It is reported that oxidative stress may play a role in the etio-pathogenesis of Autism Spectrum Disorders (ASD) (1-3), however the great heterogeneity of the syndrome makes difficult to assess whether this finding is occasional and whether it is restricted to a sub-group of patients. Moreover, not all oxidative stress markers appear to be altered in patients, and it is still unknown whether oxidative stress, if really present, is secondary to a generic inflammatory status or related to genetic alterations still to be recognized. Moreover, most researchers addressing this problem have a tendency to evaluate few markers at a time, thus making it very difficult to compare data obtained in different patient’s subgroups (4,5).The aim of our study is to evaluate a high number of oxidative stress parameters, focusing on erythrocyte membrane functional features and lipid composition, along with some peripheral markers of oxidative stress. Twenty-five autistic children (Au) aged 6 to 12 years, were age-matched with 23 typically developing children (TD). Dietary habits were assessed by a Food Questionnaire. We analysed: 1) the fatty acid membrane profile, the membrane fluidity and the Na+,K+-ATPase activity in erythrocytes; 2) the urinary levels of isoprostane, 8-hydroxy-2'-deoxyguanosine (8-oxo-dG) and Hexanoyl-Lys (HEL); 3) the plasma Total Antioxidant Capacity by ORAC method. At present, both the plasma level of carbonyl groups and the erythrocyte SOD and catalase activities are still under study. The most relevant of our finding (see figure) is a significant reduction of both Na+,K+-ATPase and membrane fluidity in Au compared to TD. Moreover in erythrocyte membrane of Au a significant increase of MUFA and ω6/ω3 ratio, and a decrease of EPA and DHA was shown. Omega-3 deficit was not related to dietary habits. The imbalance of ω6/ω3 ratio may lead to the proinflammatory status that has been reported in ASD, and DHA deficit may play a role in the reduction of both erythrocyte Na+,K+-ATPase activity and membrane fluidity. These results are partially superimposable to those reported in (6). While urinary isoprostane levels were elevated in AU, no differences were found in two other urinary oxidative stress biomarker, 8-oxo-dG and HEL, as well as in Total Antioxidant Capacity of the plasma. Taken together, these results show that Au display significant erythrocyte membrane alterations, at structural and functional levels, suggesting a possible role of these modifications in the pathogenesis of ASD. Future work will be addressed at understanding the reason(s) of the impairment of the Na+,K+-ATPase, the possible consequences of such impairment and their relevance to the pathogenesis of ASD, the possibility of exploiting this finding for a more precise or an earlier diagnosis of ASD, and, last but not least, the possibility to correct the defect by means of nutraceutic tools. References: 1. Chauhan A and Chauhan V. Pathophysiology 2006;13:171–81. 2. James SJ et al, Am J Clin Nutr 2004;80:1611 7. 3. James SJ, et al, Am J Med Genet B Neuropsychiatr Genet 2006;141: 947–56. 4. Meguid NA et al, Biol Trace Elem Res 2011;143:58-65 5. Pecorelli A et al, Brain Dev 2012 Apr 23. [Epub ahead of print] 6. Bell JG et al, Br J of Nutr 2010;103:1160-7.

Alterations in erythrocyte cell membrane and oxidative stress markers in autistic children

BOLOTTA, ALESSANDRA;GHEZZO, ALESSANDRO;ABRUZZO, PROVVIDENZA MARIA;MARINI, MARINA
2012

Abstract

It is reported that oxidative stress may play a role in the etio-pathogenesis of Autism Spectrum Disorders (ASD) (1-3), however the great heterogeneity of the syndrome makes difficult to assess whether this finding is occasional and whether it is restricted to a sub-group of patients. Moreover, not all oxidative stress markers appear to be altered in patients, and it is still unknown whether oxidative stress, if really present, is secondary to a generic inflammatory status or related to genetic alterations still to be recognized. Moreover, most researchers addressing this problem have a tendency to evaluate few markers at a time, thus making it very difficult to compare data obtained in different patient’s subgroups (4,5).The aim of our study is to evaluate a high number of oxidative stress parameters, focusing on erythrocyte membrane functional features and lipid composition, along with some peripheral markers of oxidative stress. Twenty-five autistic children (Au) aged 6 to 12 years, were age-matched with 23 typically developing children (TD). Dietary habits were assessed by a Food Questionnaire. We analysed: 1) the fatty acid membrane profile, the membrane fluidity and the Na+,K+-ATPase activity in erythrocytes; 2) the urinary levels of isoprostane, 8-hydroxy-2'-deoxyguanosine (8-oxo-dG) and Hexanoyl-Lys (HEL); 3) the plasma Total Antioxidant Capacity by ORAC method. At present, both the plasma level of carbonyl groups and the erythrocyte SOD and catalase activities are still under study. The most relevant of our finding (see figure) is a significant reduction of both Na+,K+-ATPase and membrane fluidity in Au compared to TD. Moreover in erythrocyte membrane of Au a significant increase of MUFA and ω6/ω3 ratio, and a decrease of EPA and DHA was shown. Omega-3 deficit was not related to dietary habits. The imbalance of ω6/ω3 ratio may lead to the proinflammatory status that has been reported in ASD, and DHA deficit may play a role in the reduction of both erythrocyte Na+,K+-ATPase activity and membrane fluidity. These results are partially superimposable to those reported in (6). While urinary isoprostane levels were elevated in AU, no differences were found in two other urinary oxidative stress biomarker, 8-oxo-dG and HEL, as well as in Total Antioxidant Capacity of the plasma. Taken together, these results show that Au display significant erythrocyte membrane alterations, at structural and functional levels, suggesting a possible role of these modifications in the pathogenesis of ASD. Future work will be addressed at understanding the reason(s) of the impairment of the Na+,K+-ATPase, the possible consequences of such impairment and their relevance to the pathogenesis of ASD, the possibility of exploiting this finding for a more precise or an earlier diagnosis of ASD, and, last but not least, the possibility to correct the defect by means of nutraceutic tools. References: 1. Chauhan A and Chauhan V. Pathophysiology 2006;13:171–81. 2. James SJ et al, Am J Clin Nutr 2004;80:1611 7. 3. James SJ, et al, Am J Med Genet B Neuropsychiatr Genet 2006;141: 947–56. 4. Meguid NA et al, Biol Trace Elem Res 2011;143:58-65 5. Pecorelli A et al, Brain Dev 2012 Apr 23. [Epub ahead of print] 6. Bell JG et al, Br J of Nutr 2010;103:1160-7.
XIV AIBG
65
65
Bolotta A; Ghezzo A; Abruzzo PM; Visconti P; Ferreri C; Vignini A; Mazzanti L; Marini M
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11585/144505
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