Aidi injection reduces doxorubicin-induced cardiotoxicity by inhibiting carbonyl reductase 1 expression
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...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2022-12-01
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| Series: | Pharmaceutical Biology |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/13880209.2022.2110127 |
| _version_ | 1811214499103899648 |
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| author | Yuan Lu Wen Liu Ting Lv Yanli Wang Ting Liu Yi Chen Yang Jin Jin Huang Lin Zheng Yong Huang Yan He Yongjun Li |
| author_facet | Yuan Lu Wen Liu Ting Lv Yanli Wang Ting Liu Yi Chen Yang Jin Jin Huang Lin Zheng Yong Huang Yan He Yongjun Li |
| author_sort | Yuan Lu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T06:05:43Z |
| format | Article |
| id | doaj.art-04b941f61047447589391cdb7206c2d4 |
| institution | Directory Open Access Journal |
| issn | 1388-0209 1744-5116 |
| language | English |
| last_indexed | 2024-04-12T06:05:43Z |
| publishDate | 2022-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Pharmaceutical Biology |
| spelling | doaj.art-04b941f61047447589391cdb7206c2d42022-12-22T03:44:52ZengTaylor & Francis GroupPharmaceutical Biology1388-02091744-51162022-12-016011616162410.1080/13880209.2022.2110127Aidi injection reduces doxorubicin-induced cardiotoxicity by inhibiting carbonyl reductase 1 expressionYuan Lu0Wen Liu1Ting Lv2Yanli Wang3Ting Liu4Yi Chen5Yang Jin6Jin Huang7Lin Zheng8Yong Huang9Yan He10Yongjun Li11State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang, ChinaThe Affiliated Hospital of Guizhou Medical University, Guiyang, ChinaSchool of Pharmacy, Guizhou Medical University, Guiyang, ChinaSchool of Pharmacy, Guizhou Medical University, Guiyang, ChinaEngineering Research Center for the Development and Application of Ethnic Medicine and TCM (Ministry of Education), Guizhou Medical University, Guiyang, ChinaSchool of Pharmacy, Guizhou Medical University, Guiyang, ChinaSchool of Pharmacy, Guizhou Medical University, Guiyang, ChinaSchool of Pharmacy, Guizhou Medical University, Guiyang, ChinaState Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang, ChinaState Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang, ChinaThe Affiliated Hospital of Guizhou Medical University, Guiyang, ChinaEngineering Research Center for the Development and Application of Ethnic Medicine and TCM (Ministry of Education), Guizhou Medical University, Guiyang, ChinaContext 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.https://www.tandfonline.com/doi/10.1080/13880209.2022.2110127Traditional Chinese medicinedoxorubicinolH9c2 cellsUPLC-MS/MS |
| spellingShingle | Yuan Lu Wen Liu Ting Lv Yanli Wang Ting Liu Yi Chen Yang Jin Jin Huang Lin Zheng Yong Huang Yan He Yongjun Li Aidi injection reduces doxorubicin-induced cardiotoxicity by inhibiting carbonyl reductase 1 expression Pharmaceutical Biology Traditional Chinese medicine doxorubicinol H9c2 cells UPLC-MS/MS |
| title | Aidi injection reduces doxorubicin-induced cardiotoxicity by inhibiting carbonyl reductase 1 expression |
| title_full | Aidi injection reduces doxorubicin-induced cardiotoxicity by inhibiting carbonyl reductase 1 expression |
| title_fullStr | Aidi injection reduces doxorubicin-induced cardiotoxicity by inhibiting carbonyl reductase 1 expression |
| title_full_unstemmed | Aidi injection reduces doxorubicin-induced cardiotoxicity by inhibiting carbonyl reductase 1 expression |
| title_short | Aidi injection reduces doxorubicin-induced cardiotoxicity by inhibiting carbonyl reductase 1 expression |
| title_sort | aidi injection reduces doxorubicin induced cardiotoxicity by inhibiting carbonyl reductase 1 expression |
| topic | Traditional Chinese medicine doxorubicinol H9c2 cells UPLC-MS/MS |
| url | https://www.tandfonline.com/doi/10.1080/13880209.2022.2110127 |
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