Interactions of ethanol and folate deficiency in development of alcoholic liver disease in the micropig.
Folate deficiency is present in most patients with alcoholic liver disease (ALD), whereas folate regulates and alcoholism perturbs intrahepatic methionine metabolism, and S-adenosyl-methionine prevents the development of experimental ALD. Our studies explored the hypothesis that abnormal methionine metabolism is exacerbated by folate deficiency and promotes the development of ALD in the setting of chronic ethanol exposure. Using the micropig animal model, dietary combinations of folate deficiency and a diet containing 40% of kcal as ethanol were followed by measurements of hepatic methionine metabolism and indices of ALD. Alcoholic liver injury, expressed as steatohepatitis in terminal 14 week liver specimens, was evident in micropigs fed the combined ethanol containing and folate deficient diet but not in micropigs fed each diet separately. Perturbations of methionine metabolism included decreased hepatic S-adenosylmethionine and glutathione with increased products of DNA and lipid oxidation. Thus, the development of ALD is linked to abnormal methionine metabolism and is accelerated in the presence of folate deficiency.
Halsted
Charles H
CH
University of California, Davis, California and National Toxicological Research Center, Jefferson, Arkansas, USA.
Villanueva
Jesus A
JA
Devlin
Angela M
AM
James
S Jill
SJ
D000818:Animals; D004195:Disease Models, Animal; D000431:Ethanol / Q000008:administration & dosage; D005494:Folic Acid Deficiency / Q000150:complications* / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000378:metabolism; D008108:Liver Diseases, Alcoholic / Q000209:etiology* / Q000378:metabolism; D008297:Male; D008715:Methionine / Q000378:metabolism; D013552:Swine; D013556:Swine, Miniature
D000431:Ethanol; D008715:Methionine