Protective Effects of Ulinastatin against Ischemia–Reperfusion Injury

• Published in: The Journal of surgical research 1999-03, Vol.82 (1), p.34-42
• Main Authors: Okuhama, Yukihiro, Shiraishi, Masayuki, Higa, Takao, Tomori, Hirofumi, Taira, Kaoru, Mamadi, Toure, Muto, Yoshihiro
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Digestive system; Glycoproteins - pharmacology; In Vitro Techniques; ischemia–reperfusion injury; Liver - drug effects; Liver - injuries; Liver - pathology; Liver Circulation - drug effects; Male; Medical sciences; Microscopy, Electron; Neutrophils - drug effects; Neutrophils - pathology; Pharmacology. Drug treatments; Rats; Rats, Wistar; Reperfusion Injury - pathology; Reperfusion Injury - physiopathology; Reperfusion Injury - prevention & control; Time Factors; Trypsin Inhibitors - pharmacology; ulinastatin
• ISSN: 0022-4804; 1095-8673
• DOI: 10.1006/jsre.1998.5496

We investigated the protective effect of urinary trypsin inhibitor (ulinastatin: UTI)in vitro,in relation to the neutrophil activity in hepatic ischemia/reperfusion (I/R) injury. The rat liver was removed and preserved in cold Ringer's lactate solution for 60 min, followed by 120 min of reperfusion with oxygenated perfusate. The rats were divided into four groups (n= 8 in each group). The livers were perfused with Krebs–Henseleit (K-H) solution containing no additives in group 1, 50,000 U/kg of UTI in group 2, 3.5 × 106of neutrophils in group 3, and both neutrophils and UTI in group 4. In group 3, the AST and ALT levels were always higher than those in other three groups at any point evaluated (P< 0.01) and the LDH levels were observed to be significantly higher than those in other three groups at 0, 5, 10, 60, and 90 min after reperfusion (P< 0.01). These increase were suppressed by additional pretreatment with UTI in group 4. The bile flow during reperfusion was significantly suppressed in group 3 compared to that of group 4, at both 30 (P< 0.01) and 60 (P< 0.05) min after reperfusion. The MPO activity after reperfusion in group 3 also significantly increased compared to other three groups (P< 0.01). These data thus suggest that UTI ameliorated the ischemia/reperfusion injuryin vitroby inhibiting of neutrophil accumulation in the postischemic liver.