Berberine hydrochloride alleviates imatinib mesylate - induced cardiotoxicity through the inhibition of Nrf2-dependent ferroptosis
作者全名："Song, Chengzhu; Li, Dongning; Zhang, Jie; Zhao, Xiaoyan"
作者地址："[Song, Chengzhu; Li, Dongning; Zhao, Xiaoyan] Southwest Univ, Inst Pharmaceut Sci, Chongqing 400716, Peoples R China; [Zhang, Jie] Chongqing Med Univ, Affiliated Hosp 2, Dept Neurol, Chongqing 400000, Peoples R China; [Zhao, Xiaoyan] Minist Educ, Engn Res Ctr Coptis Dev & Utilizat, Chongqing, Peoples R China"
通信作者："Zhao, XY (通讯作者)，Southwest Univ, Inst Pharmaceut Sci, Chongqing 400716, Peoples R China.; Zhang, J (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Dept Neurol, Chongqing 400000, Peoples R China.; Zhao, XY (通讯作者)，Minist Educ, Engn Res Ctr Coptis Dev & Utilizat, Chongqing, Peoples R China."
来源：FOOD & FUNCTION
摘要："Imatinib mesylate (IMA) belonging to the selective tyrosine kinase inhibitor family has been proven to induce cardiotoxic effects along with therapeutic strategies. Nrf2-dependent ferroptosis has been implicated in the cardiotoxicity induced by IMA. The present study was designed to investigate the protective effects of berberine hydrochloride (Ber) on cardiac injuries induced by IMA and to explore its potential mechanisms. In H9c2 cells, cell viability, the generation of reactive oxygen species (ROS), mitochondrial membrane potential (MMP) and labile iron pool (LIP) levels were measured. In a mouse model of IMA-induced cardiomyopathy, serum biomarkers and cardiac tissues were examined. A western blot assay was performed to evaluate the expression of ferroptosis-related proteins in vitro and in vivo. Our results indicated that Ber increased cell viability and MMP and decreased cellular ROS and iron levels in comparison to the IMA group of H9c2 cells. In mice, Ber significantly improved cardiac status and attenuated the level of ferroptosis biomarkers including malonaldehyde (MDA) and iron content. Additionally, Ber downregulated the expression of transferrin receptor (TfR) and P53 and upregulated the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), NAD(P)H quinone oxidoreductase-1 (NQO1), ferritin heavy chain-1 (FTH1), and glutathione peroxidase 4 (GPX4) in H9c2 cells and mice. The present data indicated that Ber has the potential to protect against IMA-induced cardiotoxicity, partly via inhibiting Nrf2-dependent ferroptosis."
基金机构："Chongqing Research Program of Basic Research and Frontier Technology, China [cstc2021jcyj-msxmX0106]; Chongqing Postdoctoral Science Foundation [Xm2017083]; Chinese Medicine Rehabilitation - the Key Discipline Constructed by Chongqing Health Bureau [2021-4322190044]"
基金资助正文："The present study was supported by the Chongqing Research Program of Basic Research and Frontier Technology, China (Grant No. cstc2021jcyj-msxmX0106), the Chongqing Postdoctoral Science Foundation (Grant No. Xm2017083) and Chinese Medicine Rehabilitation - the Key Discipline Constructed by Chongqing Health Bureau (Grant No. 2021-4322190044)."