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- Title
Mechanisms of Antioxidant Induction with High-Dose N-Acetylcysteine in Childhood Cerebral Adrenoleukodystrophy.
- Authors
Kartha, Reena; Zhou, Jie; Basso, Lisa; Schröder, Henning; Orchard, Paul; Cloyd, James; Kartha, Reena V; Schröder, Henning; Orchard, Paul J
- Abstract
<bold>Background: </bold>Childhood cerebral adrenoleukodystrophy (CCALD), a progressive demyelinating disease affecting school-aged boys, causes death within a few years. Oxidative stress is an important contributing factor. N-acetylcysteine (NAC; 280 mg/kg/day) added as adjunctive therapy to reduced-intensity hematopoietic cell transplantation (HCT) improves survival in advanced cases. However, the mechanisms underlying the benefits of NAC are unclear.<bold>Objective: </bold>The aim of this study was to understand the mechanism of action of NAC in the setting of HCT in CCALD.<bold>Methods: </bold>Immunoassays were carried out to determine changes in heme oxygenase-1 (HO-1) and ferritin expression in plasma samples collected from boys with CCALD at three different timepoints during the course of transplantation. In addition, the induction of HO-1 was also confirmed in normal fibroblasts following incubation with 10-100 µmol/L NAC for 4 h.<bold>Results: </bold>Following NAC therapy we observed an increase in expression of the antioxidants HO-1 (~4-fold) and its effector ferritin (~160-fold) in patient samples as compared with baseline. We also observed that NAC exposure significantly increased HO-1 expression in fibroblasts.<bold>Conclusion: </bold>Our data suggest that HO-1 is a possible target protein of NAC and a mediator of its cytoprotective effects in these patients.
- Subjects
ANTIOXIDANTS; ACETYLCYSTEINE; ADRENOLEUKODYSTROPHY; OXIDATIVE stress; SCHOOLBOYS; HEALTH; RNA metabolism; BLOOD testing; CELL culture; CLINICAL trials; COMPARATIVE studies; ENZYME-linked immunosorbent assay; FERRITIN; FIBROBLASTS; RESEARCH methodology; MEDICAL cooperation; OXIDOREDUCTASES; RESEARCH; EVALUATION research; TREATMENT effectiveness; PHARMACODYNAMICS
- Publication
CNS Drugs, 2015, Vol 29, Issue 12, p1041
- ISSN
1172-7047
- Publication type
journal article
- DOI
10.1007/s40263-015-0300-9