Aidi injection reduces doxorubicin-induced cardiotoxicity by inhibiting carbonyl reductase 1 expression

Abstract

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.

The Link between Prostanoids and Cardiovascular Diseases

“…In addition to PGE2, it has a broad specificity of substrate and is expressed in many tissues. CBR1 is involved in the metabolism of anticancer drugs and produces cardiotoxic compounds from the metabolization of these drugs; in contrast, its inhibition exerts a cardioprotective role [ 138 , 139 ]. Furthermore, an aminoacidic substitution, Val88Ile, reduces the kinetics of anthracyclines and PGE2 metabolization [ 140 ].…”

Combination of Brucea javanica oil emulsion and Aidi injection associated with the long‑term survival of a patient with colon cancer and lung metastases post‑chemotherapy: A case report

“…In the antitumor process, ADI promotes apoptosis and inhibits angiogenesis and cell proliferation ( 17 – 19 ). ADI also exhibits a protective effect on normal cells and tissues ( 20 ).…”