Background

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.

Objectives

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.

Methods

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.

Results

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.

Conclusions

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.

中文翻译：

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揭示三手烟引起的肝损伤的代谢变化

 背景

三手烟 (THS) 是嵌入材料中的烟草烟雾气体和颗粒的积累。先前的研究得出结论，THS 暴露会诱发肝脏氧化应激和肝脂肪变性。尽管人们知道接触 THS 的危险越来越大，但肝脏引起的代谢紊乱仍然没有明确的定义。

 目标

本研究的目的是调查雄性小鼠肝脏中因 THS 暴露引起的代谢紊乱，并评估抗氧化治疗对暴露小鼠的影响。

 方法

我们研究了三组小鼠的肝脏：未暴露于 THS 的小鼠、在模拟人类暴露条件下暴露于 THS 的小鼠以及经过抗氧化剂处理的 THS 暴露小鼠。使用多平台非靶向代谢组学方法分析肝脏样本，包括核磁共振 ( ¹ H NMR)、液相色谱与高分辨率质谱 (LC-HRMS) 和激光解吸/电离质谱成像 (MSI)，能够绘制脂质图谱在肝组织中。

 结果

我们的多平台方法可以对因 THS 暴露而改变的 88 种代谢物进行注释，包括氨基酸、核苷酸和几种类型的脂质。 THS暴露引起的主要失调途径是D-谷氨酰胺和D-谷氨酸代谢、甘油磷脂代谢以及氧化磷酸化和谷胱甘肽代谢，最后两个与氧化应激相关。 THS暴露小鼠还表现出较高的脂质积累和参与磷酸胆碱合成的代谢物减少，以及胆碱缺乏，这与非酒精性脂肪肝病和脂肪性肝炎有关。有趣的是，对接触 THS 的小鼠进行抗氧化治疗减少了某些脂质的积累，但无法恢复所有代谢变化，包括一些与线粒体功能受损相关的变化。

 结论

THS 在分子水平上改变肝功能，使许多代谢途径失调。这里提供的分子证据证实了THS是肝脏脂肪变性的一个新因素，并为未来这方面的研究提供了基础。