3,4-Dichloroaniline promotes fatty liver in zebrafish larvae
MOLECULAR & CELLULAR TOXICOLOGY
Authors: Park, Ji-Seon; Song, Jeongah; Park, Jong-Su; Lee, Sangwoo; Lee, Jieon; Park, Han-Jin; Kim, Woo-Keun; Yoon, Seokjoo; Chun, Hang-Suk
Abstract
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-mu M 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, ppar gamma, 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-mu M 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-1 beta 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.
Hesperidin Protects against Acute Alcoholic Injury through Improving Lipid Metabolism and Cell Damage in Zebrafish Larvae
EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE
Authors: Zhou, Zhenting; Zhong, Weichao; Lin, Haiyan; Huang, Peng; Ma, Ning; Zhang, Yuqing; Zhou, Chuying; Lai, Yuling; Huang, Shaohui; Huang, Shiying; Gao, Lei; Lv, Zhiping
Abstract
Alcoholic liver disease (ALD) is a series of abnormalities of liver function, including alcoholic steatosis, steatohepatitis, and cirrhosis. Hesperidin, the major constituent of flavanone in grapefruit, is proved to play a role in antioxidation, anti-inflammation, and reducing multiple organs damage in various animal experiments. However, the underlying mechanism of resistance to alcoholic liver injury is still unclear. Thus, we aimed to investigate the protective effects of hesperidin against ALD and its molecular mechanism in this study. We established an ALD zebrafish larvae model induced by 350 mM ethanol for 32 hours, using wildtype and transgenic line with liver-specific eGFP expression Tg (lfabp10 alpha:eGFP) zebrafish larvae (4 dpf). The results revealed that hesperidin dramatically reduced the hepatic morphological damage and the expressions of alcohol and lipid metabolism related genes, including cyp2y3, cyp3a65, hmgcra, hmgcrb, fasn, and fads2 compared with ALD model. Moreover, the findings demonstrated that hesperidin alleviated hepatic damage as well, which is reflected by the expressions of endoplasmic reticulum stress and DNA damage related genes (chop, gadd45 alpha a, and edem1). In conclusion, this study revealed that hesperidin can inhibit alcoholic damage to liver of zebrafish larvae by reducing endoplasmic reticulum stress and DNA damage, regulating alcohol and lipid metabolism.
COA
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