Comparative suppression of phthalate monoesters and phthalate diesters on calcium signalling coupled to nicotinic acetylcholine receptors

Abstract

-Phthalates, such as butyl benzyl phthalate (BBP), di-n-butyl phthalate (DBP), and their known to obstruct normal development in mammals. BBP and DBP have been reported to have estrogenic activity, while MBP and MBzP exhibit weak or no estrogenic effects. We previously showed that BBP and DBP have inhibitory roles on nicotinic acetylcholine receptors. Nicotinic acetylcholine receptors are widely distributed and have roles in developmental processes. In this study, the effects of BBP, DBP, induced [Ca 2+ ] c increase, the IC 50 s of BBP, DBP, MBzP and MBP were 3.41, 5.01, 432 and 695 microM -2+ ] c increase, the suppression was less than --cium signaling pathway coupled to nicotinic receptors.

The SH-SY5Y human neuroblastoma cell line, a relevant in vitro cell model for investigating neurotoxicology in human: Focus on organic pollutants

“…Phthalates such as BBzP, DEHP, Di(n-butyl) phthalate (DnBP), Dicyclohexyl phthalate (DCHP), Monobenzyl phthalate (MBzP), Diethyl phthalate (DEP) and Mono-n-butyl phthalate (MnBP) can inhibit the calcium signaling coupled with nAChR signaling through non-competitive blocking of the receptor [212,213]. The suppression potency depended on the amount of alkyl groups.…”

“…The longer the number of carbons, the more hydrophobicity and more suppression potency, but high number of carbons can also cause steric hindrances in fitting the binding site [212]. Also, the observation that BBzP (IC 50 = 0.28 µM) and DnBP (IC 50 = 0.44 µM) had a higher suppression power than their metabolites MBzP (IC 50 = 58 µM), MnBP (IC 50 = 116 µM) and phthalic acid (PA, IC 50 = 505 µM) suggests that diesters are more toxic than monoesters [213]. Finally, this antagonistic effect persists over time, DnBP treatment over 5 days (10 µM) maintained the suppression characteristics on nAChR [213].…”

Research Progresses on the Relationship Between the Phthalates Exposure and Children’s Neurodevelopmental Disorders

“…In the testis of zebrafish Danio rerio, acute exposure to bis (2-ethylhexyl) phthalate (BEHP) disrupts testicular Ca 2+ homeostasis by increasing Ca 2+ influx [18]. In human cell lines, BBP and DBP metabolites interfere with calcium signal transduction coupled with nicotinic acetylcholine receptors (nAChRs) [10,19].…”

New Analytical Method for Determination of Phthalates in Wastewater by on Line LC-GC-MS Using the TOTAD Interface and Fraction Collector

“…PAEs have been detected in many environmental samples, including surface runoff [10], river sediment [11], wastewater [12], sewage sludge [10] and landfill leachate [13]. PAEs are Processes 2021, 9, 920 2 of 13 considered to be endocrine disruptors and have been proved to present estrogenic and antiandrogenic action [14,15], making them dangerous to human health [16]. DEHP and DBP are classified as highly dangerous substances in EU regulations [17] and six PAEs (DBP, DEP, DMP, di-n-octyl phthalate (DOP), DEHP and benzyl butyl phthalate (BBP)) have been included in the lists of priority pollutants by the European Union [18].…”