A certain role of SOD/CAT imbalance in pathogenesis of autism spectrum disorders

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The real impact of reactive oxygen species, antioxidant enzymes, mitochondrial dysfunction and chronic inflammation on the development of autism spectrum disorders (ASD) remains unclear, and even controversial. In this study we compared the plasma levels of antioxidant enzymes and their cofactors, markers of oxidative damage, and the respiratory burst in peripheral blood polymorphonuclear leucocytes (PMNL) as surrogate marker of chronic inflammation obtained from 10 children (4–10 year old) who met DSM-5 criteria and their siblings. We demonstrated diminished superoxide dismutase (SOD) and enhanced catalase (CAT) activities resulting in a markedly decreased SOD/CAT ratio and enhanced carbonyl content in the plasma of ASD patients. A strong correlation was present between SOD and CAT activities in the control group, which was not noted in ASD patients. Moreover, in autistic patients, we observed negative correlation between SOD activity on one side, and carbonyl content in plasma, 8-Hydroxy-2-deoxyguanosin content in urine, and respiratory burst intensity in PMNL on the other side. At the same time, low SOD level in autistic children was positively correlated with the magnesium content in the packed RBCs, which might indicate the involvement of the mitochondrial MnSOD in ASD pathogenesis, and therefore the consequent partaking of mitochondrial dysfunction in the development of ASD. Altogether, these results indicate that decreased antioxidant capacity and increased oxidative stress in ASD patients may have functional consequence in terms of increased superoxide leakage, oxidative protein damage, chronic inflammatory response, and, finally, neuronal cell abnormal functioning or death.

Graphical abstract

Suggested mechanism of ASD pathogenesis. Environmental factors such as heavy metals may cause a mitochondrial damage. This leads to the malfunction of electron transport chain and decrease of SOD activity. Both of these lead to enhanced production and diminished scavenging of ROS. Further, dysfunctional mitochondria can create a self-perpetuating cycle of progressive damage that amplifies functional deficits, affects cellular proteins/DNA, and induce persistent inflammatory signals via DAMPs release.

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