Effects of metformin and donepezil on the prevention of doxorubicin-induced cardiotoxicity in breast cancer: a randomized controlled trial
Abstract Doxorubicin (DOX) causes deleterious cardiotoxicity. We aimed to investigate the protective roles of metformin and donepezil against DOX-induced cardiotoxicity. In this randomized-controlled trial, 143 female breast cancer patients were enrolled. Metformin (n = 43), donepezil (n = 52), or p...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-08-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-40061-4 |
| _version_ | 1797576894145626112 |
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| author | Nichanan Osataphan Arintaya Phrommintikul Krit Leemasawat Areewan Somwangprasert Nattayaporn Apaijai Supanai Suksai Wachiranun Sirikul Siriluck Gunaparn Siriporn C. Chattipakorn Nipon Chattipakorn |
| author_facet | Nichanan Osataphan Arintaya Phrommintikul Krit Leemasawat Areewan Somwangprasert Nattayaporn Apaijai Supanai Suksai Wachiranun Sirikul Siriluck Gunaparn Siriporn C. Chattipakorn Nipon Chattipakorn |
| author_sort | Nichanan Osataphan |
| collection | DOAJ |
| description | Abstract Doxorubicin (DOX) causes deleterious cardiotoxicity. We aimed to investigate the protective roles of metformin and donepezil against DOX-induced cardiotoxicity. In this randomized-controlled trial, 143 female breast cancer patients were enrolled. Metformin (n = 43), donepezil (n = 52), or placebo (n = 48) were prescribed during DOX treatment. The primary endpoint was a proportion of patients with high sensitivity troponin-I (hsTnI) more than the 99th percentile value (> 15.6 ng/L) after DOX treatment. The secondary outcomes were the changes in the hsTnI, N-terminal pro-B-type natriuretic peptide (NT-proBNP), left ventricular ejection fraction (LVEF), global longitudinal strain (GLS) and peripheral blood mononuclear cells analysis for mitochondrial respiration. Baseline characteristics were similar between the groups. The primary endpoint occurred in 58.54% of metformin group, 76.92% in donepezil group, and 69.77% in placebo group (p = 0.215). The level of hsTnI increased after receiving DOX with subsequent decline in LVEF and GLS. Metformin and donepezil did not attenuate hsTnI elevation, LVEF or GLS reduction. There was no significant change in NT-proBNP level. Mitochondrial respiratory dysfunction was observed in the placebo and donepezil groups. However, metformin preserved mitochondrial respiration during DOX therapy. In conclusion, co-treatment with metformin or donepezil did not prevent myocardial injury. Metformin had a favorable mitochondrial outcome and warranted future studies. |
| first_indexed | 2024-03-10T22:00:16Z |
| format | Article |
| id | doaj.art-3ad21cfb071c41f498c7899335f58c00 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-10T22:00:16Z |
| publishDate | 2023-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-3ad21cfb071c41f498c7899335f58c002023-11-19T12:58:08ZengNature PortfolioScientific Reports2045-23222023-08-0113111210.1038/s41598-023-40061-4Effects of metformin and donepezil on the prevention of doxorubicin-induced cardiotoxicity in breast cancer: a randomized controlled trialNichanan Osataphan0Arintaya Phrommintikul1Krit Leemasawat2Areewan Somwangprasert3Nattayaporn Apaijai4Supanai Suksai5Wachiranun Sirikul6Siriluck Gunaparn7Siriporn C. Chattipakorn8Nipon Chattipakorn9Division of Cardiology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai UniversityDivision of Cardiology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai UniversityDivision of Cardiology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai UniversityDepartment of Surgery, Faculty of Medicine, Chiang Mai UniversityCardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai UniversityCardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai UniversityDepartment of Community Medicine, Faculty of Medicine, Chiang Mai UniversityDivision of Cardiology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai UniversityCardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai UniversityCardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai UniversityAbstract Doxorubicin (DOX) causes deleterious cardiotoxicity. We aimed to investigate the protective roles of metformin and donepezil against DOX-induced cardiotoxicity. In this randomized-controlled trial, 143 female breast cancer patients were enrolled. Metformin (n = 43), donepezil (n = 52), or placebo (n = 48) were prescribed during DOX treatment. The primary endpoint was a proportion of patients with high sensitivity troponin-I (hsTnI) more than the 99th percentile value (> 15.6 ng/L) after DOX treatment. The secondary outcomes were the changes in the hsTnI, N-terminal pro-B-type natriuretic peptide (NT-proBNP), left ventricular ejection fraction (LVEF), global longitudinal strain (GLS) and peripheral blood mononuclear cells analysis for mitochondrial respiration. Baseline characteristics were similar between the groups. The primary endpoint occurred in 58.54% of metformin group, 76.92% in donepezil group, and 69.77% in placebo group (p = 0.215). The level of hsTnI increased after receiving DOX with subsequent decline in LVEF and GLS. Metformin and donepezil did not attenuate hsTnI elevation, LVEF or GLS reduction. There was no significant change in NT-proBNP level. Mitochondrial respiratory dysfunction was observed in the placebo and donepezil groups. However, metformin preserved mitochondrial respiration during DOX therapy. In conclusion, co-treatment with metformin or donepezil did not prevent myocardial injury. Metformin had a favorable mitochondrial outcome and warranted future studies.https://doi.org/10.1038/s41598-023-40061-4 |
| spellingShingle | Nichanan Osataphan Arintaya Phrommintikul Krit Leemasawat Areewan Somwangprasert Nattayaporn Apaijai Supanai Suksai Wachiranun Sirikul Siriluck Gunaparn Siriporn C. Chattipakorn Nipon Chattipakorn Effects of metformin and donepezil on the prevention of doxorubicin-induced cardiotoxicity in breast cancer: a randomized controlled trial Scientific Reports |
| title | Effects of metformin and donepezil on the prevention of doxorubicin-induced cardiotoxicity in breast cancer: a randomized controlled trial |
| title_full | Effects of metformin and donepezil on the prevention of doxorubicin-induced cardiotoxicity in breast cancer: a randomized controlled trial |
| title_fullStr | Effects of metformin and donepezil on the prevention of doxorubicin-induced cardiotoxicity in breast cancer: a randomized controlled trial |
| title_full_unstemmed | Effects of metformin and donepezil on the prevention of doxorubicin-induced cardiotoxicity in breast cancer: a randomized controlled trial |
| title_short | Effects of metformin and donepezil on the prevention of doxorubicin-induced cardiotoxicity in breast cancer: a randomized controlled trial |
| title_sort | effects of metformin and donepezil on the prevention of doxorubicin induced cardiotoxicity in breast cancer a randomized controlled trial |
| url | https://doi.org/10.1038/s41598-023-40061-4 |
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