Cardiac molecular pathways influenced by doxorubicin treatment in mice

Scientific Reports
Ben F BultenPaola A Erba

Abstract

Doxorubicin (DOX) is a potent chemotherapeutic with distinct cardiotoxic properties. Understanding the underlying cardiotoxic mechanisms on a molecular level would enable the early detection of cardiotoxicity and implementation of prophylactic treatment. Our goal was to map the patterns of different radiopharmaceuticals as surrogate markers of specific metabolic pathways induced by chemotherapy. Therefore, cardiac distribution of 99mTc-sestamibi, 99mTc-Annexin V, 99mTc-glucaric acid and [18F]FDG and cardiac expression of Bcl-2, caspase-3 and -8, TUNEL, HIF-1α, and p53 were assessed in response to DOX exposure in mice. A total of 80 mice (64 treated, 16 controls) were evaluated. All radiopharmaceuticals showed significantly increased uptake compared to controls, with peak cardiac uptake after one (99mTc-Annexin V), two (99mTc-sestamibi), three ([18F]FDG), or four (99mTc-glucaric acid) cycles of DOX. Strong correlations (p < 0.01) were observed between 99mTc-Annexin V, caspase 3 and 8, and TUNEL, and between [18F]FDG and HIF-1α. This suggests that the cardiac DOX response starts with apoptosis at low exposure levels, as indicated by 99mTc-Annexin V and histological apoptosis markers. Late process membrane disintegration can possi...Continue Reading

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Citations

Feb 7, 2021·Current Treatment Options in Oncology·Michele RussoAlessandra Ghigo
Feb 6, 2021·Oxidative Medicine and Cellular Longevity·Xin SuYanwei Xing
Dec 12, 2020·ACS Applied Materials & Interfaces·Yan TanWeihong Tan
Jun 1, 2021·Toxicology Mechanisms and Methods·Julio César Córdoba-AdayaKeila Isaac-Olivé
Jul 18, 2021·Journal of Biochemical and Molecular Toxicology·Khalid AlhazzaniMohammed Alswayyed

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Methods Mentioned

BETA
imaging techniques
fluorescence-activated cell sorting
FACS
sedation

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