4-Methylesculetin alleviated aflatoxin B1-induced liver injury and ferritinophagy through AMPK- TOR-Ulk axis in grass carp (Ctenopharyngodon idella)

作者：Xiangning He, Jiajia Zhang, Wei‐Dan Jiang, Pei Wu, Liu Yang, Hongmei Ren, Xiao‐Wan Jin, He-Qun Shi, Lin Feng, Xiaoqiu Zhou · 发表于：Animal nutrition · 年份：2025 · DOI：10.1016/j.aninu.2025.03.018 · 被引用次数：3 · 研究领域：Autophagy in Disease and Therapy、Aquaculture disease management and microbiota、Quinazolinone synthesis and applications

The mycotoxin aflatoxin B1 (AFB1), frequently identified in animal feed and raw materials, induces oxidative stress as a primary toxicological consequence. The coumarin compound 4-methylesculetin (4-ME) possesses notable antioxidant properties, leading to its application in medical contexts. Given that the liver is the principal organ targeted by AFB1, this study investigated the potential mechanism through which 4-ME mitigated hepatic injury induced by AFB1 in grass carp. The grass carp (initial body weight of 11.40 ± 0.01 g) were randomly divided into 4 treatment groups (3 replicates/treatment and 60 fish/replicate), which were control group (Control), 60 μg/kg AFB1 group (AFB1), 10 mg/kg 4-ME group (4-ME) and 60 μg/kg AFB1 + 10 mg/kg 4-ME group (AFB1 + 4-ME). The present study found that AFB1 caused liver injury, dietary 4-ME supplementation enhanced the antioxidant capacity through the Nrf2 pathway, decreased the levels of AFB1-NDA adducts ( P < 0.001) and total bile acid (TBA) ( P < 0.001) in liver, and decreased the protein expression of CYP3A4 in liver ( P < 0.001), inhibited the transcriptional levels of endoplasmic reticulum stress (ERS)-related genes (including XBP1 , IRE1 , ATF6 , Chop , EIF2α , PERK and GRP78 ) ( P < 0.05), autophagy-related genes (including beclin 1, LC3 and ATG12 ) ( P < 0.05) and apoptosis-related genes (including Bax , caspase-8 and caspase-3) ( P < 0.05). Dietary 4-ME supplementation also decreased the contents of iron ( P = 0.004), and incre...