Experimental study of FR167653 in simultaneous pancreas and kidney transplantation from non-heart-beating donor

2003 Fiscal Year Final Research Report Summary

• Project/Area Number: 14571142
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General surgery
• Research Institution: Kyushu University
• Principal Investigator: SUGITANI Atushi Kyushu Univ., Kidney Care Unit, Assistant Professor, 大学病院, 講師 (00294934)
• Co-Investigator(Kenkyū-buntansha): KATANO Mitsuo Kyushu Univ., Graduate school of Medical Science, Professor, 大学院・医学研究院, 教授 (10145203) ; YAMAMOTO Hirofumi Kyushu Univ., Surgery and Oncology, Assistant Professor, 大学病院, 助手
• Project Period (FY): 2002 – 2003
• Keywords: pancreas transplantation / kidney transplantation / warm ischemia / ischemia-reperfusion / FR167653 / cytokine

Research Abstract

Background. Inflammatory cytokines are known to contribute to ischemia-reperfusion (LIR) injury. We investigated the effect of FR167653 (FR), a suppressor of interleukin (IL)-1β and tumor necrosis factor (TNF)-α, on I/R injury of the kidney in dogs.
Methods. The left kidney was subjected to ischemia for 60 minutes followed by removal of the right kidney. A control group (n=10) and an FR group (n=8) were evaluated for tissue blood flow ; resistive_index, pulsatilitv_index arterial oxygen pressure (PaO_2), serum creatinine, blood urea nitrogen (BUN), aspartate transaminase (AST), and alanine transaminase (ALT) levels ; IL-1β mRNA expression in the peripheral blood ; apoptotic index ; and histopathology.
Results. The FR group showed lower creatinine, BUN, AST, and ALT levels (p<0.038 each) : and lower IL-1β mRNA expression and apoptotic index (p<0.041 each) than did the control group. PaO_2 during 120 minutes after reperfusion in the FR group dropped but recovered quickly (p=0.024). Renal tissue damage in the FR group was less than that in the control group (p=0.036).
Conclusions. FR ameliorates I/R injury of the kidney potentially via reduced production of inflammatory cytokines that may contribute to damage to the ischeniic kidney and the distant organs.