Is aryl hydrocarbon receptor antagonism after ischemia effective in alleviating acute hepatic ischemia-reperfusion injury in rats?
Jae-Im Kwon,
Hwon Heo,
Yeon Ji Chae,
Joongkee Min,
Do-Wan Lee,
Sang Tae Kim,
Monica Young Choi,
Yu Sub Sung,
Kyung Won Kim,
Yoonseok Choi,
Dong Cheol Woo,
Chul-Woong Woo
Affiliations
Jae-Im Kwon
Department of Medical Science, AMIST, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
Hwon Heo
Asan Institute for Life Sciences, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, Republic of Korea
Yeon Ji Chae
Asan Institute for Life Sciences, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, Republic of Korea
Joongkee Min
Asan Institute for Life Sciences, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, Republic of Korea
Do-Wan Lee
Asan Institute for Life Sciences, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, Republic of Korea
Sang Tae Kim
Convergence Medicine Research Center, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, Republic of Korea
Monica Young Choi
Asan Institute for Life Sciences, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, Republic of Korea
Yu Sub Sung
Clinical Research Center, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, Republic of Korea
Kyung Won Kim
Department of Radiology, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, Republic of Korea
Yoonseok Choi
Medical Research Institute, Gangneung Asan Hospital, 38, Bangdong-gil, Sacheon-myeon, Gangneung-si, Gangwon-do, Republic of Korea
Dong Cheol Woo
Department of Medical Science, AMIST, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea; Convergence Medicine Research Center, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, Republic of Korea
Chul-Woong Woo
Convergence Medicine Research Center, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, Republic of Korea; Corresponding author
Aryl hydrocarbon receptors (AhRs) have been reported to be important mediators of ischemic injury in the brain. Furthermore, the pharmacological inhibition of AhR activation after ischemia has been shown to attenuate cerebral ischemia-reperfusion (IR) injury. Here, we investigated whether AhR antagonist administration after ischemia was also effective in ameliorating hepatic IR injury. A 70% partial hepatic IR (45-min ischemia and 24-h reperfusion) injury was induced in rats. We administered 6,2′,4′-trimethoxyflavone (TMF, 5 mg/kg) intraperitoneally 10 min after ischemia. Hepatic IR injury was observed using serum, magnetic resonance imaging-based liver function indices, and liver samples. TMF-treated rats showed significantly lower relative enhancement (RE) values and serum alanine aminotransferase (ALT) and aspartate aminotransferase levels than did untreated rats at 3 h after reperfusion. After 24 h of reperfusion, TMF-treated rats had significantly lower RE values, ΔT1 values, serum ALT levels, and necrotic area percentage than did untreated rats. The expression of the apoptosis-related proteins, Bax and cleaved caspase-3, was significantly lower in TMF-treated rats than in untreated rats. This study demonstrated that inhibition of AhR activation after ischemia was effective in ameliorating IR-induced liver injury in rats.
