Open AccessDietary iso-α-acids prevent acetaldehyde-induced liver injury through Nrf2-mediated gene expression
Author(s) -
Takahito Takase,
Tsudoi Toyoda,
Naoyuki Kobayashi,
Takashi Inoue,
Tomoko Ishijima,
Keiko Abe,
Hiroshi Kojima,
Youichi Tsuchiya,
Shinji Okada
Publication year - 2021
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0246327
Subject(s) - acetaldehyde , aldehyde dehydrogenase , liver injury , chemistry , alcohol dehydrogenase , biochemistry , lipid peroxidation , glutathione , hepatocyte , ethanol metabolism , ethanol , reactive oxygen species , oxidative stress , pharmacology , enzyme , biology , in vitro
Acetaldehyde is the major toxic metabolite of alcohol (ethanol) and enhances fibrosis of the liver through hepatic stellate cells. Additionally, alcohol administration causes the accumulation of reactive oxygen species (ROS), which induce hepatocyte injury-mediated lipid peroxidation. Iso-α-acids, called isohumulones, are bitter acids in beer. The purpose of this study was to investigate the protective effects of iso-α-acids against alcoholic liver injury in hepatocytes in mice. C57BL/6N mice were fed diets containing isomerized hop extract, which mainly consists of iso-α-acids. After 7 days of feeding, acetaldehyde was administered by a single intraperitoneal injection. The acetaldehyde-induced increases in serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were suppressed by iso-α-acids intake. Hepatic gene expression analyses showed the upregulation of detoxifying enzyme genes, glutathione-S-transferase (GST) and aldehyde dehydrogenase (ALDH). In vitro, iso-α-acids upregulated the enzymatic activities of GST and ALDH and induced the nuclear translocation of nuclear factor-erythroid-2-related factor 2 (Nfe2l2; Nrf2), a master regulator of antioxidant and detoxifying systems. These results suggest that iso-α-acid intake prevents acetaldehyde-induced liver injury by reducing oxidative stress via Nrf2-mediated gene expression.