Toxic Effects And Mechanisms Of BUVSs In Zebrafish Brain

Benzotriazole ultraviolet stabilizers(BUVSs)are a class of widely-used chemicals in industrial and personal care products for their absorptive capacity in the full spectrum of UV-light.Due to their high production volume,BUVSs have been widely detected in aquatic ecosystems in recent years.BUVSs have raised wide concerns for their persistence and bioaccumulation.However,the toxicologic studies of BUVSs in aquatic organisms are not well documented.The toxic effects as well as the mechanisms of BUVSs in teleost brain are still unclear.In this study,juvenile zebrafish were exposed to either 4 common BUVSs(UV-234,UV-326,UV-329,or UV-P)in 10 or 100 ?g/L for 28 days.RNA Sequencing(RNA-Seq),toxic pathways analysis and quantitative real-time PCR were used to analyze and compare the possible toxic effects of BUVSs in zebrafish.The major findings were summarized as follows:Eighty-one pathways were observed to be affacted by all 4 BUVSs,accounting for only 9.9 % of all pathways detected.Among these pathways,several immune-related cell processes were affected,including T-cell recruitment,B-cell activation,leucocyte differentiation,immunostimulation,immunomodulation and complement activation,and alternative pathway.Additionally,following UV-234,UV-326,UV-329 or UV-P exposure,there were 97,106,68,116 specific pathways affected,respectively.In 100 ?g/L UV-234 groups,mitochondrial dysfunction might be induced in zebrafish.UV-326 inhibited the role of HMGB1 and IL1 B in neuronal hyperexcitation in epilepsy.For UV-329 treatment,the dopamine uptake and initated neurotoxicity were influenced.In UV-P groups,the adrenergic signaling pathways were disturbed and oxidative stress might be induced.Transcriptional levels of several relevant genes were verified.The expression level of mgst1.1 was significantly increased in 100 ?g/L UV-329 exposure,while pck2 was significantly decreased in 10 and 100 ?g/L UV-P exposure.Taken together,these results indicated that BUVSs might disturb the innate immune system of zebrafish and induce neuro-immune toxicity.Moreover,the toxicity and mechanisms of BUVSs may be structure-dependent.