Unravelling the metabolic alterations of liver damage induced by thirdhand smoke.

Sònia Torres, Sara Samino, Pere Ràfols, Manuela Martins-Green, Xavier Correig, Noelia Ramírez

Environment international 2021 Jan

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Thirdhand smoke (THS) is the accumulation of tobacco smoke gases and particles that become embedded in materials. Previous studies concluded that THS exposure induces oxidative stress and hepatic steatosis in liver. Despite the knowledge of the increasing danger of THS exposure, the metabolic disorders caused in liver are still not well defined. The aim of this study is to investigate the metabolic disorders caused by THS exposure in liver of male mice and to evaluate the effects of an antioxidant treatment in the exposed mice. We investigated liver from three mice groups: non-exposed mice, exposed to THS in conditions that mimic human exposure and THS-exposed treated with antioxidants. Liver samples were analyzed using a multiplatform untargeted metabolomics approach including nuclear magnetic resonance (1H NMR), liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS) and laser desorption/ionization mass spectrometry imaging (MSI), able to map lipids in liver tissues. Our multiplatform approach allowed the annotation of eighty-eight metabolites altered by THS exposure, including amino acids, nucleotides and several types of lipids. The main dysregulated pathways by THS exposure were D-glutamine and D-glutamate metabolism, glycerophospholipid metabolism and oxidative phosphorylation and glutathione metabolism, being the last two related to oxidative stress. THS-exposed mice also presented higher lipid accumulation and decrease of metabolites involved in the phosphocholine synthesis, as well as choline deficiency, which is related to Non-Alcoholic Fatty Liver Disease and steatohepatitis. Interestingly, the antioxidant treatment of THS-exposed mice reduced the accumulation of some lipids, but could not revert all the metabolic alterations, including some related to the impairment of the mitochondrial function. THS alters liver function at a molecular level, dysregulating many metabolic pathways. The molecular evidences provided here confirm that THS is a new factor for liver steatosis and provide the basis for future research in this respect. Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Citation

Sònia Torres, Sara Samino, Pere Ràfols, Manuela Martins-Green, Xavier Correig, Noelia Ramírez. Unravelling the metabolic alterations of liver damage induced by thirdhand smoke. Environment international. 2021 Jan;146:106242