title: Environmental Tobacco Smoke Alters Metabolic Systems in Adult Rats.
abstract: Human exposure to environmental tobacco smoke (ETS) is associated with an increased incidence of pulmonary and cardiovascular disease and possibly lung cancer. Metabolomics can reveal changes in metabolic networks in organisms under different physio-pathological conditions. Our objective was to identify spatial and temporal metabolic alterations with acute and repeated subchronic ETS exposure to understand mechanisms by which ETS exposure may cause adverse physiological and structural changes in the pulmonary and cardiovascular systems. Established and validated metabolomics assays of the lungs, hearts. and blood of young adult male rats following 1, 3, 8, and 21 days of exposure to ETS along with day-matched sham control rats (n = 8) were performed using gas chromatography time-of-flight mass spectrometry, BinBase database processing, multivariate statistical modeling, and MetaMapp biochemical mapping. A total of 489 metabolites were measured in the lung, heart, and blood, of which 142 metabolites were identified using a standardized metabolite annotation pipeline. Acute and repeated subchronic exposure to ETS was associated with significant metabolic changes in the lung related to energy metabolism, defense against reactive oxygen species, substrate uptake and transport, nucleotide metabolism, and substrates for structural components of collagen and membrane lipids. Metabolic changes were least prevalent in heart tissues but abundant in blood under repeated subchronic ETS exposure. Our analyses revealed that ETS causes alterations in metabolic networks, especially those associated with lung structure and function and found as systemic signals in the blood. The metabolic changes suggest that ETS exposure may adversely affects the mitochondrial respiratory chain, lung elasticity, membrane integrity, redox states, cell cycle, and normal metabolic and physiological functions of the lungs, even after subchronic ETS exposure.
authors: West Coast Metabolomics Center, UC Davis Genome Center , Davis, California 95616, United States.
authors: Dinesh K
authors: DK
authors: Barupal
authors: UC Davis Center for Health and the Environment , Davis, California 95616, United States.
authors: Kent E
authors: KE
authors: Pinkerton
authors: UC Davis Center for Health and the Environment , Davis, California 95616, United States.
authors: Carol
authors: C
authors: Hood
authors: West Coast Metabolomics Center, UC Davis Genome Center , Davis, California 95616, United States.
authors: Tobias
authors: T
authors: Kind
authors: West Coast Metabolomics Center, UC Davis Genome Center , Davis, California 95616, United States.
authors: Oliver
authors: O
authors: Fiehn
mesh_terms: D000818:Animals; D002319:Cardiovascular System / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008297:Male; D053858:Metabolic Networks and Pathways; D055432:Metabolomics; D051381:Rats; D017207:Rats, Sprague-Dawley; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*
chemical_list: D014028:Tobacco Smoke Pollution