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邻苯二甲酸二(2-乙基)己酯(DEHP)通过激活 LXR/SREBP-1c/PPARα/γ 和 NF-κB 信号通路诱导肝脏脂质代谢紊乱。

Di-2-ethylhexyl phthalate (DEHP) induced lipid metabolism disorder in liver via activating the LXR/SREBP-1c/PPARα/γ and NF-κB signaling pathway.

机构信息

College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, PR China.

College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, PR China; Department of Physiology and Pharmacology, Faculty of Animal Science and Veterinary Medicine, Patuakhali Science and Technology University, Barishal, 8210, Bangladesh.

出版信息

Food Chem Toxicol. 2022 Jul;165:113119. doi: 10.1016/j.fct.2022.113119. Epub 2022 May 7.

DOI:10.1016/j.fct.2022.113119
PMID:35537648
Abstract

Di-2-ethylhexyl phthalate (DEHP) has been widely used in many fields (agricultural products, medical instruments, and food packing). As an environmental contaminant, DEHP has a negative impact on human and animal health, and thus toxicity caused by DEHP is increasingly serious health concern. Nevertheless, DEHP-induced liver damage in quail remains unclear. To investigate the mechanism of liver damage caused by DEHP, male quail were treated with DEHP (250, 500, and 750 mg/kg) by gavage. Notably, DEHP exposure results in increased blood lipids and the accumulation of triglycerides (TG), total cholesterol (TC), and non-esterified fatty acid (NEFA) in the liver. Histopathological analysis showed that steatosis and inflammatory cell infiltration were observed in the liver tissue of quails exposed to DEHP. The results of Oil Red O staining displayed that DEHP induced lipid storage in the liver. Moreover, DEHP induced lipid metabolism disorders by activating the LXR/SREBP-1c and PPARα/γ signaling pathway. DEHP exposure obviously caused the up-regulation of pro-inflammatory cytokines (NF-κB, IL-6, IL-8, IL-1β, and TNF-a). This study showed that DEHP could induce lipid metabolism disorders and inflammatory response via LXR/SREBP-1c/PPARα/γ and NF-κB signaling pathways.

摘要

邻苯二甲酸二(2-乙基)己酯(DEHP)已广泛应用于许多领域(农产品、医疗器械和食品包装)。作为一种环境污染物,DEHP 对人类和动物的健康有负面影响,因此 DEHP 的毒性越来越受到关注。然而,DEHP 对鹌鹑肝脏的损伤作用尚不清楚。为了研究 DEHP 引起的肝脏损伤的机制,雄性鹌鹑通过灌胃给予 DEHP(250、500 和 750mg/kg)。值得注意的是,DEHP 暴露会导致血液中脂质增加,以及肝脏中甘油三酯(TG)、总胆固醇(TC)和非酯化脂肪酸(NEFA)的积累。组织病理学分析显示,暴露于 DEHP 的鹌鹑肝脏组织中出现脂肪变性和炎症细胞浸润。油红 O 染色的结果表明 DEHP 诱导了肝脏中的脂质储存。此外,DEHP 通过激活 LXR/SREBP-1c 和 PPARα/γ 信号通路诱导脂质代谢紊乱。DEHP 暴露明显导致促炎细胞因子(NF-κB、IL-6、IL-8、IL-1β 和 TNF-a)的上调。本研究表明,DEHP 可通过 LXR/SREBP-1c/PPARα/γ 和 NF-κB 信号通路诱导脂质代谢紊乱和炎症反应。

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