The protective effect of a purified extract of Withania somnifera against doxorubicin-induced cardiac toxicity in rats
The therapeutic value of doxorubicin as an effective antineoplastic agent is limited by its cardiotoxic side-effects. The administration of doxorubicin (10 mg/kg) to male Wistar rats induced necrosis and apoptosis in heart tissues. It also caused oxidative stress damage as evidenced by the elevation of malondialdehyde and protein carbonyl levels and catalase activity, accompanied by the concurrent depletion of total antioxidant capacity and of superoxide dismutase level in cardiac tissues. The doxorubicin-induced cardiotoxicity and oxidative stress damage were also accompanied by increases of myeloperoxidase activity, total calcium content, and the expression of Bcl-2 protein in heart tissues. Most of these doxorubicin-induced biochemical and histological alterations were effectively attenuated by prior administration of purified standardized extract (1.5% withanolides; manufactured by Idea Sphere Inc., American Fork, UT, USA) of Withania somnifera (300 mg/kg). Thus, Withania may play a role in the protection against cardiotoxicity and thus might be a useful adjuvant therapy where doxorubicin is the cancer-treating drug.
KeywordsDoxorubicin Cardiotoxicity Protection Withania Apoptosis
ferric reducing antioxidant power
reactive oxygen species
total antioxidant capacity
terminal deoxynucleotidyl transferase mediated dUTP nick end labelling
Withania somnifera Dunal
We are grateful to Ms. Duaa Al-Harbawi for her valuable assistance. We also thank Professor Waleed Hamza (Biology Department Head) for his continuous help and support throughout this work.
- Gupta SK, Dua A, Vohra BP. Withania somnifera (Ashwagandha) attenuates antioxidant defense in aged spinal cord and inhibits copper induced lipid peroxidation and protein oxidative modifications. Drug Metab Drug Interact 2003;19:211–22.Google Scholar
- Nicholls S, Hazen SL. Myloperoxidase and cardiovascular disease. Arterioscler Thromb Vasc Biol 2005;25:274–8.Google Scholar