Goyal Sameer N, Mahajan Umesh B, Chandrayan Govind, Kumawat Vivek S, Kamble Sarika, Patil Pradip, Agrawal Yogeeta O, Patil Chandragouda R, Ojha Shreesh
Department of Pharmacology, Cardiovascular Pharmacology Division, R. C. Patel Institute of Pharmaceutical Education and Research Shirpur- Dist-Dhule, Maharashtra, India.
Department of Pharmaceutics and Quality Assurance, R. C. Patel Institute of Pharmaceutical Education and Research Shirpur- Dist-Dhule, Maharashtra, India.
Am J Transl Res. 2016 Jan 15;8(1):60-9. eCollection 2016.
The prevention of doxorubicin (Dox) induced cardiotoxicity may be co-operative to recover future Dox treatment. The aim of this study was to explore the cardioprotective effects of oleanolic acid (OA), an antioxidant agent, on Dox induced cardiotoxicity. OA is a triterpenoid compound, which exist widely in plant kingdom in free acid form or as a glycosidic triterpenoids saponins. Cardiotoxicity was induced in Wistar rats with single intravenous injection of doxorubicin at dose of 67.75 mg/kg i.v for 48 hrs. At 12 hrs of interval following Dox administration the cardioprotective effect of OA (1.5 mg/kg, i.v.) and Amifostine (AMF) (90 mg/kg i.v., single dose prior 30 min) were evaluated. Induction of cardiotoxicity was confirmed by increase in systolic, diastolic, mean arterial pressures, maximal positive rate of developed left ventricular pressure (+LVdP/dtmax, an indicator of myocardial contraction), maximal negative rate of developed left ventricular pressure (-LVdP/dtmax, a meter of myocardial relaxation) and an increase in left ventricular end-diastolic pressure (LVEDP, a marker of pre-load). Cardiac markers in such as CK-MB, LDH and alterations in ECG. Dox administration showed alteration in Biochemical parameters and endogenous antioxidants. Administration of OA Showed maximal protection against Dox induced cardiac toxicity as observed by reduction in blood pressure, prevention of left ventricular function and attenuation of biochemical and antioxidant parameters. Based on the findings, its concluded that OA can be used as an adjuvant with Dox therapy in treating cancers.
预防阿霉素(Dox)诱导的心脏毒性可能有助于恢复未来的Dox治疗。本研究的目的是探讨抗氧化剂齐墩果酸(OA)对Dox诱导的心脏毒性的心脏保护作用。OA是一种三萜类化合物,以游离酸形式或作为糖苷三萜皂苷广泛存在于植物界。通过单次静脉注射67.75mg/kg的阿霉素,连续48小时诱导Wistar大鼠产生心脏毒性。在给予Dox后间隔12小时,评估OA(1.5mg/kg,静脉注射)和氨磷汀(AMF)(90mg/kg静脉注射,在30分钟前单次给药)的心脏保护作用。通过收缩压、舒张压、平均动脉压升高,左心室压力最大上升速率(+LVdP/dtmax,心肌收缩指标)、左心室压力最大下降速率(-LVdP/dtmax,心肌舒张指标)增加以及左心室舒张末期压力(LVEDP,前负荷标志物)升高来确认心脏毒性的诱导。心脏标志物如CK-MB、LDH以及心电图的改变。给予Dox显示生化参数和内源性抗氧化剂发生改变。给予OA显示出对Dox诱导的心脏毒性具有最大程度的保护作用,表现为血压降低、左心室功能得到预防以及生化和抗氧化参数得到减轻。基于这些发现,得出结论:OA可作为Dox治疗癌症的辅助药物。