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.

16S rRNA Long-Read Sequencing of the Granulation Tissue from Nonsmokers and Smokers-Severe Chronic Periodontitis Patients

“…This differential dominance of these species among nonsmokers led significant minor upregulation of KEGG pathways involved in primary immunodeficiency which may increase the susceptibility to infections in smokers as supported by Ballow et al [ 34 ] that primary immunodeficiency is uncommon, chronic, and severe disorders of the immune system in which patients cannot mount a sufficiently protective immune response, leading to an increased susceptibility to infections. We also observed upregulation of citrate cycle, metabolism of Vitamin B6, butanoate, glycine, serine and threonine in smokers which has also been shown by Barupal et al, [ 35 ], where they reported that environmental tobacco smoke (ETS) exposure in adult rats shows adverse effects on the mitochondrial respiratory chain, lung elasticity, membrane integrity, redox states, cell cycle, and normal metabolic and physiological functions of lungs, even after subchronic ETS exposure. Further, alteration in metabolism of thiamine, D-glutamine and D-glutamate, D-arginine, and D-ornithine has also been earlier reported [ 36 ] and inhibition of pancreatic acinar mitochondrial thiamin pyrophosphate uptake by the cigarette smoke component 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone was suggested.…”

Cigarette Smoke Reduces Fatty Acid Catabolism, Leading to Apoptosis in Lung Endothelial Cells: Implication for Pathogenesis of COPD

“…Compared to nonsmokers, primary basal stem/progenitor cells in the airways in healthy smoker had reduced metabolites in the tricarboxylic acid cycle, including acetyl-CoA, NADH, and FADH2 (Deeb et al, 2016). In contrast, an animal study has shown that CS exposure increased the levels of malate, citrate, and fumarate in rat lungs (Barupal et al, 2016). These studies suggest that CS may affect mitochondrial oxidative phosphorylation in a cell-specific manner.…”

Chemical Similarity Enrichment Analysis (ChemRICH) as alternative to biochemical pathway mapping for metabolomic datasets

“…Metabolism produces energy and building blocks which are used for reproduction 5 , protection 6 , communication 7 , maintenance 8 and structure 9 of cells. Diseases, genetic and environmental factors interact with quantitative and qualitative changes in metabolism 10 – 12 . Understanding those changes and their biological effects on organism’s life is one of the basic questions of biology with importance ranging from synthetic biology to understanding the onset and progress of chronic diseases 13 .…”