FR167653 improves survival and pulmonary injury after partial hepatectomy under ischemia/reperfusion in rats.
BACKGROUND
FR167653 is a potent suppressant of production of tumor necrosis factor (TNF)-alpha and interleukin (IL)-1 beta, which play an important role in hepatic and pulmonary injury due to ischemia/reperfusion of the liver and in liver regeneration after hepatectomy. We examined the effects of FR167653 on hepatectomy under ischemia/reperfusion in rats.


METHODS
After initial 15-min ischemia and 5-min reperfusion, 70% hepatectomy was performed during the second 15-min ischemia period in FR167653-treated (FR group) and saline-treated (saline group) rats. The survival rate, relative liver weight, TNF-alpha, IL-1 beta, DNA synthesis rate of the remnant liver, and histological change and adhesion molecule (ICAM-1) of the lung were examined. Serum glutamic pyruvic transaminase and hepatic malondialdehyde were also measured.


RESULTS
Expressions of TNF-alpha and IL-1 beta in the remnant liver were significantly inhibited in the FR group compared to the saline group. The survival was significantly better and pulmonary damage was less in the FR group after hepatectomy under ischemia/reperfusion. ICAM-1 expression of the lung was not altered after hepatectomy and was not significantly different between the two groups. Liver regeneration and injury were not significantly different between the two groups.


CONCLUSIONS
FR167653 does not affect liver injury and regeneration after hepatectomy under ischemia/reperfusion, while it ameliorates pulmonary injury and improves the survival.
Watanabe
M
M
Department of Surgery and Oncology, Graduate School of Medical Sciences, Fukuoka 812-8582, Japan.
Yamaguchi
K
K
Chijiiwa
K
K
Tanaka
M
M
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D006498:Hepatectomy / Q000401:mortality*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D007511:Ischemia / Q000473:pathology; D008099:Liver / Q000098:blood supply; D008115:Liver Regeneration; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D011720:Pyrazoles / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D015424:Reperfusion; D015996:Survival Rate
C104334:FR 167653; D007166:Immunosuppressive Agents; D011720:Pyrazoles; D011725:Pyridines; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1; D008315:Malondialdehyde; D000410:Alanine Transaminase