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World J Gastroenterol. Jan 7, 2016; 22(1): 37-49
Published online Jan 7, 2016. doi: 10.3748/wjg.v22.i1.37
Relationships among alcoholic liver disease, antioxidants, and antioxidant enzymes
Kyu-Ho Han, Naoto Hashimoto, Michihiro Fukushima
Kyu-Ho Han, Michihiro Fukushima, Department of Food Science, Obihiro University of Agriculture and Veterinary Medicine, Inada, Obihiro, Hokkaido 080-8555, Japan
Naoto Hashimoto, Upland Farming Resource Research Division, NARO Hokkaido Agricultural Research Center, Kasai, Hokkaido 082-0071, Japan
Author contributions: Han KH and Hashimoto N contributed to the collection of references and writing this manuscript; Hashimoto N and Fukushima M were responsible for the organization and revision of this manuscript.
Supported by JSPS KAKENHI Grant Number 25450196 and grants-in-aid from The Ministry of Agriculture, Forestry and Fisheries of Japan.
Conflict-of-interest statement: The authors declare that there is no conflict of interest related to this review.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Naoto Hashimoto, PhD, Upland Farming Resource Research Division, NARO Hokkaido Agricultural Research Center, Minami 9-4, Shinsei, Memuro, Kasai, Hokkaido 082-0071, Japan. hasshy@affrc.go.jp
Telephone: +81-155-629278 Fax: +81-155-612127
Received: April 24, 2015
Peer-review started: April 24, 2015
First decision: June 2, 2015
Revised: June 25, 2015
Accepted: September 2, 2015
Article in press: September 2, 2015
Published online: January 7, 2016
Processing time: 250 Days and 22.3 Hours
Abstract

Excessive consumption of alcoholic beverages is a serious cause of liver disease worldwide. The metabolism of ethanol generates reactive oxygen species, which play a significant role in the deterioration of alcoholic liver disease (ALD). Antioxidant phytochemicals, such as polyphenols, regulate the expression of ALD-associated proteins and peptides, namely, catalase, superoxide dismutase, glutathione, glutathione peroxidase, and glutathione reductase. These plant antioxidants have electrophilic activity and may induce antioxidant enzymes via the Kelch-like ECH-associated protein 1-NF-E2-related factor-2 pathway and antioxidant responsive elements. Furthermore, these antioxidants are reported to alleviate cell injury caused by oxidants or inflammatory cytokines. These phenomena are likely induced via the regulation of mitogen-activating protein kinase (MAPK) pathways by plant antioxidants, similar to preconditioning in ischemia-reperfusion models. Although the relationship between plant antioxidants and ALD has not been adequately investigated, plant antioxidants may be preventive for ALD because of their electrophilic and regulatory activities in the MAPK pathway.

Keywords: Electrophile; Mitogen-activating protein kinase; Plant antioxidants; Reactive oxygen species; Preconditioning

Core tip: The metabolic process of ethanol generates reactive oxygen species, which play a significant role in the deterioration of alcoholic liver disease (ALD). Antioxidant phytochemicals, such as polyphenols, upregulate the expression of antioxidant enzymes and peptides via the Kelch-like ECH-associated protein 1-NF-E2-related factor-2 pathway, which leads to antioxidant responsive elements in animal models. Furthermore, these antioxidants alleviate cell injury caused by oxidants or inflammatory cytokines via impairment of hyperactivation of mitogen-activating protein kinase pathways, similar to preconditioning in ischemia-reperfusion models. Although the relationship between plant antioxidants and ALD has not been adequately investigated, plant antioxidants may be preventive for ALD.