Managing cardiotoxicity associated with immune checkpoint inhibitors

Immuno-oncology is a fast evolving field of cancer therapy and immune checkpoint inhibitors (ICIs) are clearly a breakthrough in this field. Cardiotoxicity with conventional anti-cancer therapies has been well studied in the past and clear guidelines for management of these side effects are available in the literature. However, cardiotoxicity with novel agents such as ICIs has been fairly under-reported and/or underestimated and we are yet to formulate clear guidelines for management of these rare side effects. In the last few years, there has been an overall increase in the number of cases of cardiotoxicity related to ICIs. In this literature review, we describe the mechanism of action of the most widely used ICIs and their related cardiotoxicities. The increase in number of case reports about the potential of cardiotoxicities with these novel agents clearly indicates the need for a new insight into the field of cardio-immuno-oncology.     

辅酶Q10对大鼠阿霉素心脏毒性的保护作用

目的：研究辅酶Q10（CoQ10）对大鼠阿霉素心脏毒性的保护作用，并探讨可能的机理。方法：采用离体心脏灌流方法，实验分3组：对照组、阿霉素组、CoQ10组，监测大鼠心肌收缩幅度、冠脉流量、心电图的变化，并测定冠脉流出液肌酸磷酸激酶（CPK）活力和大鼠心肌丙二醛含量、超氧化物歧化酶、谷胱甘肽过氧化物酶（GSH-Px）活力以及电镜下超微结构的改变。结果：CoQ10可改善阿霉素引起的大鼠心肌收缩幅度、冠脉流量下降，减少心律失常的发生，降低冠脉流出液CPK活力；CoQ10组心肌丙二醛含量明显低于阿霉素组、SOD和GSH-Px活力高于阿霉素组，电镜下超微结构变化亦优于阿霉素组。结论：CoQ10对阿霉素引起的心脏毒性具有保护作用，其机理可能与CoQ10拮抗阿霉素的氧自由基损伤有关。     

Supraventricular arrhythmia: A complication of 5-fluorouracil therapy

5-Fluorouracil is an S-phase-specific, synthetic pyrimidine antimetabolite, which is used as a cytostatic agent for a variety of malignant lesions, either singly or in multidrug regimens. Gastrointestinal toxicity and myelosuppression are the most common adverse reactions, but, of late, clinical cardiotoxicity has been reported in both prospective and retrospective studies. We present our experience of clinical cardiotoxicity in five patients.     

Bioactivation to an aldehyde metabolite—Possible role in the onset of toxicity induced by the anti-HIV drug abacavir

Aldehydes are highly reactive molecules, which can be generated during numerous physiological processes, including the biotransformation of drugs. Several non-P450 enzymes participate in their metabolism albeit alcohol dehydrogenase and aldehyde dehydrogenase are the ones most frequently involved in this process. Endogenous and exogenous aldehydes have been strongly implicated in multiple human pathologies. Their ability to react with biomacromolecules (e.g. proteins) yielding covalent adducts is suggested to be the common primary mechanism underlying the toxicity of these reactive species.