Effects of Defined Mixtures of Persistent Organic Pollutants (POPs) on Pre-lethal Cytotoxicity in the Human A-498 Kidney Cell Line In Vitro

AbstractA total mixture of 29 persistent organic pollutants (POPs) modelled from Scandinavian blood concentrations was used to expose human A-498 kidney cells for 24 h over a concentration range spanning below to above blood level (1/10x, 1x, 50x, 100x, 500x). Its constituent submixtures (PFAA, Br, Cl) and co-mixtures (PFAA + Br, PFAA + Cl, Br + Cl) were also tested. Valinomycin (12 µM) was used as a cytotoxic comparative compound. Cell number (CN), nuclear area (NA), nuclear intensity (NI), mitochondrial membrane potential (MMP), and mitochondrial mass (MM) were assessed using high content analysis (HCA). Only the co-mixtures (PFAA + Cl, PFAA + Br) at 50x and 50x, 500x decreased CN, respectively. NI was increased by the total mixture at 500x and Cl mixture at all concentrations tested. MMP was increased by the total mixture at 100x and 500x, PFAA at 1x, Br + Cl and PFAA + Cl at 100x and 500x, respectively. MM was decreased by the total mixture at 500x. In contrast, valinomycin decreased CN and surviving cells showed a decrease in MMP and an increase in MM. In conclusion, POP exposure altered mitochondrial metabolism and induced cell death via an alternative mechanism to valinomycin. Only specific combinations of individual chemical classes, but not the total mixture, affected cell number.

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A Human Relevant Defined Mixture of Persistent Organic Pollutants (POPs) Affects In Vitro Secretion of Glucagon-Like Peptide 1 (GLP-1), but Does Not Affect Translocation of Its Receptor

Toxicological Sciences ◽

10.1093/toxsci/kfz192 ◽

2019 ◽

Vol 172 (2) ◽

pp. 359-367 ◽

Cited By ~ 1

Author(s):

Maeve Shannon ◽

Yuling Xie ◽

Steven Verhaegen ◽

Jodie Wilson ◽

Hanne F Berntsen ◽

...

Keyword(s):

Organic Pollutants ◽

Persistent Organic Pollutants ◽

Complex Mixture ◽

Blood Levels ◽

Environmental Toxicants ◽

Blood Concentrations ◽

Total Mixture ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1

Abstract Environmental exposure to persistent organic pollutants (POPs) has been suggested as a contributing factor for the increased rate of type 2 diabetes and obesity. A complex mixture of 29 POPs (Total mixture), based on human blood concentrations, was used to expose a glucagon-like peptide 1 (GLP-1) secreting enteroendocrine cell line (pGIP/neo: STC-1) in vitro for 3 and 24 h. Significant increases of GLP-1 occurred when cells were exposed to the Total mixture at ×500 blood levels. Six sub-mixtures representing chlorinated (Cl), brominated (Br), and perfluorinated chemicals (PFAA), and their combinations (Cl + Br, Cl + PFAA, Br + PFAA) were also tested at ×500. Secretion levels seen for these remained lower than the Total mixture, and the Br mixture had no effect. After 24 h, increased secretion was seen with all mixtures at ×1 blood levels. Cytotoxicity was present for ×100 and ×500 blood levels. When tested in a GLP-1 receptor translocation assay (U2OS-GLP1R-EGFP), neither agonistic nor antagonist effects on receptor internalization were seen for any of the mixtures. We conclude individual classes of POPs, alone or in combination, can affect GLP-1 secretion and may contribute as a molecular mechanism linking environmental toxicants and diabetes.

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Reductions in blood concentrations of persistent organic pollutants in the general population of Barcelona from 2006 to 2016

The Science of The Total Environment ◽

10.1016/j.scitotenv.2021.146013 ◽

2021 ◽

pp. 146013

Author(s):

Miquel Porta ◽

José Pumarega ◽

Luis A. Henríquez-Hernández ◽

Magda Gasull ◽

Xavier Bartoll ◽

...

Keyword(s):

General Population ◽

Organic Pollutants ◽

Persistent Organic Pollutants ◽

Blood Concentrations

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Antropogenic ecotoxicity evaluation in vitro and its relation to the occurrence of some persistent organic pollutants in water and sediment samples collected from Ankara River

Toxicology Letters ◽

10.1016/j.toxlet.2016.06.1754 ◽

2016 ◽

Vol 258 ◽

pp. S207

Author(s):

B. Yurdakok Dikmen ◽

O. Kuzukiran ◽

H. Tutun ◽

S. Sevin ◽

F. Aydin ◽

...

Keyword(s):

Organic Pollutants ◽

Persistent Organic Pollutants ◽

Sediment Samples ◽

Water And Sediment ◽

Water And Sediment Samples

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A mixture of persistent organic pollutants relevant for human exposure inhibits the transactivation activity of the aryl hydrocarbon receptor in vitro

Environmental Pollution ◽

10.1016/j.envpol.2019.113098 ◽

2019 ◽

Vol 254 ◽

pp. 113098 ◽

Cited By ~ 3

Author(s):

T.Q. Doan ◽

H.F. Berntsen ◽

S. Verhaegen ◽

E. Ropstad ◽

L. Connolly ◽

...

Keyword(s):

Aryl Hydrocarbon Receptor ◽

Organic Pollutants ◽

Persistent Organic Pollutants ◽

Human Exposure ◽

Transactivation Activity ◽

Aryl Hydrocarbon

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Effects of a human-based mixture of persistent organic pollutants on the in vivo exposed cerebellum and cerebellar neuronal cultures exposed in vitro

Environment International ◽

10.1016/j.envint.2020.106240 ◽

2021 ◽

Vol 146 ◽

pp. 106240

Author(s):

Hanne Friis Berntsen ◽

Nur Duale ◽

Cesilie Granum Bjørklund ◽

Oscar Daniel Rangel-Huerta ◽

Kine Dyrberg ◽

...

Keyword(s):

Organic Pollutants ◽

Persistent Organic Pollutants ◽

Neuronal Cultures

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Hydrophobized Reversed-Phase Adsorbent for Protection of Dairy Cattle against Lipophilic Toxins from Diet. Efficiensy In Vitro and In Vivo

Toxins ◽

10.3390/toxins11050256 ◽

2019 ◽

Vol 11 (5) ◽

pp. 256

Author(s):

Alexander Sotnichenko ◽

Evgeny Pantsov ◽

Dmitry Shinkarev ◽

Victor Okhanov

Keyword(s):

Dairy Cattle ◽

Organic Pollutants ◽

Persistent Organic Pollutants ◽

Polyaromatic Hydrocarbons ◽

Reversed Phase ◽

Chemical Pollution ◽

Lipophilic Toxins ◽

Cattle Feeds

The steady growth of inflammatory diseases of the udder in dairy cattle forces us to look for the causes of this phenomenon in the context of growing chemical pollution of the environment and feeds. Within the framework of this concept, an analysis was made of the polarity level of the three toxic impurity groups, which are commonly present in dairy cattle feeds. These impurities are presented by mycotoxins, polyaromatic hydrocarbons (PAH) and persistent organic pollutants (POP). It has been determined that 46% of studied mycotoxins (n = 1500) and 100% of studied polyaromatic hydrocarbons (n = 45) and persistent organic pollutants (n = 55) are lipophilic compounds, prone to bioaccumulation. A comparative evaluation of the sorption capacity of four adsorbents of a different nature and polarity with respect to the simplest PAH, naphthalene and lipophilic estrogenic mycotoxin, zearalenone in vitro has been carried out. The highest efficiency in these experiments was demonstrated by the reversed-phase polyoctylated polysilicate hydrogel (POPSH). The use of POPSH in a herd of lactating cows significantly reduced the transfer of aldrin, dieldrin and heptachlor, typical POPs from the “dirty dozen”, to the milk. The relevance of protecting the main functional systems of animals from the damaging effects of lipophilic toxins from feeds using non-polar adsorbents, and the concept of evaluating the effectiveness of various feed adsorbents for dairy cattle by their influence on the somatic cell count in the collected milk are discussed.

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