Environmental relevant concentrations of benzophenone-3 induced developmental neurotoxicity in zebrafish

Tao, Junyan; Bai, Chenglian; Chen, Yuanhong; Zhou, Huanhuan; Liu, Yahui; Shi, Qingyu; Pan, Wenhao; Dong, Haojia; Li, Luyi; Xu, Hui; Tanguay, Robyn L; Huang, Changjiang; Dong, Qian

doi:10.1016/j.scitotenv.2020.137686

Cited by 58 publications

(18 citation statements)

References 52 publications

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“…Based on these original data, the chemical UV filter benzophenone-3 changes the expression and disrupts the functions of estrogen receptors (ESR1, ESR2, and GPER1), retinoid X receptors (RXRα, RXRβ, and RXRγ) and PPARγ, which are crucial receptors for the proper development and functioning of the nervous system. The latest data from zebrafish confirmed that benzophenone-3 induced developmental neurotoxicity, such as delayed axonal growth, and altered cell proliferation and cell apoptosis, through a mechanism mediated by the RXRβ receptor (Tao et al, 2020). The aforementioned effects of benzophenone-3 are consistent with our observations that benzophenone-3 impairs the expression of genes associated with neurogenesis and neurotransmitters, for which the abovementioned receptors may be partially responsible.…”

Section: Benzophenone-3 Changes the Expression And Impairs The Functions Of Receptors Crucial For The Proper Development And Functioning supporting

confidence: 89%

Is the commonly used UV filter benzophenone-3 a risk factor for the nervous system?

Wnuk

Kajta

2021

Acta Biochim Pol

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Benzophenone-3 (2-hydroxy-4-methoxybenzophenone, oxybenzone, or BP-3) is one of the most frequently used UV radiation absorbents, which are commonly referred to as sunscreen filters. Its widespread use in industrial applications provides protection against the photodegradation of a wide range of products but at the same time creates the risk of human exposure to benzophenone-3 unbeknownst to the individuals exposed. Topically applied benzophenone-3 penetrates individual skin layers, enters the bloodstream, and is excreted in the urine. In addition, benzophenone-3 easily crosses the placental barrier, which creates the risk of exposure to this substance in the prenatal period. Despite the widespread use and occurrence of benzophenone-3 in the human environment, little knowledge of the mechanisms underlying the effect of benzophenone-3 on the nervous system was available until recently. Only the most recent research, including studies by our group, has enabled the identification of new molecular mechanisms through which benzophenone-3 affects embryonic neuronal cells and the developing mammalian brain. Benzophenone-3 has been shown to induce neurotoxicity and apoptotic processes and inhibit autophagy in embryonic neuronal cells. Benzophenone-3 also alters expression and impairs function of receptors necessary for the proper development and function of the nervous system. The most worrying finding seems to be that benzophenone-3 contributes to an increased risk of developmental abnormalities and/or epigenetically based degeneration of neuronal cells by changing the epigenetic status of neuronal cells.

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Section: Benzophenone-3 Changes the Expression And Impairs The Functions Of Receptors Crucial For The Proper Development And Functioning supporting

confidence: 89%

Is the commonly used UV filter benzophenone-3 a risk factor for the nervous system?

Wnuk

Kajta

2021

Acta Biochim Pol

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“…21 It is worth noting that the light/dark locomotor response assay used in our study is sensitive to detecting many neurotoxic compounds at very low concentrations. 20,22,23 As a well-known DA neurotoxin, MPTP is believed to exert its toxicity by first crossing the blood−brain barrier due to its highly lipophilic nature, converted to active metabolite MPP + by MAO-B in the astrocytes, then selectively transported into DA neurons via the dopamine transporter (DAT) where it inhibits mitochondrial electron transport complex I and subsequently leads to an increase in ROS and an impairment of energy metabolism leading to DA neuron death. 24 We also found increased cell apoptosis, oxidative stress, and reduced ATP production immediately after MPTP exposure at 96 hpf.…”

Section: ■ Discussionmentioning

confidence: 99%

Characterization of Developmental Neurobehavioral Toxicity in a Zebrafish MPTP-Induced Model: A Novel Mechanism Involving Anemia

Dong

Mao

Bai

et al. 2022

ACS Chem. Neurosci.

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Zebrafish represent an economical alternative to rodents for developmental neurotoxicity (DNT) testing. Mechanistic understanding is the key to successfully translating zebrafish findings to humans. In the present study, we used a well-known dopaminergic (DA) neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) as a model chemical to uncover the molecular pathways for observed DNT effects. To enhance the specificity of potential molecular targets, we restricted our exposure to a concentration that is nonteratogenic yet exhibits high DNT effects and an exposure window sensitive to MPTP. Our DNT assessment based on a battery of motor and social behavioral tests revealed an effective concentration of 1 μM and a sensitive window of 48−96 h postfertilization (hpf) for MPTP-induced hypoactivity. It is worth noting that this hypoactivity persisted into later larval development until 28 dpf. We observed increased cell apoptosis, oxidative stress, and decreased ATP levels in larvae immediately after exposure at 96 hpf. Significant reductions of DA neurons were found in the retina at 72, 96, and 120 hpf. No visible deformity was found in motoneurons at 72, 96, and 120 hpf. Transcriptome analysis uncovered a novel pathway manifested by significant upregulation of genes enriched with erythropoiesis. Sensitive window exposure of MPTP and other DA neurotoxins rotenone and paraquat exhibited a concentration-dependent effect on transcriptional changes of embryonic hemoglobins and anemia. Given that anemia is a significant risk factor for Parkinson's disease and MPTP is known to cause parkinsonism in humans, we concluded that anemia resulting from dysregulation of primitive erythropoiesis during embryonic development might serve as a common mechanism underlying DA neurotoxin-induced DNT effects between zebrafish and humans.

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“…Indeed, BP3 was shown to disrupt the endocrine system by inducing estrogenic activity in an in vitro gene assay of zebrafish [29] and to induce a vitellogenin protein in male Japanese rice fish [30]. BP3 can also cause developmental neurotoxicity in zebrafish [31]. The genotoxic potential of this UV filter was also demonstrated in the coral Stylophora pistillata [32].…”

Section: Sed /D0mentioning

confidence: 99%

Transfer of 7 Organic UV Filters from Sediment to the Ragworm Hediste diversicolor: Bioaccumulation of Benzophenone-3 and Further Proof of Octocrylene Metabolism

et al. 2022

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Organic UV filters are continuously released in aquatic ecosystems due to their widespread use, especially in touristic coastal environments. Generally, organic UV filters are poorly soluble in water and tend to accumulate in the sediment compartment. This represents a conceivable risk for sediment-dwelling organisms and a potential for transfer of the UV filters up the food chain. This study aimed to assess the potential transfer of seven UV filters including benzophenone-3 (BP3), bis-ethylhexyloxyphenol methoxyphenyl triazine (BEMT), butyl methoxydibenzoylmethane (BM), methylene bis-benzotriazolyl tetramethylbutylphenol (MBBT), 2-ethylhexyl salicylate (ES), diethylhexyl butamido triazone (DBT), and octocrylene (OC) from artificial spiked sediment (10 µg·g−1 dry weight) to sediment-dwelling worms. All UV filters were detected in the worms after 28 days of exposure, but only BP3 was apparently bioaccumulated, with a biota sediment accumulation factor (BSAF) of 12.38 ± 4.65. However, metabolomic profiling revealed that OC was metabolized by the worms into 11 fatty acid conjugates, demonstrating that OC did also accumulate in the worms in the form of OC–fatty acid conjugates. Here, the sole quantification of the parent organic UV filter underestimated the accumulation factor and the exposure of organisms. In general, it is therefore important to pair the conventional method (BSAF calculus) with other techniques, such as metabolomics, to assess the actual potential for bioaccumulation of xenobiotics including transformed xenobiotics.

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Environmental relevant concentrations of benzophenone-3 induced developmental neurotoxicity in zebrafish

Cited by 58 publications

References 52 publications

Is the commonly used UV filter benzophenone-3 a risk factor for the nervous system?

Is the commonly used UV filter benzophenone-3 a risk factor for the nervous system?

Characterization of Developmental Neurobehavioral Toxicity in a Zebrafish MPTP-Induced Model: A Novel Mechanism Involving Anemia

Transfer of 7 Organic UV Filters from Sediment to the Ragworm Hediste diversicolor: Bioaccumulation of Benzophenone-3 and Further Proof of Octocrylene Metabolism

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