The Study On The Developmental Toxicity Mechnism Of Zebrafish Induced By 2,6-Dichlorobenzoquinone

Halobenzoquinones?HBQs?,the emerging disinfection by-products?DBPs?,are a kind of highly toxic nitrogen-contained DBPs and have received great concerns due to their extremely high health risk.Among them,2,6-dichloro-1,4-benzoquinone has attracted attention due to its high detective probability and content.In recent years,a lot of studies manifested that 2,6-DCBQ induced toxicity in different species and also proposed that reactive oxygen species?ROS?played a crucial role in 2,6-DCBQ-induced toxicity.However,limited information is avilable on 2,6-DCBQ-mediated toxicity.In this study,zebrafish were selected as the study object,utilizing zebrafish embryo toxicity test as the method to investigate the possible developmental toxicity mechanisms of 2,6-DCBQ from individual,cell and molecule levels.The aim of this study was to evaluate the potential human health effects of 2,6-DCBQ and provide laboratory basis to DBPs research.The result are as following:?1?2,6-DCBQ induced embryonic developmental toxicity in zebrafish.It belongs to extremely dangerous exogenous chemicals.2,6-DCBQ decreased zebrafish's survival rate and increased its aberration rate at high concentration group(?90?g L^-1).At these concentrations,rupture of pericardium,pericardium edema and tail curvature were observed exposure to2,6-DCBQ.The heart rate of exposed group were reduced when the exposure concentration increased.And exposure to 2,6-DCBQ showed no effect on body length of zebrafish larvae.?2?2,6-DCBQ induced oxidative stress,the immune toxicity and interference of biomacromolecular metabolism in zebrafish embryo.2,6-DCBQ induced significantly increase of the activity of SOD and disturbances of oxidative stress related genes expression.Exposed to high concentration group led to lipid peroxidation.The above phenomena indicated that 2,6-DCBQ induced excessive ROS to cause oxidative damage.Meanwhile,it inhibited the mRNA expression of innate immune-related gene il1b,and led to the compensatory up-regulation of lyz,resulting in the generation of immunotoxicity.In addition,2,6-DCBQ led to maladjustment of fatty acid metabolism in zebrafish by disrupting the expression of?-oxidization-related genes.?3?2,6-DCBQ could induce DNA damage in zebrafish embryo.In 2,6-DCBQ treatment groups,the content of 8-OHdG increased markedly.At the same time,the expression of the key genes of cell cycle regulation and DNA repair was disturbed.Above all,2,6-DCBQ induced the occurrence of DNA damage,the situation of cell cycle arrest and the problem of DNA repair.?4?2,6-DCBQ induced apoptosis in zebrafish embryo.At treatment groups,the enzyme activity of caspase-3 was activated,and the transcription level of the key apoptosis pathway genes,p53,bcl-2,bax and caspase-3,was also increased.The results showed that mitochondrial signaling pathway played an important role in embryo apoptosis induced by2,6-DCBQ.However,the exact mechanism still need to be further researched.In this study,zebrafish embryo toxicity test and molecular biological technique used as the method,developmental toxicity,oxidative damage,genotoxicity and cytotoxic effects and their related toxicity mechanism of 2,6-DCBQ to zebrafish embryo were evaluated from individual,cell and molecule levels,and provided a theoretical basis for the further estimation on toxicity mechanism.