitis (CP) in the WBN/Kob rat. Four-week-old male WBN/Kob rats were fed with MB-3, and IS-741 (0.012% in MB-3) was orally administered for 12 weeks. Cytokine-induced neutrophil chemoattractant (CINC), interleukin (IL) -6, pancreatitis-associated protein (PAP), and p8 mRNAs in the pancreas were detected with semiquantitative reverse transcription-polymerase chain reaction (RT-PCR). Histological examination of the pancreas showed that hemorrhage, interstitial edema, and inflammatory cell infiltration were markedly less severe at 12 weeks, while fibrosis and acinar degeneration were also milder at 16 weeks, in the IS-741-treated rats than in untreated rats. The above-mentioned genes were significantly suppressed in IS-741-treated rats at 12 weeks. Our results show that IS-741 exerts a potentially therapeutic effect on experimental CP by suppressing the expressions of the proinflammatory cytokines (IL-6 and CINC) and pancreatic acute phase proteins (PAP and p8).