Benzotriazole ultraviolet stabilizers alter the expression of the thyroid hormone pathway in zebrafish (Danio rerio) embryos

Abstract

h i g h l i g h t sBUVSs decreased heart rate of zebrafish in all treatments by 6.9%e21.4%. BUVSs affected transcriptional levels of HPT axis-related genes. Disruption of thyroid-related transcripts was dependent on the structure of BUVSs. Gene networks and pathways were predicted using IMP. a r t i c l e i n f o a b s t r a c tBenzotriazole ultraviolet stabilizers (BUVSs) are widely used in industrial products as well as personalhygiene products to protect the material or skin from harmful UV-radiation. Due to their persistence and bioaccumulation, BUVSs have been ubiquitously detected in aquatic environments. Although the toxicological effects of BUVSs in aquatic organisms have been previously examined, the effects of BUVSs on the thyroid system have not been adequately addressed. In this study, we assessed putative thyroid disrupting effects of BUVSs (UV-234, UV-326, UV-329 and UV-P) in zebrafish embryos at 1, 10 and 100 mg/L for 96 h. The heart rate was assessed in zebrafish and was observed to be decreased by 6.9% e21.4% in exposure of tested BUVSs. We also observed that the transcript levels of HPT axis-related genes were affected by the 4 BUVSs tested in different ways. Specifically, mRNA levels of thyroid hormone receptors (thraa and thrb) in zebrafish embryos were differentially expressed and the direction of change in these transcripts was isoform and BUVSs dependent. Pathway analysis of the targeted genes measured indicated that cellular processes putatively affected by BUVSs included response to organic substance, regulation of transcription from RNA polymerase II promoter, intracellular receptor signaling pathway, and hypothyroidism. Upon expansion of the network, novel genes involved in this predicted gene network may provide insight into the mechanisms of thyroid disrupting mechanisms of BUVSs. Taken together, our results indicate that BUVSs can potentially impact the thyroid system, and that this is dependent upon the type or structure of BUVSs.

Food‐Borne Exposure of Juvenile Rainbow Trout (Oncorhynchus mykiss) to Benzotriazole Ultraviolet Stabilizers Alone and in Mixture Induces Specific Transcriptional Changes

“…A similar absence of effects on growth and life history endpoints was observed in the freshwater invertebrates C. reinhardtii and D. magna following 96 h and 21 d of exposure, respectively, to 0.01 to 10 µg/L of UV‐234 and UV‐328 alone and in mixture (Giraudo et al 2017a). Similarly, no effects were observed in the development of zebrafish embryos exposed to 1 to 100 µg/L of UV‐234 for 96 h (Liang et al 2017).…”

“…The results showed that UV‐234 and UV‐328 did not induce acute toxicity (48‐h median lethal concentration [LC50] > 10 mg/L) in the freshwater crustacean Daphnia pulex (Kim et al 2011). Exposure of zebrafish ( Danio rerio ) embryos to 1 to 100 µg/L of UV‐234 for 96 h led to altered transcript levels of 2 hypothalamic–pituitary–thyroid axis‐related genes, suggesting potential endocrine disruption of the thyroid system (Liang et al 2017). Moreover, no effects were observed on life‐history endpoints and transcriptional levels of oxidative stress‐related genes in Daphnia magna chronically exposed (for 21 d) to 0.01 to 10 µg/L of UV‐234 and UV‐328 (Giraudo et al 2017a).…”

Transcriptome analysis reveals benzotriazole ultraviolet stabilizers regulate networks related to inflammation in juvenile zebrafish (Danio rerio) brain

“…The highly specific response of zebrafish to BUVSs suggests structure‐dependent effects in the brain among these chemicals. In our previous study, BUVSs showed differential effects on transcripts of the thyroid system, and the mRNA expression patterns were proposed to be related to the type or structure of the BUVSs . Additionally, Zhuang et al reported that the antiandrogenic activity of UV‐328 and UV‐P was significantly increased and decreased respectively after their metabolism by CYP3A4, while the activity of other BUVSs showed no change.…”

“…Zhuang et al reported that the anti‐androgenic activity of metabolized UV‐328 is enhanced compared with its parent compound upon CYP3A4‐mediated biotransformation. In our previous study, transcript profiles associated with the thyroid receptor pathway of zebrafish embryos exposed to 4 BUVSs (UV‐234, UV‐326, UV‐329 and UV‐P) were affected in a structure‐dependent way . These studies indicate that BUVSs with different structures may also have different mechanisms of toxicity, especially in vivo.…”

“…3147‐75‐9, purity >98%) were purchased from J&K Chemical Ltd. (USA). All structures and physiochemical properties are provided in our previous study . Stock solution of BUVSs were prepared by dilution in HPLC‐grade acetone and then mixed with distilled‐deionized water.…”