In vivo and in vitro protective effects of shengmai injection against doxorubicin-induced cardiotoxicity
Context Shengmai injection (SMI) has been used to treat heart failure.Objective This study determines the molecular mechanisms of SMI against cardiotoxicity caused by doxorubicin (DOX).Materials and methods In vivo, DOX (15 mg/kg) was intraperitoneally injected in model, Dex (dexrazoxane), SMI-L (2....
| 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 |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/13880209.2022.2046801 |
| _version_ | 1818157578372251648 |
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| author | Peng Zhou Ge Gao Chun-chun Zhao Jing-ya Li Jian-fei Peng Shu-shu Wang Rui Song Hui Shi Liang Wang |
| author_facet | Peng Zhou Ge Gao Chun-chun Zhao Jing-ya Li Jian-fei Peng Shu-shu Wang Rui Song Hui Shi Liang Wang |
| author_sort | Peng Zhou |
| collection | DOAJ |
| description | Context Shengmai injection (SMI) has been used to treat heart failure.Objective This study determines the molecular mechanisms of SMI against cardiotoxicity caused by doxorubicin (DOX).Materials and methods In vivo, DOX (15 mg/kg) was intraperitoneally injected in model, Dex (dexrazoxane), SMI-L (2.7 mL/kg), SMI-M (5.4 mL/kg), and SMI-H (10.8 mL/kg) for 7 consecutive days. Hematoxylin-eosin (HE) and Masson staining were used to evaluate histological changes, and cardiomyocyte apoptosis was identified using TdT-mediated dUTP nick-end labelling (TUNEL). Enzymatic indexes were determined. mRNA and protein expressions were analysed through RT-qPCR and Western blotting. In vitro, H9c2 cells were divided into control group, model group (2 mL 1 μM DOX), SMI group, ML385 group, and SMI + ML385 group, the intervention lasted for 24 h. mRNA and protein expressions were analysed.Results SMI markedly improved cardiac pathology, decreased cardiomyocyte apoptosis, increased creatine kinase (CK), lactate dehydrogenase (LDH), malondialdehyde (MDA), decreased superoxide dismutase (SOD). Compared with the model group, the protein expression of nuclear factor erythroid2-related factor 2 (Nrf2) (SMI-L: 2.42-fold, SMI-M: 2.67-fold, SMI-H: 3.07-fold) and haem oxygenase-1(HO-1) (SMI-L: 1.64-fold, SMI-M: 2.01-fold, SMI-H: 2.19-fold) was increased and the protein expression of kelch-like ECH-associated protein 1 (Keap1) (SMI-L: 0.90-fold, SMI-M: 0.77-fold, SMI-H: 0.66-fold) was decreased in SMI groups and Dex group in vivo. Additionally, SMI dramatically inhibited apoptosis, decreased CK, LDH and MDA levels, and enhanced SOD activity. Our results demonstrated that SMI reduced DOX-induced cardiotoxicity via activation of the Nrf2/Keap1 signalling pathway.Conclusions This study revealed a new mechanism by which SMI alleviates DOX-induced 45 cardiomyopathy by modulating the Nrf2/Keap1 signal pathway. |
| first_indexed | 2024-12-11T15:16:25Z |
| format | Article |
| id | doaj.art-bb5d654ed4e8439ab1499c372c66e57f |
| institution | Directory Open Access Journal |
| issn | 1388-0209 1744-5116 |
| language | English |
| last_indexed | 2024-12-11T15:16:25Z |
| publishDate | 2022-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Pharmaceutical Biology |
| spelling | doaj.art-bb5d654ed4e8439ab1499c372c66e57f2022-12-22T01:00:33ZengTaylor & Francis GroupPharmaceutical Biology1388-02091744-51162022-12-0160163865110.1080/13880209.2022.2046801In vivo and in vitro protective effects of shengmai injection against doxorubicin-induced cardiotoxicityPeng Zhou0Ge Gao1Chun-chun Zhao2Jing-ya Li3Jian-fei Peng4Shu-shu Wang5Rui Song6Hui Shi7Liang Wang8School of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, ChinaSchool of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, ChinaSchool of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, ChinaSchool of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, ChinaSchool of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, ChinaSchool of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, ChinaSchool of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, ChinaNursing School, Anhui University of Chinese Medicine, Hefei, ChinaSchool of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, ChinaContext Shengmai injection (SMI) has been used to treat heart failure.Objective This study determines the molecular mechanisms of SMI against cardiotoxicity caused by doxorubicin (DOX).Materials and methods In vivo, DOX (15 mg/kg) was intraperitoneally injected in model, Dex (dexrazoxane), SMI-L (2.7 mL/kg), SMI-M (5.4 mL/kg), and SMI-H (10.8 mL/kg) for 7 consecutive days. Hematoxylin-eosin (HE) and Masson staining were used to evaluate histological changes, and cardiomyocyte apoptosis was identified using TdT-mediated dUTP nick-end labelling (TUNEL). Enzymatic indexes were determined. mRNA and protein expressions were analysed through RT-qPCR and Western blotting. In vitro, H9c2 cells were divided into control group, model group (2 mL 1 μM DOX), SMI group, ML385 group, and SMI + ML385 group, the intervention lasted for 24 h. mRNA and protein expressions were analysed.Results SMI markedly improved cardiac pathology, decreased cardiomyocyte apoptosis, increased creatine kinase (CK), lactate dehydrogenase (LDH), malondialdehyde (MDA), decreased superoxide dismutase (SOD). Compared with the model group, the protein expression of nuclear factor erythroid2-related factor 2 (Nrf2) (SMI-L: 2.42-fold, SMI-M: 2.67-fold, SMI-H: 3.07-fold) and haem oxygenase-1(HO-1) (SMI-L: 1.64-fold, SMI-M: 2.01-fold, SMI-H: 2.19-fold) was increased and the protein expression of kelch-like ECH-associated protein 1 (Keap1) (SMI-L: 0.90-fold, SMI-M: 0.77-fold, SMI-H: 0.66-fold) was decreased in SMI groups and Dex group in vivo. Additionally, SMI dramatically inhibited apoptosis, decreased CK, LDH and MDA levels, and enhanced SOD activity. Our results demonstrated that SMI reduced DOX-induced cardiotoxicity via activation of the Nrf2/Keap1 signalling pathway.Conclusions This study revealed a new mechanism by which SMI alleviates DOX-induced 45 cardiomyopathy by modulating the Nrf2/Keap1 signal pathway.https://www.tandfonline.com/doi/10.1080/13880209.2022.2046801Nrf2/Keap1 signal pathwayapoptosisoxidativeDOX |
| spellingShingle | Peng Zhou Ge Gao Chun-chun Zhao Jing-ya Li Jian-fei Peng Shu-shu Wang Rui Song Hui Shi Liang Wang In vivo and in vitro protective effects of shengmai injection against doxorubicin-induced cardiotoxicity Pharmaceutical Biology Nrf2/Keap1 signal pathway apoptosis oxidative DOX |
| title | In vivo and in vitro protective effects of shengmai injection against doxorubicin-induced cardiotoxicity |
| title_full | In vivo and in vitro protective effects of shengmai injection against doxorubicin-induced cardiotoxicity |
| title_fullStr | In vivo and in vitro protective effects of shengmai injection against doxorubicin-induced cardiotoxicity |
| title_full_unstemmed | In vivo and in vitro protective effects of shengmai injection against doxorubicin-induced cardiotoxicity |
| title_short | In vivo and in vitro protective effects of shengmai injection against doxorubicin-induced cardiotoxicity |
| title_sort | in vivo and in vitro protective effects of shengmai injection against doxorubicin induced cardiotoxicity |
| topic | Nrf2/Keap1 signal pathway apoptosis oxidative DOX |
| url | https://www.tandfonline.com/doi/10.1080/13880209.2022.2046801 |
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