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A Doxorubicin-induced Cardiomyopathy Model in Adult Zebrafish
Published on: June 7, 2018
Doxorubicin-Induced Cardiomyopathy: A Preliminary Study on the Cardioprotective Benefits of 7-Hydroxyflavanone
Nonhlakanipho F Sangweni1,2, Kwazi Gabuza1, Ruzayda van Aarde1
1Biomedical Research and Innovation Platform (BRIP), South African Medical Research Council, Tygerberg, Cape Town 7505, South Africa.
Abstract:
The therapeutic properties of flavonoids are reported to offer cardioprotective benefits against doxorubicin (Dox)-induced cardiotoxicity (DIC). In the current study, we aimed to investigate the prophylactic properties of 7-hydroxyflavanone (7H), a flavonoid with antioxidative properties, against DIC. An in vitro model of DIC was established by exposing H9c2 cardiomyoblasts to Dox for 6 days. Similarly, cells were also co-treated with 7H to assess its ability to mitigate DIC. The data obtained indicate that 7H, as a co-treatment, alleviates Dox-induced oxidative stress by enhancing total glutathione content (p ≤ 0.001) and superoxide dismutase activity (p ≤ 0.001) whilst decreasing ROS (p ≤ 0.001), malondialdehyde production (p ≤ 0.001) and the secretion of interleukin-6 (p ≤ 0.001). The data also showed an improvement in mitochondrial function as shown via enhanced bioenergetics, mitochondrial membrane potential, and PGC1-alpha (p ≤ 0.05) and pAMPK (p ≤ 0.001) expression. The cardioprotective potential of 7H was further highlighted by its ability attenuate Dox-induced caspase 3/7 activity (p ≤ 0.001), apoptosis (p ≤ 0.001) and necrosis (p ≤ 0.05). In conclusion, our findings demonstrated the cardioprotective benefits of 7H and thus suggests that it could be a suitable candidate cardioprotective agent against DIC.
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