Original Article
Copyright ©2012 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Jul 21, 2012; 18(27): 3520-3526
Published online Jul 21, 2012. doi: 10.3748/wjg.v18.i27.3520
Edaravone inhibits apoptosis caused by ischemia/reperfusion injury in a porcine hepatectomy model
Mitsugi Shimoda, Yoshimi Iwasaki, Toshie Okada, Keiichi Kubota
Mitsugi Shimoda, Yoshimi Iwasaki, Toshie Okada, Keiichi Kubota, Second Department of Surgery, Dokkyo Medical University, 880 Kita Kobayashi, Mibu, Tochigi 321-0293, Japan
Author contributions: Kubota K made substantial contributions to conception and design, drafting the article and revising it critically for important intellectual content; Iwasaki Y analyzed the data; all authors approved the version to be published.
Correspondence to: Mitsugi Shimoda, MD, PhD, Second Department of Surgery, Dokkyo Medical University, 880 Kita Kobayashi, Mibu, Tochigi 321-0293, Japan. mshimoda@dokkyomed.ac.jp
Telephone: +81-282-872158 Fax: +81-282-866317
Received: April 16, 2011
Revised: September 9, 2011
Accepted: May 12, 2012
Published online: July 21, 2012
Abstract

AIM: To investigate the effect of E3-methyl-1-phenyl-2-pyrazolin-5-one (Edr) on hepatic ischemia-reperfusion (I/R) injury and liver regeneration in a porcine hepatectomy model.

METHODS: One hour ischemia was induced by occluding the vessels and the bile duct of the right and median lobes. A 40% left hepatectomy was performed after reperfusion. Six animals received Edr (3 mg/kg per hour) intravenously and six control animals received saline just before reperfusion. Remnant liver volume, hemodynamics, aspartate aminotransferase (AST), alanine aminotransferase, lactate dehydrogenase and lactic acid, were compared between the groups. The expression of transforming growth factor-β (TGF-β1) and toll-like receptor (TRL) mRNA in hepatic tissues was examined using reverse transcription polymerase chain reaction. Apoptosis was demonstrated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, respectively.

RESULTS: Serum AST (P = 0.029), and toll like receptor 4 level (P = 0.043) were significantly lower after 3 h in animals receiving Edr. In addition, TUNEL staining in Edr-treated pigs showed significantly fewer hepatocytes undergoing apoptosis compared with control pigs. After 1 mo, all factors were non-significantly different between the two groups.

CONCLUSION: Edr is considered to reduce hepatic injury in the early stage of I/R injury in a porcine model.

Keywords: Edaravone; Ischemia-reperfusion injury; Liver resection; Transforming growth factor-β; Toll like receptor 4