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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Autophagy upregulation promotes survival and attenuates doxorubicin-induced cardiotoxicity
Biochemical Pharmacology, Volume 85, No. 1, Year 2013
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Description
This study evaluated whether the manipulation of autophagy could attenuate the cardiotoxic effects of doxorubicin (DXR) in vitro as well as in a tumour-bearing mouse model of acute doxorubicin-induced cardiotoxicity. We examined the effect of an increase or inhibition of autophagy in combination with DXR on apoptosis, reactive oxygen species (ROS) production and mitochondrial function. H9C2 rat cardiac myoblasts were pre-treated with bafilomycin A1 (autophagy inhibitor, 10 nM) or rapamycin (autophagy inducer, 50 μM) followed by DXR treatment (3 μM). The augmentation of autophagy with rapamycin in the presence of DXR substantially ameliorated the detrimental effects induced by DXR. This combination treatment demonstrated improved cell viability, decreased apoptosis and ROS production and enhanced mitochondrial function. To corroborate these findings, GFP-LC3 mice were inoculated with a mouse breast cancer cell line (EO771). Following the appearance of tumours, animals were either treated with one injection of rapamycin (4 mg/kg) followed by two injections of DXR (10 mg/kg). Mice were then sacrificed and their hearts rapidly excised and utilized for biochemical and histological analyses. The combination treatment, rather than the combinants alone, conferred a cardioprotective effect. These hearts expressed down-regulation of the pro-apoptotic protein caspase-3 and cardiomyocyte cross-sectional area was preserved. These results strongly indicate that the co-treatment strategy with rapamycin can attenuate the cardiotoxic effects of DXR in a tumour-bearing mouse model. © 2012 Elsevier Inc.
Authors & Co-Authors
Sishi, Balindiwe J.N.
South Africa, Stellenbosch
Stellenbosch University
Loos, Ben
South Africa, Stellenbosch
Stellenbosch University
van Rooyen, Jacques
South Africa, Bellville
Cape Peninsula University of Technology
Engelbrecht, Anna Mart
South Africa, Stellenbosch
Stellenbosch University
Statistics
Citations: 132
Authors: 4
Affiliations: 2
Identifiers
Doi:
10.1016/j.bcp.2012.10.005
ISSN:
00062952
e-ISSN:
18732968
Research Areas
Cancer
Noncommunicable Diseases
Study Design
Cross Sectional Study