New insights into the metabolic alterations induced by thirdhand smoke exposure

Identificador:  TDX:3762

Handle: https://hdl.handle.net/20.500.11797/TDX3762

Autores:  Merino Ruiz, Carla

Resumen:
Thirdhand smoke (THS) is a form of passive exposure to residues of tobacco smoke that deposits, ages and remains in fabrics, surfaces, and airborne and settled dust particles long after smoking has ceased. Due to the intrinsic ubiquitous presence of THS residues, characterizing the impact of THS exposure on health has turned into a major public health issue, particularly in vulnerable populations including young children. To date, the study of THS-derived toxicity effects is constrained to those anticipated mechanisms, studied through targeted and rather reductionist methods. This thesis aims to expand the current knowledge of the health effects derived from THS exposure by using advanced untargeted metabolomics approaches for the first time. Two vertebrate models have been used to this end: mice exposed to THS mimicking exposure of non-smokers living in smokers’ homes, and zebrafish embryos, an emerging model to study toxicity during early development. The results presented here demonstrate a THS-induced metabolic response in mice upon its exposure with the tryptophan metabolism among the top disrupted pathways. This response is compatible with increased oxidative stress, which can be monitored non-invasively in urine. The results also demonstrate that the exposure to specific THS toxicants induce embryotoxicity in an early development zebrafish model, and that this model is capable of metabolizing such toxicants indicating its suitability for THS-toxicity based assays as an alternative animal model compliant with the twenty-first century guidelines on toxicity testing.