Disease relevance of Camostat

• Administration of 0.1% FOY-305 in the diet suppressed the incidence of carcinomas induced by repeated local application of the carcinogen 3-methylcholanthrene (MCA) (P less than .05) in mouse skin and delayed the time of appearance of the skin tumors (P less than .001) [1].
• The favorable effect on survival time and rate in the early phase of these two severe experimental forms of pancreatitis may justify an evaluation of FOY-305 in a clinically controlled study [2].
• Prevention of rat hepatic fibrosis by the protease inhibitor, camostat mesilate, via reduced generation of active TGF-beta [3].
• Feedback-mediated hyperplasia of the rat exocrine pancreas induced by oral treatment of rats with the protease inhibitor camostate (FOY-305) was preceded by a 15-fold transient elevation of PRG1 mRNA levels [4].
• In mice fed camostat for 7 days, the ratio of pancreatic to body weight increased by 143%, but when rapamycin was administered daily this was reduced to a 22% increase [5].

High impact information on Camostat

• We explored this idea using camostat mesilate, a serine protease inhibitor, to determine its effects and mechanisms of action in vivo [3].
• Camostat treatment markedly increased the phosphorylation of both PHAS-I and eIF4E and the formation of eIF4E-eIF4G complex [6].
• We also evaluated the effect of endogenous CCK by administering a synthetic trypsin inhibitor, camostat (100 mg/kg) [6].
• BACKGROUND & AIMS: Feedback regulation of pancreatic enzyme secretion is well established in animals, and their pancreases are able to adapt to intraduodenal inhibition of pancreatic enzymes by proteinase inhibitors such as Camostate (FOY-305; Schwarz GmbH, Monheim, Germany) [7].
• Intraduodenal administration of a synthetic trypsin inhibitor, camostat, resulted in significant increases in plasma concentration of both secretin and cholecystokinin in a dose-related manner that paralleled a significant increase in exocrine pancreatic secretion [8].

Chemical compound and disease context of Camostat

• Camostate (FOY-305) improves the therapeutic effect of peritoneal lavage on taurocholate induced pancreatitis [9].
• Conclusions: Camostat mesilate is superior to famotidine for relieving epigastralgia in patients with functional dyspepsia [10].
• Additionally, camostat showed strong anti-influenza effects on an amantadine-resistant type A virus and a type B virus infection in vitro [11].
• There was a significant increase in well differentiated cancer cells in mice treated with FOY-305 and heparin in combination, suggesting that co-administration of FOY-305 and heparin may be useful for the treatment of squamous cell carcinoma [12].
• The guanidino acid esters (FOY, FOY-305) represent a new class of potent proteinase inhibitors and are thought to have a beneficial effect on the course of acute pancreatitis [13].

Biological context of Camostat

• Intraduodenal infusion of beta-conglycinin peptone inhibited food intake in a dose-dependent manner, but that of whole soy peptone or camostat did not [14].
• Camostat, at a high dose of 10 mg, caused significant increases in the secretory rate, bicarbonate concentration and output of pancreatic juice over their basal levels, but had little influence on the protein concentration [15].
• The intestinal absorption of insulin and (Asu(1,7))eel-calcitonin after oral administration of the azopolymer-coated pellets containing these peptides with camostat mesilate was evaluated by measuring the hypoglycemic and hypocalcemic effects, respectively [16].
• The cell proliferation stimulated by PDGF was inhibited by the application of FOY-007 dose dependently (1-100 microM) and FOY-305 at 100 microM [17].
• The effects of proteolytic enzyme inhibitors, aprotinin, soybean trypsin inhibitor and camostat mesilate as absorption enhancers on the transdermal iontophoretic delivery of salmon calcitonin (SCT) have been examined in rats [18].

Anatomical context of Camostat

• By using nonabsorbable markers, cumulative trypsin, chymotrypsin, lipase, and amylase activities were measured as delivered to duodenum, midjejunum, and distal ileum, with or without simultaneous duodenal perfusion of the protease inhibitor camostat at graded doses [19].
• Histologic examination revealed widespread repopulation of the pancreas with acinar cells in the bombesin- and FOY-305-treated groups [20].
• For camostat mesilate, the ED50 (required to improve the survival rate of influenza virus-infected chick embryos by 50%) was 0.80 micrograms/g, and its selectivity index, based on the ratio of the 50% toxic dose (required to reduce the viability of chick embryos by 50%) to ED50, was 280 [21].
• Effects of camostat, a synthetic protease inhibitor, on endocrine and exocrine pancreas of the rat [22].
• Camostat mesilate attenuates pancreatic fibrosis via inhibition of monocytes and pancreatic stellate cells activity [23].

Associations of Camostat with other chemical compounds

• A cholecystokinin receptor antagonist, MK-329, also inhibited significantly the camostat-induced increase in pancreatic secretion; volume and bicarbonate output were reduced by 35% each and amylase output by 73% [8].
• Stimulation of the growth of azaserine-induced nodules in the rat pancreas by dietary camostate (FOY-305) [24].
• Gabexate and camostat, synthetic proteinase inhibitors, as direct inducing factors of water and bicarbonate secretion in the isolated and blood-perfused dog pancreas [15].
• The increase in plasma CCK induced by camostat was not blocked by CsA or FK506 [25].
• Intraduodenal administration of camostat or intravenous infusion of CCK-8 stimulated pancreatic secretion in control rats but not in capsaicin-treated rats [26].

Gene context of Camostat

• Three- and seven-day treatments with camostat did not affect pancreatic wet weight in CCK-A receptor (+/-) mice [27].
• The invasion in the Matrigel assay stimulated by HGF was inhibited by protease inhibitors, aprotinin and FOY-305, as well as by anti-HGF antibody [28].
• In mice fed chow containing the synthetic protease inhibitor camostat, protein synthetic rates and phosphorylation of two downstream targets of mTOR, eukaryotic initiation factor 4E binding protein 1 (4E-BP1) and the ribosomal protein S6 (S6), increased in comparison with fasted controls [5].
• The camostat-induced increases in protein synthesis and 4E-BP1 and S6 phosphorylation were almost totally abolished by administration of the mTOR inhibitor rapamycin 1 h prior to camostat feeding [5].
• METHODS: Eight-week-old Wistar rats were divided into the following groups: preadministration of loxiglumide (40 mg/kg) intravenously at 120, 60, and 0 minutes before endogenous CCK stimulation induced by a single oral administration of camostat (50 mg/kg) or exogenous CCK stimulation by a subcutaneous injection of CCK-8 (6 g/kg body weight) [29].

Analytical, diagnostic and therapeutic context of Camostat

• Effect of FOY-305 (camostate) on severe acute pancreatitis in two experimental animal models [2].
• The levels of c-myc, c-raf-1, and c-Ki-ras mRNAs were increased in regenerating pancreata following surgical partial pancreatectomy and following administration of camostat [30].
• We investigated the clinical usefulness and antitrypsin activity after treatment with a trypsin inhibitor, camostat mesilate, against the reflux esophagitis after distal gastrectomy reconstructed with Billroth-I anastomosis [31].
• Camostat mesylate, a synthetic serine protease inhibitor that is available for the treatment of chronic pancreatitis, demonstrated a striking effect of inhibiting blistering in organ culture of normal human skin with recessive dystrophic epidermolysis bullosa blister fluids [32].
• We have produced biodegradable or enteric-coated microspheres containing camostat mesylate, a protease inhibitor, using a water-oil-water emulsion solvent evaporation method [33].

References