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四溴双酚A通过活性氧/核因子κB途径导致胃黏膜炎症和细胞死亡。

TBBPA causes inflammation and cell death via the ROS/NF-κB pathway in the gastric mucosa.

作者信息

Xu Shuang, Sun Xiaoran, Wu Jiawei, Li Kan, Li Xueying, Zhang Yanhe, Gao Xue-Jiao

机构信息

College of Veterinary Medicine, Northeastern Agricultural University, Harbin, Heilongjiang Province, People's Republic of China.

College of Veterinary Medicine, Northeastern Agricultural University, Harbin, Heilongjiang Province, People's Republic of China.

出版信息

Ecotoxicol Environ Saf. 2023 Jul 31;262:115320. doi: 10.1016/j.ecoenv.2023.115320.

Abstract

Tetrabromobisphenol A (TBBPA) is a common brominated flame retardant that has a wide range of toxic effects on organisms. However, the mechanism of the toxic effects of TBBPA on the digestive system has rarely been studied. The purpose of this study was to investigate the mechanism of TBBPA toxicity on the gastric mucosa. In this study, TBBPA (mixed with corn oil) was administered by gavage at doses of 0 mg/kg (CG), 10 mg/kg and 20 mg/kg. The results showed that the levels of ROS, MDA and LPO were increased, and the activities of antioxidant enzymes were decreased. Large amounts of ROS activated the NF-κB pathway, leading to the development of an inflammatory response. The expression of BCL family and Caspase (Cas) family genes was increased, inducing apoptosis. The RIP3/MLKL pathway was activated, leading to cell necrosis. In summary, TBBPA can cause damage to the gastric mucosa through oxidative stress, leading to increased ROS activation of the NF-κB pathway. Treatment with the antioxidant NAC alleviated the damage to the gastric mucosa caused by TBBPA.

摘要

四溴双酚A(TBBPA)是一种常见的溴化阻燃剂,对生物体具有广泛的毒性作用。然而,TBBPA对消化系统的毒性作用机制鲜有研究。本研究旨在探讨TBBPA对胃黏膜的毒性作用机制。在本研究中,TBBPA(与玉米油混合)以0 mg/kg(CG)、10 mg/kg和20 mg/kg的剂量经口灌胃给药。结果表明,活性氧(ROS)、丙二醛(MDA)和脂质过氧化物(LPO)水平升高,抗氧化酶活性降低。大量ROS激活核因子κB(NF-κB)通路,导致炎症反应发生。BCL家族和半胱天冬酶(Cas)家族基因的表达增加,诱导细胞凋亡。受体相互作用蛋白3(RIP3)/混合谱系激酶结构域样蛋白(MLKL)通路被激活,导致细胞坏死。综上所述,TBBPA可通过氧化应激对胃黏膜造成损伤,导致ROS激活NF-κB通路增加。用抗氧化剂N-乙酰半胱氨酸(NAC)治疗可减轻TBBPA对胃黏膜的损伤。

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