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Edaravone, A Free Radical Scavenger, Ameliorates Early-Phase Ischemia/Reperfusion Injury and Increases Hepatocyte Proliferation in A Pig Hepatectomy Model

Mitsugi Shimoda, Yoshimi Iwasaki, Toshie Okada, Tokihiko Sawada, Keiichi Kubota.

Cited by (1)

Background: The effects of Edaravone (Edr) on hepatic ischemia-reperfusion (I/R) injury and liver regeneration were examined in a pig hepatectomy model.
Methods: One hour of ischemia was induced by occluding the vessels and the bile duct of the right and median lobes. About a 40% left hepatectomy was performed after reperfusion. Six animals received Edr (3 mg/kg/h) intravenously and six control animals received saline just before reperfusion. Remnant liver volume, hemodynamics, and levels of AST, ALT, LDH, and LA were compared between the groups. Expression of TGF-β1 and IL-6 mRNA in hepatic tissues was examined using RT-PCR. Apoptosis and cell proliferation were demonstrated by TUNEL and Ki-67 staining, respectively.
Results: Serum AST, LDH, and LA levels were significantly lower at 3 hours and 1 week after perfusion in animals that had received Edr. In the Edr group, hepatic tissues showed a greater tendency for the expression of TGF-β1 mRNA to be inhibited at 1 week, although the difference was not significant. Also at 1 week in the Edr group, TUNEL-positive cells in the hepatic sinusoidal endothelium were significantly fewer, and Ki-67-positive cells were significantly more numerous.
Conclusion: We conclude that Edr reduces hepatic injury and supports tissue regeneration after I/R injury in this pig model.

Key words: Edaravone (Edr), hepatic ischemia-reperfusion injury (I/R), apoptosis, hepatocyte proliferation, hepatectomy, TGF-β, Ki-67, liver resection, pig

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