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Methylene Blue Protects the Liver from Steatohepatitis via AMPK Activation
Author(s) -
WU HONGMIN,
Shin Seo Young,
Kim Tae Hyun,
Kim Sang Geon
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.621.2
Subject(s) - ampk , steatohepatitis , amp activated protein kinase , mitochondrial biogenesis , mitochondrion , oxidative stress , protein kinase a , glycogen , chemistry , toxicant , oxidative phosphorylation , liver injury , endocrinology , fatty liver , medicine , pharmacology , biology , biochemistry , kinase , toxicity , disease
Methylene blue (MB) has been under clinical trials for expanded therapeutic applications. This study investigated the effects of MB on mitochondrial dysfunction and steatohepatitis caused by toxicant or high‐fat diet feeding, and the underlying basis. MB treatment enabled HepG2 cells to survive against oxidative stress elicited by severe oxidative stress, restore GSH content, and decrease H 2 O 2 production. Consistently, mitochondria dysfunction was abrogated. MB treatment enhanced hepatic mitochondrial DNA contents and oxygen consumption rates. In an animal model, MB treatment protected the liver from injury against toxicant. In mice fed on a high‐fat diet, MB treatment inhibited hepatic fat accumulation and steatohepatitis. MB activated AMP‐activated protein kinase (AMPK)both in vivo and in vitro . MB activation of AMPK caused to inhibition of glycogen synthase kinase‐3b(GSK3b), contributing to protecting mitochondria and hepatocytes. Consistently, the activation of AMPK enhanced the expression of carnitine palmitoyltrasnferase‐1 (CPT‐1) and peroxisome proliferator‐activated receptor a (PPARa), which promoted mitochondrial biogenesis. These results show that MB has the ability to protect the liver from the insult of toxicant or metabolic dysfunction in association with AMPK activation, implying its potential therapeutic impact on energy metabolism.