Protective Effect of Eupatilin Pretreatment Against Hepatic Ischemia-Reperfusion Injury in Mice.
BACKGROUND
Eupatilin, a pharmacologically active flavone derived from Artemisia species, is known to have antioxidant and antiinflammatory activities. Ischemia-reperfusion injury (IRI) is a major critical event that commonly occurs after liver transplantation and resection. Furthermore, inflammatory responses to IRI exacerbate the resultant hepatic injury. In this study, we investigated whether eupatilin protects against IR-induced acute liver injury in mice.


METHODS
Partial (70%) hepatic IRI was induced in male C57BL/6 mice by portal triad pedicle occlusion for 90 minutes followed by reperfusion for 6 hours. Eupatilin (10 mg/kg body weight, oral) was administered 4 days before the IRI.


RESULTS
Treatment with eupatilin significantly decreased serum alanine aminotransferase and serum aspartate aminotransferase as well as liver histologic changes. Eupatilin also prevented hepatic glutathione depletion and increased malondialdehyde levels induced by IRI. Western blotting indicated that eupatilin significantly increased the levels of heat shock protein and B-cell lymphoma 2 protein, attenuated inducible nitric oxide synthase, and cleaved caspase-3 levels 6 hours after IRI. The expression of the Toll-like receptor 2/4, and phosphorylated nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor was significantly decreased in the eupatilin pretreatment group.


CONCLUSIONS
Eupatilin improved the acute hepatic IRI by reducing inflammation and apoptosis. These findings suggest that eupatilin is a promising therapeutic agent against acute IR-induced hepatic damage.
Department of Anesthesia and Pain Medicine, Ulsan University, College of Medicine, Gangneung Asan Hospital, Gangneung, South Korea.
H M
HM
Lee
Department of Surgery, Ulsan University, College of Medicine, Gangneung Asan Hospital, Gangneung, South Korea. Electronic address: jhj@gnah.co.kr.
H J
HJ
Jang
Department of Anesthesia and Pain Medicine, Ulsan University, College of Medicine, Gangneung Asan Hospital, Gangneung, South Korea.
S S
SS
Kim
Department of Surgery, Ulsan University, College of Medicine, Gangneung Asan Hospital, Gangneung, South Korea.
H J
HJ
Kim
Department of Surgery, Ulsan University, College of Medicine, Gangneung Asan Hospital, Gangneung, South Korea.
S Y
SY
Lee
Department of Surgery, Ulsan University, College of Medicine, Gangneung Asan Hospital, Gangneung, South Korea.
M Y
MY
Oh
Natural Medicine Center, Korea Institute of Science and Technology (KIST), Gangneung, South Korea.
H C
HC
Kwan
Department of Pharmaceutical Science, College of Pharmacy, Kyung Hee University, Seoul, South Korea.
D S
DS
Jang
Department of Pathology, Ulsan University, College of Medicine, Gangneung Asan Hospital, Gangneung, South Korea.
D W
DW
Eom
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000378:metabolism; D004334:Drug Administration Schedule; D005419:Flavonoids / Q000627:therapeutic use*; D008099:Liver / Q000378:metabolism / Q000473:pathology; D016031:Liver Transplantation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020011:Protective Agents / Q000627:therapeutic use*; D011897:Random Allocation; D015427:Reperfusion Injury / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D016896:Treatment Outcome
D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D005419:Flavonoids; D020011:Protective Agents; C045325:eupatilin