The effect of bone marrow transplantation on oxidative stress in X-linked adrenoleukodystrophy

• Published in: Molecular genetics and metabolism Vol. 106; no. 2; pp. 231 - 236
• Main Authors: Rockenbach, Francieli J., Deon, Marion, Marchese, Daiane P., Manfredini, Vanusa, Mescka, Caroline, Ribas, Graziela S., Habekost, Clarissa T., Castro, Claudio G., Jardim, Laura B., Vargas, Carmen R.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-06-2012
• Subjects: Adolescent; Adrenoleukodystrophy; Adrenoleukodystrophy - metabolism; Adrenoleukodystrophy - therapy; Blood Proteins - metabolism; Bone Marrow Transplantation; carbonyls; Child; Child, Preschool; Data processing; Free radicals; Humans; Lipid peroxidation; Male; Malondialdehyde; Malondialdehyde - blood; Neurodegenerative diseases; Oxidative Stress; Plasma levels; Protein damage; Sulfhydryl Compounds - blood; Transplantation; Transplants; X chromosome; Bone marrow transplantation; Lipid peroxidation; Oxidative stress; Adrenoleukodystrophy; Free radicals; Protein damage
• ISSN: 1096-7192; 1096-7206
• DOI: 10.1016/j.ymgme.2012.03.019

Oxidative stress plays an important role in the pathophysiology of neurodegenerative diseases, including X-linked adrenoleukodystrophy (X-ALD). In the present work, we evaluated lipid (malondialdehyde [MDA] content) and protein (sulfhydryl and carbonyl contents) oxidative damage parameters in plasma from X-ALD patients before and after bone marrow transplant (BMT), in order to verify if this treatment is capable to alter the oxidative parameters studied. We also evaluated the plasma concentration of hexacosanoic acid (C26:0) from X-ALD patients and correlated it with the oxidative damage parameters investigated. We observed that MDA content was significantly increased in plasma of X-ALD patients before BMT and after BMT when compared to controls, and that it was significantly reduced in plasma of X-ALD after BMT when compared to the before BMT group. These results indicate that lipid peroxidation is stimulated in X-ALD patients but there is a significant reduction of lipid peroxidation after BMT. Next, we observed a significant reduction of sulfhydryl content in plasma of X-ALD patients before BMT compared to controls indicating protein oxidative damage and that this measurement was increased in these patients after BMT as compared to before BMT. We found no significant differences in plasma carbonyl content in X-ALD patients before and after BMT as compared to controls. However, we observed a significant reduction in this parameter in X-ALD patients after BMT compared to before BMT. Finally, C26:0 plasma concentration was significantly reduced in X-ALD patients after BMT when compared to before BMT. We found no significant correlations between MDA and carbonyl values with C26:0 levels of the patients before BMT and after BMT, but a significant inverse correlation between sulfhydryl content and C26:0 levels was detected. In conclusion, the present study reinforces the hypothesis that lipid peroxidation and protein damage are induced in plasma of X-ALD patients and, in addition, demonstrates that BMT treatment is capable to reduce this pathogenic process. Taken together, the data obtained from plasma of X-ALD patients before and after BMT showing induction and protection, respectively, of oxidative stress, allowed to suggest that BMT, when well succeeded and under the recommendations, is effective to reduce C26:0 plasma levels and the increased lipid and protein oxidative damage in X-ALD.
► Oxidative stress was examined in X-ALD patients before and after BMT. ► Lipid and protein oxidative damage are induced in plasma of X-ALD patients. ► BMT is effective to reduce C26:0 plasma levels. ► BMT is effective to reduce the induction of protein oxidative damage in X-ALD. ► BMT is effective to reduce the increased lipid oxidative damage in X-ALD.