Stage Dependent Enantioselective Metabolism of Bifenthrin in Embryos of Zebrafish (<i>Danio rerio</i>) and Japanese Medaka (<i>Oryzias latipes</i>)

Ji, Chenyang; Tanabe, Philip; Shi, Qingyang; Qian, Le; McGruer, Victoria; Magnuson, Jason T.; Wang, Xinru; Gan, Jay; Gadepalli, Rama S; Rimoldi, John M.; Schlenk, Daniel

doi:10.1021/acs.est.1c01663

Cited by 18 publications

(4 citation statements)

References 67 publications

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“…More details of exposure design and all sequences data have been described in our previous work . The quantification method and measured concentrations of 2,6-DTBP and 2,6-DTBQ in mice livers and serums are provided in Text S1 and Table S1. − Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was performed based on differential expressed genes (DEGs) induced by 2,6-DTBP and 2,6-DTBQ.…”

Section: Methodsmentioning

confidence: 99%

Carcinogenic Risk of 2,6-Di-tert-Butylphenol and Its Quinone Metabolite 2,6-DTBQ Through Their Interruption of RARβ: In Vivo, In Vitro, and In Silico Investigations

Cui

Zhan

et al. 2021

Environ. Sci. Technol.

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Thousands of contaminants are used worldwide and eventually released into the environment, presenting a challenge of health risk assessment. The identification of key toxic pathways and characterization of interactions with target biomacromolecules are essential for health risk assessments. The adverse outcome pathway (AOP) incorporates toxic mechanisms into health risk assessment by emphasizing the relationship among molecular initiating events (MIEs), key events (KEs), and adverse outcome (AO). Herein, we attempted the use of AOP to decipher the toxic effects of 2,6-di-tert-butylphenol (2,6-DTBP) and its para-quinone metabolite 2,6-di-tert-butyl-1,4-benzoquinone (2,6-DTBQ) based on integrated transcriptomics, molecular modeling, and cell-based assays. Through transcriptomics and quantitative real-time PCR validation, we identified retinoic acid receptor β (RARβ) as the key target biomacromolecule. The epigenetic analysis and molecular modeling revealed RARβ interference as one MIE, including DNA methylation and conformational changes. In vitro assays extended subsequent KEs, including altered protein expression of p-Erk1/2 and COX-2, and promoted cancer cell H4IIE proliferation and metastasis. These toxic effects altogether led to carcinogenic risk as the AO of 2,6-DTBP and 2,6-DTBQ, in line with chemical carcinogenesis identified from transcriptome profiling. Overall, our simplified AOP network of 2,6-DTBP and 2,6-DTBQ facilitates relevant health risk assessment.

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Section: Methodsmentioning

confidence: 99%

Carcinogenic Risk of 2,6-Di-tert-Butylphenol and Its Quinone Metabolite 2,6-DTBQ Through Their Interruption of RARβ: In Vivo, In Vitro, and In Silico Investigations

Cui

Zhan

et al. 2021

Environ. Sci. Technol.

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“…This lack of embryonic sensitivity may result from the chorion preventing the uptake of the chemicals. Similar trends of embryos being resistant to chemical toxicity have been observed with polychlorinated biphenyls (PCBs) [ 49 ], 2,3,7,8-tetrachlorodibenzo- p -dioxin (TCDD) [ 50 ], and bifenthrin [ 51 ], all of which are known to be more toxic in larvae. This is a known occurrence mainly for hydrophobic chemicals [ 52 ] but can also be influenced by several other factors, such as species-specific chorion properties and exposure conditions [ 53 , 54 ].…”

Section: Discussionmentioning

confidence: 69%

Mixture Effects of Per- and Polyfluoroalkyl Substances on Embryonic and Larval Sheepshead Minnows (Cyprinodon variegatus)

Tanabe,

Key,

Chung

et al. 2024

Toxics

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Per- and polyfluoroalkyl substances (PFAS) are ubiquitous and persistent environmental contaminants originating from many everyday products. Perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) are two PFAS that are commonly found at high concentrations in aquatic environments. Both chemicals have previously been shown to be toxic to fish, as well as having complex and largely uncharacterized mixture effects. However, limited information is available on marine and estuarine species. In this study, embryonic and larval sheepshead minnows (Cyprinodon variegatus) were exposed to several PFAS mixtures to assess lethal and sublethal effects. PFOS alone was acutely toxic to larvae, with a 96 h LC50 of 1.97 mg/L (1.64–2.16). PFOS + PFOA resulted in a larval LC50 of 3.10 (2.62–3.79) mg/L, suggesting an antagonistic effect. These observations were supported by significant reductions in malondialdehyde (105% ± 3.25) and increases in reduced glutathione concentrations (43.8% ± 1.78) in PFOS + PFOA exposures compared to PFOS-only treatments, indicating reduced oxidative stress. While PFOA reduced PFOS-induced mortality (97.0% ± 3.03), perfluorohexanoic acid (PFHxA) and perfluorobutanoic acid (PFBA) did not. PFOS alone did not affect expression of peroxisome proliferator-activated receptor alpha (pparα) but significantly upregulated apolipoprotein A4 (apoa4) (112.4% ± 17.8), a downstream product of pparα, while none of the other individually tested PFAS affected apoa4 expression. These findings suggest that there are antagonistic interactions between PFOA and PFOS that may reduce mixture toxicity in larval sheepshead minnows through reduced oxidative stress. Elucidating mechanisms of toxicity and interactions between PFAS will aid environmental regulation and management of these ubiquitous pollutants.

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“…Unfortunately, we were not able to test this hypothesis, as 4-OH bifenthrin was not commercially available. However, this metabolic pathway (CYP hydroxylation followed by UGT-conjugation) has been previously observed by Ji et al (2021) for fish [ 113 ] and has been considered the main metabolic pathways of bifenthrin in vertebrates, next to esterase-mediated hydrolysis [ 114 ]. Although previous research on the bifenthrin-resistant MR-VL strain did not show PBO synergism [ 45 ], evidence towards the involvement of CYPs was given for a different T. urticae strain by showing the increased susceptibility towards bifenthrin after the RNAi silencing of cytochrome P450 reductase (CPR), an essential enzyme that serves as an electron donor for CYPs [ 115 ].…”

Section: Discussionmentioning

confidence: 99%

High-Resolution Genetic Mapping Combined with Transcriptome Profiling Reveals That Both Target-Site Resistance and Increased Detoxification Confer Resistance to the Pyrethroid Bifenthrin in the Spider Mite Tetranychus urticae

Beer

Vandenhole

Njiru

et al. 2022

Biology

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Pyrethroids are widely applied insecticides in agriculture, but their frequent use has provoked many cases of resistance, in which mutations in the voltage-gated sodium channel (VGSC), the pyrethroid target-site, were shown to play a major role. However, for the spider mite Tetranychus urticae, it has also been shown that increased detoxification contributes to resistance against the pyrethroid bifenthrin. Here, we performed QTL-mapping to identify the genomic loci underlying bifenthrin resistance in T. urticae. Two loci on chromosome 1 were identified, with the VGSC gene being located near the second QTL and harboring the well-known L1024V mutation. In addition, the presence of an L925M mutation in the VGSC of a highly bifenthrin-resistant strain and its loss in its derived, susceptible, inbred line indicated the importance of target-site mutations in bifenthrin resistance. Further, RNAseq experiments revealed that genes encoding detoxification enzymes, including carboxyl/choline esterases (CCEs), cytochrome P450 monooxygenases and UDP-glycosyl transferases (UGTs), were overexpressed in resistant strains. Toxicity bioassays with bifenthrin (ester pyrethroid) and etofenprox (non-ester pyrethroid) also indicated a possible role for CCEs in bifenthrin resistance. A selection of CCEs and UGTs were therefore functionally expressed, and CCEinc18 was shown to metabolize bifenthrin, while teturUGT10 could glycosylate bifenthrin-alcohol. To conclude, our findings suggest that both target-site and metabolic mechanisms underlie bifenthrin resistance in T. urticae, and these might synergize high levels of resistance.

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Stage Dependent Enantioselective Metabolism of Bifenthrin in Embryos of Zebrafish (Danio rerio) and Japanese Medaka (Oryzias latipes)

Cited by 18 publications

References 67 publications

Carcinogenic Risk of 2,6-Di-tert-Butylphenol and Its Quinone Metabolite 2,6-DTBQ Through Their Interruption of RARβ: In Vivo, In Vitro, and In Silico Investigations

Carcinogenic Risk of 2,6-Di-tert-Butylphenol and Its Quinone Metabolite 2,6-DTBQ Through Their Interruption of RARβ: In Vivo, In Vitro, and In Silico Investigations

Mixture Effects of Per- and Polyfluoroalkyl Substances on Embryonic and Larval Sheepshead Minnows (Cyprinodon variegatus)

High-Resolution Genetic Mapping Combined with Transcriptome Profiling Reveals That Both Target-Site Resistance and Increased Detoxification Confer Resistance to the Pyrethroid Bifenthrin in the Spider Mite Tetranychus urticae

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