TY - JOUR
T1 - Oxidative changes in cerebral spinal fluid phosphatidylcholine during treatment for acute lymphoblastic leukemia
AU - Miketova, Petra
AU - Kaemingk, Kris
AU - Hockenberry, Marilyn
AU - Pasvogel, Alice
AU - Hutter, John
AU - Krull, Kevin
AU - Moore, Ida M.
PY - 2005/1
Y1 - 2005/1
N2 - Central nervous system (CNS) treatment contributes to improved long-term disease-free survival from childhood acute lymphoblastic leukemia (ALL) by sigificantly 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.
AB - Central nervous system (CNS) treatment contributes to improved long-term disease-free survival from childhood acute lymphoblastic leukemia (ALL) by sigificantly 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.
KW - Childhood leukemia
KW - Lipid peroxidation
KW - Methotrexate
KW - Oxidative stress
KW - Phosphatidylcholine
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U2 - 10.1177/1099800404271916
DO - 10.1177/1099800404271916
M3 - Article
C2 - 15583359
AN - SCOPUS:16644366977
SN - 1099-8004
VL - 6
SP - 187
EP - 195
JO - Biological Research for Nursing
JF - Biological Research for Nursing
IS - 3
ER -