茶多酚通过调节鲤鱼体内的活性氧-磷脂酰肌醇-3激酶/蛋白激酶B-核因子κB信号通路减轻四溴双酚A诱导的肾损伤()

Tea Polyphenols Mitigate TBBPA-Induced Renal Injury Through Modulation of ROS-PI3K/AKT-NF-κB Signalling in Carp ().

作者信息

Han Fuxin, Xu Ran, Wang Hongru, Gao Xuejiao, Guo Mengyao

机构信息

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

出版信息

Animals (Basel). 2025 Aug 6;15(15):2307. doi: 10.3390/ani15152307.

Abstract

Tetrabromobisphenol A (TBBPA), a widely utilised brominated flame retardant, demonstrates toxicological effects in aquatic organisms. Tea polyphenols (TPs), natural compounds found in tea leaves, exhibit both antioxidant and anti-inflammatory activities. The kidney is one of the major metabolic organs in common carp and serves as a target organ for toxic substances. This study evaluated the therapeutic potential of TPs in mitigating TBBPA-induced nephrotoxicity in common carp. Common carp were exposed to 0.5 mg/L TBBPA in water and/or fed a diet supplemented with 1 g/kg TPs for 14 days. In vitro, primary renal cells were treated with 60 μM TBBPA and/or 2.5 μg/L TPs for 24 h. Methods included histopathology, TUNEL assay for apoptosis, ROS detection, and molecular analyses. Antioxidant enzymes (SOD, CAT) and inflammatory cytokines (IL-1β, IL-6, TNF-α) were quantified using ELISA kits. Results showed that TBBPA induced oxidative stress, and activated the ROS-PI3K/AKT-NF-κB pathway, thereby resulting in inflammatory responses. TBBPA upregulated apoptosis-related genes (, , and ) and induced apoptosis. TBBPA upregulated the expression of RIPK3/MLKL, thereby exacerbating necroptosis. TPs intervention significantly mitigated these effects by reducing ROS, suppressing NF-κB activation, and restoring antioxidant enzyme activities (SOD, CAT). Moreover, TPs attenuated apoptosis and necrosis in the carp kidney, thereby enhancing the survival ability and immunity of common carp.

摘要

四溴双酚A(TBBPA)是一种广泛使用的溴化阻燃剂,对水生生物具有毒理学效应。茶多酚(TPs)是茶叶中含有的天然化合物,具有抗氧化和抗炎活性。肾脏是鲤鱼的主要代谢器官之一,也是有毒物质的靶器官。本研究评估了TPs对减轻鲤鱼TBBPA诱导的肾毒性的治疗潜力。将鲤鱼暴露于水中0.5 mg/L的TBBPA和/或喂食添加1 g/kg TPs的饲料14天。在体外,将原代肾细胞用60 μM TBBPA和/或2.5 μg/L TPs处理24小时。方法包括组织病理学、凋亡的TUNEL检测、ROS检测和分子分析。使用ELISA试剂盒对抗氧化酶(SOD、CAT)和炎性细胞因子(IL-1β、IL-6、TNF-α)进行定量。结果表明,TBBPA诱导氧化应激,并激活ROS-PI3K/AKT-NF-κB通路,从而导致炎症反应。TBBPA上调凋亡相关基因(、和)并诱导凋亡。TBBPA上调RIPK3/MLKL的表达,从而加剧坏死性凋亡。TPs干预通过降低ROS、抑制NF-κB激活和恢复抗氧化酶活性(SOD、CAT)显著减轻了这些影响。此外,TPs减轻了鲤鱼肾脏的凋亡和坏死,从而提高了鲤鱼的生存能力和免疫力。

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