Mitochonic acid 5 rescues cardiomyocytes from doxorubicin-induced toxicity via repressing the TNF-α/NF-κB/NLRP3-mediated pyroptosis

心脏毒性 阿霉素 药理学 上睑下垂 氧化应激 炎症 肿瘤坏死因子α 生物 活性氧 细胞凋亡 癌症研究 医学 程序性细胞死亡 毒性 免疫学 内科学 生物化学 化疗
作者
Wenliang Zha,Qian Zhao,Ye Xiao,Yuanyuan Gan,Junjun Wei,Mengqi Yu,Yanmei Xu,Qiongyao Xu,Shi Wu,Wei Yu
出处
期刊:International Immunopharmacology [Elsevier BV]
卷期号:123: 110736-110736 被引量:12
标识
DOI:10.1016/j.intimp.2023.110736
摘要

Doxorubicin (DOX) is an effective anti-tumor drug, but the cardiotoxicity severely limits its clinical use. Interestingly, a hypothesis has emerged suggesting an association between DOX-induced cardiotoxicity and mitochondrial disorders and oxidative stress. The mitochonic acid 5 (MA5) shows promise in alleviating mitochondrial dysfunction by promoting mitochondrial ATP synthesis and reducing reactive oxygen species (ROS) accumulation, though its potential in ameliorating DOX-induced cardiotoxicity remains elusive.Network pharmacology approach, molecular docking techniques, and molecular dynamics simulation (MDS) were used to reveal the specific drug targets and pharmaceutical mechanisms involved in the treatment of DOX-induced cardiotoxicity using MA5. For experimental verification, cardiomyocytes (H9c2) and mice were exposed to DOX in the presence or absence of MA5. Our investigation involved the assessment of echocardiographic parameters, cardiac enzymes, inflammatory factors, mitochondrial function, myocardial structure, and cardiomyocyte pyroptosis.Among the 100 core targets identified in network pharmacology, MA5 was pharmacologically active against DOX-induced cardiotoxicity via pathways implicated in cancer, prostate cancer, lipids and atherosclerosis. Molecular docking analysis confirmed that MA5 docked well with TNF-α, interleukin-6 (IL-6), and caspase-3. Furthermore, MA5 exhibited a stronger affinity toward TNF-α than IL-6 and caspase-3. Subsequent MDS revealed the stability of binding between MA5 and TNF-α. The DOX-challenged mice also displayed abnormal myocardial enzymogram, disrupted systolic and diastolic function, and elevated inflammation and cardiomyocyte pyroptosis, which could be mitigated by the administration of MA5. Similarly, H9c2 cells exposed to DOX showed increased intracellular ROS production and impaired mitochondrial function, which were relieved by MA5 treatment.Our findings suggest that MA5 attenuates DOX-induced cardiac anomalies through the TNF-α-mediated regulation of inflammation and pyroptosis. These insights offer a potential therapeutic strategy for managing DOX-induced cardiac complications, thereby improving the safety and efficacy of cancer treatments.
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
PDF的下载单位、IP信息已删除 (2025-6-4)

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
潇湘雪月发布了新的文献求助10
1秒前
2秒前
如意枫叶发布了新的文献求助10
2秒前
Rondab应助卡卡罗特采纳,获得10
5秒前
9秒前
13秒前
14秒前
芋孟齐发布了新的文献求助10
14秒前
18秒前
18秒前
一路生花完成签到,获得积分10
18秒前
orixero应助小慧儿采纳,获得10
18秒前
Ava应助科研通管家采纳,获得10
18秒前
18秒前
SYLH应助科研通管家采纳,获得10
18秒前
田様应助科研通管家采纳,获得10
19秒前
丘比特应助科研通管家采纳,获得10
19秒前
潇湘雪月发布了新的文献求助10
19秒前
今后应助科研通管家采纳,获得10
19秒前
科研通AI2S应助科研通管家采纳,获得10
19秒前
情怀应助科研通管家采纳,获得10
19秒前
打打应助科研通管家采纳,获得10
19秒前
19秒前
香蕉觅云应助科研通管家采纳,获得10
19秒前
19秒前
斯文败类应助科研通管家采纳,获得10
19秒前
wanci应助科研通管家采纳,获得10
19秒前
19秒前
爆米花应助科研通管家采纳,获得10
19秒前
SYLH应助科研通管家采纳,获得30
19秒前
星辰大海应助科研通管家采纳,获得10
19秒前
栗惠完成签到 ,获得积分20
19秒前
星辰大海应助科研通管家采纳,获得10
19秒前
李爱国应助科研通管家采纳,获得10
19秒前
猪猪hero发布了新的文献求助10
20秒前
科目三应助科研通管家采纳,获得10
20秒前
20秒前
20秒前
Bob完成签到,获得积分10
20秒前
23秒前
高分求助中
A new approach to the extrapolation of accelerated life test data 1000
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
‘Unruly’ Children: Historical Fieldnotes and Learning Morality in a Taiwan Village (New Departures in Anthropology) 400
Indomethacinのヒトにおける経皮吸収 400
Phylogenetic study of the order Polydesmida (Myriapoda: Diplopoda) 370
基于可调谐半导体激光吸收光谱技术泄漏气体检测系统的研究 350
Robot-supported joining of reinforcement textiles with one-sided sewing heads 320
热门求助领域 (近24小时)
化学 材料科学 医学 生物 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 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3989242
求助须知:如何正确求助?哪些是违规求助? 3531393
关于积分的说明 11253753
捐赠科研通 3270010
什么是DOI,文献DOI怎么找? 1804868
邀请新用户注册赠送积分活动 882084
科研通“疑难数据库(出版商)”最低求助积分说明 809136