title: Preventive and therapeutic effects of the protease inhibitor camostat on pancreatic fibrosis and atrophy in CCK-1 receptor-deficient rats.
abstract: OBJECTIVE
  Recent studies have demonstrated that synthetic protease inhibitors could ameliorate the progression of pancreatic fibrosis in some animal models. Since oral administration of protease inhibitors increases the plasma cholecystokinin (CCK) levels and causes hypertrophy of the pancreas in rats, there is a possibility that the protease inhibitor inhibits fibrosis in the pancreas via endogenous CCK release. We examined the effects of camostat, a synthetic protease inhibitor, on histopathologic changes in Otsuka Long-Evans Tokushima Fatty (OLETF) rat that has genetically no expression of CCK-1 receptor and displays inflammation and degeneration of the pancreas.
  
  
  METHODS
  Three groups of OLETF rats received a camostat-rich diet (200 mg/100 g normal diet) from 12 to 28 weeks of age or from 12 or 28 weeks of age to the age of 72 weeks, while the fourth group received standard rat diet.
  
  
  RESULTS
  Pancreatic wet weight and pancreatic contents of protein, DNA, amylase, lipase, and trypsin in camostat-treated rats were significantly higher than those in the untreated control rats. Immunohistochemical studies of the pancreas showed that expressions of interleukin-1beta, interleukin-6, tumor necrosis factor-alpha, and alpha-smooth muscle actin in camostat-treated rats were greatly suppressed compared with those in the untreated control rats. Atrophy and fibrosis in the pancreas observed in the untreated control rats were not found in camostat-fed rats.
  
  
  CONCLUSIONS
  The results of the present study suggest that camostat greatly inhibits pancreatic inflammation and prevents and reverses fibrosis and atrophy of the pancreas in the genetically obese and CCK-1 receptor-deficient OLETF rats.
authors.affiliation: Third Department of Internal Medicine, University of Occupational and Environmental Health Japan, School of Medicine, Kitakyushu, Japan.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Jia
authors.forename: Masashi
authors.initials: M
authors.lastname: Taguchi
authors.forename: Makoto
authors.initials: M
authors.lastname: Otsuki
mesh_terms: D000199:Actins / Q000378:metabolism; D000681:Amylases / Q000378:metabolism; D000818:Animals; D001284:Atrophy; D004435:Eating; D004952:Esters; D005355:Fibrosis; D016670:Gabexate / Q000031:analogs & derivatives* / Q000494:pharmacology; D006146:Guanidines; D015850:Interleukin-6 / Q000378:metabolism; D008049:Lipase / Q000378:metabolism; D008297:Male; D009765:Obesity / Q000150:complications; D009929:Organ Size; D010179:Pancreas / Q000201:enzymology / Q000473:pathology; D050500:Pancreatitis, Chronic / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D011480:Protease Inhibitors / Q000494:pharmacology*; D051381:Rats; D020334:Rats, Inbred OLETF; D043886:Receptor, Cholecystokinin A / Q000172:deficiency* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014357:Trypsin / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000199:Actins; D004952:Esters; D006146:Guanidines; D015850:Interleukin-6; D011480:Protease Inhibitors; D043886:Receptor, Cholecystokinin A; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; C034532:camostat; D016670:Gabexate; D008049:Lipase; D000681:Amylases; D014357:Trypsin