Lactoferrin Relieves Deoxynivalenol-Induced Oxidative Stress and Inflammatory Response by Modulating the Nrf2/MAPK Pathways in the Liver
Lactoferrin Relieves Deoxynivalenol-Induced Oxidative Stress and Inflammatory Response by Modulating the Nrf2/MAPK Pathways in the Liver
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DOI：
10.1021/acs.jafc.3c01035
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发表时间：
2023-05-19
影响因子：
6.1
通讯作者：
Cai，Demin
中科院分区：
文献类型：
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作者：
Hu，Ping;Liu，Yaya;Cai，Demin
脱氧雪腐镰刀菌烯醇（DON）是最常见的污染食品和饲料的真菌毒素之一，已被证明具有肝毒性。人乳中富含的乳铁蛋白（LF）是一种重要的功能性食品成分，具有保肝作用。在此，我们的目的是探索膳食补充LF是否可以保护小鼠和α小鼠肝12（AML 12）肝细胞免受DON诱导的肝毒性，并揭示其潜在机制。通过修复肝脏组织形态学，降低血浆丙氨酸氨基转移酶（ALT）水平和血液白色细胞（WBC）和中性粒细胞（Neu）。LF还能降低肝脏活性氧（ROS）和丙二醛（MDA）的积累，增强肝脏GSH-px活性和Nrf 2、GPX 4蛋白表达，从而逆转DON诱导的肝脏氧化应激。此外，LF还能下调DN暴露小鼠肝脏中促炎反应相关基因（IL 1 β、TNFα和Tlr 4）的表达以及IKK、IκBα和p38的磷酸化水平。此外，体外研究证实，LF改善了DON诱导的氧化还原失衡、炎症反应以及DON诱导的肝毒性中Nrf 2和MAPK通路的相关核心调节剂。总之，LF通过调节Nrf 2/MAPK信号通路来执行肝脏抗氧化和抗炎功能，从而减少DON诱导的肝毒性。
Deoxynivalenol (DON), one of the most common mycotoxins contaminating food and feed, has been shown to induce hepatotoxicity. Lactoferrin (LF) enriched in human milk is a critical functional food component and performs the hepatoprotection function. Here, we aimed to explore whether dietary LF supplementation can protect from DON-induced hepatotoxicity and uncover the underlying mechanism in mice and alpha mouse liver 12 (AML12) hepatocytes.In vivoresults revealed that LF alleviated DON-induced liver injury, reflected by repairing the hepatic histomorphology and decreasing the plasma alanine aminotransferase (ALT) level and the number of blood white blood cells (WBC) and neutrophils (Neu). Moreover, LF decreased the hepatic reactive oxygen species (ROS) and malondialdehyde (MDA) accumulation and enhanced the hepatic GSH-px activity and protein expression of Nrf2 and GPX4 to reverse the DON-induced hepatic oxidative stress. Furthermore, LF downregulated the pro-inflammatory-response-related gene expressions (IL1β,TNFα, andTlr4) and the phosphorylation levels of IKK, IκBα, and p38 in the liver of DON-exposed mice. Additionally,in vitrostudies confirmed that LF ameliorated the DON-induced oxidation–reduction imbalance, inflammatory responses, and associated core modulators of the Nrf2 and MAPK pathways in DON-induced hepatotoxicity. In conclusion, LF performs hepatic antioxidative and anti-inflammatory functions by regulating the Nrf2/MAPK signaling pathways, thus reducing DON-induced hepatotoxicity.