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胆汁酸促进肉鸡肝脏黄曲霉毒素B1的生物转化和排泄

Bile acids promote hepatic biotransformation and excretion of Aflatoxin B1 in broiler chickens

作者：Liang Chen,Tian Wen,Aizhi Cao,Jianmin Wang,Hua Pan and Ruqian Zhao.

发布期刊：Toxins (Basel). 2023 Dec 9;15(12):694.

黄曲霉毒素B1 (AFB1 )是一种有害的真菌毒素，经常污染动物饲料，动物摄入后会导致严重的肝损伤。肝脏是AFB1主要的解毒器官，其解毒的过程主要通过酶催化的外源物质代谢和胆汁酸相关的外泄来实现。在该研究中，尝试探讨在肉鸡养殖中添加外源胆汁酸，能否提高其肝脏对AFB1解毒能力，进而缓解AFB1导致的肝损伤。将5日龄肉仔鸡随机分为3组。对照组和AFB1组饲喂基础日粮；AFB1 +胆汁酸组饲喂含250 mg / kg胆汁酸的基础日粮，试验期20天。预饲3天后，AFB1组和AFB1 +胆汁酸组按照体重，每天灌喂250 μg/kg的AFB1，对照组组灌胃不含AFB1的缓冲液。结果显示，日粮添加胆汁酸对AFB1诱导的肝脏炎症和氧化应激具有保护作用。肝脏将AFB1转化为其主要代谢物AFBO的效率提高，并加速排泄至胆囊和盲肠中。相应地，通过添加胆汁酸避免了因AFB1导致的肝脏解毒基因表达的下调，这些解毒基因包括细胞色素P450酶，谷胱甘肽S -转移酶和胆盐输出泵。此外，LXR α的活性在AFB1组中受到抑制，而在AFB1 +胆汁酸组中，其活性有所增强。上述结果表明，日粮中添加胆汁酸可通过调控LXR α在内的酶促反应来实现肝脏对AFB1的解毒和排泄能力的提高。

Aflatoxin B1 (AFB1) is a hazardous mycotoxin that often contaminates animal feed and may potentially induce severe liver damage if ingested. The liver is the primary organ responsible for AFB1 detoxification through enzyme-catalyzed xenobiotic metabolism and bile acid (BA)-associated excretion. In this study, we sought to investigate whether exogenous BA improves hepatic AFB1 detoxification to alleviate AFB1-induced liver injury in broiler chickens. Five-day-old broiler chicks were randomly assigned to three groups. CON and AFB1 received a basal diet; AFB1 + BA received a basal diet with 250 mg/kg BA for 20 days. After a 3-day pre-feed, AFB1 and AFB1 + BA were daily gavaged with 250 μg/kg BW AFB1, while CON received gavage solvent for AFB1 treatment. Dietary BA supplementation protected chickens from AFB1-induced hepatic inflammation and oxidative stress. The hepatic biotransformation of AFB1 to its metabolite AFBO was improved, with accelerated excretion to the gallbladder and cecum. Accordantly, AFB1-induced down-regulation of detoxification genes, including cytochrome P450 enzymes, glutathione S-transferases, and the bile salt export pump, was rescued by BA supplementation. Moreover, liver X receptor α, suppressed by AFB1, was enhanced in BA-treated broiler chickens. These results indicate that dietary BA supplementation improves hepatic AFB1 detoxification and excretion through LXRα-involved regulation of xenobiotic enzymes.

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