Prolonged feeding with guanidinoacetate, a methyl group consumer, exacerbates ethanol-induced liver injury

Natalia A Osna, Dan Feng, Murali Ganesan, Priya F. Maillacheruvu, David J. Orlicky, Samuel W. French, Dean J. Tuma, Kusum Kharbanda

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3 Scopus citations

Abstract

AIM To investigate the hypothesis that exposure to guanidinoacetate (GAA, a potent methyl-group consumer) either alone or combined with ethanol intake for a prolonged period of time would cause more advanced liver pathology thus identifying methylation defects as the initiator and stimulator for progressive liver damage. METHODS Adult male Wistar rats were fed the control or ethanol Lieber DeCarli diet in the absence or presence of GAA supplementation. At the end of 6 wk of the feeding regimen, various biochemical and histological analyses were conducted. RESULTS Contrary to our expectations, we observed that GAA treatment alone resulted in a histologically normal liver without evidence of hepatosteatosis despite persistence of some abnormal biochemical parameters. This protection could result from the generation of creatine from the ingested GAA. Ethanol treatment for 6 wk exhibited changes in liver methionine metabolism and persistence of histological and biochemical defects as reported before. Further, when the rats were fed the GAA-supplemented ethanol diet, similar histological and biochemical changes as observed after 2 wk of combined treatment, including inflammation, macroand micro-vesicular steatosis and a marked decrease in the methylation index were noted. In addition, rats on the combined treatment exhibited increased liver toxicity and even early fibrotic changes in a subset of animals in this group. The worsening liver pathology could be related to the profound reduction in the hepatic methylation index, an increased accumulation of GAA and the inability of creatine generated to exert its hepato-protective effects in the setting of ethanol. CONCLUSION To conclude, prolonged exposure to a methyl consumer superimposed on chronic ethanol consumption causes persistent and pronounced liver damage.

Original languageEnglish (US)
Pages (from-to)8497-8508
Number of pages12
JournalWorld Journal of Gastroenterology
Volume22
Issue number38
DOIs
StatePublished - Oct 14 2016

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Keywords

  • Alcohol
  • Guanidinoacetate
  • Methyl balance
  • S-adenosylhomocysteine
  • S-adenosylmethionine

ASJC Scopus subject areas

  • Gastroenterology

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