Immunotoxic Effect Of Buvss On Danio Rerio

Benzotriazole ultraviolet stabilizers(BUVSs)are widely used in industrial materials(e.g.plastics)and personal care products that protect them from harmful ultraviolet.Due to their high production volume,ubiquitous use,potential to bioaccumulate and persistent in aquatic environment,BUVSs have become emerging pollutants.It is reported that BUVSs can cause chronic toxicity and activate aryl hydrocarbon receptor(AHR)pathway in fish.However,toxicological effects as well as underlying mechanism of BUVSs congeners are still unclear.In this study,juvenile zebrafish(Danio rerio)were exposed to 10 and 100 ?g /L 4 BUVSs(UV-234,UV-326,UV-329,and UV-P)for 28 days.Hepatic pathological examination and transcriptomic analysis revealed that pathways related to inflammations that were affected by BUVSs.Based upon these data,we measured the expression levels of genes and protein content involved in AHR-IL17/IL22 pathway in zebrafish embroys exposed to each BUVSs at one dose of either 10 or 100 ?g/L for 6 days.In addition,locomotor behavior in response to 1-100 ?g/L BUVSs were measured.The main conclusions are as follows:(1)After 28 d exposure,hepatic vacuolization and nuclei pyknosis of juvenile zebrafish(Danio rerio)were induced by 100 ?g/L UV-234 and 100 ?g/L UV-329.(2)According to transcriptome profile,pathways related to immune system activation and inflammatory response that were commonly affected by UV-234,UV-326,UV-329 and UV-P.Additionally,transcript levels of il17 a,il22,il6,il6 r,il1b and tgf1 b were significantly up-regulated.(3)Based upon transcriptomic data,the expression levels of 9 genes involved in AHR-IL17/IL22 pathway were measured in zebrafish larvae exposed to each BUVSs at one dose of either 10 or 100 ?g/L for 6 days.The results showed that levels of interleukins il17 a and il22 were decreased,while il6 mRNA was increased after exposure to BUVSs.Moreover,cyp1a1 and ahr2 levels were increased in larvae treated with 100?g/L UV-P.In addition,the protein abundance of IL22 was decreased by 29% with exposure to 100 ?g/L UV-P.(4)No change in the distance moved and activity of zebrafish larvae was observed following 1-100 ?g/L BUVSs treatments for 5 days.The results showed that the immune response of BUVSs at the molecular level did not induce the abnormal locomotor behavior of zebrafish larvae at the current concentrations.In conclusion,these results demonstrate that exposure to different benzotriazole congeners may casue immunotoxicity in zebrafish through disrupting the AHR-IL17/IL22 pathway,and induce hepatic damage with prolonged exposures.However,the immunotoxic effects of BUVSs in early-staged zebrafish need to be further studied in combination with other biological endpoints.