Apoptosis in Adriamycin Cardiomyopathy and Its Modulation by Probucol
- 1 February 2001
- journal article
- research article
- Published by Mary Ann Liebert Inc in Antioxidants and Redox Signaling
- Vol. 3 (1), 135-145
- https://doi.org/10.1089/152308601750100641
Abstract
The dose-dependent cardiomyopathy and heart failure due to adriamycin have been shown to be due to increased oxidative stress and loss of myocytes. We examined the incidence of myocardial apoptosis as well as changes in the expression of apoptotic regulatory gene products in an established animal model of adriamycin cardiomyopathy. Rats were treated with adriamycin (cumulative dose, 15 mg/kg), and the hearts were examined for apoptosis as well as expression of Bax, caspase 3, and Bcl-2 at 0, 4, 10, 16, and 21 days after the treatment. A significant increase in the incidence of apoptosis was seen at 4 days, followed by a decline at 10 and 16 days of posttreatment. At 21 days, the number of apoptotic cells increased again and included cells of the conducting system. Expression of Bax corresponded to these biphasic changes, whereas the converse was true for the expression of Bcl-2. The latter peaked at 10 days followed by a decline at 16 and 21 days. The Bax/Bcl-2 ratio also correlated with the incidence of apoptosis. Expression of caspase 3 correlated with increased apoptosis, but only at early time points. Probucol (cumulative dose, 120 mg/kg), a known antioxidant as well as promoter of endogenous antioxidants, significantly reduced the incidence of apoptosis as well as expression of Bax. Adriamycin-induced hemodynamic changes were also prevented by probucol. These data suggest that adriamycin-induced apoptosis is mediated by oxidative stress and may play a role in the development of heart failure.Keywords
This publication has 38 references indexed in Scilit:
- Thermal preconditioning protects rat cardiac muscle cells from doxorubicin-induced apoptosisLife Sciences, 1999
- Myocyte Cell Death in the Diseased HeartCirculation Research, 1998
- Alterations in Fatty Acid Metabolism in Adriamycin CardiomyopathyJournal of Molecular and Cellular Cardiology, 1994
- Oxidative stress as a mediator of apoptosisImmunology Today, 1994
- Role of the glutathione-glutathione peroxidase cycle in the cytotoxicity of the anticancer quinonesPharmacology & Therapeutics, 1990
- Free radicals induced by adriamycin-sensitive and adriamycin-resistant cells: a spin-trapping studyBiochemistry, 1989
- Direct detection of paramagnetic species in adriamycin perfused rat heartsBiochemical and Biophysical Research Communications, 1988
- Anthracycline CardiotoxicityAdvances in experimental medicine and biology, 1983
- Early anthracycline cardiotoxicityAmerican Journal Of Medicine, 1978
- Fine structural changes in rat myocardium induced by daunorubicinPathology, 1973