Influence of Chemotherapy on the Lipid Peroxidation and Antioxidant Status in Patients with Acute Myeloid Leukemia
Abstract
Chemotherapeutic agents used in patients with cancer cause to generate the enormous amounts of free radicals associated with cell injury. In this study we assess the effects of chemotherapy regimen on oxidant/antioxidant status in patients with acute myeloid leukemia (AML). 38 newly diagnosed patients with acute myeloid leukemia were recruited in this study. All patients received cytarabine and daunorubicin as chemotherapy regimen. Plasma levels of malondialdehyde (MDA), total antioxidant status (TAS), and the levels of erythrocyte activity of superoxide dismutase (SOD) and glutathione peroxidase (GPx) were determined before chemotherapy and 14 days after chemotherapy with cytarabine and daunorubicin. Plasma MDA concentrations increased significantly (from 2.68±0.89 nmol/L to 3.14±1.29 nmol/L) during the 14days post-chemotherapy period (P=0.04). Plasma TAS concentrations changed with chemotherapy from 1.09±0.15 mmol/L to 1.02±0.14 mmol/L with P=0.005. Erythrocyte SOD and GPX activity decreased overtime from 1157.24±543.61 U/g Hb to 984.01±419.09 U/g Hb (P=0.04) and 46.96±13.70 U/g Hb to 41.40±6.44 U/g Hb (P=0.02) respectively. We report here that there is an increase in malondialdehyde levels and a decrease in the levels of antioxidant enzymes and total antioxidant status. This suggests that chemotherapy causes these changes as a result of enormous production of reactive oxygen species in the patients with AML. Antioxidant supplementation must be approached with caution because of the probability of reduction the therapeutic efficacy of these cytotoxic drugs.
Er TK, Tsai SM, Wu SH, Chiang W, Lin HC, Lin SF et al. Antioxidant status and superoxide anion radical generation in acute myeloid leukemia. Clinical Biochemistry 2007;40(13-14):1015-1019.
Colvin GA, Elfenbein GJ. The latest treatment advances for acute myelogenous leukemia. Med Health R I 2003;86(8):243-6.
Ries LAG, Eisner MP, Kosary CL, Hankey BF, Miller BA, Clegg L, Mariotto A, Feuer EJ, Edwards BK, editors. SEER Cancer Statistics Review, 1975-2002. National Cancer Institute. Bethesda, MD. [Internet] 2004 Nov [cited 2012 May 15]; Available from: http://seer.cancer.gov/csr/1975_2002/
Löwenberg B, Downing JR, Burnett A. Acute myeloid leukemia. N Engl J Med 1999;341(14):1051-62.
Devi GS, Prasad MH, Saraswathi I, Raghu D, Rao DN,mReddy PP. Free radicals antioxidant enzymes and lipid peroxidation in different types of leukemias. Clin Chim Acta 2000;293(1-2):53-62.
Sabitha KE, Shyamaladevi CS. Oxidant and antioxidant activity changes in patients with oral cancer and treated with radiotherapy. Oral Oncol 1999;35(3):273-7.
Yates JW, Wallace HJ Jr, Ellison RR, Holland JF. Cytosine arabinoside (NSC-63878) and daunorubicin (NSC-83142) therapy in acute nonlymphocytic leukemia. Cancer Chemother Rep 1973;57(4):485-8.
Injac R, Strukelj B. Recent advances in protection against doxorubicin-induced toxicity. Technol Cancer Res Treat 2008;7(6):497-516.
Geller HM, Cheng KY, Goldsmith NK, Romero AA, Zhang AL, Morris EJ, Grandison L. Oxidative stress mediates neuronal DNA damage and apoptosis in response to cytosine arabinoside. J Neurochem 2001;78(2):265-75.
Sheng-Tanner X, Bump EA, Hedley DW. An oxidative stress-mediated death pathway in irradiated human leukemia cells mapped using multilaser flow cytometry. Radiat Res 1998;150(6):636-47.
Hedley DW, McCulloch EA. Generation of reactive oxygen intermediates after treatment of blasts of acute myeloblastic leukemia with cytosine arabinoside: role of bcl-2. Leukemia 1996;10(7):1143-9.
Pejić S, Kasapović J, Todorović A, Stojiljković V, Pajović SB. Lipid peroxidation and antioxidant status in blood of patients with uterine myoma, endometrial polypus, hyperplastic and malignant endometrium. Biol Res 2006;39(4):619-29.
McCord JM, Fridovich I. Superoxide dismutase. An enzymic function for erythrocuprein (hemocuprein). Journal of Biological Chemistry 1969;244(22):6049.
Paglia DE, Valentine WN. Studies on the quantitative andqualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med 1967;70(1):158-69.
Lapenna D, Ciofani G, Pierdomenico SD, Giamberardino MA, Cuccurullo F. Reaction conditions affecting the relationship between thiobarbituric acid reactivity and lipid peroxides in human plasma. Free Radic Biol Med 2001;31(3):331-5.
Gille L, Nohl H. Analyses of the molecular mechanism of adriamycin-induced cardiotoxicity. Free Radic Biol Med 1997;23(5):775-82.
Conklin KA. Cancer chemotherapy and antioxidants. J Nutr 2004;134(11):3201S-3204S.
Childs AC, Phaneuf SL, Dirks AJ, Phillips T, Leeuwenburgh C. Doxorubicin treatment in vivo causes cytochrome C release and cardiomyocyte apoptosis, as well as increased mitochondrial efficiency, superoxide dismutase activity, and Bcl-2:Bax ratio. Cancer Res 2002;62(16):4592-8.
Abd El-Gawad HM, El-Sawalhi MM. Nitric oxide and oxidative stress in brain and heart of normal rats treated with doxorubicin: role of aminoguanidine. J Biochem Mol Toxicol 2004;18(2):69-77.
Miller NJ, Rice-Evans C, Davies MJ, Gopinathan V, Milner A. A novel method for measuring antioxidant capacity and its application to monitoring the antioxidant status in premature neonates. Clin Sci (Lond) 1993;84(4):407-12.
Rajneesh CP, Manimaran A, Sasikala KR, Adaikappan P. Lipid peroxidation and antioxidant status in patients with breast cancer. Singapore Med J 2008;49(8):640-3.
Pigeolet E, Corbisier P, Houbion A, Lambert D, MichielsC, Raes M, Zachary MD, Remacle J. Glutathione peroxidase, superoxide dismutase, and catalase inactivation by peroxides and oxygen derived free radicals. Mech Ageing Dev 1990;51(3):283-97.
Aydin A, Arsova-Sarafinovska Z, Sayal A, Eken A, Erdem O, Erten K, Ozgök Y, Dimovski A. Oxidative stress andantioxidant status in non-metastatic prostate cancer andbenign prostatic hyperplasia. Clin Biochem 2006;39(2):176-9.
Arshad MA, Bhadra S, Cohen RM, Subbiah MT. Plasmalipoprotein peroxidation potential: a test to evaluateindividual susceptibility to peroxidation. Clin Chem 1991;37(10 Pt 1):1756-8.
Battisti V, Maders LD, Bagatini MD, Santos KF, Spanevello RM, Maldonado PA, Brulé AO, Araújo Mdo C, Schetinger MR, Morsch VM. Measurement of oxidative stress and antioxidant status in acute lymphoblastic leukemia patients. Clin Biochem 2008;41(7-8):511-8.
Kaya E, Keskin L, Aydogdu I, Kuku I, Bayraktar N, Erkut MA. Oxidant/antioxidant parameters and their relationshipwith chemotherapy in Hodgkin's lymphoma. J Int Med Res 2005;33(6):687-92.
Gadjeva V, Dimov A, Georgieva N. Influence of therapy on the antioxidant status in patients with melanoma. J Clin Pharm Ther 2008;33(2):179-85.
Files | ||
Issue | Vol 50, No 7 (2012) | |
Section | Original Article(s) | |
Keywords | ||
Acute myeloid leukemia Chemotherapy Oxidative stress Antioxidant |
Rights and permissions | |
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |