O efeito do consumo crônico de etanol na medula óssea em uma perspectiva metabolômica

Abstract

The hypothesis of this study is that ethanol metabolism affects the metabolic pathways of bone marrow cells, resulting in alterations in the metabolite profile that may be linked to the functional programming of the immune system. To test this hypothesis, we utilized a murine model of chronic ethanol consumption and evaluated the bone marrow cell metabolome through three approaches: (i) gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS) using (ii) methanol or (iii) a mixture of chloroform, methanol, and water as extracting solvents. GC-MS analysis identified 19 metabolites, of which 5 showed lower abundance in the ethanol-treated group: nicotinamide, succinate, uracil, proline, and tyrosine. On the other hand, LC-MS analysis using methanol as the extraction solvent allowed the identification of 519 molecular features, of which 40 showed significant differences between the groups. Similarly, analysis using the mixture of methanol, chloroform, and water identified 656 molecular features, with 53 of them showing significant differences between the analyzed groups. Different chemical classes have been identified, such as amino acids, carbohydrates, and lipids. Overall, the results obtained demonstrated that ethanol consumption has a significant impact on lipid metabolism in the bone marrow. There was an inhibition in the degradation and activation of fatty acid metabolism. These changes resulted in an increase in the abundance of glycerophospholipids, sphingolipids, and eicosanoids, which are lipid components with important functions in cell structure and signaling, energy storage, as well as in the inflammatory process and functional regulation of the immune system. These findings highlight the influence of ethanol consumption on the metabolic processes involved in the inflammatory response and immune system modulation.Keywords: alcoholism, bone marrow, metabolome, fatty acid metabolism, glycerophospholipids, sphingolipids, eicosanoids, immune system.