Astaxanthin alleviated ethanol-induced liver injury by inhibition of oxidative stress and inflammatory responses via blocking of STAT3 activity

Ji Hye Han,Jung Heun Ju,Mi Hee Park,Yong Sun Lee,Yoon Seok Roh,Ju Ho Park,Sang Bae Han,In Jun Yeo,Jin Tae Hong

doi:10.1038/s41598-018-32497-w

Ji Hye Han, Jung Heun Ju + Show 7 more

Open Access

https://doi.org/10.1038/s41598-018-32497-w

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Journal: Scientific Reports	Publication Date: Sep 20, 2018
Citations: 40	License type: open-access

Affiliation: Chungbuk National University

Abstract

Astaxanthin (AXT) is classified as a xanthophyll carotenoid compound which have broader functions including potent antioxidant, anti-inflammatory and neuroprotective properties. Considerable researches have demonstrated that AXT shows preventive and therapeutic properties against for Diabetes, Osteoarthritis and Rheumatoid Arthritis. However, the protective effect of AXT on liver disease has not yet been reported. In this study, we investigated effects of AXT on ethanol-induced liver injury in chronic plus binge alcohol feeding model. The hepatic steatosis and inflammation induced by ethanol administration were alleviated by AXT. Serum levels of aspartate transaminase and alanine transaminase were decreased in the livers of AXT administrated group. The ethanol-induced expression of cytochrome P450 2E1 (CYP2E1), pro-inflammatory proteins, cytokines, chemokines and reactive oxygen species (ROS) levels were also reduced in the livers of AXT administrated group. Moreover, ethanol-induced infiltration of neutrophils was decreased in the livers of AXT administrated group. Docking model and pull-down assay showed that AXT directly binds to the DNA binding site of STAT3. Moreover, AXT decreased STAT3 phosphorylation in the liver of AXT administration group. Therefore, these results suggest that AXT could prevent ethanol-induced hepatic injury via inhibition of oxidant and inflammatory responses via blocking of STAT3 activity.

Highlights

Alcoholic liver disease (ALD) is considered to be a major cause of morbidity and mortality worldwide[1,2]
We demonstrated AXT alleviated ethanol-induced oxidative stress, liver inflammation and liver injury by inhibition of Signal transducer and activator of transcription 3 (STAT3) activity
AXT administration reduced ethanol-induced aspartate transaminase (AST) and alanine transaminase (ALT) levels accompanied by increased of liver lipid droplet

Summary

Result

Astaxanthin alleviated ethanol-induced liver inflammation and liver damages in mice. Chronic ethanol exposure induces hepatic steatosis and liver damages. Because chronic-binge ethanol exposure induces oxidative stress, we determined iNOS and CYP2E1 expression and ROS levels in the livers of pair-fed mice, ethanol-fed mice and ethanol with AXT-fed mice. Immunohistochemistry showed that decrease of the number of iNOS-reactive cells in the liver of ethanol with AXT-fed mice (Fig. 2B). Ethanol with AXT-fed mice showed a significant decrease in the levels of pro-inflammatory cytokines such as IL-6, TNF-α and IL-1β, and chemokines such as MCP-1 and MIP-1β (Fig. 3C,D). Immunohistochemistry of Ly6G demonstrated level of hepatic neutrophil infiltration was lower in ethanol with AXT-fed mice (Fig. 4C). The expression vascular cell adhesion molecule (VCAM-1) that controlled neutrophil recruitment was significantly increased in ethanol-fed mice but decreased in ethanol with AXT-fed mice (Fig. 4D). Ethanol-induced p-STAT3 expression was lowered in ethanol with AXT-fed mice than ethanol-fed mice (Fig. 5C)

Discussion

Findings

Materials and Methods