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怀孕和哺乳期的亲代小鼠接触黄曲霉毒素B会促进子代小鼠的肝毒性。

Exposure of pregnant and lactating parental mice to aflatoxin B promotes hepatotoxicity in offspring mice.

作者信息

Liu Bingxue, Xia Shijie, Xiao Wanzhe, Yu Xiaoqing, Zhang Jiexing, Wei Xiangjian, Long Wenyuan, Shen Binglei, Lv Hongming

机构信息

Key Laboratory of Bovine Disease Control in Northeast China, Ministry of Agriculture and Rural Affairs, Heilongjiang Provincial Key Laboratory of Prevention and Control of Bovine Diseases, College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing, 163319, China.

Ultrasound Department of the physical examination center, Baicheng Central Hospital, Baicheng, China.

出版信息

Arch Toxicol. 2025 Apr;99(4):1517-1529. doi: 10.1007/s00204-024-03955-4. Epub 2025 Feb 2.

DOI:10.1007/s00204-024-03955-4
PMID:39893609
Abstract

Aflatoxin B1 (AFB) taints feeds stuffs, endangering livestock's health and resulting in the liver and breast damage. At the same time, while breastfeeding, AFB crosses the mammary glands and enters the milk, harming the offspring. This study investigated the liver damaging effects of maternal AFB exposure during pregnancy and lactation in offspring mice. The livers of 8-day-old offspring mice were obtained from female mice who were administered AFB (2 mg/kg) 1 week prior to and 1 week following birth. The results showed that AFB increased the levels of malondialdehyde (MDA), alanine aminotransferase (ALT), aspartate aminotransferase (AST), pro-inflammatory-related proteins (iNOS, COX-2, IL-6), and apoptosis-related proteins (Caspase-3, Caspase-9, Bax) by AFB-induced in liver of offspring mice. Furthermore, the use of F40/80, HE, and TUNEL staining further demonstrated the existence of inflammation and apoptosis in the liver. Intriguingly, in the liver of offspring mice, AFB increased antioxidant protein and inhibit ferroptosis-related protein activity (FTH, GPX4), mitochondrial function-associated proteins (UQCRC2, COX IV, Cyt C), lipid metabolism-associated proteins (HMGCR, SPEBE1, FAS), and autophagy-related proteins (Atg7, Beclin-1, LC3I/II) in the liver of mice. In conclusion, AFB enters the liver of offspring mice through milk, which in turn causes liver injury. This outcome explains how AFB exposure affects female animals and their progeny and lays the strategy for livestock prevention.

摘要

黄曲霉毒素B1(AFB)污染饲料,危害家畜健康,导致肝脏和乳腺损伤。同时,在母乳喂养期间,AFB会穿过乳腺进入乳汁,危害后代。本研究调查了孕期和哺乳期母体接触AFB对后代小鼠肝脏的损伤作用。8日龄后代小鼠的肝脏取自于在出生前1周和出生后1周给予AFB(2毫克/千克)的雌性小鼠。结果表明,AFB可使后代小鼠肝脏中丙二醛(MDA)、丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、促炎相关蛋白(诱导型一氧化氮合酶、环氧化酶-2、白细胞介素-6)以及凋亡相关蛋白(半胱天冬酶-3、半胱天冬酶-9、Bax)的水平升高,这是由AFB诱导所致。此外,使用F40/80、苏木精-伊红(HE)和TUNEL染色进一步证实了肝脏中存在炎症和凋亡。有趣的是,在后代小鼠肝脏中,AFB可增加抗氧化蛋白含量,并抑制铁死亡相关蛋白活性(铁蛋白重链、谷胱甘肽过氧化物酶4)、线粒体功能相关蛋白(泛醌细胞色素c还原酶核心蛋白2、细胞色素c氧化酶亚基IV、细胞色素c)、脂质代谢相关蛋白(3-羟基-3-甲基戊二酰辅酶A还原酶、硬脂酰辅酶A去饱和酶1、脂肪酸合酶)以及自噬相关蛋白(自噬相关蛋白7、Beclin-1、微管相关蛋白1轻链3I/II)。总之,AFB通过乳汁进入后代小鼠肝脏,进而导致肝脏损伤。这一结果解释了AFB暴露如何影响雌性动物及其后代,并为家畜预防提供了策略。

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