Comprehensive analysis of organophosphorus flame retardant-induced mitochondrial abnormalities: Potential role in lipid accumulation

Le, Yifei; Shen, Haiping; Yang, Zhen; Lu, Dezhao; Wang, Cui

doi:10.1016/j.envpol.2021.116541

Cited by 25 publications

(9 citation statements)

References 48 publications

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“…Moreover, other OPFR or xenobiotics may contribute to the associated thyroid and estrogen disruption in those studies. Although we focused our investigation on TDCPP-induced modulation of nuclear receptors, there are other potential mechanisms by which TDCPP can cause insulin resistance such as TDCPP-induced mitochondrial dysfunction ( Kim et al, 2008 ; Le et al, 2021 ; Lee et al, 2019 ; Marroqui et al, 2018 ). The mechanisms by which TDCPP causes metabolic syndrome in men remains to be determined, and may include modulation of nuclear receptors, mitochondrial dynamics, and others yet to be uncovered.…”

Section: Discussionmentioning

confidence: 99%

Tris(1,3-dichloro-2-propyl) phosphate is a metabolism-disrupting chemical in male mice

et al. 2023

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Section: Discussionmentioning

confidence: 99%

Tris(1,3-dichloro-2-propyl) phosphate is a metabolism-disrupting chemical in male mice

et al. 2023

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“…The reduced content of mitochondrial networks was confirmed to be one of the pathological phenomena caused by the mitochondrial dysfunction of OPFRs. 31) In addition, a recent study by Zhang et al showed that the disorder of mitochondrial fusion and fission results in further reduction of the number of mitochondria so that it is not enough to clear excessive ROS, and mitochondrial structure changes to form mitochondrial membrane permeable transport pores (mPTPs), which leads to cell necrosis and apoptosis, organ failure, and metabolic dysfunction, increasing morbidity and mortality. 32) These findings support our data suggesting that soman toxicity will cause a decrease in the number of mitochondria, which is due to morphological damage caused by mitochondrial fusion and fission.…”

Section: Discussionmentioning

confidence: 99%

PGC 1α-Mediates Mitochondrial Damage in the Liver by Inhibiting the Mitochondrial Respiratory Chain as a Non-cholinergic Mechanism of Repeated Low-Level Soman Exposure

Jin¹,

Zhang²,

Cui³

et al. 2023

Biological & Pharmaceutical Bulletin

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This work aimed to assess whether mitochondrial damage in the liver induced by subacute soman exposure is caused by peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1α) and whether PGC-1α regulates mitochondrial respiratory chain damage. Toxicity mechanism research may provide theoretical support for developing anti-toxic drugs in the future. First, a soman animal model was established in male Sprague-Dawley (SD) rats by subcutaneous soman injection. Then, liver damage was biochemically evaluated, and acetylcholinesterase (AChE) activity was also determined. Transmission electron microscopy (TEM) was performed to examine liver mitochondrial damage, and high-resolution respirometry was carried out for assessing mitochondrial respiration function. In addition, complex I-IV levels were quantitatively evaluated in isolated liver mitochondria by enzyme-linked immunosorbent assay (ELISA). PGC-1α levels were detected with a Jess capillary-based immunoassay device. Finally, oxidative stress was analyzed by quantifying superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), oxidized glutathione (GSSG), and reactive oxygen species (ROS) levels. Repeated low-level soman exposure did not alter AChE activity, while increasing morphological damage of liver mitochondria and liver enzyme levels in rat homogenates. Complex I, II and I II activities were 2.33, 4.95, and 5.22 times lower after treatment compared with the control group, respectively. Among complexes I-IV, I-III decreased significantly (p < 0.05), and PGC-1α levels were 1.82 times lower after soman exposure than in the control group. Subacute soman exposure significantly increased mitochondrial ROS production, which may cause oxidate stress. These findings indicated dysregulated mitochondrial energy metabolism involves PGC-1α protein expression imbalance, revealing non-cholinergic mechanisms for soman toxicity.

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“…Wu et al [ 175 ] reported that polychlorinated biphenyls-153 (PCB-153) disturbed glucose and lipid metabolism via decreased hepatocyte nuclear factor 1b (HNF1b) expression, elevated reactive oxygen species (ROS) levels, and enhanced nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)-mediated inflammation, resulting in an increased accumulation of lipid and inhibition of insulin-stimulated glucose uptake in AML-12 cells. A study by Le et al [ 176 ] showed that chlorinated-organophosphorus flame retardants (OPFRs) such as tris (2-chloroethyl) phosphate (TCEP), tris (2-chloroisopropyl) phosphate (TCPP), tris-(2-chloro-1- (chloromethyl) ethyl) phosphate (TDCPP), triphenyl phosphate (TPhP) and tricresyl phosphate (TCP) increased the cell lipid area by 2.3-, 2.5-, 2.7-, 3.3- and 5.2-fold, respectively.…”

Section: Hepatic Cellular Modelsmentioning

confidence: 99%

Application of In Vitro Models for Studying the Mechanisms Underlying the Obesogenic Action of Endocrine-Disrupting Chemicals (EDCs) as Food Contaminants—A Review

Kowalczyk

Piwowarski

Wardaszka

et al. 2023

IJMS

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Obesogenic endocrine-disrupting chemicals (EDCs) belong to the group of environmental contaminants, which can adversely affect human health. A growing body of evidence supports that chronic exposure to EDCs can contribute to a rapid increase in obesity among adults and children, especially in wealthy industrialized countries with a high production of widely used industrial chemicals such as plasticizers (bisphenols and phthalates), parabens, flame retardants, and pesticides. The main source of human exposure to obesogenic EDCs is through diet, particularly with the consumption of contaminated food such as meat, fish, fruit, vegetables, milk, and dairy products. EDCs can promote obesity by stimulating adipo- and lipogenesis of target cells such as adipocytes and hepatocytes, disrupting glucose metabolism and insulin secretion, and impacting hormonal appetite/satiety regulation. In vitro models still play an essential role in investigating potential environmental obesogens. The review aimed to provide information on currently available two-dimensional (2D) in vitro animal and human cell models applied for studying the mechanisms of obesogenic action of various industrial chemicals such as food contaminants. The advantages and limitations of in vitro models representing the crucial endocrine tissue (adipose tissue) and organs (liver and pancreas) involved in the etiology of obesity and metabolic diseases, which are applied to evaluate the effects of obesogenic EDCs and their disruption activity, were thoroughly and critically discussed.

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Comprehensive analysis of organophosphorus flame retardant-induced mitochondrial abnormalities: Potential role in lipid accumulation

Cited by 25 publications

References 48 publications

Tris(1,3-dichloro-2-propyl) phosphate is a metabolism-disrupting chemical in male mice

Tris(1,3-dichloro-2-propyl) phosphate is a metabolism-disrupting chemical in male mice

PGC 1α-Mediates Mitochondrial Damage in the Liver by Inhibiting the Mitochondrial Respiratory Chain as a Non-cholinergic Mechanism of Repeated Low-Level Soman Exposure

Application of In Vitro Models for Studying the Mechanisms Underlying the Obesogenic Action of Endocrine-Disrupting Chemicals (EDCs) as Food Contaminants—A Review

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