The Impact of Chemotherapy on Oxidant and Antioxidant Status in Acute Lymphoblastic Leukemia
Impact of Chemotherapy on Oxidant and Antioxidant Status
DOI:
https://doi.org/10.63841/iue3261023Keywords:
Acute lymphoblastic leukemia, Antioxidant, Chemotherapy, Oxidative stress, Reactive oxygen species.Abstract
Acute lymphoblastic leukemia (ALL) is a malignant disorder of lymphoid lineage. Chemotherapy remains the mainstay of treatment, yet it induces systemic damage partly through oxidative stress, which may worsen prognosis, increase relapse risk, and impair responsiveness to therapy.
A total of 64 individuals participated in the study: 21 newly diagnosed ALL (ND-ALL) patients with a median age of 10 years (IQR 3-27.5), 23 patients receiving maintenance chemotherapy with a median age of 13 years (IQR 5-23), and 20 healthy controls with a median age of 11.5 years (IQR 5-23), (cross-sectional study). Following remission induction treatment, ND-ALL patients were also reassessed (longitudinal study). ELISA kits were used to detect superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), total antioxidant capacity (T-AOC), malondialdehyde (MDA), 8-hydroxy-2′-deoxyguanosine(8-OHdG), and protein carbonyl (PC).
In the cross-sectional study, MDA (p = 0.05) and 8-OHdG (p = 0.001) were significantly higher in ND-ALL patients. SOD demonstrated a considerable decline (p = 0.001), the antioxidants GSH-PX and T-AOC also decreased significantly (p = 0.01). There were no significant differences between the maintenance group and the controls. Significant increases in MDA, 8-OHdG, and PC (p = 0.05, 0.01, 0.01, respectively), and decreases in GSH-PX, SOD, and T-AOC (p = 0.01, 0.05, 0.01, respectively) were observed following treatment.
Chemotherapy significantly alters the oxidant-antioxidant balance in patients with ALL. Treatment was associated with an increase in oxidative stress markers, accompanied by a marked reduction in antioxidant defense capacity.
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References
H. Skhoun et al., "Cytogenetic abnormalities and TP53 and RAS gene profiles of childhood acute lymphoblastic leukemia in Morocco," Archives de Pédiatrie, vol. 31, no. 4, pp. 238-244, 2024/05/01/ 2024.
F. Pasha, D. Urbančič, R. Maxhuni, S. Krasniqi, V. Grajçevci Uka, and I. Mlinarič-Raščan, "Prevalence and Treatment Outcomes of Childhood Acute Lymphoblastic Leukemia in Kosovo," (in eng), Cancers (Basel), vol. 16, no. 11, May 23 2024.
M. Herb and M. Schramm, "Functions of ROS in Macrophages and Antimicrobial Immunity," (in eng), Antioxidants (Basel), vol. 10, no. 2, Feb 19 2021.
C. Fan, X. Yang, L. Yan, and Z. Shi, "Oxidative stress is two-sided in the treatment of acute myeloid leukemia," (in eng), Cancer Med, vol. 13, no. 9, p. e6806, May 2024.
A. Valavanidis, T. Vlachogianni, and C. Fiotakis, "8-hydroxy-2' -deoxyguanosine (8-OHdG): A critical biomarker of oxidative stress and carcinogenesis," (in eng), J Environ Sci Health C Environ Carcinog Ecotoxicol Rev, vol. 27, no. 2, pp. 120-39, Apr 2009.
B. Spoto et al., "8-hydroxy-2′-deoxyguanosine, a biomarker of oxidative DNA injury, in diabetic kidney disease," Nutrition, Metabolism and Cardiovascular Diseases, vol. 35, no. 2, p. 103722, 2025/02/01/ 2025.
B. Yeşiloğlu et al., "Oxidative DNA Damage Diminishes After Treatment of Unipolar and Bipolar Depressive Episodes: A Systematic Review and Meta-Analysis of Longitudinal Studies," medRxiv, p. 2025.05.20.25327903, 2025.
A. V. Kudryavtseva et al., "Mitochondrial dysfunction and oxidative stress in aging and cancer," (in eng), Oncotarget, vol. 7, no. 29, pp. 44879-44905, Jul 19 2016.
A. Rodríguez-García, R. García-Vicente, M. L. Morales, A. Ortiz-Ruiz, J. Martínez-López, and M. Linares, "Protein Carbonylation and Lipid Peroxidation in Hematological Malignancies," (in eng), Antioxidants (Basel), vol. 9, no. 12, Dec 1 2020.
A. T. Mekonnen and T. G. Wondmeneh, "Evaluation of liver function tests to identify hepatotoxicity among acute lymphoblastic leukemia patients who are receiving chemotherapy induction," (in eng), Sci Rep, vol. 12, no. 1, p. 13215, Aug 2 2022.
T. Terwilliger and M. Abdul-Hay, "Acute lymphoblastic leukemia: a comprehensive review and 2017 update," (in eng), Blood Cancer J, vol. 7, no. 6, p. e577, Jun 30 2017.
C. R. Rausch, E. J. Jabbour, H. M. Kantarjian, and T. M. Kadia, "Optimizing the use of the hyperCVAD regimen: Clinical vignettes and practical management," Cancer, vol. 126, no. 6, pp. 1152-1160, 2020.
M. R. Luskin and D. J. DeAngelo, "Mini-Hyper-CVD Combinations for Older Adults: Results of Recent Trials and a Glimpse into the Future," Clinical Lymphoma Myeloma and Leukemia, vol. 20, pp. S44-S47, 2020/09/01/ 2020.
N. A. A. AL-DAHHAN, A. J. T. ALMZAIEL, and A. JABBAR, "Role of Lipid Peroxidation and Antioxidants as Biomarkers for Prostate Cancer," International Journal of Pharmaceutical Research, no. 1, 2020.
G. Software, "GraphPad Prism version 9.0.0 for Windows," ed. San Diego, California, USA GraphPad Software, 2020.
L. N. Toksvang, S. H. R. Lee, J. J. Yang, and K. Schmiegelow, "Maintenance therapy for acute lymphoblastic leukemia: basic science and clinical translations," Leukemia, vol. 36, no. 7, pp. 1749-1758, 2022/07/01 2022.
P. Chaudhary, S. Kumari, P. Dewan, S. Gomber, R. S. Ahmed, and M. Kotru, "Chemotherapy-Induced Oxidative Stress in Pediatric Acute Lymphoblastic Leukemia," (in eng), Cureus, vol. 15, no. 3, p. e35968, Mar 2023.
T. L. Dormandy, "An approach to free radicals," (in eng), Lancet, vol. 2, no. 8357, pp. 1010-4, Oct 29 1983.
P. A. Cerutti, "Oxy-radicals and cancer," (in eng), Lancet, vol. 344, no. 8926, pp. 862-3, Sep 24 1994.
K. Abdoulrahman, "Evaluation of advanced glycation end products and other biochemical parameters in patients with leukemia," Journal of Kufa for Chemical Sciences, vol. 2, no. 10, pp. 91-108, 2023.
A. Rafeeinia, G. Asadikaram, M. Karimi-Darabi, M. Abolhassani, M. Abbasi-Jorjandi, and V. Moazed, "Organochlorine pesticides, oxidative stress biomarkers, and leukemia: a case-control study," (in eng), J Investig Med, vol. 70, no. 8, pp. 1736-1745, Dec 2022.
H. Yang et al., "The role of cellular reactive oxygen species in cancer chemotherapy," (in eng), J Exp Clin Cancer Res, vol. 37, no. 1, p. 266, Nov 1 2018.
H. Li, M. Wang, and Y. Huang, "Anthracycline-induced cardiotoxicity: An overview from cellular structural perspective," Biomedicine & Pharmacotherapy, vol. 179, p. 117312, 2024/10/01/ 2024.
M. M. Alam et al., "Glucocorticoid receptor signaling represses the antioxidant response by inhibiting histone acetylation mediated by the transcriptional activator NRF2," (in eng), J Biol Chem, vol. 292, no. 18, pp. 7519-7530, May 5 2017.
A. Widnyana et al., "Level of 8-Hydroxy-2'Deoxyguanosine (8-OHdG) in children with acute lymphoblastic leukemia post-chemotherapy induction phase and post-chemotherapy maintenance phase," Intisari Sains Medis, vol. 14, pp. 445-449, 05/10 2023.
H. He, Y. Zhao, N. Wang, L. Zhang, and C. Wang, "8-Hydroxy-2′-deoxyguanosine expression predicts outcome of esophageal cancer," Annals of Diagnostic Pathology, vol. 18, no. 6, pp. 326-328, 2014/12/01/ 2014.
L. Ben Mahmoud et al., "Oxidative Stress in Tunisian Patients With Acute Lymphoblastic Leukemia and Its Involvement in Leukemic Relapse," (in eng), J Pediatr Hematol Oncol, vol. 39, no. 3, pp. e124-e130, Apr 2017.
V. Battisti et al., "Measurement of oxidative stress and antioxidant status in acute lymphoblastic leukemia patients," (in eng), Clin Biochem, vol. 41, no. 7-8, pp. 511-8, May 2008.
M. B. Almeida, E. Carrilho, and S. L. Nixdorf, "Evaluation of oxidative stress in patients with acute lymphoblastic leukemia: experimental evidence of the efficacy of MDA as cancer biomarker in young patients," Journal of the Brazilian Chemical Society, vol. 29, no. 3, pp. 615-621, 2018.
J. A. Drisko, J. Chapman, and V. J. Hunter, "The use of antioxidant therapies during chemotherapy," Gynecologic Oncology, vol. 88, no. 3, pp. 434-439, 2003.
D. D. Kennedy, R. M. Santella, Q. Wang, E. J. Ladas, and K. M. Kelly, "8-oxo-dG elevated in children during leukemia treatment," (in eng), Integr Cancer Ther, vol. 3, no. 4, pp. 301-9, Dec 2004.
M. El-Sabagh, K. Ramadan, I. El-Slam, and A. Ibrahim, "Antioxidants status in acute lymphoblastic leukemic patients," Parameters, vol. 8, no. 2.0, pp. 5.25-11.25, 2011.
H. Krenzlin et al., "Decreased Superoxide Dismutase Concentrations (SOD) in Plasma and CSF and Increased Circulating Total Antioxidant Capacity (TAC) Are Associated with Unfavorable Neurological Outcome after Aneurysmal Subarachnoid Hemorrhage," (in eng), J Clin Med, vol. 10, no. 6, Mar 12 2021.
M. Rasool et al., "Assessment of circulating biochemical markers and antioxidative status in acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) patients," (in eng), Saudi J Biol Sci, vol. 22, no. 1, pp. 106-11, Jan 2015.
M. D. Mohsin and A. Salihi, "Molecular characterization of NOS3 and SOD1 genes as markers for detecting patients with breast cancer," Molecular Biology Reports, vol. 52, no. 1, p. 467, 2025/05/19 2025.
S. Trombetti et al., "Oxidative Stress and ROS-Mediated Signaling in Leukemia: Novel Promising Perspectives to Eradicate Chemoresistant Cells in Myeloid Leukemia," (in eng), Int J Mol Sci, vol. 22, no. 5, Feb 28 2021.
D. Pande, R. Negi, R. S. Khanna, and H. D. Khanna, "Protein Damage and Antioxidant Status Alterations Caused by Oxidative Injury in Chronic Myeloid Leukemia," Einstein Journal of Biology & Medicine, vol. 27, no. 2, 2011.
Y. Wang, R. Branicky, A. Noë, and S. Hekimi, "Superoxide dismutases: Dual roles in controlling ROS damage and regulating ROS signaling," (in eng), J Cell Biol, vol. 217, no. 6, pp. 1915-1928, Jun 4 2018.
A. Naz, T. S. Shamsi, A. Sattar, and T. Mahboob, "Oxidative stress and total antioxidant status in acute leukemia at diagnosis and post remission induction phase," (in eng), Pak J Pharm Sci, vol. 26, no. 6, pp. 1123-30, Nov 2013.
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