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The effect of Aspalathin on Doxorubicin-induced Cardiotoxicity

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dc.contributor.advisor Johnson, R.
dc.contributor.advisor Kappo, A.
dc.contributor.advisor Muller, C.
dc.contributor.author Shabalala, Samukelisiwe Cynthia
dc.date.accessioned 2017-07-03T12:47:14Z
dc.date.available 2017-07-03T12:47:14Z
dc.date.issued 2017
dc.identifier.uri http://hdl.handle.net/10530/1568
dc.description A dissertation submitted to the Faculty of Science and Agriculture in fulfillment of the Degree of Master of Science in Biochemistry in the Department of Biochemistry and Microbiology at the University of Zululand, 2017 en_US
dc.description.abstract Doxorubicin is a highly effective first-line chemotherapeutic agent used in the treatment of a broad range of solid and hematological tumors. Though effective, the use of Doxorubicin in cancer therapy has been hindered by its cardio toxic side effects. As yet, no single chemical synthesized drug or compound is known to prevent the harmful action of Doxorubicin without reducing its anti-cancer efficacy. Therefore, the search for an effective and safe antagonist of Doxorubicin-induced cardiotoxicity remains a challenge. In recent years, researchers have investigated the use of plant-derived polyphenols as nutraceuticals to lower the risk of chronic diseases. Of particular interest is aspalathin, a plant polyphenol with known antioxidant properties. Aim: This study aimed to investigate the potential use of aspalathin, a dihydrochalcone C-glycoside, in alleviating Doxorubicin-induced cardiotoxicity in an in vitro H9c2 cardio myoblast cell culture model. Methods: H9c2 cardiomyocytes and Caov-3 cancer cells were cultured in Dulbecco’s modified eagle’s medium and treated with or without Doxorubicin for five days. Thereafter, cells exposed to 0.2 μM Doxorubicin were co-treated with either 20 μM Dexrazozane or 0.2 μM aspalathin daily, resulting in a cumulative dose of 1 μM Doxorubicin, 100 μM Dexrazozane and 1 μM aspalathin, respectively. Cell viability and apoptosis were evaluated using ATP and TUNEL assays. Various bioassays (glutathione, catalase, superoxide dismutase and lipid peroxidation) and gene and protein expression analyses (autophagy-related genes) were performed to assess the cardioprotective effect of aspalathin to prevent Doxorubicin-induced cardiotoxicity. Results: This study showed that aspalathin co-treatment was able to mitigate Doxorubicin-induced oxidative stress, DNA damage, lipid peroxidation and subsequently myocardial apoptosis, while enhancing autophagy in H9c2 cardiomyocytes. Interestingly, aspalathin co-treatment diminished myocardial apoptosis in H9c2 cells, whereas the effect was augmented in Caov-3 ovarian cancer cells. Furthermore, this study showed that aspalathin was able to decrease apoptosis in a p53-dependent pathway, while simultaneously inhibiting autophagy in an AMPK/Fox01-dependent and mTOR-independent manner.Conclusion: Our study was the first to show that aspalathin was able to ablate Doxorubicin-induced cardiotoxicity without decreasing the anti-cancer efficacy of Doxorubicin, in an in vitro H9c2 cardio myocyte and Caov-3 ovarian cancer cell model en_US
dc.description.sponsorship NRF Thuthuka Grant en_US
dc.publisher University of Zululand en_US
dc.subject aspalathin --doxorubicn --cardiotoxicity en_US
dc.title The effect of Aspalathin on Doxorubicin-induced Cardiotoxicity en_US
dc.type Thesis en_US

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