Tris(1,3-dichloro-2-propyl) phosphate disrupts axonal growth, cholinergic system and motor behavior in early life zebrafish

Cheng, Rui; Jia, Yali; Dai, Lili; Liu, Chunsheng; Wang, Jianghua; Li, Guangyu; Yu, Lei

doi:10.1016/j.aquatox.2017.09.003

Cited by 54 publications

(11 citation statements)

References 50 publications

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“…The spontaneous tail coiling (STC) frequency depends on the developmental stage used for the assessment. This has been reported previously (Cheng et al 2017; Saint-Amant and Drapeau 1998) and was confirmed for our experimental setup. A weak STC frequency (1 count per minute) was observed at 21 and 22 hpf, with maximum values (3.5 counts per minute) at 23 and 24 hpf, followed by a gradual decline until 31 hpf (Figure 1).…”

Section: Influence Of Experimental Parameterssupporting

confidence: 92%

“…In previous studies, the STC test has been used to analyze effects of neuroactive chemicals such as abamectin, chlorpyrifos, carbamazepine etc. (Cheng et al 2017;Selderslaghs et al 2010;Vliet et al 2017; Weichert et al 2017). STC response of these chemicals relative to negative control appears to be a promising technique to predict either the stimulatory or inhibitory mode of action (MoA) of neuroactive compounds (Ogungbemi et al 2019).…”

Section: Introductionmentioning

confidence: 99%

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Optimization of the spontaneous tail coiling test for fast assessment of neurotoxic effects in the zebrafish embryo using an automated workflow in KNIME®

Ogungbemi

Teixidó

Massei

et al. 2020

Neurotoxicology and Teratology

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Neuroactive chemicals are frequently detected in the environment. At sufficiently high concentrations or within mixtures, they could provoke neurotoxic effects and neurological diseases to organisms and humans. Fast identification of such neuroactive compounds in the environment could help in hazard assessment and risk mitigation. Behavior change is considered as an important endpoint and might be directly or indirectly connected to a neuroactive mode of action. For a fast evaluation of environmental samples and pure substances, we optimized the measurement of a behavioral endpoint in zebrafish embryos -the spontaneous tail coiling (STC). Evaluation of results is automated via the use of a workflow established with the KNIME ® software. Analysis duration and developmental stage were optimized to 1 minute and 25 ± 1 hpf respectively during measurement. Exposing the embryos in a group of 10 or 20 and acclimatizing for 30 min at room temperature proved to be reliable. The optimized method was used to investigate neurotoxic effects of 18 substances with different modes of action (MoA). The STC test accurately detected the effect of 8 out of 11 neuroactive substances (chlorpyrifos, chlorpyrifos-oxon, diazinon, paraoxon-methyl, abamectin, carbamazepine, propafenone and diazepam). Aldicarb and nicotine showed subtle effects which were considered to be conditional and imidacloprid showed no effect. For substances with unknown neuroactive MoA, 3 substances did not provoke any effect on the STC (pyraclostrobin, diuron and daunorubicin-hydrochloride) while 4 other substances provoked an increased STC (hexaconazole, aniline, dimethyl-sulfoxide and 3,4-dichloroaniline). Such unexpected effects indicate possible neuroactive side effects or unknown mechanisms of action that impact on the STC. In conclusion, the optimized STC parameters and the automated analysis in KNIME® indicate opportunities for the harmonization of the STC test and further development for prospective and diagnostic testing.

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Section: Influence Of Experimental Parameterssupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Optimization of the spontaneous tail coiling test for fast assessment of neurotoxic effects in the zebrafish embryo using an automated workflow in KNIME®

Ogungbemi

Teixidó

Massei

et al. 2020

Neurotoxicology and Teratology

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“…The locomotion and motility of fish embryos are highly associated with motor neuron development. The alteration in motor neurons is considered an important factor that leads to motor behavior alterations in zebrafish induced by many chemicals. − Therefore, we questioned whether BPF could affect motor neuron development. In this study, BPF exposure of MnGF zebrafish indicated that both 0.5 and 5.0 mg/L BPF could significantly affect motor neuron development at 72 hpf with an inhibition of axon growth (Figure S4).…”

Section: Resultsmentioning

confidence: 99%

Bisphenol F-Induced Neurotoxicity toward Zebrafish Embryos

Yuan

Qian

et al. 2019

Environ. Sci. Technol.

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In this study, the influence of bisphenol F (BPF) toward central nervous system (CNS) was assessed using zebrafish embryos. We found that BPF could induce significant neurotoxicity toward zebrafish embryos, including inhibited locomotion, reduced moving distance, and CNS cell apoptosis at an effective concentration of 0.0005 mg/L. Immunofluorescence assay showed that both microglia and astrocyte in zebrafish brain were significantly activated by BPF, indicating the existence of neuroinflammatory response. Peripheral motor neuron development was significantly inhibited by BPF at 72 hpf. RNA-seq data indicated that neuronal developmental processes and cell apoptosis pathways were significantly affected by BPF exposure, which was consistent with the phenotypic results. Chip-seq assay implied that the transcriptional changes were not mediated by ERα. Additionally, no significant change was found in neurotransmitter levels (5-hydroxytryptamine, dopamine, and acetylcholine) or acetylcholinesterase (Ache) enzyme activity after BPF exposure, indicating that BPF may not affect neurotransmission. In conclusion, BPF could lead to abnormal neural outcomes during zebrafish early life stage through inducing neuroinflammation and CNS cell apoptosis even at environmentally relevant concentration.

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“…Lower concentrations did not induce cardiac defects (typically manifested as pericardial edema) and other developmental abnormalities of zebrafish larvae at 96 hpf. MM-129 did not either affect the number of spontaneous movement, considered as a neurotoxicity marker in studies on behavioral changes due to chemical exposure [ 37 ]. Results from the zebrafish toxicity study clearly demonstrate a favorable safety profile of MM-129.…”

Section: Discussionmentioning

confidence: 99%

Preclinical Toxicity and Safety of MM-129—First-in-Class BTK/PD-L1 Inhibitor as a Potential Candidate against Colon Cancer

et al. 2021

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MM-129 is a novel inhibitor targeting BTK/PI3K/AKT/mTOR and PD-L1, as it possesses antitumor activity against colon cancer. To evaluate the safety profile of MM-129, we conducted a toxicity study using the zebrafish and rodent model. MM-129 was also assessed for pharmacokinetics features through an in vivo study on Wistar rats. The results revealed that MM-129 exhibited favorable pharmacokinetics with quick absorption and 68.6% of bioavailability after intraperitoneal administration. No serious adverse events were reported for the use of MM-129, confirming a favorable safety profile for this compound. It was not fatal and toxic to mice at an anticancer effective dose of 10 μmol/kg. At the end of 14 days of administering hematological and biochemical parameters, liver and renal functions were all at normal levels. No sublethal effects were either detected in zebrafish embryos treated with a concentration of 10 μM. MM-129 has the potential as a safe and well-tolerated anticancer formulation for future treatment of patients with colon cancer.

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Tris(1,3-dichloro-2-propyl) phosphate disrupts axonal growth, cholinergic system and motor behavior in early life zebrafish

Cited by 54 publications

References 50 publications

Optimization of the spontaneous tail coiling test for fast assessment of neurotoxic effects in the zebrafish embryo using an automated workflow in KNIME®

Optimization of the spontaneous tail coiling test for fast assessment of neurotoxic effects in the zebrafish embryo using an automated workflow in KNIME®

Bisphenol F-Induced Neurotoxicity toward Zebrafish Embryos

Preclinical Toxicity and Safety of MM-129—First-in-Class BTK/PD-L1 Inhibitor as a Potential Candidate against Colon Cancer

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