PROTECTIVE ROLE OF SYLIMARIN ON METHOTREXATE INDUCED HEPATO-NEPHROTOXICITY IN CHILDREN WITH ACUTE LYMPHOBLASTIC LEUKEMIA
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Keywords
Keywords, Sylimarin. Methotrexate, Serum cystatin C, Urinary N-acetyl-beta-D-glucosaminidase.
Abstract
Abstract
Background:ALL is the most common childhood malignancy. ALL are treated with methotrexate (MTX) based chemotherapy protocols. MTX can cause unpredictable serious hepato-renal side effects. Sylimarin has antioxidant and anti-inflammatory activities, membrane stabilizing effect,stimulate tissue regeneration and inhibit deposition of collagen fibers.This study aims to evaluate the protective effects of Sylimarin on MTX induced hepato-nephrotoxicity in children with ALL. Patients and Methods: 80 children with newly diagnosed ALL were included in the study. They were divided randomly into: Group I that included 40 children with ALL with their ages ranging from 4-13 years and mean age of 6.85± 2.89 years who received Sylimarin 420 mg/day in 3 divided doses for one week after each MTX dose and Group II that included 40 children with ALL with their ages ranging from 4-12 years and mean age value of 7.30±2.6 years who received placebo for one week after MTX therapy.For all patients liver functions including serum bilirubin, serum protein and its fractions albumin, globulin and albumin globulin ratio, alkaline phosphatase, ALT and AST, prothrombin time and activityand renal functions including blood urea and serum creatinine, serum cystatin C and urinary N-acetyl-beta-D-glucosaminidase were doneto assess hepatic and renal toxicity before and after chemotherapy. Results: There were significant differences in ALT, AST and alkaline phosphatase levels and Prothrombin time and activity between group I and II after chemotherapy, with higher level of ALT and AST (P value = 0.000), alkaline phosphatase (P value= 0.017), and lower Prothrombin activity (P value= 0.020) and prolonged prothrombin time (P value= 0.001) in group II compared with group I. There were no significant differences as regard total bilirubin (P. value=0.563), serum protein and albumin levels between group I and II. There were no significant differences between studied groups as regard kidney functions before chemotherapy while after chemotherapy, there was significant reduction in blood urea and serum creatinine, and cystatin C and urinary N-acetyl-beta-D-glucosaminidase in group I compared with group II.Conclusion: Sylimarin improved some hepatic and renal functions in children with ALL who received MTX therapy. Recommendations: Sylimarin could be recommended adjuvant hepatic and renal protective agent in patients with ALL who received MTX therapy.
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