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PLoS One. 2017 Nov 9;12(11):e0187810. doi: 10.1371/journal.pone.0187810. eCollection 2017.

Astaxanthin prevents ischemia-reperfusion injury of the steatotic liver in mice.

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Division of Transplantation Immunology, National Research Institute for Child Health and Development, Tokyo, Japan.
Department of Advanced Technology for Transplantation, Osaka University Graduate School of Medicine, Osaka, Japan.
Research Center of Molecular Biology, School of Basic Medical Sciences, Inner Mongolia Medical University, Hohhot, Inner Mongolia, China.
Clinical Medicine Research Center of Affiliated Hospital, Inner Mongolia Medical University, Hohhot, Inner Mongolia, China.
Third Department of Internal Medicine, University of Toyama, Toyama, Japan.
AIDS Research Center, National Institute of Infectious Diseases, Tokyo, Japan.
Division of Medical Genetics, National Center for Child Health and Development, Tokyo, Japan.


Steatosis has a low tolerance against ischemia-reperfusion injury (IRI). To prevent IRI in the steatotic liver, we attempted to elucidate the protective effect of astaxanthin (ASTX) in the steatotic liver model by giving mice a methionine and choline-deficient high fat (MCDHF) diet. Levels of lipid peroxidation and apoptosis, the expression of inflammatory cytokines and heme oxygenase (HO)-1, in the liver were assessed. Reactive oxygen species (ROS), inflammatory cytokines, apoptosis-related proteins and members of the signaling pathway were also examined in isolated Kupffer cells and/or hepatocytes from the steatotic liver. ASTX decreased serum ALT and AST levels, the amount of TUNEL, F4/80, or 4HNE-positive cells and the mRNA levels of inflammatory cytokines in MCDHF mice by IRI. Moreover, HO-1 and HIF-1α, phosphorylation of Akt and mTOR expressions were increased by ASTX. The inflammatory cytokines produced by Kupffer, which were subjected to hypoxia and reoxygenation (HR), were inhibited by ASTX. Expressions of Bcl-2, HO-1 and Nrf2 in hepatocytes by HR were increased, whereas Caspases activation, Bax and phosphorylation of ERK, MAPK, and JNK were suppressed by ASTX. Pretreatment with ASTX has a protective effect and is a safe therapeutic treatment for IRI, including for liver transplantation of the steatotic liver.

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