Mechanistic insight into toxicity of phthalates, the involved receptors, and the role of Nrf2, NF-κB, and PI3K/AKT signaling pathways

Mohammadi, Hamidreza; Ashari, Sorour

doi:10.1007/s11356-021-14466-5

Cited by 33 publications

(14 citation statements)

References 223 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…18,19 The PI3K/AKT, NF-κB, VEGF, and FGF pathways are modulated by ROS from cellular metabolism and have direct actions on factors related to proliferation, growth, survival and cellular metabolism. [57][58][59] Our data indicating that the mixture increased the expression of genes related to the antioxidant process (SOD1, CAT, GSR) and changed in the expression of genes involved in the cell cycle (CCNB1, CCND2), proliferation (KI67, ERα), and apoptosis (BAX, BCL2, CASP3, CASP8) support the relationship found between positive modulation of miR 141-3P and miR 184 and more aggressive cellular behavior, with possible cell proliferation and tumor progression.…”

Section: Discussionsupporting

confidence: 76%

Effects of a phthalate metabolite mixture on both normal and tumoral human prostate cells

Cavalca

Aquino

Mosele

et al. 2022

Environmental Toxicology

View full text Add to dashboard Cite

Phthalates represent a group of substances used in industry that have antiandrogenic activity and are found in different concentrations in human urine and plasma. More than 8 million tons of phthalates are used each year, predominantly as plasticizers in polyvinyl chloride (PVC) products. Phthalates are widely used in everyday consumer products and improperly discarded into the environment. Furthermore, in vivo studies carried out in our laboratory showed that a mixture of phthalates, equivalent to the mixture used in this study, deregulated the expression of genes and miRNAs associated with prostatic carcinogenic pathways. Thus, this study was designed to establish an in vitro model to assess pathways related to cell survival, proliferation, apoptosis, and biosynthesis of miRNAs, using both normal and tumoral prostatic epithelial cells exposed to an environmentally relevant mixture of phthalate metabolites.Tumor (LNCaP) and normal (PNT-2) prostatic epithelial cell lines were exposed for 24 and 72 h to vehicle control or the phthalate mixture. The selected metabolite mixture (1000 μmol/L) consisted of 36.7% monoethyl phthalate (MEP), 19.4% mono (2-ethylhexyl) phthalate (MEHP), 15.3% monobutyl phthalate (MBP), 10.2% monoisobutyl phthalate (MiBP), 10.2% monoisononyl phthalate (MiNP), and 8.2% monobenzyl phthalate (MBzP). Gene expression was performed by qRT-PCR and cell migratory potential was measured using cell migration assays. Our results showed that the mixture of phthalates increased cell turnover, oxidative stress, biosynthesis, and expression of miRNAs in LNCaP cells; thus, increasing their cellular expansive and migratory potential and modulating tumor behavior, making them possibly more aggressive.However, these effects were less pronounced in benign cells, demonstrating that, in the short term, benign cells are able to develop effective mechanisms or more resistance against the insult.

show abstract

Section: Discussionsupporting

confidence: 76%

Effects of a phthalate metabolite mixture on both normal and tumoral human prostate cells

Cavalca

Aquino

Mosele

et al. 2022

Environmental Toxicology

View full text Add to dashboard Cite

show abstract

“…While results from our analysis of ALI-dA adducts in DNA of AAI and phenanthrene or BBP coexposed cells showed the DNA repair machinery for ALI-dA adducts was not significantly affected by the exposure (Figure S5), there is growing evidence that exposure to PAHs increases the expression and activity of hepatic cytochrome P450 and cytosolic NAD(P)H:quinone oxidoreductase 1 (NQO1) enzymes, , which are key enzymes involved in the metabolic action and DNA adduct formation of AAs . Furthermore, phthalate esters, DEHP and DBP in particular, have been reported to cause the overexpression of cytochrome P450 and NQO1 . Therefore, in this study, we investigated whether this AA-activating effect would impact the mechanism underlying the above-mentioned coexposure-induced DNA adduct formation in cells.…”

Section: Results and Discussionmentioning

confidence: 92%

“…50 Furthermore, phthalate esters, DEHP and DBP in particular, have been reported to cause the overexpression of cytochrome P450 and NQO1. 51 Therefore, in this study, we investigated whether this AA-activating effect would impact the mechanism underlying the above-mentioned coexposure-induced DNA adduct formation in cells. Concentrations of ALI, which is the reductive metabolite in the metabolic activation of AAI (Figure 1), 33−35 in the cell culture media of AAI/PAH coexposed cells were also quantitated by LC-MS/MS, as described in the Materials and Methods section.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Synergistic Interaction of Polycyclic Aromatic Hydrocarbons, Phthalate Esters, or Phenol on DNA Adduct Formation by Aristolochic Acid I: Insights into the Etiology of Balkan Endemic Nephropathy

Zhang

Chan

2022

Chem. Res. Toxicol.

View full text Add to dashboard Cite

Balkan endemic nephropathy (BEN) is a multifactorial environmental disease, with chronic exposure to aristolochic acids (AAs) through AA-contaminated food being one of the major etiological mechanisms. However, the bulk of previous research has only focused on investigating the possible roles of individual pollutants in disease development and the etiological mechanism of BEN remains controversial. In this study, we investigated the exposure concentration and duration dependence of coexposure to phthalate esters and lignite coal-derived phenol and polycyclic aromatic hydrocarbons (PAHs) on the metabolism and DNA adduct formation of aristolochic acid I (AAI). Results showed that both the metabolic activation and DNA adduct formation of AAI in cultured human kidney cells were affected by their coexposure to the above-mentioned environmental pollutants. Furthermore, our results suggest that chemicals leached from lignite coal likely played a role by triggering AA-activating enzymes to produce more of the promutagenic DNA adducts, thus further elevating the nephrotoxicity and carcinogenicity of AAs and increasing the risk of BEN. It is believed that the results of this study provide a better understanding of the etiological mechanism of BEN and offer insights into methods and policies to lower the risk of this devastating disease.

show abstract

“…Treatment with a binary mixture of DEHP and DBP, with bisphenol A resulted in adverse changes related to physiology, biochemistry, hematological and hormonal parameters in Wistar rats [86]. A study conducted by Mohammadi and Ashari demonstrated the toxic implication of phthalates in hindering the pathways like nuclear factor‐κB, phosphatidylinositol‐3‐kinase/protein kinase B, and nuclear factor‐erythroid 2‐related factor 2, resulting in oxidative inflammation, stress, cancer, and apoptosis in Wistar rats [87].…”

Section: Cosmetic Chemical Pollutants Persistent In Natural Ecosystem...mentioning

confidence: 99%

Algae bioprocess to deal with cosmetic chemical pollutants in natural ecosystems: A comprehensive review

et al. 2021

View full text Add to dashboard Cite

Elevated demand and extensive exploitation of cosmetics in day-to-day life have hiked up its industrial productions worldwide. Organic and inorganic chemicals like parabens, phthalates, sulfates, and so forth are being applied as constituents towards the formulations, which tend to be the mainspring ecological complication due to their enduring nature and accumulation properties in various sections of the ecosystem. These cosmetic chemicals get accrued into the terrestrial and aquatic systems on account of various anthropogenic activities involving agricultural runoff, industrial discharge, and domestic effluents. Recently, the use of microbes for remediating persistent cosmetic chemicals has gained immense interest. Among different forms of the microbial community being applied as an environmental beneficiary, algae play a vital role in both terrestrial and aquatic ecosystems by their biologically beneficial metabolites and molecules, resulting in the biobenign and efficacious consequences. The use of various bacterial, fungal, and higher plant species has been studied intensely for their bioremediation elements. The bioremediating property of the algal cells through biosorption, bioassimilation, biotransformation, and biodegradation has made it favorable for the removal of persistent and toxic pollutants from the environment. However, the research investigation concerned with the bioremediation potential of the algal kingdom is limited. This review summarizes and provides updated and comprehensive insights into the potential remediation capabilities of algal species against ecologically hazardous pollutants concerning cosmetic chemicals.

show abstract

Mechanistic insight into toxicity of phthalates, the involved receptors, and the role of Nrf2, NF-κB, and PI3K/AKT signaling pathways

Cited by 33 publications

References 223 publications

Effects of a phthalate metabolite mixture on both normal and tumoral human prostate cells

Effects of a phthalate metabolite mixture on both normal and tumoral human prostate cells

Synergistic Interaction of Polycyclic Aromatic Hydrocarbons, Phthalate Esters, or Phenol on DNA Adduct Formation by Aristolochic Acid I: Insights into the Etiology of Balkan Endemic Nephropathy

Algae bioprocess to deal with cosmetic chemical pollutants in natural ecosystems: A comprehensive review

Contact Info

Product

Resources

About