Cardioprotective Effect of Marine Astaxanthin on Doxorubicin-Induced Cardiotoxicity in Normal Rats

Abstract

Background: Doxorubicin (DOX) is an effective antineoplastic drug indicated to treat many cancerous diseases but its clinical usefulness is limited by many side effects. The main and the most serious one is DOX induced cardiotoxicity. Many strategies have been tried to minimize this side effect such as addition of cardioprotective agent to DOX treatment protocols.
 Aims: The aim of this work was directed to investigate whether marine astaxanthin (ATX), a xanthophyll carotenoid pigment with potent antioxidant effect, could protect heart against the cardiotoxicity induced by DOX.
 Methodology: Forty Male Wister rats were divided into four equal groups and treated for one week as follow: Group I rats were treated with normal saline (2 ml/kg, x7, i.p.) and considered a control group. Group II rats were treated with ATX (40 mg/kg, x7, i.p.). Group III rats were treated with normal saline (2 ml/kg, x7, i.p.) and a single dose of DOX (20 mg/kg, i.p.) at day 7. Finally, group IV rats were treated with ATX (40 mg/kg, x7, i.p) and with a single dose of DOX (20 mg/kg, i.p.) at day 7. After 24 and 48 hrs of treatment, rats were anesthetized and prepared for collection of blood samples and heart isolation. The cardioprotective effect of ATX against DOX induced cardiotoxicity were evaluated by measurement of the serum level of cardiac enzymes CPK by colorimetric assay and CK-MB by Eliza. Also the levels of serum total antioxidant capacity (TAC) were measured colorimetrically. In addition, the Malondialdehyde (MDA), reduced glutathione, glutathione peroxidase (GPx) levels and superoxide dismutase (SOD) were determined in heart tissues homogenate by colorimetric method. In addition, Heart sample were taken for histopathology studies.
 Results: The Addition of ATX to DOX significantly (p<0.05) decreased the serum level of cardiac enzymes (CPK, CK-MB) and increased the serum total antioxidant capacity in compare with these levels in sera of rats treated with DOX only. This addition also significantly decreased the level of malondialdehyde and increased the reduced glutathione and glutathione peroxidase and superoxide dismutase significantly in the heart tissues homogenate in compare to corresponding levels in rats treated with DOX alone. Histopathological investigation of cardiac tissues confirmed the biochemical studies, where addition of ATX to DOX treatment protocol showed that the fragmentation of the muscle fiber revealed normal with central vesicular nuclei and prevented a marked disruption of normal cardiac architecture which resulted from DOX treatment.
 Conclusion: Marine astaxanthin provides excellent cardioprotective effect against doxorubicin induced cardiotoxicity in rats.