A New Drug Evaluation Method for the Treatment of Chronic Pancreatitis Using WBN/Kob Rats as a Model of Human Chronic Pancreatitis.

Abstract

A new evaluation method for the treatment of chronic pancreatitis was devised using male WBN/Kob (WBN) rats as a human chronic pancreatitis model ; in these rats, the lesion is spontaneously manifested at about 12 weeks of age. As a result of screening for drugs that inhibit the development of pancreatitic lesions in WBN rats, the inhibitory effects of estradiol (10 and 40μEg/kg, i. p., twice a week), camostat mesylate (100 mg/ kg, p.o., daily) and allopurinol (100 mg/kg p.o., daily) were observed among estrogen, testosterone lowering agent, trypsin inhibitors and depressors of active oxygen.The efficacy of camostat mesylate and allopurinol which might be safely used for the treatment of progressive chronic pancreatitis were evaluated. Camostat mesylate was found to be effective, but not allopurinol. The expression of cells at the DNA synthesis stage as determined based on Brd Uridine (BrdU) uptake was examined. The uptake of BrdU notably occurred in acinar cells adjacent to the pancreatitic area. The regeneration of the pancreas as a result of the pancreatic trophic effect is the mechanism through which camostat mesylate is effective against lesions (mainly fibrosis) of chronic pancreatitis during the progression stage. One week after camostat mesylate administration, the weight of the pancreas increased rapidly, during which the uptake of BrdU in cells increased concurrently, indicating that regeneration of the pancreas occurred during this period.The most effective parameter for evaluating the efficacy of a drug for pancreatitis is the percentage of pancreatitic area employed in our histopathological study . We concluded that the use of WBN rats is pharmacologically effective for drug evaluation.