An integrative cellular metabolomic study reveals downregulated tricarboxylic acid cycle and potential biomarkers induced by tetrabromobisphenol A in human lung A549 cells

Abstract

Tetrabromobisphenol A (TBBPA) is extensively utilized as a brominated flame retardant in numerous chemical products. As an environmental contaminant, the potential human toxicity of TBBPA has been attracting increasing attention. Nonetheless, the exact underlying mechanisms of toxicological effects caused by TBBPA remain uncertain. In this study, we investigated the potential mechanisms of TBBPA toxicity in vitro in the A549 cell line, one of the widely used type II pulmonary epithelial cell models in toxicology research. Cell viability was determined after treatment with varying concentrations of TBBPA. Liquid chromatography-mass spectrometry (LC-MS) metabolomics and metabolic flux approaches were utilized to evaluate metabolite and tricarboxylic acid (TCA) cycle oxidative flux changes. Our findings demonstrated that TBBPA significantly reduced the viability of cells and attenuated mitochondrial respiration in A549 cells. Additionally, LC-MS data showed significant reductions in TCA cycle metabolites including citrate, malate, fumarate, and alphaketoglutarate in 50 μM TBBPA-treated A549 cells. Metabolic flux analysis indicated reduced oxidative capacity in mitochondrial metabolism following TBBPA exposure.Moreover, diverse metabolic pathways, particularly alanine, aspartate, and glutamate metabolism and the TCA cycle, were found to be dysregulated. In total, 12 metabolites were significantly changed (p < .05) in response to 50 μM TBBPA exposure. Our results provide potential biomarkers of TBBPA toxicity in A549 cells and help elucidate the molecular mechanisms of pulmonary toxicity induced by TBBPA exposure.

Gut microbiome remodeling and metabolomic profile improves in response to protein pacing with intermittent fasting versus continuous caloric restriction

“…The highly-reproducible targeted LC–MS/MS method used in the current investigation was modeled after previous studies 97 – 99 . The specific metabolites included in our targeted detection panel are representative of more than 35 biological pathways most essential to biological metabolism and have been successfully leveraged for the sensitive and broad detection of effects related to diet 100 , diseases 101 , drug treatment 102 , environmental contamination 103 , and lifestyle factors 104 . Briefly, LC–MS/MS experiments were performed on an Agilent 1290 UPLC-6490 QQQ-MS system (Santa Clara, CA, USA).…”

A Review on Tetrabromobisphenol A: Human Biomonitoring, Toxicity, Detection and Treatment in the Environment

“…Liver disease and liver damage are often caused by TBBPA. There is enough evidence to prove that respiratory problems like lung diseases and pulmonary fibrosis are triggered by TBBPA exposure, even though the epidemiology of TBBPA on the respiratory system lacks clarity [ 99 ]. The production of reactive oxygen species and osteoblast apoptosis can be activated by TBBPA, which can lead to diseases of the bones [ 100 ].…”

Exploratory analysis of one versus two-day intermittent fasting protocols on the gut microbiome and plasma metabolome in adults with overweight/obesity

“…The highly reproducible targeted LC-MS/MS method used in the current investigation was modeled after previous studies (47)(48)(49). The specific metabolites included in our targeted detection panel are representative of more than 35 biological pathways most essential to central carbon metabolism, and have been successfully leveraged for the sensitive and broad detection of effects related to diet (50), disease (51), drug treatment (52), environmental contamination (53), and lifestyle factors (54). Briefly, LC-MS/MS experiments were performed on an Agilent 1290 UPLC-6490 QQQ-MS system (Santa Clara, CA, USA).…”