title: ω-3 fatty acids as an adjuvant therapy ameliorates methotrexate-induced hepatotoxicity in children and adolescents with acute lymphoblastic leukemia: A randomized placebo-controlled study.
abstract: OBJECTIVE
  Methotrexate (MTX)-induced hepatotoxicity is a significant clinical problem that may affect overall prognosis and disease outcome. Oxidative stress is a key player in its pathogenesis. The aim of this study was to investigate the role of ω-3 fatty acids as an adjuvant therapy in children and adolescents with acute lymphoblastic leukemia (ALL) during the maintenance phase of chemotherapy and the effect of ω-3 on MTX-induced hepatotoxicity.
  
  
  METHODS
  This randomized, double-blind, placebo-controlled trial included 70 patients with ALL who were in the maintenance phase. The participants were divided into two groups: group A received oral MTX and ω-3 fatty acids (1000 mg/d) and group B (received MTX and placebo). Both groups were followed-up for 6 mo with assessment of liver enzymes, total antioxidant capacity (TAC), uric acid, malondialdhyde, superoxide dismutase (SOD), and glutathione peroxidase. The trial was registered at ClinicalTrials.gov (NCT02373579).
  
  
  RESULTS
  Baseline clinical and laboratory parameters were consistent between the two groups (P > 0.05). After 6 mo, liver enzymes and malondialdhyde increased, whereas TAC, uric acid, SOD, and glutathione peroxidase decreased in group B (MTX and placebo) compared with baseline levels or with group A ALL patients receiving ω-3 fatty acids (P < 0.001). The addition of ω-3 to MTX maintained normal liver function and oxidant-antioxidant levels among group A patients at the end of treatment compared with pretherapy levels (P > 0.05). No adverse reactions due to ω-3 supplementation were reported. ALT was inversely correlated to TAC and SOD in the MTX group.
  
  
  CONCLUSIONS
  The study determined that ω-3 fatty acids ameliorated MTX-induced hepatotoxicity and could be safely used during the maintenance phase of ALL.
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Ain Shams University, Cairo, Egypt. Electronic address: nancy_elbarbary@yahoo.com.
authors.forename: Nancy Samir
authors.initials: NS
authors.lastname: Elbarbary
authors.affiliation: Department of Clinical Pathology, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
authors.forename: Eman Abdel Rahman
authors.initials: EA
authors.lastname: Ismail
authors.affiliation: Department of Clinical Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.
authors.forename: Reham Kamel
authors.initials: RK
authors.lastname: Farahat
authors.affiliation: Department of Clinical Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.
authors.forename: Manal
authors.initials: M
authors.lastname: El-Hamamsy
mesh_terms: D000293:Adolescent; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D004311:Double-Blind Method; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008727:Methotrexate / Q000009:adverse effects* / Q000627:therapeutic use; D018384:Oxidative Stress / Q000187:drug effects*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000975:Antioxidants; D015525:Fatty Acids, Omega-3; D008315:Malondialdehyde; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D008727:Methotrexate
keywords: Acute lymphoblastic leukemia; Hepatotoxicity; Methotrexate; Oxidative stress; ω-3 fatty acids