Abstract
Bisphenol A (BPA) is recognized as a major pollutant worldwide. 4-Methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene (MBP) is a major active metabolite of BPA. The epidemiological and animal studies have reported that BPA is harmful to lung function. The role of MBP in lung dysfunction after BPA exposure still remains unclear. This study investigated whether MBP would induce lung alveolar cell damage and evaluated the role of MBP in the BPA exposure-induced lung dysfunction. An in vitro type 2 alveolar epithelial cell (L2) model and an ex vivo isolated reperfused rat lung model were used to determine the effects of BPA or MBP on cell growth and lung function. MBP, but not BPA, dose-dependently increased the mean artery pressure (Pa), pulmonary capillary pressure (Pc), pulmonary capillary filtration coefficient (Kfc), and wet/dry weight ratio in isolated reperfused rat lungs. MBP significantly reduced cell viability and induced caspases-3/7 cleavage and apoptosis and increased AMP-activated protein kinas (AMPK) phosphorylation and endoplasmic reticulum (ER) stress-related molecules expression in L2 cells, which could be reversed by AMPK-siRNA transfection. These findings demonstrated for the first time that MBP exposure induced type 2 alveolar cell apoptosis and lung dysfunction through an AMPK-regulated ER stress signaling pathway.
Highlights
Several studies reported that Bisphenol A (BPA) was harmful to lung function[3,8,9]
MBP (10 and 15 μM) significantly increased Pa, Pc (Fig. 2B and D), Kfc, and wet/dry weight ratio (Fig. 3B and D). These results indicated that MBP was more potent than BPA in affecting lung function in isolated reperfused rat lungs
It has been suggested that metabolic activation to MBP may occur in the detoxification pathway of BPA when glucuronidation cannot work efficiently, the MBP metabolic activation may not be significant under usual circumstances[19]
Summary
A study investigated the effects of BPA on lung function in 208 children It showed that prenatal BPA exposure during early gestation increased the risk of wheeze and led to a persistent wheeze phenotype, which was associated with a change in forced expiratory volume in 1 s (FEV1; an FEV1/forced vital capacity (FVC) ratio of ≤80% is suggested to indicate obstructive lung disease)[9]. We hypothesized that MBP may contribute to the deterioration in pulmonary alveolar epithelial cell growth and lung function following BPA exposure. To demonstrate this hypothesis, we used an in vitro type 2 alveolar epithelial cell model and an ex vivo isolated reperfused rat lung model to investigate the effects of MBP on type 2 pulmonary alveolar epithelial cell growth and lung function
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