Serum concentrations of nitrite and malondialdehyde as markers of oxidative stress in chronic myeloid leukemia patients treated with tyrosine kinase inhibitors

Abstract

Background: Chronic myeloid leukemia is a neoplasm characterized by clonal expansion of hematopoietic progenitor cells resulting from the (9:22)(q34,11) translocation. The tyrosine kinase abl fusion protein,the initial leukemogenic event in chronic myeloid leukemia, is constitutively activated thus inducing the production of reactive oxygen species. Of particular relevance is the fact that an increase in reactive oxygen species can facilitate genomic instability and may contribute to disease progression. Objetive: To evaluate oxidative stress by determining the levels of malondialdehyde and nitrite in chronic myeloid leukemia patients under treatment with 1st and 2nd generation tyrosine kinase inhibitors monitored at a referral hospital in Fortaleza, Ceará. Methods: A cross-sectional study was performed of 64 male and female adults. Patients were stratified according to treatment. The levels of malondialdehyde and nitrite were determined by spectrophotometry. Statistical differences between groups were observed using the Student t-test and Fisher's exact test. The results are expressed as mean ± standard error of mean. The significance level was set for a p-value < 0.05 in all analyses. Results: The results show significantly higher mean concentrations of nitrite and malondialdehyde in chronic myeloid leukemia patients using second-generation tyrosine kinase inhibitors compared to patients on imatinib. Conclusion: It follows that chronic myeloid leukemia patients present higher oxidative activity and that the increases in oxidative damage markers can indicate resistance to 1st generation tyrosine kinase inhibitors.

Genotoxicity associated with the use of tyrosine kinase inhibitors in patients with chronic myeloid leukemia

“…Our research group carried out a study with the same patient population in order to evaluate the oxidative stress in patients with CML receiving first and second generation TKIs. It was demonstrated that the second generation TKIs present a picture of higher oxidative stress when compared to first generation TKIs [Petrola et al, 2012]. This result corroborates the hypothesis that the second generation TKI causes greater damage probably due to greater ROS accumulation.…”

Protective effects of oleuropein against renal injury oxidative damage in alloxan-induced diabetic rats; a histological and biochemical study

“…Oxidative stress plays a key role in most pathogenic pathways of diabetic injuries, inflammation, carcinogenesis (13,14). Antioxidants such as vitamin E, alpha-lipoic acid, and oleuropein protect the cells against oxidative stress (15,16).…”

Longer Hydroxyurea Administration Prior to Imatinib Mesylate is Risk Factor for Unsuccessful Major Molecular Response in Chronic-Phase Chronic Myeloid Leukemia: Possibility of P-Glycoprotein Role

“…Thus, low MDA level is the direct consequence of low BCR-ABL/ABL ratio caused by IM treatment (Sattler et al, 2000;Kim et al, 2005). Moreover, several studies shown different MDA level between different phase of CML (Petrola et al, 2012;Ahmad et al, 2008aAhmad et al, , 2008b. All subjects included in this study was at chronic phase, so there were no differences of MDA level between groups evaluated.…”