Jia Yuxin, Li Jing, Liu Panpan, Si Mingdong, Jin Yanyu, Wang Hongfang, Ma Donglai, Chu Li
School of Pharmacy, Hebei University of Chinese Medicine, Shijiazhuang, China.
Hebei Key Laboratory of Integrative Medicine on Liver-Kidney Patterns, Hebei University of Chinese Medicine, Shijiazhuang, China.
Front Pharmacol. 2021 Oct 13;12:758670. doi: 10.3389/fphar.2021.758670. eCollection 2021.
Hesperidin (HES) is a flavonoid glycoside found in the tangerine peel and has antioxidant properties. Arsenic trioxide (ATO) is an anti-tumour drug; however, its serious cardiotoxicity limits its clinical application. In addition, the protection of HES against ATO-induced cardiotoxicity has not been explored. The study aims to investigate and identify the underlying effect and mechanism of HES on ATO-induced cardiotoxicity. Fifty mice were randomly assigned to five groups. Mice were orally given HES:100 or 300 mg/kg/day concurrently and given ATO intraperitoneal injections: 7.5 mg/kg/day for 1 week. Blood and heart tissues were collected for examination. Evaluated in serum was the levels of creatine kinase (CK), lactate dehydrogenase (LDH) and cardiac troponin I (cTnI). In addition, evaluated in heart tissues were the levels of reactive oxygen species (ROS), superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), catalase (CAT), tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), Caspase-3, cleaved-Caspase-3, p62, Kelch-like ECH-associated protein 1 (Keap1), and nuclear factor erythroid 2-related factor 2 (Nrf2). The heart tissues were also examined for histopathology and mitochondrial ultrastructure. Compared with the ATO group, the HES treatment groups reduced the levels of CK, LDH, cTnI, ROS, MDA, TNF-α, IL-6, Bax, Caspase-3, cleaved-Caspase-3 and Keap1 and enhanced the levels of SOD, GSH, CAT, Bcl-2, p62 and Nrf2. The results demonstrate that HES protects against ATO-induced cardiotoxicity, through inhibiting oxidative stress, and subsequent inflammation and apoptosis. The underlying results are closely related to the regulation of the p62-Keap1-Nrf2 signalling pathway.
橙皮苷（HES）是一种存在于橘皮中的黄酮糖苷，具有抗氧化特性。三氧化二砷（ATO）是一种抗肿瘤药物，但其严重的心脏毒性限制了其临床应用。此外，HES对ATO诱导的心脏毒性的保护作用尚未得到研究。本研究旨在探讨和确定HES对ATO诱导的心脏毒性的潜在作用及机制。将50只小鼠随机分为五组。小鼠同时口服HES：100或300mg/kg/天，并腹腔注射ATO：7.5mg/kg/天，持续1周。收集血液和心脏组织进行检查。检测血清中肌酸激酶（CK）、乳酸脱氢酶（LDH）和心肌肌钙蛋白I（cTnI）的水平。此外，检测心脏组织中活性氧（ROS）、超氧化物歧化酶（SOD）、丙二醛（MDA）、谷胱甘肽（GSH）、过氧化氢酶（CAT）、肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）、B细胞淋巴瘤-2（Bcl-2）、Bcl-2相关X蛋白（Bax）、半胱天冬酶-3（Caspase-3）、裂解的半胱天冬酶-3（cleaved-Caspase-3）、p62、 Kelch样ECH相关蛋白1（Keap1）和核因子红细胞2相关因子2（Nrf2）的水平。还对心脏组织进行了组织病理学和线粒体超微结构检查。与ATO组相比，HES治疗组降低了CK、LDH、cTnI、ROS、MDA、TNF-α、IL-6、Bax、Caspase-3、裂解的半胱天冬酶-3和Keap1的水平，提高了SOD、GSH、CAT、Bcl-2、p62和Nrf2的水平。结果表明，HES通过抑制氧化应激以及随后的炎症和凋亡来保护机体免受ATO诱导的心脏毒性。其潜在机制与p62-Keap1-Nrf2信号通路的调节密切相关。
