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Efficacious treatment of alcoholic steatosis by a pharmaceutical composition comprising metadoxine and garlic oil
Author(s) -
Kim Sang Geon,
Ki Sung Hwan
Publication year - 2008
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.22.1_supplement.1138.11
Subject(s) - steatosis , fatty liver , triglyceride , cyp2e1 , ampk , chemistry , pharmacology , medicine , alcoholic fatty liver , alcohol , blood lipids , biochemistry , endocrinology , cholesterol , metabolism , enzyme , protein kinase a , disease , cytochrome p450
Alcoholic steatosis is the earliest and common response to heavy alcohol intake, and may precede severe forms of liver injury. As an effort to develop an efficacious pharmaceutical composition, this study evaluated the effects of metadoxine, garlic oil or their combination on alcoholic steatosis. Feeding rats an alcohol‐containing diet for 4 weeks increased hepatic triglyceride content with CYP2E1 induction. Concurrent administration of metadoxine and garlic oil (MG, 1:1 w/w ratio) to rats synergistically abrogated both fat accumulation and CYP2E1 induction compared to the individual treatment. Histopathology confirmed the ability of MG combination to inhibit lipid accumulation. Blood biochemistry verified improvement of liver function in MG‐treated rats. Alcohol administration resulted in decreases in the AMPKα and ΑCC phosphorylations, which was restored by MG treatments. Hepatic fatty acid synthase (FAS) expression was decreased after alcohol consumption, which correlated with a decrease in AMPK activity and a commensurate increase in lipid content. Combined MG treatments allowed FAS expression restored. These results demonstrate that a pharmaceutical composition comprising MG effectively treats alcoholic steatosis, which may be associated with CYP2E1 repression and recovery of AMPK activity, promising pharmaceutical therapy for alcoholic steatosis. Supported by a contract fund from the Seoul R&BD Program (2005–2010).