Overexpression of ABCB6 does not protect against doxorubicin cardiotoxicity
| العنوان: | Overexpression of ABCB6 does not protect against doxorubicin cardiotoxicity |
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| المؤلفون: | Cesar Eduardo Jacintho Moritz, Ryan N. Montalvo, Vivian Doerr, Branden L. Nguyen, Ashley J. Smuder |
| المصدر: | Physiology. 38 |
| بيانات النشر: | American Physiological Society, 2023. |
| سنة النشر: | 2023 |
| مصطلحات موضوعية: | Physiology |
| الوصف: | Doxorubicin (DOX) is a highly effective chemotherapeutic agent used in the treatment of a broad spectrum of human cancers. However, the clinical use of DOX is limited due to dose-dependent cardiotoxicity, which adversely affects quality of life and survival. Therefore, new strategies to mitigate the cardiotoxic effects of DOX are needed to improve the clinical usefulness of DOX and long-term health outcomes. The mitochondria-localized ATP-binding cassette (ABC) proteins (i.e. ABCB6, ABCB7, ABCB8 and ABCB10) are a family of transporters with the potential to mediate xenobiotic efflux and/or may play a role in maintaining mitochondrial redox balance and iron homeostasis. Previous data showed that exercise training mediated an increase in the expression of each mitochondria-localized ABC transporter in the heart. To determine the specific role of increased ABCB6 expression in the heart prior to DOX treatment female Sprague Dawley rats were randomly divided into the following groups: 1) Saline-Saline; Saline-ABCB6; 3) DOX-Saline; and 4) DOX-ABCB6. Four weeks before DOX (20 mg/kg; i.p.) or saline administration the animals received rAAV-ABCB6. Dependent measures were evaluated 48 hours after DOX/saline treatment. Cardiorespiratory fitness assessed via a graded exercise tolerance test performed just prior to endpoint demonstrated a significant effect of DOX on time to fatigue, with no beneficial adaptation of ABCB6 overexpression. Moreover, weight change from treatment to endpoint and the heart weight/tibia length ratio were also decreased after treatment in both DOX groups with no effect of ABCB6. Additionally, cardiac fractional shortening (FS) and posterior wall shortening velocity (PWSV) were reduced in both DOX groups. Similarly, myocardial performance index (MPI) increased in the DOX-Saline and DOX-ABCB6 groups. These data demonstrate that overexpression of the ABCB6 transporter in the heart is not capable to mitigate the deleterious effects of DOX treatment on the heart. Further studies are needed to investigate the potential therapeutic effects of mitochondria-localized ABC transporters as a clinical approach to prevent cardiotoxicity effects triggered by DOX. This research was funded by the National Institute of Health (NIH), R01HL144858. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process. |
| تدمد: | 1548-9221 1548-9213 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::28a3754d32bef945ab769341a0053ae8 https://doi.org/10.1152/physiol.2023.38.s1.5732546 |
| رقم الأكسشن: | edsair.doi...........28a3754d32bef945ab769341a0053ae8 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15489221 15489213 |
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