Sunitinib induces cardiotoxicity through modulating oxidative stress and Nrf2-dependent ferroptosis in vitro and in vivo

心脏毒性 体内 氧化应激 药理学 化学 谷胱甘肽 体外 内科学 毒性 生物 医学 生物化学 生物技术
作者
Dong‐Jie Li,Chengzhu Song,Chunpu Song,Xiaolin Tian,Huaibo Zhang,Jie Zhang,Xiaoyan Zhao
出处
期刊:Chemico-Biological Interactions [Elsevier]
卷期号:388: 110829-110829 被引量:6
标识
DOI:10.1016/j.cbi.2023.110829
摘要

SUN, a multi-targeted tyrosine kinase inhibitor, exerts cardiotoxicity which hinders its clinical use. It is necessary to elucidate molecular mechanism of SUN-induced cardiotoxicity. To elucidate molecular mechanism of SUN-induced cardiotoxicity and whether it is related to Nrf2-dependent ferroptosis, in vitro model with H9c2 cells derived from rat heart tissue and in vivo model (C57BL/6J male mouse) were used in the present study. In vivo model was established by oral treatment of SUN at dose of 10, 20, 40 mg/kg for 14 days. Body weight, ECG, plasma enzyme activities, histology staining were performed to evaluate heart function. Western-blot was performed to analyze the level of ferroptosis-related proteins. In vitro results indicated that SUN markedly induced ferroptosis embodied as collapsed MMP, accumulated iron and elevated ROS. In vivo results showed that SUN significantly impaired cardiac function. Abnormal electrocardiogram, increased serum CK and lactate LDH levels were significantly observed in SUN groups. Histology staining showed that SUN caused structural injuries and fibrosis deposition. Moreover, SUN increased the level of MDA and Fe2+ content, decreased the level of GSH. Both in vitro and in vivo experiments indicated that SUN reduced the expression of Nrf2, HO-1, NQO1, GPX4 and FTH1, enhanced the TfR expression. This study suggested that oxidative stress and Nrf2-dependent ferroptosis played a vital role in SUN-induced cardiotoxicity.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
大幅提高文件上传限制,最高150M (2024-4-1)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
斯文败类应助公孙朝雨采纳,获得10
1秒前
1秒前
曲初雪完成签到,获得积分10
1秒前
加油发布了新的文献求助10
3秒前
焦糖玛奇朵完成签到,获得积分10
3秒前
4秒前
zzp完成签到,获得积分10
4秒前
5秒前
科研通AI2S应助lalalall采纳,获得10
5秒前
打打应助北川六月采纳,获得10
5秒前
如约而至发布了新的文献求助10
7秒前
8秒前
8秒前
10秒前
Peng完成签到 ,获得积分10
10秒前
huyang发布了新的文献求助10
12秒前
整齐凌萱发布了新的文献求助10
13秒前
公孙朝雨发布了新的文献求助10
13秒前
14秒前
烟花应助七七采纳,获得10
15秒前
三三完成签到,获得积分10
15秒前
科研通AI2S应助小史的泡面采纳,获得10
17秒前
yizhizhu416完成签到,获得积分10
17秒前
20秒前
yizhizhu416发布了新的文献求助10
20秒前
Shuai发布了新的文献求助10
22秒前
23秒前
脑洞疼应助微笑的语芙采纳,获得10
25秒前
满意沛槐完成签到 ,获得积分10
25秒前
逸群发布了新的文献求助30
25秒前
kukudou2完成签到,获得积分10
26秒前
turbohuan完成签到,获得积分10
26秒前
echoabc发布了新的文献求助10
26秒前
万能图书馆应助huyang采纳,获得10
26秒前
陶醉白柏发布了新的文献求助10
27秒前
27秒前
34秒前
Su发布了新的文献求助10
34秒前
FashionBoy应助sci采纳,获得10
35秒前
陶醉白柏完成签到,获得积分10
35秒前
高分求助中
Sustainability in Tides Chemistry 2800
Kinetics of the Esterification Between 2-[(4-hydroxybutoxy)carbonyl] Benzoic Acid with 1,4-Butanediol: Tetrabutyl Orthotitanate as Catalyst 1000
The Young builders of New china : the visit of the delegation of the WFDY to the Chinese People's Republic 1000
Rechtsphilosophie 1000
Very-high-order BVD Schemes Using β-variable THINC Method 568
Chen Hansheng: China’s Last Romantic Revolutionary 500
Mantiden: Faszinierende Lauerjäger Faszinierende Lauerjäger 500
热门求助领域 (近24小时)
化学 医学 生物 材料科学 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 基因 遗传学 催化作用 物理化学 免疫学 量子力学 细胞生物学
热门帖子
关注 科研通微信公众号,转发送积分 3138860
求助须知:如何正确求助?哪些是违规求助? 2789795
关于积分的说明 7792655
捐赠科研通 2446147
什么是DOI,文献DOI怎么找? 1300890
科研通“疑难数据库(出版商)”最低求助积分说明 626066
版权声明 601079