Li Guangxing, Wu Menglin, Chen Kaiting, Xu Yue, Zhang Xiandan, Chen Yang, Zhang Hong, Zhang Ruili, Huang Xiaodan
College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, PR China.
Liaoning Petmate Biotechnology Co, PR China.
Poult Sci. 2025 Jan;104(1):104558. doi: 10.1016/j.psj.2024.104558. Epub 2024 Nov 22.
The widespread use of plasticizers poses a serious threat to the environment and poultry health. Di-(2-ethylhexyl) phthalate (DEHP) is a commonly used plasticizer that can cause liver damage with prolonged exposure. Oxidative stress is closely associated with DEHP toxicity. Macrophage polarization plays an important role in many physiological and pathological processes and regulates disease development. This study aims to elucidate the mechanism of chronic DEHP exposure leading to chicken liver injury through oxidative stress-induced M1 polarization-necroptosis. In this study, the DEHP exposure model of chicken liver and the single and co-culture model of LMH and HD11 cells were established. With increasing dose and time, DEHP decreased body weight, increased liver coefficient, raised activities of liver function indicators and caused pathological liver damage in chickens. Further studies revealed the increase of reactive oxygen species (ROS) level and malonaldehyde (MDA) content, and the decrease of total antioxidant capacity (T-AOC) level, total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-Px) activities, which led to excessive oxidative stress in the liver. In addition, there was increased infiltration of liver macrophages (CD68), upregulation of M1 polarization indicators (CD86, iNOS, IL-1β, TNF-α) and downregulation of M2 polarization indicators (CD163, Arg-1, IL-10, TGF-β) and appearance of necroptosis (RIPK1, RIPK3, MLKL). The vitro experiments confirmed the addition of N-acetylcysteine (NAC) inhibited M1 polarization and necroptosis. Besides, M1 polarization of HD11 cells promoted necroptosis of LMH cells in the HD11-LMH co-culture system. In brief, ROS-mediated M1 polarization-necroptosis is involved in DEHP-induced liver injury. This study provides a reference for environmental toxicant exposure in livestock and poultry farming.
增塑剂的广泛使用对环境和家禽健康构成严重威胁。邻苯二甲酸二（2-乙基己基）酯（DEHP）是一种常用的增塑剂，长期接触会导致肝脏损伤。氧化应激与DEHP毒性密切相关。巨噬细胞极化在许多生理和病理过程中起重要作用，并调节疾病发展。本研究旨在阐明慢性DEHP暴露通过氧化应激诱导的M1极化-坏死性凋亡导致鸡肝脏损伤的机制。在本研究中，建立了鸡肝脏DEHP暴露模型以及LMH和HD11细胞的单培养和共培养模型。随着剂量和时间的增加，DEHP降低了鸡的体重，增加了肝脏系数，提高了肝功能指标活性，并导致鸡肝脏病理损伤。进一步研究发现活性氧（ROS）水平和丙二醛（MDA）含量增加，总抗氧化能力（T-AOC）水平、总超氧化物歧化酶（T-SOD）和谷胱甘肽过氧化物酶（GSH-Px）活性降低，导致肝脏氧化应激过度。此外，肝脏巨噬细胞（CD68）浸润增加，M1极化指标（CD86、iNOS、IL-1β、TNF-α）上调，M2极化指标（CD163、Arg-1、IL-10、TGF-β）下调，坏死性凋亡（RIPK1、RIPK3、MLKL）出现。体外实验证实添加N-乙酰半胱氨酸（NAC）可抑制M1极化和坏死性凋亡。此外，HD11-LMH共培养系统中HD11细胞的M1极化促进了LMH细胞的坏死性凋亡。简而言之，ROS介导的M1极化-坏死性凋亡参与了DEHP诱导的肝脏损伤。本研究为畜禽养殖中环境毒物暴露提供了参考。
