Prevention and Treatment of Doxorubicin and Trastuzumab-Induced Cardiotoxicity with Compound Danshen Dripping PillOA
Objective:To elucidate the therapeutic effect and mechanism of Compound Danshen Dripping Pill(CDDP)on cardiotoxicity caused by doxorubicin(DOX)and trastuzumab(TRZ).Methods:Eighteen SpragueDawley(SD)rats were randomly divided into the normal group(normal saline),the model group(DOX/TRZ),and CDDP administration group(DOX/TRZ+CDDP),by a random number table,with 6 rats in each group.Rats were administered either DOX or saline via tail vein injection 6 times over an 11-day period.One week later,they received either TRZ or saline via intraperitoneal injection 6 times over another 11-day period.All rats received CDDP or saline via oral gavage continuously for 36 days.Then,echocardiography was performed on the rats,and biochemical parameters of blood and heart samples were determined.Rats''feces were taken for intestinal flora testing and plasma metabolites were analyzed using untargeted metabolomics.Results:Echocardiographic assessment in rats demonstrated that DOX/TRZ induced cardiac dysfunction,whereas CDDP significantly ameliorated this impairment(P<0.05 or P<0.01).Furthermore,results revealed that DOX/TRZ elevated cardiac injury indicators(left ventricular ejection fraction,fractional shortening,cardiac troponin I,creatine kinase,creatine kinase-MB),while CDDP treatment significantly reduced these levels(P<0.05 or P<0.01).Plasma metabolite analysis revealed enrichment in tryptophan metabolism,tricarboxylic acid cycle,and phenylalanine metabolism.Intestinal microbiota analysis showed increased richness and altered abundance of certain bacteria(ClostridiaUCG-014 and Lactobacillus)with CDDP treatment.Conclusions:CDDP can prevent and protect against DOX/TRZ-induced cardiac injury.It influences tryptophan metabolism by modulating ClostridiaUCG-014 abundance,inhibits indole-3-carboxylic acid levels,increases kynurenine levels,thereby exerting anti-cardiotoxic effects.
YU Nuo-xian;LIN Meng-meng;XU Jing;CAO Bo;YANG Jia-hui;LI Rui-sheng;LI Guo-hui;LI Chun-yu
Department of Pharmacy,the First Affiliated Hospital of China Medical University,Shenyang,110001,China National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing,100021,ChinaDepartment of Clinical Pharmacy,Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province,Affiliated Hangzhou First People’s Hospital,School of Medicine,Westlake University,Hangzhou,310006,ChinaNational Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing,100021,ChinaNational Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing,100021,ChinaNational Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing,100021,ChinaResearch Center for Clinical and Translational Medicine,the Fifth Medical Center of Chinese PLA General Hospital,Beijing,100039,ChinaNational Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing,100021,ChinaDepartment of Pharmacy,the First Affiliated Hospital of China Medical University,Shenyang,110001,China National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing,100021,China
医药卫生
cardiotoxicitydoxorubicintrastuzumabCompound Danshen Dripping Pillmulti-omics analysisChinese medicine
《Chinese Journal of Integrative Medicine》 2026 (1)
P.25-33,9
Supported by Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(No.2021-I2M-1-014)。
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