Journal of Leukemia
Open Access

Abstract

Protective Effect of Nigella sativa Oil against Methotrexate Induced Hepatotoxicity in Children with Acute Lymphoblastic Leukemia

Adel A Hagag, Ahmed M Abd Elaal, Ayman Elsheik and Enas Arafa Elzamarany

Background: Acute Lymphoblastic Leukemia (ALL) is the most common childhood malignancies representing about one third of all pediatric cancers. Adding methotrexate to leukemia treatment protocols has been associated with an increased survival rate in children with ALL. The efficacy of this agent is often limited by its toxicity which can be reduced if supplemented with anti-oxidants. Nigella sativa has antioxidant property through different mechanisms. Objective: The aim of this work was to study the role of Nigella sativa oil in the protection against hepatotoxicity induced by methotrexate therapy in children with ALL and the impact on the treatment outcome. Patients and methods: The present study was conducted in the period between July 2010 and July 2013 on 40 children with newly diagnosed ALL including 28 males and 12 females, with mean age value of 9.17 ± 3.81 years and they were divided into 20 patients of ALL under methotrexate therapy included in ALL treatment protocol, delayed leukovorin rescue (10 mg/m2 orally or IV every 6 hours for five doses beginning 48 hours after start of methotrexate infusion and Nigella sativa oil in form of soft gelatin capsule 450 mg in dose of 80 mg/kg/day on three divided doses for one week after each methotrexate dose (Group II) and 20 patients of ALL under methotrexate therapy included in ALL treatment protocol, delayed leukovorin rescue (10 mg/m2 orally or IV every 6 hours for five doses beginning 48 hours after start of methotrexate infusion and placebo for one week after each methotrexate dose (Group III). This study also included 20 healthy children as a control group (11 males and 9 females) with their mean age value of 9.1+ 2.9 (Group I). All patients included in the study were subjected to the following investigations: Complete blood picture, bone marrow aspiration, cytochemistry, immunophenotyping and liver function testes. Results: There were no significant difference in serum bilirubin, alanine aminotransferase, aspartate aminotransferase, alkaline phosphase levels and prothrombin time between group II and group III but there was significant difference between group II and group III compared to controls. There was no significant difference in total protein, albumin, globulin levels, and albumin globulin ratio between studied groups. There were non-significant increase in total, direct and indirect serum bilirubin, serum ALT, AST, and alkaline phosphatase levels and prothrombin time in group II after methotrexate and Nigella sativa oil therapy but there was significant increase in group III after treatment with methotrexate and placebo with significant difference between group II and III after therapy. There were significant differences in overall and disease free survival between group II and group III. Conclusion: Oral administration of Nigella sativa oil in leukemic children can prevent MTX hepatotoxicity and improved survival in patients with ALL. Recommendations: Nigella sativa oil is recommended adjuvant drug as hepatoprotective agent in patients with ALL who received methotrexate therapy.