Environmental Tobacco Smoke Alters Metabolic Systems in Adult Rats

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.