Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.
Tianjin Key Laboratory of Chinese Medicine Pharmacology, Tianjin, China.
Drug Chem Toxicol. 2022 Jul;45(4):1818-1824. doi: 10.1080/01480545.2021.1881537. Epub 2021 Feb 8.
Psoralen is the main coumarin component of . Previously, we have found that psoralen induced hepatocytes apoptosis via PERK and ATF6 related ER stress pathways . In this study, we investigated the toxicity and ER stress induced by psoralen in female C57 mice. Mice were fed with 80 mg/kg of psoralen intra-gastrically for either 3, 7, or 21 days. Liver and kidney were weighed and their coefficients were calculated. The serum was isolated to examine the biochemical parameters including alanine aminotransferase (ALT) activity, aspartate aminotransferase (AST) activity, alkaline phosphatase (ALP) activity, blood urea nitrogen (BUN), total bile acid (TBA), total bilirubin (TBIL), and creatinine (CRE). The transcription and expression of ER stress-related markers were determined by Wes-automated Protein Simple system, Western blot and RT-PCR. Psoralen administration for 3 days significantly increased liver coefficients but decreased kidney coefficients of mice. Histopathological examination showed minimal inflammatory cell foci and vacuolar degeneration in the liver. Besides, serum levels of ALT, TBA, BUN, and CRE were markedly altered by psoralen. Moreover, psoralen significantly increased expression and transcription levels of ER stress related markers, including Grp78, PERK, eIF2α, ATF4, IRE1α, ATF6, and XBP1. These results illustrated that psoralen induced liver injuries through ER stress signaling in female mice.
补骨脂素是香豆素的主要成分。先前，我们发现补骨脂素通过 PERK 和 ATF6 相关的内质网应激途径诱导肝细胞凋亡。在这项研究中，我们研究了补骨脂素对雌性 C57 小鼠的毒性和内质网应激的诱导作用。小鼠经灌胃给予 80mg/kg 的补骨脂素，连续 3、7 或 21 天。称重肝脏和肾脏，并计算其脏器系数。分离血清，检测丙氨酸氨基转移酶（ALT）活性、天冬氨酸氨基转移酶（AST）活性、碱性磷酸酶（ALP）活性、血尿素氮（BUN）、总胆汁酸（TBA）、总胆红素（TBIL）和肌酐（CRE）等生化参数。通过 Wes-automated Protein Simple 系统、Western blot 和 RT-PCR 测定内质网应激相关标志物的转录和表达。补骨脂素给药 3 天可显著增加小鼠肝脏系数，但降低肾脏系数。组织病理学检查显示肝脏有轻微的炎性细胞灶和空泡变性。此外，补骨脂素还显著改变了血清 ALT、TBA、BUN 和 CRE 水平。而且，补骨脂素显著增加了内质网应激相关标志物 Grp78、PERK、eIF2α、ATF4、IRE1α、ATF6 和 XBP1 的表达和转录水平。这些结果表明，补骨脂素通过内质网应激信号途径诱导雌性小鼠肝脏损伤。
