Review articleRole of oxidative stress in cardiotoxicity of antineoplastic drugs
Graphical abstract
Introduction
Cancer is the leading cause of death, shortening life expectancy, and ranking first or second in most countries, according to statistical data from the World Health Organization (WHO) in 2015 [1]. The World Cancer Report 2014, released in 2015, represents a series of the volume that began in 2003 when it was estimated that 5.3 million men and 4.7 million women had malignant tumors each year, of which 6.2 million died of the disease. In 2014, it was determined that 14.1 million people have cancer each year [2]. With the development of medical research and modern equipment, the methods and techniques of tumor therapy have been greatly improved, and the survival rate of cancer patients has been significantly increased [3]. But at the same time, a variety of treatment methods can also lead to multiple complications. The cardiotoxicity (CTX) is not only the most critical adverse reaction of antineoplastic drugs but also the primary cause of increased mortality of tumor survivors, which directly affects the efficacy of anti-tumor drugs [4]. Currently, the antineoplastic drugs, including anthracyclines(ANTs), alkylating agents, anti-microtubules, antimetabolites, metal platinum drugs, and new molecular targeted drugs all have certain CTX [5,6].
The CTX of antineoplastic drugs has become a “heart disease” for oncologists. Therefore, “cardio-oncology” has attracted a lot of attention of scholars as a hot issue in the field of cancer and cardiovascular disease (CVD). In recent years, the mechanism of CTX induced by antineoplastic drugs is still not completely clear [7], but the relationship between oxidative stress (OS) and CTX has attracted more and more attention of scholars. A large number of data have confirmed that OS is closely related to CTX induced by antineoplastic drugs [8]. Therefore, this paper reviews the role of OS in CTX of antineoplastic drugs.
Section snippets
Cardiotoxicity of antineoplastic drugs
The CTX of antineoplastic drugs mainly includes myocardial damage, hypertension, left ventricular (LV) systolic and diastolic dysfunction, heart failure(HF), thrombosis, pericardial disease, myocardial ischemia, arrhythmia and vasospasm [5,[8], [9], [10]]. The exact definition of CTX of tumor therapy is: (1) cardiomyopathy with reduced left ventricular ejection fraction(LVEF), which is characterized by decreased overall function or decreased ventricular septal motion; (2) symptoms associated
Oxidative stress
In cells and tissues, oxidative stress (OS) is caused by the imbalance between the production and accumulation of reactive oxygen species (ROS) and the ability of biological systems to detoxify these products [16]. ROS are normally generated as by-products of oxygen metabolism, or by nicotinamide adenine dinucleotide phosphate (NAPDH) oxidase and xanthine oxidase(XOR), although they could be formed by exogenous stimuli such as UV light, etc. [[16], [17], [18]]. So in other words, OS is a state
Antineoplastic drugs cardiotoxicity and oxidative stress
The clinical manifestations of CTX induced by antineoplastic drugs are complex and diverse, and their mechanisms of action are different [36,37]. Clinical manifestations including arrhythmia, myocardial ischemia, coronary artery disease(CAD), abnormal blood pressure, myocardial dysfunction, ECG and myocardial enzyme abnormalities, and even develop into HF [8,38]. Traditionally, there are two main anticancer drugs causing CTX: one is conventional chemotherapy drugs, including ANTs (DOX,
Conclusions and perspective
Current anti-tumor therapy has dramatically improved the survival of cancer patients, but whether ANTs, alkylating agents, antimetabolites, anti-microtubules, platinum drugs or new molecular targeted medicines have brought CTX [8,14,39]. OS is directly or indirectly involved in CTX induced by different anticancer drugs [8,22]. ANTs produce excessive ROS through various pathways, which leads to oxidative modification of cell macromolecules, induces mitochondrial dysfunction, inhibits protein
Declaration of Competing Interest
There is no conflict of interest among the authors.
Acknowledgements
This work was supported by Young Talent Lifting Project of China Association of Chinese Medicine (no. CACM-2018-QNRC2-B04).
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