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Published on: June 7, 2018
Aidi injection reduces doxorubicin-induced cardiotoxicity by inhibiting carbonyl reductase 1 expression
Yuan Lu1,2,3, Wen Liu2,4, Ting Lv4
1State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang, China.
Insights
Aidi injection (ADI) mitigates doxorubicin (DOX)-induced cardiotoxicity by inhibiting CBR1 expression. This study provides a scientific rationale for using ADI alongside DOX in cancer treatment.
Area of Science:
- Cardiology
- Pharmacology
- Oncology
Background:
- Aidi injection (ADI), a traditional Chinese medicine, is clinically used with doxorubicin (DOX) to treat malignant tumors.
- ADI is known to ameliorate DOX-induced cardiotoxicity, but the underlying mechanism remains unclear.
Purpose of the Study:
- To investigate the protective effects of ADI against DOX-induced cardiotoxicity.
- To elucidate the mechanism by which ADI exerts its cardioprotective effects.
Main Methods:
- ICR mice were treated with DOX alone or in combination with ADI.
- Cardiac pathology, serum enzyme levels (AST, LDH, CK, CK-MB, BNP), and doxorubicinol (DOXol) concentrations were assessed.
- H9c2 cells were used to evaluate cell viability, caspase-3 activity, nuclear morphology, and CBR1 expression.
Main Results:
- High-dose ADI significantly reduced DOX-induced cardiac pathological changes and elevated cardiac enzyme levels.
- ADI treatment improved H9c2 cell viability, increased IC50, and reduced caspase-3 activity in a dose-dependent manner.
- High-dose ADI inhibited CBR1 protein expression and decreased DOXol levels in cardiac tissue, serum, and H9c2 cells.
Conclusions:
- ADI effectively reduces doxorubicin-induced cardiotoxicity in both in vivo and in vitro models.
- The cardioprotective mechanism involves the inhibition of CBR1 expression, leading to reduced levels of cardiotoxic metabolite DOXol.
- This study provides a scientific basis for the combined use of ADI and DOX in cancer therapy.
Context:
Aidi injection (ADI), a traditional Chinese medicine antitumor injection, is usually combined with doxorubicin (DOX) for the treatment of malignant tumours. The cardiotoxicity of DOX is ameliorated by ADI in the clinic. However, the relevant mechanism is unknown.
Objective:
To investigate the effects of ADI on DOX-induced cardiotoxicity and its mechanism.
Materials And Methods:
ICR mice were randomly divided into six groups: control, ADI-L, ADI-H, DOX, DOX + ADI-L and DOX + ADI-H. DOX (i.p., 0.03 mg/10 g) was administered in the presence or absence of ADI (i.p., 0.1 or 0.2 mL/10 g) for two weeks. Heart pathology and levels of AST, LDH, CK, CK-MB and BNP were assessed. H9c2 cells were treated with DOX in the presence or absence of ADI (1, 4, 10%). Cell viability, caspase-3 activity, nuclear morphology, and CBR1 expression were then evaluated. DOX and doxorubicinol (DOXol) concentrations in heart, liver, kidneys, serum, and cells were analysed by UPLC-MS/MS.
Results:
High-dose ADI significantly reduced DOX-induced pathological changes and the levels of AST, LDH, CK, CK-MB and BNP to normal. Combined treatment with ADI (1, 4, 10%) improved the cell viability, and IC50 increased from 68.51 μM (DOX alone) to 83.47, 176.9, and 310.8 μM, reduced caspase-3 activity by 39.17, 43.96, and 61.82%, respectively. High-dose ADI inhibited the expression of CBR1 protein by 32.3%, reduced DOXol levels in heart, serum and H9c2 cells by 59.8, 72.5 and 48.99%, respectively.
Discussion And Conclusions:
ADI reduces DOX-induced cardiotoxicity by inhibiting CBR1 expression, which provides a scientific basis for the rational use of ADI.
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