Cypermethrin Has The Potential To Induce Apoptosis And Immunotoxicity In Zebrafish(Danio Rerio)

Cypermethrin (CYP) is the most widely used Type II pyrethroid pesticide. It is used to control many pests, including moths, pests of cotton and soybean. As a result of its popularity, CYP enters the aquatic ecosystem mainly through runoff. To better understand the aquatic effects induced by CYP, we determined the gene expression related to oxidation system, apoptosis and immune system in zebrafish. Furthermore, the gene expression profiles in zebrafish during the embryo stage induced by CYP were also analyzed by gene microarray.First of all, we found that CYP has the potential to induce hepatic oxidative stress, DNA damage and apoptosis in zebrafish. Hepatic mRNA levels for the genes encoding antioxidant proteins, such as Cu/Zn-Sod, Mn-Sod, Cat, and Gpx, were significantly up-regulated when zebrafish were exposed to various concentrations of CYP for4or8days. In addition, the main genes related to fatty acid β-oxidation, the mitochondrial genesrelated to respiration and ATP synthesis were also significantly up-regulated after exposure to high concentrations (1and3μg/L) of CYP for4or8days. Moreover, in a comet assay of zebrafish hepatocytes, tail DNA, tail length, tail moment and Olive tail moment increased in a concentration-dependent manner. Furthermore, several apoptosis-related genes, such as p53, Apqf1and Cas3, were significantly upregulated after CYP exposure especially in groups treated with1and3μig/L CYP for8days.Secondly, the mRNA levels of some key genes including p53, puma, bax, Apaf1, cas9and cas3on the mitochondrial pathway of cell apoptosis were significantly up-regulated at the concentration of3and10μg/L CYP. Correspondingly, the activities of CAS3and CAS9increased significantly. In addition, the mRNA levels of iNOS and the total content of NO were also up-regulated significantly after CYP exposure. Moreover, it was also observed that the mRNA levels of IFN, CXCL-cl, CC-chem and C3, which are closely related to the innate immune system, were affected in newly hatched zebrafish when exposed to3and10μg/L CYP.Finally, zebrafish GeneChip (Affymetrix) was used to further identify the alterations in gene expression of zebrafish after CYP exposure. Totally28genes were differentially expressed, in which26genes were elevated and2were decreased. According to GOstat analysis, mainly influenced the mitogen-activated protein kinases (MAPK) signaling pathways and butanoate metabolism.In summary, CYP has the potential to cause hepatic oxidative stress, apoptosis and innate immune system disruption in zebrafish. The information presented in this study will be helpful in fully understanding the mechanism of CYP-induced toxicity in fish.