洞察线粒体肌酸激酶:研究肌酸补充剂在多柔比星诱发的心脏毒性中的预防作用。

IF 3.2 4区 医学 Q1 Pharmacology, Toxicology and Pharmaceutics Toxicology Mechanisms and Methods Pub Date : 2024-08-21 DOI:10.1080/15376516.2024.2393825
Salaheddin M Sharif, David Hydock
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引用次数: 0

摘要

多柔比星(Dox)是一种有效且常用的抗癌药物,但它会导致多种副作用,包括心脏毒性,从而导致癌症患者的生活质量下降。肌酸(Cr)是缓解 Dox 引起的心脏毒性的一种很有前景的干预措施。本研究的目的是检测在使用 Dox 之前服用 Cr 对心脏线粒体肌酸激酶(MtCK)的影响。雄性大鼠被随机分配到两种为期 4 周的铬饮食干预(标准铬饮食或铬负荷饮食)或对照饮食(Con,n = 20)中的一种。标准铬饮食(Cr1,n = 20)中的大鼠连续 4 周喂食 2% 的铬。铬负荷饮食(Cr2,n = 20)中的大鼠先喂 1 周 4% 的铬,然后喂 3 周 2% 的铬。4 周后,大鼠接受 15 毫克/千克 Dox 或安慰剂生理盐水注射(Sal)。注射后五天切除左心室(LV),并使用 Western 印迹和 ELISA 分析 MtCK 的表达。通过 Western 印迹,观察到药物对左心室质量有明显影响(p post hoc 测试显示,Con + Dox 和 Cr2 + Dox 的左心室质量明显低于 Con + Sal(p p = 0.03)。通过酶联免疫吸附试验,观察到 MtCK 存在明显的药物效应(p = 0.03)和交互作用(p = 0.02)。事后检验显示,Cr2 + Dox 的 MtCK 明显高于 Cr1 + Sal 和 Cr2 + Sal。数据表明,左心室质量和MtCK的减少可能会导致Dox诱导的心脏毒性,而补充Cr可能会通过保护线粒体CK而在减轻心脏毒性方面发挥潜在作用。
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Insights into mitochondrial creatine kinase: examining preventive role of creatine supplement in doxorubicin-induced cardiotoxicity.

Doxorubicin (Dox) is an effective and commonly used anticancer drug; however, it leads to several side effects including cardiotoxicity which contributes to poor quality of life for cancer patients. Creatine (Cr) is a promising intervention to alleviate Dox-induced cardiotoxicity. This study aimed to examine the effects of Cr beforeDox on cardiac mitochondrial creatine kinase (MtCK). Male rats were randomly assigned to one of two 4-week Cr feeding interventions (standard Cr diet or Cr loading diet) or a control diet (Con, n = 20). Rats in the standard Cr diet (Cr1, n = 20) were fed 2% Cr for 4-weeks. Rats in the Cr loading diet (Cr2, n = 20) were fed 4% Cr for 1-week followed by 2% Cr for 3-weeks. After 4-weeks, rats received either a bolus injection of 15 mg/kg Dox or a placebo saline injection (Sal). Five days post-injections left ventricle (LV) was excised and analyzed for MtCK expression using Western blot and ELISA. A significant drug effect was observed for LV mass (p < 0.05), post hoc testing revealed LV mass of Con + Dox and Cr2 + Dox was significantly lower than Con + Sal (p < 0.05). A significant drug effect was observed for MtCK (p = 0.03) through Western blot. A significant drug effect (p = 0.03) and interaction (p = 0.02) was observed for MtCK using ELISA. Post hoc testing revealed that Cr2 + Dox had significantly higher MtCK than Cr1 + Sal and Cr2 + Sal. Data suggest that a reduction in LV mass and MtCK may contribute to Dox-induced cardiotoxicity, and Cr supplementation may play a potential role in mitigating cardiotoxicity by preserving mitochondrial CK.

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来源期刊
CiteScore
6.60
自引率
3.10%
发文量
66
审稿时长
6-12 weeks
期刊介绍: Toxicology Mechanisms and Methods is a peer-reviewed journal whose aim is twofold. Firstly, the journal contains original research on subjects dealing with the mechanisms by which foreign chemicals cause toxic tissue injury. Chemical substances of interest include industrial compounds, environmental pollutants, hazardous wastes, drugs, pesticides, and chemical warfare agents. The scope of the journal spans from molecular and cellular mechanisms of action to the consideration of mechanistic evidence in establishing regulatory policy. Secondly, the journal addresses aspects of the development, validation, and application of new and existing laboratory methods, techniques, and equipment. A variety of research methods are discussed, including: In vivo studies with standard and alternative species In vitro studies and alternative methodologies Molecular, biochemical, and cellular techniques Pharmacokinetics and pharmacodynamics Mathematical modeling and computer programs Forensic analyses Risk assessment Data collection and analysis.
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