[PMID]: | 27784962 |
[Au] Autor: | Osna NA; Feng D; Ganesan M; Maillacheruvu PF; Orlicky DJ; French SW; Tuma DJ; Kharbanda KK |
[Ad] Endereço: | Natalia A Osna, Dan Feng, Murali Ganesan, Dean J Tuma, Kusum K Kharbanda, Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE 68105, United States. |
[Ti] Título: | Prolonged feeding with guanidinoacetate, a methyl group consumer, exacerbates ethanol-induced liver injury. |
[So] Source: | World J Gastroenterol;22(38):8497-8508, 2016 Oct 14. |
[Is] ISSN: | 2219-2840 |
[Cp] País de publicação: | United States |
[La] Idioma: | eng |
[Ab] Resumo: | 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, macro- and 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. |
[Mh] Termos MeSH primário: |
Etanol/efeitos adversos Glicina/análogos & derivados Hepatopatias/fisiopatologia
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[Mh] Termos MeSH secundário: |
Alanina Transaminase/sangue Amidinotransferases/metabolismo Animais Aspartato Aminotransferases/sangue Peso Corporal Proteínas de Ligação ao Cálcio/metabolismo Colesterol/química Proteínas de Ligação a DNA/metabolismo Suplementos Nutricionais Etanol/administração & dosagem Ácidos Graxos/química Fígado Gorduroso Glicina/administração & dosagem Guanidinoacetato N-Metiltransferase/metabolismo Homocisteína/sangue Inflamação Insulina/química Fígado/fisiopatologia Masculino Proteínas do Tecido Nervoso/metabolismo Complexo de Endopeptidases do Proteassoma/metabolismo Ratos Ratos Wistar S-Adenosil-Homocisteína/química S-Adenosilmetionina/química Triglicerídeos/química
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[Pt] Tipo de publicação: | JOURNAL ARTICLE |
[Nm] Nome de substância:
| 0 (Calcium-Binding Proteins); 0 (DNA-Binding Proteins); 0 (Fatty Acids); 0 (Insulin); 0 (Nerve Tissue Proteins); 0 (Triglycerides); 0 (nucleobindin); 0LVT1QZ0BA (Homocysteine); 3K9958V90M (Ethanol); 7LP2MPO46S (S-Adenosylmethionine); 979-92-0 (S-Adenosylhomocysteine); 97C5T2UQ7J (Cholesterol); EC 2.1.1.2 (Gamt protein, rat); EC 2.1.1.2 (Guanidinoacetate N-Methyltransferase); EC 2.1.4.- (Amidinotransferases); EC 2.1.4.1 (glycine amidinotransferase); EC 2.6.1.1 (Aspartate Aminotransferases); EC 2.6.1.2 (Alanine Transaminase); EC 3.4.25.1 (Proteasome Endopeptidase Complex); GO52O1A04E (glycocyamine); TE7660XO1C (Glycine) |
[Em] Mês de entrada: | 1706 |
[Cu] Atualização por classe: | 170627 |
[Lr] Data última revisão:
| 170627 |
[Sb] Subgrupo de revista: | IM |
[Da] Data de entrada para processamento: | 161028 |
[St] Status: | MEDLINE |
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