Effect of methotrexate and doxorubicin cumulative doses on superoxide dismutase levels in childhood acute lymphoblastic leukemia

  • Khalida Fetriyani Ningsih Department of Child Health, Gadjah Mada University Medical School/Dr. Sardjito Hospital, Yogyakarta, Indonesia
  • Sri Mulatsih Department of Child Health, Gadjah Mada University Medical School/Dr. Sardjito Hospital, Yogyakarta, Indonesia
  • Sasmito Nugroho Department of Child Health, Gadjah Mada University Medical School/Dr. Sardjito Hospital, Yogyakarta, Indonesia
Keywords: acute lymphoblastic leukemia, methotrexate, doxorubicin, superoxide dismutase

Abstract

Background Acute lymphoblastic leukemia (ALL) is the most
common malignancy in children. Chemotherapeutic drugs for
ALL such as methotrexate (Mtx) and doxorubicin produce
reactive oxygen species (ROS), a type of free radical. The ROS
can reduce levels of antioxidants in the body, including superoxide
dismutase (SOD). Decreased SOD levels can cause DNA, lipid,
and protein damage, which in turn may lead to adverse effects
and treatment failure.


Objective To determine the effect of Mtx and doxorubicin
cumulative doses on SOD levels in children with ALL.

Methods We conducted a retrospective cohort study in children
with ALL who underwent chemotherapy in Dr. Sardjito Hospital
in October 2011 who had completed the induction phase. Risk
factors for decreased SOD levels were analyzed by Cox regression
and hazard ratio, with a significant level of P <0.05.

Results Of 40 patients enrolled, Mtx ≥ 3000 mg/m2 significantly
decreased SOD levels (HR 9.959; 95%CI 2.819 to 35.183; P=0.001). However, doxorubicin ≥90 mg/m2 did not significantly
decrease SOD levels (HR 0.59 95%CI 0.194 to 1.765; P=0.34).

Conclusion Methotrexate is associated with decreased SOD levels
in children with ALL. However, doxorubicin is not associated with
decreased SOD levels in the same patient population.

References

Mulatsih S, Sumadiono, Sutaryo, Purwanto. The result of treating children’s acute lymphoblastic leukemia (ALL) in Dr. Sardjito Hospital with WK-LLA protocol 1999-2002. Buletin Ilmu Kesehatan Anak FK UNAIR. Tahun XXXI. 2004;17:808-19.

Al–Tonbary Y, Al-Haggar M, El-Ashry R, El-Dakroory S, Azzam H, Fouda A. Vitamin e and N-acetylcysteine as antioxidant adjuvant therapy in children with acute lymphoblastic leukemia. Adv Hematol. 2009;15:1-5.

Cetin T, Arpaci F, Yilmaz MI, Saglam K, Ozturk B, Komurcu S, et al. Oxidative stress in patients undergoing high-dose chemotherapy plus peripheral blood stem cell transplantation. Biol Trace Elem Res. 2004;97:237-47.

Tavazzi B, Di Pierro D, Amorini AM, Fazzina G, Tuttobene M, Giardina B, et al. Energy metabolism and lipid peroxidation of human erythrocytes as a function of increased oxidative stress. Eur J Biochem. 2000;267:684-9.

Coleshowers CL, Oguntibeju OO, Ukpong M, Truter EJ. Effect of methotrexate on antioxidant enzyme status in a rodent model. Med Technol. 2010;24:5-9.

Esfahani A, Ghoreishi Z, Nikanfar A, Sanaat Z, Ghorbanihaghjo, A, Rashtchizaden N. Influence of chemotherapy on the oxidant/antioxidant status in patients with acute myeloid leukemia. IJHOSCR. 2009;3:3-4.

Gonzales R, Auclair C, Voisin E, Gautero H, Dhermy D, Boivin P. Superoxide dismutase, catalase, and glutathione peroxidase in red blood cells from patients with malignant disease. Cancer Res. 1984;44:4137-9.

Khan AU, Sheikh MU, Intekhab K. Pre-existing malnutrition and treatment outcome in children with acute lymphoblastic leukaemia. J Pak Med Assoc. 2006;56:171-3.

Asci H, Ozer MK, Calapoglu M, Savran M, Oncu M, Yesilot S, et al. Effects of misoprostol on methotrexate induced hepatic and renal damages. J Biol Life Sci. 2011;2:32-7.

Devrim E, Cetin R, Kilicoglu B, Erguder B, Avci A, Durak I. Methotrexate causes oxidative stress in rat kidney tissues. Ren Fail. 2005;27:771-3.

Alkreathy H, Damanhouri ZA, Amhed N, Slevin M, Ali SS, Osman AM. Aged garlic extract protects against doxorubicin-induced cardiotoxicity in rats. Food Chem Toxicol. 2010;48:951–6.

Singh G, Maulik SK, Jaiswal A, Kumar P, Parshad R. Effect on antioxidant levels in patients of breast carcinoma during neoadjuvant chemotherapy and mastectomy. Malays J Med Sci. 2010;17:24-8.

Conklin KA. Chemotherapy-associated oxidative stress: impact on chemotherapeutic effectiveness. Integr Cancer Ther. 2004;3:294-300.

Tandon VR, Sharma S, Mahajan A, Bardi GH. Oxidative stress: a novel strategy in cancer treatment. JK Science. 2000;7:1-6.

Yokus B, Mete N, Cakir UD, Toprak G. Effect of active and passive smoking on antioxidant enzymes and antioxidant micronutrients. Biotechnol & Biotechnol Eq. 2005;19:1-5.

Sharda B. Free radicals: emerging challenge in environmental health reseach in childhood and neonatal disorders. Int J Environ Res Public Health. 2006;3:286-91.

Published
2015-10-01
How to Cite
1.
Ningsih K, Mulatsih S, Nugroho S. Effect of methotrexate and doxorubicin cumulative doses on superoxide dismutase levels in childhood acute lymphoblastic leukemia. PI [Internet]. 1Oct.2015 [cited 23Dec.2024];55(5):239-2. Available from: https://paediatricaindonesiana.org/index.php/paediatrica-indonesiana/article/view/42
Received 2016-02-01
Published 2015-10-01