Oxidative Changes in Cerebral Spinal Fluid Phosphatidylcholine during Treatment for Acute Lymphoblastic Leukemia

Abstract

Central nervous system (CNS) treatment contributes to improved long-term disease-free survival from childhood acute lymphoblastic leukemia (ALL) by significantly decreasing the rate of disease relapse. Methotrexate (MTX), a drug commonly used for CNS treatment, has been associated with cognitive and academic problems, white-matter changes, perfusion defects, and brain atrophy. This study investigated oxidative stress as a possible mechanism of chemotherapy induced CNS injury. Unoxidized and oxidized components of phosphatidylcholine (PC), the most prevalent phospholipid in CNS cellular membranes, were measured in cerebral spinal fluid (CSF) samples obtained from 21 children diagnosed with low (n = 7), standard (n= 7), or high (n= 7) risk ALL. Children with high-risk ALL received the most MTX, especially during the most intensive phase of treatment (consolidation). Phospholipids were extracted from CSF samples obtained at diagnosis and during the induction, consolidation, and continuation treatment phases. Unoxidized and oxidized PC were measured by normal phase high-performance liquid chromatography at 2 ultraviolet wavelengths (206 and 234 nm, respectively). Data were analyzed by 2-way repeated-measures analysis of variance. Results support the hypotheses that the highest levels of oxidized PC would be observed during the most intensive phase of ALL therapy and in the high-risk ALL group. Findings provide preliminary evidence for chemotherapy-induced oxidative stress in CNS membrane phospholipids.

Increase in Oxidative Stress as Measured by Cerebrospinal Fluid Lipid Peroxidation During Treatment for Childhood Acute Lymphoblastic Leukemia

“…Therefore, PC and PI can be simultaneously monitored at these two wavelengths. 54, 56 Chromatograms showing separation of the components of PI (elution time approximately 14 minutes) and PC (elution time approximately 31.5 minutes) are illustrated in Figure 1.…”

Bupivacain ile Yapılan Spinal Anestezi ile Spinal Sıvı Lipid Peroksidasyon Düzeyi ve Antioksidan Sisteminde Meydana Gelen Değişiklikler

“…It is likely that the increased levels of lipid peroxides in the spinal CSF may cause lipid peroxidation. Some disease [24][25][26] and some drugs used to treat illness 13,27 causes alteration on the free radical defence mechanisms and lipid peroxidation products in CSF. So, it is suggested that the oxidation of CSF lipoproteins play a role in the pathogenesis of neurodegenerative diseases.…”

Decrease of adenosine deaminase activity and increase of the lipid peroxidation after acute methotrexate treatment in young rats: protective effects of grape seed extract

“…Furthermore, to measure biochemical parameters in the serum and urine that may be correlated with the MTX effects in tissues. 13 At last, we intend to assess to what extend GSE, a potent free radical scavenger, could ameliorate the acute MTX-induced effects in young specimens investigated.…”