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
everything发布了新的文献求助10
1秒前
control完成签到,获得积分10
1秒前
月秋发布了新的文献求助10
3秒前
复杂的夜蓉完成签到,获得积分10
3秒前
yoona完成签到,获得积分10
4秒前
4秒前
qks发布了新的文献求助10
5秒前
泡芙不甜完成签到 ,获得积分10
5秒前
6秒前
8秒前
8秒前
冬瓜完成签到 ,获得积分10
9秒前
Fu发布了新的文献求助10
9秒前
tuanheqi应助旷野天采纳,获得30
10秒前
10秒前
材料诚完成签到,获得积分10
10秒前
LabRat完成签到 ,获得积分10
10秒前
caibai发布了新的文献求助10
11秒前
幽默不乐完成签到,获得积分20
11秒前
Bzz完成签到,获得积分10
12秒前
13秒前
研友_VZG7GZ应助乐白采纳,获得10
13秒前
oldfive发布了新的文献求助10
13秒前
14秒前
在水一方应助月秋采纳,获得10
14秒前
小鸟芄完成签到,获得积分10
14秒前
Michael发布了新的文献求助10
15秒前
阔达的扬完成签到,获得积分10
15秒前
琪琪的发布了新的文献求助10
16秒前
HanQing完成签到,获得积分20
16秒前
18秒前
19秒前
丘比特应助不过尔尔采纳,获得10
20秒前
自觉秋发布了新的文献求助10
20秒前
小贺完成签到,获得积分10
22秒前
学术小白发布了新的文献求助10
22秒前
N7完成签到,获得积分10
22秒前
qgjvjypm发布了新的文献求助10
22秒前
23秒前
搜集达人应助枯木逢春采纳,获得10
23秒前
高分求助中
Sustainability in Tides Chemistry 2000
Microlepidoptera Palaearctica, Volumes 1 and 3 - 13 (12-Volume Set) [German] 1122
Дружба 友好报 (1957-1958) 1000
The Data Economy: Tools and Applications 1000
Mantiden - Faszinierende Lauerjäger – Buch gebraucht kaufen 700
PraxisRatgeber Mantiden., faszinierende Lauerjäger. – Buch gebraucht kaufe 700
A Dissection Guide & Atlas to the Rabbit 600
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 3101389
求助须知:如何正确求助?哪些是违规求助? 2752795
关于积分的说明 7621022
捐赠科研通 2405111
什么是DOI,文献DOI怎么找? 1276127
科研通“疑难数据库(出版商)”最低求助积分说明 616705
版权声明 599058