3,4-Dichloroaniline promotes fatty liver in zebrafish larvae

Backgrounds 3,4-Dichloroaniline (3,4-DCA) is a transformation product of herbicides that is commonly used as a reference in developmental toxicity studies (OECD TG 236) (Bonnet et al. in Environ Toxicol 22:78–91, 2007 ). However, the mechanisms underlying 3,4-DCA-induced hepatotoxicity are not well known. Methods We exposed zebrafish larvae at 72 hpf to 3,4-DCA for 3 days and observed lipid accumulation in liver treated with 10-μM 3,4-DCA using oil red O staining. Subsequently, we performed qRT-PCR analysis to determine the genes involved in the observed lipid accumulation. Results We found that genes related to lipogenesis ( srebp1 , pparγ , lipin1 , and scd1 ) and ER stress ( bip , atf4 , ddit3 , dnajc3 , and edem1 ) were significantly upregulated. In addition, we found that ROS generation increased in the larvae treated with 10-μM 3,4-DCA. Moreover, glutathione- S -transferase activity in these larvae was increased by 3,4-DCA in a dose-dependent manner, and the expression of the inflammation marker il - 1β increased. Conclusion Our results indicated that exposure to 3,4-DCA induced fatty liver in zebrafish larvae and that this, in association with additional factors such as ER stress response, can promote liver damage. We accordingly suggest that 3,4-DCA could be used to induce fatty liver in zebrafish larvae.