Abstract
The balance between antioxidant capacity and oxidative stress-induced free radicals may be crucial in the pathophysiological development factor of autism spectrum disorder (ASD). We measured the following urinary and plasma biomarker levels of oxidative stress and antioxidants. As urinary biomarkers, (1) hexanoyl-lysine (HEL), which is a new biomarker of oxidative stress, (2) the total antioxidant capacity (TAC), and (3) 8-hydroxy-2′-deoxyguanosine (8-OHdG), as a product of oxidative modifications to DNA; and the plasma levels of (4) the antioxidant protein superoxide dismutase (SOD), which is the crucial defense again oxygen reactive species, and (5) transferrin and (6) ceruloplasmin, which are biomarkers of iron and copper neurotransmission and oxidant-antioxidant systems. We examined the relationship between these urinary and plasma biomarkers and behavioral symptoms in 19 individuals with ASD (mean age, 10.8 ± 5.2 years) and 10 age-matched healthy controls (mean age, 14.2 ± 7.0 years). Behavioral symptoms were estimated using the Aberrant Behavior Checklist (ABC). Urinary TAC levels were significantly lower, whereas urinary HEL levels were significantly increased in the ASD group as compared with the control group. The five ABC subscale and total scores were significantly raised in the autism group than in the control group. The results of a linear regression analysis revealed that plasma SOD levels may be a more accurate predictor of differences in ABC scores between individuals with ASD and control individuals. The present study firstly revealed the important findings that the cooperation between the urinary antioxidant TAC and plasma SOD levels may contribute to the ABC subscale scores of stereotypy. Urinary TAC activity and antioxidant protein SOD may be associated with incomplete mineral body store and antioxidant-related transcription factor and browning reactions. Consequently, a critical imbalance between TAC urinary levels and plasma SOD levels may be an important contributor to autistic behavioral symptoms.
Highlights
A lot of evidence indicated that interactions between genetic and environmental factors at the time of early childhood are critically important in the development of autism spectrum disorders (ASD) [1]
We previously reported that increased plasma levels of docosahexaenoic acid (DHA)/arachidonic acid (ARA) and eicosapentaenoic acid (EPA)/ARA may be associated with reduced plasma levels of neuroprotective properties of Cp, diminishing the defensive activity against brain damage, and may impart to the pathophysiology of autistic behaviors in individuals with ASD [9, 15]
The aims of the present study were 3-fold: we examined the associations between the urinary concentrations of HEL, total antioxidant capacity (TAC), and 8-OHdG, and plasma levels of Cp, Tf, superoxide dismutase (SOD), and PUFAs, such as ARA, DHA, EPA, Linolenic acid (LA), ALA, GLA, and DGLA; their associations among the core symptoms of behavioral symptoms in individuals with ASD; and the relationship between urinary TAC levels and plasma SOD levels because SOD 1 is a powerful antioxidant enzyme that binds copper and zinc ions under neurodegenerative conditions [25]
Summary
A lot of evidence indicated that interactions between genetic and environmental factors at the time of early childhood are critically important in the development of autism spectrum disorders (ASD) [1]. Recent ASD studies reported a reduced total antioxidant capacity (TAC) [3], higher levels of 8-hydroxy2′-deoxyguanosine (8-OHdG), a biomarker of oxidative modifications to DNA [4], and elevated urinary hexanoyl-lysine (HEL) levels [5, 6]. Recent studies on ASD reported significantly lower urinary TAC levels, indicating heightened vulnerability to oxidative damage [3] and significantly increased urinary 8-OHdG concentrations [7]. Urinary HEL levels were found to be heightened in children with ASD, on the other hand, higher HEL levels associated with the hyperactivity component of the Childhood Autism Rating Scale [5]. The relationships between core ASD behavioral symptoms and urinary HEL, TAC, and 8-OHdG levels have not yet been elucidated
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