Effect of FOY-305 (camostate) on severe acute pancreatitis in two experimental animal models

Lankisch, P. G.; Pohl, U.; Göke, Burkhard; Otto, J.; Wereszczyńska-Siemiątkowska, Urszula; Gröne, Hermann Josef; Rahlf, G

doi:10.1016/0016-5085(89)90780-4

Cited by 36 publications

(13 citation statements)

References 27 publications

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“…Protease inhibitors, including camostate, have been reported to have preventive effects in several models of acute pancreatitis such as caerulein-, trypsin-, taurocho late and CDE (choline-deficient ethionine-supplemented) diet-induced pancreatitis (24)(25)(26)(27). However, camostate did not show any preventive effect on pancreatic duct ligation-induced pancreatitis.…”

Section: Discussionmentioning

confidence: 99%

Effect of T-0632, a CholecystokininA Receptor Antagonist, on Experimental Acute Pancreatitis.

Taniguchi¹,

Yomota²,

Kume³

et al. 1997

Jpn.J.Pharmacol

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Section: Discussionmentioning

confidence: 99%

Effect of T-0632, a CholecystokininA Receptor Antagonist, on Experimental Acute Pancreatitis.

Taniguchi¹,

Yomota²,

Kume³

et al. 1997

Jpn.J.Pharmacol

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“…Trypsin Inhibitor in Rat Pancreatitis vealed beneficial effects after the induction of pancreatitis in rats [5,6], suggesting that it is important to use the agents in the early phase of acute pancreatitis for more effective treatment of the disease.…”

Section: Discussionmentioning

confidence: 99%

“…No report has shown a therapeutic effect concerning aprotinin [17,18]. Recently, low molecular trypsin inhibitors were synthesized and their effects on experimental pancreatitis have been reported [2][3][4][5][6], Most of them showed the prophylactic effects on the survival of acute experimental pancreatitis. Two reports even re 94 Sobajima/Hayakawa/Kondo/Shibata/ Kitagawa/Sakai/Ishiguro/Tanikawa/Nakae…”

Section: Discussionmentioning

confidence: 99%

“…Concerning pancreatic enzymes, trypsin plays an important role in the onset and further development of the disease, because trypsin is considered as an activator of trypsinogen and other pancreatic proen zymes [1], Following this idea, several synthetic trypsin inhibitors have been developed as a specific therapy to interrupt the enzyme cascade for acute pancreatitis and have been reported to have favorable effects on experi mental pancreatitis [2][3][4][5][6]. Most of the trials succeeded to reveal only prophylactic effects of the inhibitors but not therapeutic effects [2][3][4], Recently, we also reported the therapeutic effect for experimental pancreatitis, but the direct effect on the pancreas, such as improvement of histopathological findings, was not clear.…”

Section: Introductionmentioning

confidence: 99%

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Monitoring Serum Tryptic Activity and Effect of Trypsin Inhibitor on Rat Acute Pancreatitis

et al. 1994

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The effect of a novel synthetic trypsin inhibitor, 4-(2-succinimidoethylthio)-phenyl 4-guanidinobenzoate methanesulfonate (E3123), on severe acute pancreatitis was studied in trypsin-taurocholate-induced acute experimental pancreatitis in rats. Rats were divided into four groups according to difference of subdivided doses of E3123 with fixing the total dose at 3 mg/kg body weight. Group A: 1.5 mg/kg of E3123 subcutaneously (SC) each at 1 h before and after induction of pancreatitis. Group B: 1 mg/kg SC each at 1 h before, 1 and 3 h after induction. Group C: 1.5 mg/kg SC each at 1 and 3 h after induction. Group D: 1.5 mg/kg SC each at 3 and 5 h after induction of pancreatitis. The survival rate at 24 h was significantly improved in group B (77% in group B, vs. 36% in paired control; p < 0.01) and in group C (70 vs. 38%; p < 0.05), but not in group A or D. Residual tryptic activity of serum α₂-macroglobulin trypsin complex (α2M-TRY) was reduced after the injection of E3123 though immunoreactive trypsin remained unchanged in the early phase of pancreatitis. The reduction of α2M-TRY reflected the inhibitory capacity of E3123 in plasma. E3123 showed favorable effects on the initial stage of severe acute pancreatitis and the effects were probably based on the inhibition of α2M-TRY activity in serum.

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“…A new synthetic protease inhibitor, FUT-175, is a guanidino acid ester which has been reported to inhibit several key enzymes in pancreatitis such as trypsin and phospholipase A2 [7], FUT-175 has also been reported to be about ten times as potent as compared with other pro tease inhibitors such as gabexate mesilate (FOY) or camostat mesilate [20,21]. There have been a few reports on the protective effects of such a type of synthetic protease inhibitors in experimental models of pancreatitis [8,9], On the contrary, there have been a few reports regarding the bad results of trials using such a low-molecular-weight synthetic protease inhibitor, FOY [22,23], Such a dis crepancy is probably due to the fact that when the patients come to hospitals, pancreatitis is already completed.…”

Section: Discussionmentioning

confidence: 99%

A New Protease Inhibitor, Nafamostat Mesilate (FUT-175), Protects Pancreatic Acinar Cells in CDE-Diet-lnduced Pancreatitis in Mice

Hirano¹,

Takeuchi²

1993

Dig Surg

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This study was designed to evaluate the role of lysosomal enzymes in the pathogenesis of acute pancreatitis and also evaluate the protective effects of a new synthetic protease inhibitor, naf amostat mesilate (FUT-175), against pancreatic injuries in mice with severe acute pancreatitis induced by a cho-line-defïcient ethionine-supplemented (CDE) diet. The CDE diet induced a significant redistribution of cathepsin B activity from the lysosomal fraction (about 30% of the total activity) to the zymogen fraction (about 50%) as compared with the control mice (about 50 and 30%, respectively), which indicated a colocalization of lysosomal enzymes with digestive enzymes in the same sub-cellular compartment. The CDE diet also caused a significant activation of trypsinogen in the pancreatic tissue (14 ± 3 U/mg DNA at 24 h and 21 ± 4U/mg DNA at 48 h). However, FUT-175 exerted significant protective effects against pancreatic injuries induced by CDE diet such as hyperamylasemia (15 ± 2 U/ml at 24 h and 10 ± 3 U/ml at 48 h), high mortality rate (17% at 3 days, 30% at 4 days and 43% at 5 days) as compared with only CDE diet mice (29 ± 3 U/ml at 24 h and 22 ± 3 U/ml at 48 h; 43% at 3 days, 57% at 4 days and 70% at 5 days, respectively). FUT-175 also significantly inhibited the redistribution of cathepsin B activity and activation of trypsinogen (7 ± 2 U/mg DNA at 24 h and 9 ± 2 U/mg DNA at 48 h). These results suggest that lysosomal enzyme, particularly cathepsin B, seems to play an important role in the development of severe acute pancreatitis and that protease inhibitors such as FUT-175 may be clinically beneficial in the treatment of acute pancreatitis.

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Effect of FOY-305 (camostate) on severe acute pancreatitis in two experimental animal models

Cited by 36 publications

References 27 publications

Effect of T-0632, a CholecystokininA Receptor Antagonist, on Experimental Acute Pancreatitis.

Effect of T-0632, a CholecystokininA Receptor Antagonist, on Experimental Acute Pancreatitis.

Monitoring Serum Tryptic Activity and Effect of Trypsin Inhibitor on Rat Acute Pancreatitis

A New Protease Inhibitor, Nafamostat Mesilate (FUT-175), Protects Pancreatic Acinar Cells in CDE-Diet-lnduced Pancreatitis in Mice

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