Qi Xiaoyan, Liu Qiong, Wei Zuxing, Hou Xuyang, Jiang Yuhong, Sun Yin, Xu Shu, Yang Leping, He Jun, Liu Kuijie
Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China.
Department of Stomatology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China.
Toxicol Sci. 2024 Apr 29;199(1):120-131. doi: 10.1093/toxsci/kfae024.
The effect of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47), a persistent environmental pollutant commonly used as a flame retardant in various consumer products, on pancreatitis has not been clearly elucidated, although it has been reported to be toxic to the liver, nervous system, and reproductive system. Acute pancreatitis (AP) and chronic pancreatitis (CP) models were induced in this study by intraperitoneal injection of caerulein. The aim was to investigate the impact of BDE-47 on pancreatitis by exposing the animals to acute (1 week) or chronic (8 weeks) doses of BDE-47 (30 mg/kg in the low-concentration group and 100 mg/kg in the high-concentration group). Additionally, BDE-47 was utilized to stimulate mouse bone marrow-derived macrophages, pancreatic primary stellate cells, and acinar cells in order to investigate the impact of BDE-47 on pancreatitis. In vivo experiments conducted on mice revealed that chronic exposure to BDE-47, rather than acute exposure, exacerbated the histopathological damage of AP and CP, leading to elevated fibrosis in pancreatic tissue and increased infiltration of inflammatory cells in the pancreas. In vitro experiments showed that BDE-47 can promote the expression of the inflammatory cytokines Tnf-α and Il-6 in M1 macrophages, as well as promote acinar cell apoptosis through the activation of the PERK and JNK pathways via endoplasmic reticulum stress. The findings of this study imply chronic exposure to BDE-47 may exacerbate the progression of both AP and CP by inducing acinar cell apoptosis and dysregulating inflammatory responses.
2,2',4,4'-四溴二苯醚（BDE-47）是一种持久性环境污染物，常用于各种消费品中作为阻燃剂，其对胰腺炎的影响尚未明确阐明，尽管已有报道称其对肝脏、神经系统和生殖系统有毒性。本研究通过腹腔注射蛙皮素诱导急性胰腺炎（AP）和慢性胰腺炎（CP）模型。目的是通过让动物暴露于急性（1周）或慢性（8周）剂量的BDE-47（低浓度组为30mg/kg，高浓度组为100mg/kg）来研究BDE-47对胰腺炎的影响。此外，利用BDE-47刺激小鼠骨髓来源的巨噬细胞、胰腺原代星状细胞和腺泡细胞，以研究BDE-47对胰腺炎的影响。对小鼠进行的体内实验表明，长期暴露于BDE-47而非急性暴露会加剧AP和CP的组织病理学损伤，导致胰腺组织纤维化增加和胰腺中炎症细胞浸润增多。体外实验表明，BDE-47可促进M1巨噬细胞中炎性细胞因子Tnf-α和Il-6的表达，并通过内质网应激激活PERK和JNK途径促进腺泡细胞凋亡。本研究结果表明，长期暴露于BDE-47可能通过诱导腺泡细胞凋亡和炎症反应失调而加剧AP和CP的进展。
