Qiu Ting, Shi Jia-Xue, Cheng Chao, Jiang Hong, Ruan Hai-Nan, Li Jun, Liu Chan-Min
School of Life Science, Jiangsu Normal University, No.101, Shanghai Road, Tongshan New Area, Xuzhou City, Jiangsu Province 21-1116, PR China.
Toxicol Res (Camb). 2023 Apr 21;12(3):417-424. doi: 10.1093/toxres/tfad028. eCollection 2023 Jun.
Lead (Pb), an environmental hazard, causes severe diseases in the liver, kidney, cardiovascular system, hematopoietic system, reproductive system, and nervous system. Avicularin (AVI), the main dietary flavonoid found in many citrus fruits, exhibited potential protective properties on organs. However, the molecular mechanisms of these protective actions are currently not clear. In our study, the effects of AVI on Pb-induced hepatotoxicity were evaluated using ICR mice. Changes in oxidative stress, inflammation, lipid metabolism, and related signaling were evaluated. We found for the first time that treatment with AVI significantly reduced hepatic steatosis, inflammation, and oxidative stress induced by Pb. AVI attenuated Pb-induced liver dysfunction and lipid metabolism disorder in mice. AVI decreased the serum biochemical indicators of lipid metabolism. AVI decreased the expression levels of lipid metabolism-related protein SREBP-1c, acetyl-CoA carboxylase (ACC), and FAS. AVI suppressed Pb-induced inflammation in livers, as indicated by decreasing the TNF-α and IL-1β levels. AVI suppressed oxidative stress by increasing the activation of SOD, CAT, and GPx. Furthermore, AVI inhibited the activities of JNK, ERK, p38, and NF-κB. AVI further decreased the levels of HSP60, NLRP3, p-IκBα, and p-p65 in the livers of mice. Collectively, this study indicated that AVI mitigated Pb-induced hepatic steatosis, oxidative stress, and inflammation by regulating the SREBP-1c and MAPK/HSP60/NLRP3 signaling pathways.
铅（Pb）是一种环境危害物，会在肝脏、肾脏、心血管系统、造血系统、生殖系统和神经系统引发严重疾病。杨梅素（AVI）是许多柑橘类水果中含有的主要膳食类黄酮，对器官具有潜在的保护作用。然而，这些保护作用的分子机制目前尚不清楚。在我们的研究中，使用ICR小鼠评估了AVI对铅诱导的肝毒性的影响。评估了氧化应激、炎症、脂质代谢及相关信号通路的变化。我们首次发现，AVI治疗可显著减轻铅诱导的肝脂肪变性、炎症和氧化应激。AVI减轻了小鼠铅诱导的肝功能障碍和脂质代谢紊乱。AVI降低了脂质代谢的血清生化指标。AVI降低了脂质代谢相关蛋白SREBP-1c、乙酰辅酶A羧化酶（ACC）和脂肪酸合酶（FAS）的表达水平。AVI抑制了肝脏中铅诱导的炎症，表现为TNF-α和IL-1β水平降低。AVI通过增加超氧化物歧化酶（SOD）、过氧化氢酶（CAT）和谷胱甘肽过氧化物酶（GPx）的活性来抑制氧化应激。此外，AVI抑制了JNK、ERK、p38和NF-κB的活性。AVI进一步降低了小鼠肝脏中HSP60、NLRP3、p-IκBα和p-p65的水平。总体而言，本研究表明，AVI通过调节SREBP-1c和MAPK/HSP60/NLRP3信号通路减轻了铅诱导的肝脂肪变性、氧化应激和炎症。
