[Effects of E3123 on pancreatic injury in the isolated, perfused rat pancreas and in a pancreatic slice].
We studied the effect of E3123 on pancreatic injury induced in the isolated, perfused pancreas or in a pancreatic slice. Exposure of the isolated, perfused rat pancreas to trypsin-taurocholate or phospholipase A2 caused the leakage of pancreatic enzyme (lipase) into the perfusate. In trypsin-taurocholate-induced pancreatic injury, E3123 and nafamostat mesilate suppressed the leakage of lipase at concentrations of 0.1-1 microM and 1-10 microM, respectively. In phospholipase A2 induced pancreatic injury, E3123 at 10 microM significantly suppressed the enzyme leakage, and nafamostat mesilate had a weak suppressive effect. Exposure of a rat pancreatic slice to phospholipase A2 also caused the leakage of pancreatic enzyme, while the inhibition of enzyme leakage by E3123 was similar to that observed in the isolated, perfused pancreas; nafamostat mesilate was not effective. This finding suggests the possible involvement of a unique mechanism of action in the protection against pancreatic injury by E3123. Therefore, we studied the effect of E3123 on hemolysis by osmotic shock using rat red blood cells. E3123 demonstrated a potent protective effect against the hemolysis, suggesting that a membrane-stabilizing action may contribute to the protection E3123 affords against pancreatic injury.
Tsukuba Research Laboratories, Eisai Co., Ltd., Ibaraki, Japan.
K
K
Miyamoto
J
J
Nagakawa
N
N
Nagaoka
I
I
Hishinuma
J
J
Nagaoka
T
T
Yamanaka
T
T
Wakabayashi
D000818:Animals; D006146:Guanidines / Q000494:pharmacology / Q000627:therapeutic use*; D006461:Hemolysis / Q000187:drug effects; D066298:In Vitro Techniques; D008049:Lipase / Q000378:metabolism; D010179:Pancreas / Q000201:enzymology; D010182:Pancreatic Diseases / Q000139:chemically induced / Q000201:enzymology / Q000517:prevention & control*; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D013656:Taurocholic Acid; D014357:Trypsin
D006146:Guanidines; C057059:4-(2-succinimidoethylthio)phenyl 4-guanidinobenzoate; D013656:Taurocholic Acid; D008049:Lipase; D014357:Trypsin