Inhibiton of NF-kappaB activation during ischemia reduces hepatic ischemia/reperfusion injury in rats.
The aim of this study was to determine whether nuclear factor-kappaB (NF-kappaB) inhibitors are efficient against hepatic ischemia/reperfusion (I/R) injury. We previously demonstrated that xanthine oxidase-derived reactive oxygen species activate NF-kappaB during ischemia. However, the role of NF-kappaB activation during ischemia in post-reperfusion injury remains unclear. Therefore, while we examined the effects of NF-kappaB inhibitors, sulfasalazine and pyrrolidinedithiocarbamate on hepatic I/R injury using a rat lobar hepatic I/R model, we estimated the relationship between NF-kappaB activation during ischemia and following hepatic damage caused by reperfusion. The portal vein and the hepatic artery were clamped for 1 hr followed by reperfusion for up to 24 hr. NF-kappaB activation was determined by Western blot analysis. NF-kappaB activation was observed in the ischemic lobe of the liver, and the activation was prevented by pre-administration with NF-kappaB inhibitors. Although the serum ALT level, hepatic MPO activity and BSP clearance, as an index of hepatic injury, were increased after reperfusion, the increase was attenuated by pre-administration with NF-kappaB inhibitors. These findings suggest that NF-kappaB activation during ischemia is relevant to hepatic I/R injury. Moreover, we first showed that pre-administration with NF-kappaB inhibitors is effective against hepatic I/R injury.
Matsui
Nobuaki
N
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Tokushimashi, Japan.
Kasajima
Kazumi
K
Hada
Masazumi
M
Nagata
Tomomi
T
Senga
Nobuko
N
Yasui
Yumiko
Y
Fukuishi
Nobuyuki
N
Akagi
Masaaki
M
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D007511:Ischemia / Q000378:metabolism*; D008099:Liver / Q000098:blood supply*; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D011392:Proline / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000517:prevention & control*; D013448:Sulfobromophthalein / Q000378:metabolism; D013859:Thiocarbamates / Q000494:pharmacology
D016328:NF-kappa B; D013859:Thiocarbamates; D013448:Sulfobromophthalein; C066229:prolinedithiocarbamate; D011392:Proline; D009195:Peroxidase; D000410:Alanine Transaminase