scholarly journals Metabolomics Reveals That Bisphenol Pollutants Impair Protein Synthesis-Related Pathways in Daphnia magna

Metabolites ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 666
Author(s):  
Erico A. Oliveira Pereira ◽  
Lisa M. Labine ◽  
Sonya Kleywegt ◽  
Karl J. Jobst ◽  
André J. Simpson ◽  
...  

Bisphenols are used in the production of polycarbonate plastics and epoxy resins. Bisphenol A (BPA) has been widely studied and is believed to act as an endocrine disruptor. Bisphenol F (BPF) and bisphenol S (BPS) have increasingly been employed as replacements for BPA, although previous studies suggested that they yield similar physiological responses to several organisms. Daphnia magna is a common model organism for ecotoxicology and was exposed to sub-lethal concentrations of BPA, BPF, and BPS to investigate disruption to metabolic profiles. Targeted metabolite analysis by liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to measure polar metabolites extracted from D. magna, which are linked to a range of biochemical pathways. Multivariate analyses and individual metabolite changes showed similar non-monotonic concentration responses for all three bisphenols (BPA, BPF, and BPS). Pathway analyses indicated the perturbation of similar and distinct pathways, mostly associated with protein synthesis, amino acid metabolism, and energy metabolism. Overall, we observed responses that can be linked to a chemical class (bisphenols) as well as distinct responses that can be related to each individual bisphenol type (A, F, and S). These findings further demonstrate the need for using metabolomic analyses in exposure assessment, especially for chemicals within the same class which may disrupt the biochemistry uniquely at the molecular-level.

Metabolites ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 100
Author(s):  
Lisa M. Labine ◽  
Myrna J. Simpson

Halogenated acetic acids (HAAs) are amongst the most frequently detected disinfection by-products in aquatic environments. Despite this, little is known about their toxicity, especially at the molecular level. The model organism Daphnia magna, which is an indicator species for freshwater ecosystems, was exposed to sub-lethal concentrations of dichloroacetic acid (DCAA), trichloroacetic acid (TCAA) and dibromoacetic acid (DBAA) for 48 h. Polar metabolites extracted from Daphnia were analyzed using liquid chromatography hyphened to a triple quadrupole mass spectrometer (LC-MS/MS). Multivariate analyses identified shifts in the metabolic profile with exposure and pathway analysis was used to identify which metabolites and associated pathways were disrupted. Exposure to all three HAAs led to significant downregulation in the nucleosides: adenosine, guanosine and inosine. Pathway analyses identified perturbations in the citric acid cycle and the purine metabolism pathways. Interestingly, chlorinated and brominated acetic acids demonstrated similar modes of action after sub-lethal acute exposure, suggesting that HAAs cause a contaminant class-based response which is independent of the type or number of halogens. As such, the identified metabolites that responded to acute HAA exposure may serve as suitable bioindicators for freshwater monitoring programs.


Author(s):  
Seyoung Kim ◽  
Eunjung Park ◽  
Eun-Kyo Park ◽  
Seulbi Lee ◽  
Jeoung-A Kwon ◽  
...  

Bisphenols are endocrine disruptors that may be associated with altered fetal growth in humans, and they have similar biological functions to mimic hormones. In addition, aggregated chemicals showed an adverse effect although individual concentration was at a low level. However, most studies between bisphenols and birth outcomes have focused on the effect of individual bisphenol. Thus, we explored the associations of urinary bisphenol mixtures with birth outcomes. We conducted a prospective birth cohort study in South Korea. One hundred eighty mother-infant pairs were recruited from 2017 to 2019. Bisphenol A (BPA), bisphenol F (BPF), and bisphenol S (BPS) in one spot urine were analyzed using ultra-performance liquid chromatography–tandem mass spectrometry. We used two statistical approaches to examine potential associations of BPA, BPF, and BPS with birth weight and gestational age: (1) multivariable linear regression; (2) Bayesian kernel machine regression (BKMR). The geometric means of BPA, BPF, and BPS were 2.1, 0.2, and 0.1 μg/L, respectively. In stratified linear analyses by each median value, a higher BPF was positively associated with birth weight (g) (β = 125.5; 95% CI: 45.0 to 205.9). Mixture analyses using BKMR suggested an inverse association between bisphenol mixtures and birth weight. Our findings suggest that in utero bisphenol exposure may influence birth weight and that such relationships may differ considering non-linearity and the combined effect.


2021 ◽  
Vol 83 (1) ◽  
Author(s):  
Miao Yang ◽  
Jie Wei ◽  
Yuan Wang ◽  
Chenchen Shen ◽  
Xi Xie

1999 ◽  
Vol 276 (2) ◽  
pp. L280-L288 ◽  
Author(s):  
Elizabeth R. Jacobs ◽  
Richard M. Effros ◽  
John R. Falck ◽  
K. Malla Reddy ◽  
William B. Campbell ◽  
...  

Rabbit airway tissue is a particularly rich source of cytochrome P-4504A protein, but very little information regarding the effect(s) of 20-hydroxyeicosatetraenoic acid (20-HETE) on bronchial tone is available. Our studies examined the response of rabbit bronchial rings to 20-HETE and the metabolism of arachidonic acid and 20-HETE from airway microsomes. 20-HETE (10−8 to 10−6 M) produced a concentration-dependent relaxation of bronchial rings precontracted with KCl or histamine but not with carbachol. Relaxation to 20-HETE was blocked by indomethacin or epithelium removal, consistent with the conversion of 20-HETE to a bronchial relaxant by epithelial cyclooxygenase. A cyclooxygenase product of 20-HETE also elicited relaxation of bronchial rings. [14C]arachidonic acid was converted by airway microsomes to products that comigrated with authentic 20-HETE (confirmed by gas chromatography-mass spectrometry as 19- and 20-HETE) and to unidentified polar metabolites. [3H]20-HETE was metabolized to indomethacin-inhibitable products. These data suggest that 20-HETE is an endogenous product of rabbit airway tissue and may modulate airway resistance in a cyclooxygenase-dependent manner.


1991 ◽  
Vol 55 (6) ◽  
pp. 1449-1453
Author(s):  
Kazumi Yagasaki ◽  
Kouichi Saito ◽  
Michihito Yamaguchi ◽  
Ryuhei Funabiki

2021 ◽  
Author(s):  
Tomas Prudencio ◽  
Luther Swift ◽  
Devon Guerrelli ◽  
Blake Cooper ◽  
Marissa Reilly ◽  
...  

ABSTRACTBackgroundBisphenol A (BPA) is a high-production volume chemical that is commonly used to manufacture consumer and medical-grade plastic products. Due to its ubiquity, the general population can incur daily environmental exposure to BPA, while heightened BPA exposure has been reported in intensive care patients and industrial workers. Due to health concerns, structural analogues are being explored as replacements for BPA.ObjectiveThis study aimed to examine the direct nongenomic effects of BPA on cardiac electrophysiology and compare its safety profile to recently developed alternatives, including BPS (bisphenol S) and BPF (bisphenol F).MethodsWhole-cell voltage-clamp recordings were performed on cell lines transfected with Nav1.5, hERG, or Cav1.2. Results of single channel experiments were validated by conducting electrophysiology studies on human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) and intact, whole heart preparations.ResultsOf the chemicals tested, BPA was the most potent inhibitor of both fast (INa-P) and late (INa-L) sodium channel (IC50 = 55.3 and 23.6 μM, respectively), L-type calcium channel (IC50 = 30.8 μM) and hERG channel current (IC50 = 127 μM). The inhibitory effects of BPA and BPF on L-type calcium channels were supported by microelectrode array recordings, which revealed shortening of the extracellular field potential (akin to QT interval). Further, BPA and BPF exposure impaired atrioventricular conduction in intact, whole heart experiments. BPS did not alter any of the cardiac electrophysiology parameters tested.DiscussionResults of this study demonstrate that BPA and BPF exert an immediate inhibitory effect on cardiac ion channels, and that BPS may be a safer alternative. Intracellular signaling or genomic effects of bisphenol analogues were not investigated; therefore, additional mechanistic studies are necessary to fully elucidate the safety profile of bisphenol analogues on the heart.


Chemosphere ◽  
2018 ◽  
Vol 209 ◽  
pp. 508-516 ◽  
Author(s):  
Asad Ullah ◽  
Madeeha Pirzada ◽  
Sarwat Jahan ◽  
Hizb Ullah ◽  
Ghazala Shaheen ◽  
...  

1991 ◽  
Vol 260 (4) ◽  
pp. E581-E587
Author(s):  
W. M. Bennet ◽  
M. W. Haymond

To assess the contributions of leucine and alpha-ketoisocaproate (KIC) derived from the portal vein vs. hepatic artery for hepatic protein synthesis, 14-postabsorptive dogs were infused simultaneously with [1-14C]- and [4,5-3H]leucine or [1-14C]- and [4,5-3H]KIC. On one occasion one tracer was infused via a leg vein and the other via mesenteric infusion catheters, and dogs were restudied with both tracers infused systemically. The ratios of systemically to portally infused tracers in portal and arterial plasma leucine were used as indexes of the radioactivity in the potential precursor pools and in fibrinogen-bound leucine as a paradigm of hepatic protein synthesis. In the dogs given leucine tracers, the relative proportions of systemically to portally infused radioactivity in portal free leucine (0.50 +/- 0.06) were lower (P less than 0.001) than in arterial free leucine (1.22 +/- 0.03) and not different from that bound in fibrinogen (0.43 +/- 0.02). In the dogs infused intraportally with KIC, these values were 0.81 +/- 0.04, 0.97 +/- 0.05, and 0.74 +/- 0.05, respectively. In the control studies these ratios were not significantly different from the expected value of 1.0. The results suggest that, in postabsorptive dogs, fibrinogen is exclusively synthesized from portally delivered leucine with little or no contribution from the hepatic artery, whereas portally delivered KIC contributes little directly to fibrinogen synthesis. These data are consistent with zonation of hepatic amino acid metabolism and/or protein synthesis.


2020 ◽  
Vol 21 (10) ◽  
pp. 3529 ◽  
Author(s):  
Magdalena Zaborowska ◽  
Jadwiga Wyszkowska ◽  
Agata Borowik

The choice of the study objective was affected by numerous controversies and concerns around bisphenol F (BPF) and bisphenol S (BPS)—analogues of bisphenol A (BPA). The study focused on the determination and comparison of the scale of the BPA, BPF, and BPS impact on the soil microbiome and its enzymatic activity. The following parameters were determined in soil uncontaminated and contaminated with BPA, BPF, and BPS: the count of eleven groups of microorganisms, colony development (CD) index, microorganism ecophysiological diversity (EP) index, genetic diversity of bacteria and activity of dehydrogenases (Deh), urease (Ure), catalase (Cat), acid phosphatase (Pac), alkaline phosphatase (Pal), arylsulphatase (Aryl) and β-glucosidase (Glu). Bisphenols A, S and F significantly disrupted the soil homeostasis. BPF is regarded as the most toxic, followed by BPS and BPA. BPF and BPS reduced the abundance of Proteobacteria and Acidobacteria and increased that of Actinobacteria. Unique types of bacteria were identified as well as the characteristics of each bisphenol: Lysobacter, Steroidobacter, Variovorax, Mycoplana, for BPA, Caldilinea, Arthrobacter, Cellulosimicrobium and Promicromonospora for BPF and Dactylosporangium Geodermatophilus, Sphingopyxis for BPS. Considering the strength of a negative impact of bisphenols on the soil biochemical activity, they can be arranged as follows: BPS > BPF > BPA. Urease and arylsulphatase proved to be the most susceptible and dehydrogenases the least susceptible to bisphenols pressure, regardless of the study duration.


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