Prevention of ischemic reperfusion injury in the fatty liver. The challenge to activation, induction, and control of apoptosis

2001 Fiscal Year Final Research Report Summary

• Project/Area Number: 11671156
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General surgery
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: KAWABE Akihiro University Hospital, Hamamatsu University School of Medicine Assistant Professor, 医学部附属病院, 講師 (00291401)
• Co-Investigator(Kenkyū-buntansha): WADA Hidetoshi University Hospital, Hamamatsu University School of Medicine Instructor, 医学部・附属病院, 助手 (20273196) ; YOSHIDA Masayuki University Hospital, Hamamatsu University School of Medicine Instructor, 医学部・附属病院, 助手 (10201013)
• Project Period (FY): 1999 – 2000
• Keywords: apoptosis / liver / ischemic reperfusion injury / fatty liver / caspase inhibitor / Z-VAD

Research Abstract

It has been reported that oxygen-derived free radicals and nitric oxide may play an important role in ischemic reperfusion injury of the liver. But recently attention has been paid to the relation between apoptosis and reperfusion injury. We sometimes experience primary nonfunction of liver due to reperfusion injury after liver transplantation. And it has been reported that donor liver with fatty change result in such primary nonfunction. We evaluated the influence of apoptosis on ischemic reperfusion injury of the liver, the activation of apoptosis during reperfusion in normal and fatty livers, and the possibility of controlling reperfusion injury in the fatly liver.
In rat liver suffering ischemia for 60 minutes, GOT levels were highest 1 hour after reperfusion and GPT levels were highest 3 hours after reperfusion in the normal and fatty livers. The levels were higher in the fatty liver than in the normal liver.
In the TUNEL method and flow cytometry, no activation of apoptosis was found immediately after reperfusion in normal and fatty livers. One hour after reperfusion, a few apoptosis were observed, and 3 hours after reperfusion, apoptosis showed the highest activation. But 6 hours after reperfusion, apoptosis decreased. Apoptosis was activated more in the fatty liver than in the normal liver.
We demonstrated that the control of apoptosis may be able to prevent ischemic reperfusion injury of the fatty liver.
We injected Z-VAD, a caspase inhibitor, that controls apoptosis, to the fatty liver before ischemia. The increase in transaminase and activation of apoptosis tended to be inhibited, but not significantly.
In future, the selection of caspase inhibitor along with its delivery method, and other possible ways to control apoptosis should be investigated.