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The
Effects of Gabexate Mesilate on the lshemia-Reperfusion injury in the Rabbit Liver
Young
Do Shin, M,D,, Sang Mok Lee, M.D. Young Gwan Ko, M.D, Kee Hyung Lee, M.D.,
Suck
Hwan Koh, M.D., Sung Wha Hong, M.D. and Soo Myung Oh, M.D.
Purpose:
lschemia-reperfusion is an important pathologic process that leads to impairment
of the liver after major surgery. lschmia-reperfusion injury includes both hypoxia
and an inflammatory response associated with reperfusion; the former is caused by
the lack of microvascular perfusion and the latter is mediated by cytyokines and
oxygen free radicals. In addition to inhibiting thrombin, plasmin, kalikrein, trypsin,
and neutrophil elastase, gabexate mesilate also plays an important role in inhibiting
cytokines and oxygen free radical production. The purpose of this study was to investigate
the effects of gabexate mesilate on ischemia-reperfusion injury in the liver.
Methods:
Twenty-four New Zealand white rabbits were divided into three groups, Clamping was
not done in group A(n=8), although it was done in group B(n=8) and group C(n=8).
Group C received intravenous infusion of gabexate mesilate (10mg/kg/hr) continuously
during the process of clamping, Serum alanine aminotrasferase (ALT) and purine nucleoside
phophorylase (PNP) were measured immediately before clamping, following 30-minute
ischemia, and after 60-minute reperfusion. Hepatic tissue adenosine triphophate(ATP),
xanthine oxidase, and malondialdehyde(MDA) plus 4-hydroxyalcenals (4HA) were measured
after reperfusion.
Results:
Compared with group A, group B and group C demonstrated a significant increase in
ALT and PNP levels following ischemia and reperfusion, as well as in xanthine oxidase
and MDA plus 4HA levels following reperfusion. However ATP levels showed no significant
differences among the three groups, ALT levels were significantly 1ower in group
C than in group B following reperfusion (P<0.01),
although
there was no significant differences in PNP 1eve1s between them. Xanthine oxidase
and MDA plus 4HA levels were significantly lower in group C than in group B (P<0.05).
The results suggest that gabexate mesilate inhibits an increase in ALT, xanthine
oxidase, and MDA plus 4 HA levels.
Conclusion:
Gabexate mesilate inhibits oxygen free radical production of xanthine oxidase and
results in a reduction of hepatic ischemia-reperfusion injury.
Key
Words: Gabexate mesilate, lschemia-reperfusion Liver
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