Protection and reversal of hepatic fibrosis by red wine polyphenols in hyperhomocysteinemic mice.
ABSTRACT Hyperhomocysteinemia leads to several clinical manifestations and, particularly, liver disease. Lowering homocysteine through nutrition or other means might offer preventive or therapeutic benefits. Polyphenols are natural compounds known for their antioxidant and healing properties for vessels. In a previous study we have shown a beneficial effect of a red wine polyphenolic extract (PE) administration on plasma homocysteine level in cystathionine beta synthase deficient mice, a murine model of hyperhomocysteinemia. These mice also develop hepatic fibrosis. As increased matrix metalloproteinase (MMP) 2 has been shown to be involved in the development of hepatic fibrosis, we then focused on the effect of PE administration on expression and activity of MMP-2 in liver of hyperhomocysteinemic mice and its impact on hepatic fibrosis development. PE was added for four weeks to the drinking water of heterozygous cystathionine beta synthase-deficient mice fed a high-methionine diet. Effects of PE administration were examined by histological analysis with Sirius red staining, zymography, immunobloting, real-time quantitative reverse transcriptase polymerase chain reaction, peroxynitrite level, catalase activity and nicotinamide adenine dinucleotide phosphate oxidase activity. We show that administration of PE had a beneficial effect (i) on MMP-2 expression via modulation of nitrotyrosine-modified total protein level and (ii) on MMP-2 activity via modulation of its activator/inhibitor balance. We also demonstrated a reversal effect of PE supplementation on hepatic fibrosis development. Our results demonstrate a preventive action of PE administration on biomarkers of hepatic dysfunction due to hyperhomocysteinemia.
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ABSTRACT: Both polyamines and methionine derivatives are nitrogen compounds directly related to the regulation of gene expression. In silico predictions and experimental evidence suggest a cross-talk between polyamine and methionine metabolism in mammalian tissues. Since liver is the major organ that controls nitrogen metabolism of the whole organism, it is the best tissue to further test this hypothesis in vivo. In this work, we studied the effects of the chronic administration of a methionine-supplemented diet (0.5% Met in drinking water for 5 months) on the liver of mice (designated as MET-mice). Metabolic and proteomic approaches were performed and the data obtained were subjected to biocomputational analysis. Results showed that a supplemental methionine intake can indeed regulate biogenic amine metabolism in an in vivo model by multiple mechanisms including metabolic regulation and specific gene demethylation. Furthermore, putative systemic effects were investigated by molecular and cellular biology methods. Among other results, altered expression levels of multiple inflammation and cell proliferation/death balance markers were found and macrophage activation was observed. Overall, the results presented here will be of interest across a variety of biomedical disciplines, including nutrition, orphan diseases, immunology and oncology.Amino Acids 08/2011; 42(2-3):577-95. · 3.91 Impact Factor
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ABSTRACT: Hepatic fibrosis, as a major medical problem, is characterized with significant morbidity and mortality. Acupuncture has potential advantages in treating hepatic fibrosis as acupuncture functions well to reduce Qi and Blood stagnation, resolve stasis and enhance body immunity, which are important factors in treating hepatic fibrosis. The aim of this review was to appraise the current limited evidence of acupuncture in treating hepatic fibrosis from both animal experiments and clinical trials by using both Chinese and western databases and to provide recommendations for future studies.African Journal of Traditional, Complementary and Alternative Medicines 01/2012; 9(4):452-8. · 0.52 Impact Factor