Toxicity and accumulation of 6-OH-BDE-47 and newly synthesized 6,6′-diOH-BDE-47 in early life-stages of Zebrafish (Danio rerio)

Zhang, Mengtao; Zhao, Feng; Zhang, Jiawei; Shi, Jianghong; Tao, Huanyu; Ge, Hui; Guo, Wei; Liu, Dong; Cai, Zongwei

doi:10.1016/j.scitotenv.2020.143036

Cited by 14 publications

(10 citation statements)

References 44 publications

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“…Also the natural metabolites as hydroxylated (OH-BDE) and methoxylated (MeO-BDE) and, recently, diOH-BDEs (Zhang et al 2020), have been found in a wide diversity of environmental samples (Sun et al 2020). Several studies have evidenced that metabolites maintain bioactive remains, exhibiting similar or even greater toxicity than the native PBDEs due to their hydrophobic properties (Liu et al, 2011;Usenko et al 2012) raising the concern about these compounds.…”

Section: Introductionmentioning

confidence: 99%

“…Polybrominated diphenyl ethers (PBDEs) are industrial substances that have been widely used as flame retardants for decades in commercial products due to their good thermal stability and low cost (Wen et al, 2015). Their proven toxicity (Zhang, Zhao, et al, 2020; Zhang, Zhou, et al, 2020) and structural similarity to thyroid hormones and thyroxine in particular, which induce neurodevelopmental and endocrine disrupting effects in humans (Butryn et al, 2020), have meant that nowadays some commercial PBDEs mixtures are banned, and they have been identified as Persistent Organic Pollutants by the Stockholm Convention since 2009 (United Nations Environmental Program, 2019). However, as a consequence of this persistence in the environment through long‐term use and recycling processes, these chemicals are still detected at potentially dangerous levels in humans and in a wide range of biological and environmental samples (De la Torre et al, 2020; Klinčić et al, 2020; Liu et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

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Bioaccumulation and Biotransformation of BDE‐47 Using Zebrafish Eleutheroembryos (Danio rerio)

Oro‐Carretero

Sanz‐Landaluze

2023

Enviro Toxic and Chemistry

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Polybrominated diphenyl ethers (PBDEs) industrially used as ame retardants are nowadays considered emerging pollutants as they are endocrine disrupting chemicals (EDCs), persistent in the environment, bioaccumulative and in addition, its hydroxylated (OH-BDEs) and methoxylated (MeO-BDEs) metabolites have similar ecotoxic properties. The aim of this work was to develop an analytical method to be applied in the study of the bioconcentration and biotransformation of BDE-47 due to its bioavailability, toxicity and high persistence and abundance in environmental samples, including humans. So, a dependable ultrasonic extraction process followed to dispersive SPE clean-up step and GC-MS-μECD detection has worked out for the determination of BDE-47 and its main biotransformation products (MeO-BDEs and OH-BDEs), considering the polarity difference. In addition, an alternative method to bioconcentration o cial guideline OECD 305, developed previously with zebra sh (Danio rerio) eleutheroembryos (i.e., hatched but not yet free feeding embryos) is used, reducing dramatically the animal suffering but also time and reagents. Bioconcentration factors (BCF) were calculated using rst order one-compartment toxicokinetic model. The pro les found show rapid absorption in the rst hours of larval development and great bioaccumulative with capacity, nding bioconcentration factors (BCF) of 6631 and 44210 at nominal concentrations of 10 and 1 μg•L -1 (< 1% LC50), respectively. Metabolization studies show increasing concentrations of the metabolites BDE-28, 2'-OH-BDE-28 and 5-MeO-BDE-47 throughout the exposure time. The results obtained show the feasibility of the method for bioaccumulation and opens the possibility of metabolic studies with zebra sh eleutheroembryos, which is a very underdeveloped eld without o cial testing or regulation.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Bioaccumulation and Biotransformation of BDE‐47 Using Zebrafish Eleutheroembryos (Danio rerio)

Oro‐Carretero

Sanz‐Landaluze

2023

Enviro Toxic and Chemistry

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“…First, in addition to the significantly lower levels of TRH and TSH in the brain, zebrafish treated with TCEP also had significantly lower T3 and higher T4 levels in their plasma, resulting in a marked decline in the T3/T4 ratio (Figure S2). Since circulating T3, the bioactive form of thyroid hormone, is derived from the peripheral monodeiodination of the outer aromatic ring of T4, the disrupted equilibrium between T3 and T4 (indicated by alterations in T3 and T4 as well as a reduction in the T3/T4 ratio) suggests evidence of HPT-axis dysfunction. ,,, Because the synthesis of thyroid hormones is primarily regulated by TRH and TSH, which are secreted by the hypothalamus and pituitary gland, respectively, the disturbance of T3 and T4 may be due to TCEP-induced suppression of TRH and TSH. , …”

Section: Discussionmentioning

confidence: 99%

“…Since circulating T3, the bioactive form of thyroid hormone, is derived from the peripheral monodeiodination of the outer aromatic ring of T4, the disrupted equilibrium between T3 and T4 (indicated by alterations in T3 and T4 as well as a reduction in the T3/T4 ratio) suggests evidence of HPT-axis dysfunction. 38,39,81,82 Because the synthesis of thyroid hormones is primarily regulated by TRH and TSH, which are secreted by the hypothalamus and pituitary gland, respectively, the disturbance of T3 and T4 may be due to TCEP-induced suppression of TRH and TSH. 38,83 In this study, disruption of the HPT axis was further confirmed by the expression analysis of its target genes.…”

Section: Discussionmentioning

confidence: 99%

“…To efficiently fulfill its metabolic functions, the liver is under sophisticated regulation of the neuroendocrine system, such as the hypothalamic–pituitary–thyroid (HPT) axis. , Briefly, thyrotropin-releasing hormone (TRH) is synthesized in the hypothalamus and delivered to the pituitary to stimulate the release of thyroid-stimulating hormone (TSH), which triggers the synthesis of triiodothyronine (T3) and thyroxine (T4). − Although far from being fully understood, the binding of thyroid hormones (mainly the bioactive form T3) to their specific receptors (TRα and TRβ) in the liver can effectively regulate the hepatic metabolism of lipids, cholesterol, and glucose, primarily by modulating the transcriptional activities of related target genes. − Thus, HPT axis dysfunction may disturb liver health. , Although a few case studies have suggested that TCEP might cause the disruption of thyroid endocrine in fish species, ,, the intrinsic association between TCEP-induced HPT axis dysfunction and potential hepatotoxicity has not yet been investigated.…”

Section: Introductionmentioning

confidence: 99%

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Tris(2-chloroethyl) Phosphate Exerts Hepatotoxic Impacts on Zebrafish by Disrupting Hypothalamic–Pituitary–Thyroid and Gut–Liver Axes

Tian

et al. 2023

Environ. Sci. Technol.

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The ubiquitous environmental presence of tris(2chloroethyl) phosphate (TCEP) poses a potential threat to animals; however, little is known about its hepatotoxicity. In this study, the effects of TCEP exposure (0.5 and 5.0 μg/L for 28 days) on liver health and the potential underlying toxification mechanisms were investigated in zebrafish. Our results demonstrated that TCEP exposure led to hepatic tissue lesions and resulted in significant alterations in liver-injury-specific markers. Moreover, TCEP-exposed fish had significantly lower levels of thyrotropin-releasing hormone and thyroid-stimulating hormone in the brain, evidently less triiodothyronine whereas more thyroxine in plasma, and markedly altered expressions of genes from the hypothalamic−pituitary−thyroid (HPT) axis in the brain or liver. In addition, a significantly higher proportion of Bacteroidetes in the gut microbiota, an elevated bacterial source endotoxin lipopolysaccharide (LPS) in the plasma, upregulated expression of LPSbinding protein and Toll-like receptor 4 in the liver, and higher levels of proinflammatory cytokines in the liver were detected in TCEP-exposed zebrafish. Furthermore, TCEP-exposed fish also suffered severe oxidative damage, possibly due to disruption of the antioxidant system. These findings suggest that TCEP may exert hepatotoxic effects on zebrafish by disrupting the HPT and gut− liver axes and thereafter inducing hepatic inflammation and oxidative stress.

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Miniaturized method for the quantification of persistent organic pollutants and their metabolites in HepG2 cells: assessment of their biotransformation

Oro‐Carretero

Sanz‐Landaluze

2023

Anal Bioanal Chem

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Biotransformation can greatly influence the accumulation and, subsequently, toxicity of substances in living beings. Although traditionally these studies to quantify metabolization of a compound have been carried out with in vivo species, currently, in vitro test methods with very different cell lines are being developed for their evaluation. However, this is still a very limited field due to multiple variables of a very diverse nature. So, an increasing number of analytical chemists are working with cells or other similar biological samples of very small size. This makes it necessary to address the development of analytical methods that allow determining their concentration both inside the cells and in their exposure medium. The aim of this study is to develop a set of analytical methodologies for the quantification of polycyclic aromatic hydrocarbons, PAHs (phenanthrene, PHE), and polybrominated diphenyl ethers, PBDEs (2,2′,4,4′-tetrabromodiphenyl ether, BDE-47), and their major metabolites in cells and their exposure medium. Analytical methodologies, based on miniaturized ultrasound probe-assisted extraction, gas chromatography–mass spectrometry–microelectron capture detector (GC–MS-µECD), and liquid chromatography–fluorescence detector (LC-FL) determination techniques, have been optimized and then applied to a biotransformation study in HepG2 at 48 h of exposure. Significant concentrations of the major metabolites of PHE (1-OH, 2-OH, 3-OH, 4-OH-, and 9-OH-PHE) and BDE-47 (5-MeO-, 5-OH-, and 3-OH-BDE-47) were detected and quantified inside the cells and in the exposure medium. These results provide a new method for determination and improve information on the metabolization ratios for a better knowledge of the metabolic pathways and their toxicity. Graphical abstract

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Toxicity and accumulation of 6-OH-BDE-47 and newly synthesized 6,6′-diOH-BDE-47 in early life-stages of Zebrafish (Danio rerio)

Cited by 14 publications

References 44 publications

Bioaccumulation and Biotransformation of BDE‐47 Using Zebrafish Eleutheroembryos (Danio rerio)

Bioaccumulation and Biotransformation of BDE‐47 Using Zebrafish Eleutheroembryos (Danio rerio)

Tris(2-chloroethyl) Phosphate Exerts Hepatotoxic Impacts on Zebrafish by Disrupting Hypothalamic–Pituitary–Thyroid and Gut–Liver Axes

Miniaturized method for the quantification of persistent organic pollutants and their metabolites in HepG2 cells: assessment of their biotransformation

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