The free radical oxidation role in the development of anthracycline-induced cardiotoxicity in patients with acute leukemia in the presence of concomitant ischemic heart disease

Abstract

Anthracycline antibiotics (AA) are included into the most modern acute leukemia (AL) treatment regimens. The AA assignment in polychemotherapy (PCT) programs contributes to the clinical-hematological remission percentage growth, and the improvement of pts survival. However, the formation of anthracycline-induced cardiotoxic effects can be significant limiting factor of PCT full dose conducting, which certainly leads to reduced effectiveness of anticancer therapy. In this aspect particularly important becomes the assessment of the heart tissue injuries potential risks. The incidence of cardiotoxicity depends on the cumulative dose (CD) of AA. The generally toxic AA CD is 550 mg/m2 for doxorubicin. An additional risk factor for anthracycline cardiotoxicity is considered to be the concomitant ischemic heart disease (IHD). The imbalance between generation and inactivation mechanisms of aggressive free radicals as a risk factor of heart tissue AA-induced injury in patients with AL with concomitant ischemic heart disease remain insufficiently studied. The aim – To assess the prooxidant-antioxidant imbalance status in pts with AL in the dynamics of AA treatment taking into account concomitant IHD. Methods: The study involved 41 patients with acute leukemia (acute lymphoblastic leukemia - 13 pts, acute myeloid leukemia - 28 pts), aged 16–72 years, 23 (56%) men and 18 (44%) women, which PCT included AA. Patients were divided into two groups according to the presence of concomitant IHD: I (n=24) – without concomitant IHD; II (n=17) – with the concomitant IHD. The general condition assessment of pts of the both groups was performed twice: before specific therapy and after reaching AA cumulative dose from 100 to 200 mg/m2. The POL processes activity was determined by the malondialdehyde (MDA) level, the antioxidant protection (AOP) – the serum catalase concentration. Results Before treatment in patients of group I without concomitant IHD the MDA concentration in serum exceeded the upper limit of normal in 1.2 times, the catalase level – in 1.1 times. In patients of group II with concomitant IHD the MDA level was increased in 1.46 times with the simultaneous tendency to reduce the catalase concentration in serum compared to normal, indicating that the exhaustion of antioxidant protection on the IHD background. Upon reaching the AA CD of 100-200 mg/m2 MDA concentration in serum was in 1.54 times higher in pts of group II compared with pts of group I (4.81 ± 0.38 mmol/l vs 3.12 ± 0.28 mmol/l; p <0.05). Simultaneously, with the presence of concomitant IHD in pts of group II the catalase level in serum was in 2.1 times lower in comparison with pts of group I (72.5 ± 8.7 mkkat/l vs 33.8 ± 3.2 mkkat/l; p <0.05). Therefore, concomitant IHD in patients with AL during the treatment AA is an additional risk factor for cardiotoxicity, due to exhaustion antioxidant protection system and deepening imbalance between the formation and inactivation of free radicals.