{"title":"靶向线粒体的小分子:对抗多柔比星诱导的心脏毒性的机制方法","authors":"Chinmay Pal","doi":"10.1007/s12012-024-09941-7","DOIUrl":null,"url":null,"abstract":"<p><p>Doxorubicin (Dox) is a commonly used chemotherapy drug effective against a range of cancers, but its clinical application is greatly limited by dose-dependent and cumulative cardiotoxicity. Mitochondrial dysfunction is recognized as a key factor in Dox-induced cardiotoxicity, leading to oxidative stress, disrupted calcium balance, and activation of apoptotic pathways. Recent research has emphasized the potential of small molecules that specifically target mitochondria to alleviate these harmful effects. This review provides a comprehensive analysis of small molecules that offer cardioprotection by preserving mitochondrial function in the context of doxorubicin-induced cardiotoxicity (DIC). The mechanisms of action include the reduction of reactive oxygen species (ROS) production, stabilization of mitochondrial membrane potential, enhancement of mitochondrial biogenesis, and modulation of key signaling pathways involved in cell survival and apoptosis. By targeting mitochondria, these small molecules present a promising therapeutic strategy to prevent or reduce the cardiotoxic effects associated with Dox treatment. This review not only discusses the mechanistic actions of these agents but also emphasizes their potential in improving cardiovascular outcomes for cancer patients. Gaining insight into these mechanisms can help in creating more effective strategies to safeguard the heart during chemotherapy, allowing for the ongoing use of Dox with a lower risk to the patient's cardiovascular health. This review highlights the critical role of mitochondria-targeted therapies as a promising approach in addressing DIC.</p>","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":" ","pages":""},"PeriodicalIF":3.4000,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Small Molecules Targeting Mitochondria: A Mechanistic Approach to Combating Doxorubicin-Induced Cardiotoxicity.\",\"authors\":\"Chinmay Pal\",\"doi\":\"10.1007/s12012-024-09941-7\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Doxorubicin (Dox) is a commonly used chemotherapy drug effective against a range of cancers, but its clinical application is greatly limited by dose-dependent and cumulative cardiotoxicity. Mitochondrial dysfunction is recognized as a key factor in Dox-induced cardiotoxicity, leading to oxidative stress, disrupted calcium balance, and activation of apoptotic pathways. Recent research has emphasized the potential of small molecules that specifically target mitochondria to alleviate these harmful effects. This review provides a comprehensive analysis of small molecules that offer cardioprotection by preserving mitochondrial function in the context of doxorubicin-induced cardiotoxicity (DIC). The mechanisms of action include the reduction of reactive oxygen species (ROS) production, stabilization of mitochondrial membrane potential, enhancement of mitochondrial biogenesis, and modulation of key signaling pathways involved in cell survival and apoptosis. By targeting mitochondria, these small molecules present a promising therapeutic strategy to prevent or reduce the cardiotoxic effects associated with Dox treatment. This review not only discusses the mechanistic actions of these agents but also emphasizes their potential in improving cardiovascular outcomes for cancer patients. Gaining insight into these mechanisms can help in creating more effective strategies to safeguard the heart during chemotherapy, allowing for the ongoing use of Dox with a lower risk to the patient's cardiovascular health. This review highlights the critical role of mitochondria-targeted therapies as a promising approach in addressing DIC.</p>\",\"PeriodicalId\":9570,\"journal\":{\"name\":\"Cardiovascular Toxicology\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":3.4000,\"publicationDate\":\"2024-11-04\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cardiovascular Toxicology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s12012-024-09941-7\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CARDIAC & CARDIOVASCULAR SYSTEMS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cardiovascular Toxicology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s12012-024-09941-7","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CARDIAC & CARDIOVASCULAR SYSTEMS","Score":null,"Total":0}
Small Molecules Targeting Mitochondria: A Mechanistic Approach to Combating Doxorubicin-Induced Cardiotoxicity.
Doxorubicin (Dox) is a commonly used chemotherapy drug effective against a range of cancers, but its clinical application is greatly limited by dose-dependent and cumulative cardiotoxicity. Mitochondrial dysfunction is recognized as a key factor in Dox-induced cardiotoxicity, leading to oxidative stress, disrupted calcium balance, and activation of apoptotic pathways. Recent research has emphasized the potential of small molecules that specifically target mitochondria to alleviate these harmful effects. This review provides a comprehensive analysis of small molecules that offer cardioprotection by preserving mitochondrial function in the context of doxorubicin-induced cardiotoxicity (DIC). The mechanisms of action include the reduction of reactive oxygen species (ROS) production, stabilization of mitochondrial membrane potential, enhancement of mitochondrial biogenesis, and modulation of key signaling pathways involved in cell survival and apoptosis. By targeting mitochondria, these small molecules present a promising therapeutic strategy to prevent or reduce the cardiotoxic effects associated with Dox treatment. This review not only discusses the mechanistic actions of these agents but also emphasizes their potential in improving cardiovascular outcomes for cancer patients. Gaining insight into these mechanisms can help in creating more effective strategies to safeguard the heart during chemotherapy, allowing for the ongoing use of Dox with a lower risk to the patient's cardiovascular health. This review highlights the critical role of mitochondria-targeted therapies as a promising approach in addressing DIC.
期刊介绍:
Cardiovascular Toxicology is the only journal dedicated to publishing contemporary issues, timely reviews, and experimental and clinical data on toxicological aspects of cardiovascular disease. CT publishes papers that will elucidate the effects, molecular mechanisms, and signaling pathways of environmental toxicants on the cardiovascular system. Also covered are the detrimental effects of new cardiovascular drugs, and cardiovascular effects of non-cardiovascular drugs, anti-cancer chemotherapy, and gene therapy. In addition, Cardiovascular Toxicology reports safety and toxicological data on new cardiovascular and non-cardiovascular drugs.