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.

中文翻译：

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3,4-二氯苯胺促进斑马鱼幼虫的脂肪肝

背景资料

3,4-二氯苯胺（3,4-DCA）是除草剂的转化产物，通常在发育毒性研究中用作参考（OECD TG 236）（Bonnet等人，Environ Toxicol 22：78-91，2007） 。但是，3，4-DCA诱导的肝毒性的潜在机制尚不清楚。

方法

我们将斑马鱼幼虫在72 hpf下暴露于3,4-DCA 3天，并用油红O染色观察到用10μM3,4-DCA处理的肝脏中脂质的积累。随后，我们进行了qRT-PCR分析，以确定参与观察到的脂质堆积的基因。

结果

我们发现与脂肪生成相关的基因（srebp1，pparγ，lipin1和scd1）和内质网应激（bip，atf4，ddit3，dnajc3和edem1）均显着上调。此外，我们发现用10μM3,4-DCA处理的幼虫中ROS的产生增加。此外，这些幼虫中的谷胱甘肽-S-转移酶活性被3，4-DCA以剂量依赖性方式增加，并且炎症标志物il - 1β的表达增加。

结论

我们的结果表明，暴露于3,4-DCA诱导的斑马鱼幼虫中的脂肪肝，这与诸如ER应激反应等其他因素相关，可促进肝损伤。因此，我们建议3,4-DCA可用于诱导斑马鱼幼虫中的脂肪肝。