Metabolomics reveals metabolic disorders in mice exposed to thirdhand tobacco smoke

摘要

Thirdhand tobacco smoke (THS) is a novel and poorly understood pathway of tobacco exposure that is produced by the deposition and ageing of tobacco smoke particles and toxicants in surfaces and dust. This aged tobacco smoke becomes increasingly toxic with age, re-emitted into the air or react with other chemicals in the environment to yield new toxicants, including carcinogens. Furthermore, THS remains in indoor environments long after smokers move out, which makes THS a serious health problem, especially for children with smoking parents, which are the most vulnerable population to this pathway of tobacco exposure. Although the increasing evidences of THS hazards, the specific cellular and molecular consequences of exposure to THS remain to be fully elucidated. To address this, here we present the first non-targeted metabolomics approach applied to THS-exposed animal model: C57BL/6 mice, exposed to THS under conditions that mimic exposure of humans in homes of smokers. THS-exposed mice showed alterations in multiple organ systems including non-alcoholic fatty liver disease, inflammation in the lung, poor healing of cutaneous wounds, hyperactivity, hyperglycemia and insulin resistance in the form of non-obese type II diabetes (NODII) through oxidative stress. Urine samples from THS-exposed mice and control ones were analyzed using GC-QTOF and reverse phase HPLC-QJOF in both ionization modes. Accurate multivariate analysis revealed hundreds of differently expressed metabolites. Interestingly, some of the altered metabolites coincide with those reported in metabolomics studies of current smokers. Nevertheless, this study also reveals for the first time other metabolic pathways altered by this passive way of tobacco exposure, not related to tobacco until now. Furthermore, biomarkers of tobacco exposure have been also detected in the urine of the THS-exposed animals using a target HPLC-Q.Q.Q approach in concentrations similar to those reported in children exposed to second hand smoke. This study demonstrates the power of metabolomics for identifying the health hazards of THS exposure and, if confirmed in humans, would have a major impact on current tobacco health and environmental policies.