Doxorubicin Cardiotoxicity in Acute Lymphoblastic Leukemia: Possible Protective Role of Grape Seed Extract Proanthocyanidins

Abstract

Aim: To evaluate early doxorubicin (DOX) cardiotoxicity in asymptomatic leukemic patients and to explore whether Grape seed extract (GSE) proanthocyanidins would prevent the DOX-induced cardiotoxicity. Study Design: Prospective randomized double blind study. Place and Duration of Study: This study was conducted in Mansoura University Hospital, between January 2011 and May 2013. Forty two newly diagnosed acute lymphoblastic leukemia (ALL) patients were enrolled, their ages ranged from 9 to14 years. They were divided into two groups; group I received Doxorubicin-containing chemotherapy while Group II was treated with Doxorubicin-containing chemotherapy plus GSE all over the study period. All patients underwent clinical, echocardiographic and laboratory evaluations at the end of induction (phase I) and at the end of CNS intensification (phase II). Serum malondialdehyde (MDA) level, high sensitive cardiac troponin T (hscTnT), N-terminal pro brain natriuretic peptide (NT-proBNP), creatine kinase (CK) and CK -MB isoenzyme activity were determined Results: There were significant reduction in mean values of ejection fraction (EF), fractional shortening (FS) and Vitamin C, while there were highly significant increase in mean values of hscTnT, NT- ProBNP and significant increase in mean values of CK and MDA at the end of phase II in both groups. There were also significant negative correlations between each of CK and NT-proBNP and EF at the end of phase I & II. Coadminstration of DOX and GSE (group II) significantly improved echocardiographic findings (EF and FS) as well as vitamin C level. It also significantly reduced the DOX cardiotoxicity as revealed by decrement in the elevated values of biochemical cardiac markers (hscTnT, NT-pro BNP and CK activity) and oxidative injury marker (MDA). Conclusion: Biochemical cardiac markers have the potential to be used, besides echocardiographic measurements, in the early detection of DOX-induced subclinical cardiotoxicity. GSE is promising as a cardioprotective agent against DOX induced cardiotoxicity in children with ALL.