Saliva nitrite is higher in male children with autism spectrum disorder and positively correlated with serum nitrate

Yao, Lulu; Fu, Huimin; Bai, Lijun; Deng, Wenwen; Xie, Fang; Liu, Ying; Xu, Xinjie; Wang, Ting; Lai, Shenghan; Wang, Jun

doi:10.1080/13510002.2021.1959133

Cited by 5 publications

(5 citation statements)

References 77 publications

(107 reference statements)

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“…In a study with the SHANK3 mutated mouse model showed that, involvement of NO-related molecular changes in the brain might affect the development of ASD [ 113 ]. Elevated levels of NO have been found in the blood plasma, saliva, urine, and cerebrospinal fluid of individuals with ASD [ 50 , 51 , 114 ]. Our results are in agreement with these findings showing high levels of iNOS and NO suggesting nitrosative stress in Cntnap2 − / − rats.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Altered Blood Brain Barrier Permeability and Oxidative Stress in Cntnap2 Knockout Rat Model

Memis

Mittal

Furar

et al. 2022

JCM

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Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by three core symptoms, specifically impaired social behavior, stereotypic/repetitive behaviors, and sensory/communication deficits. Although the exact pathophysiology of ASD is still unknown, host genetics, oxidative stress, and compromised blood brain barrier (BBB) have been implicated in predisposition to ASD. With regards to genetics, mutations in the genes such as CNTNAP2 have been associated with increased susceptibility of developing ASD. Although some studies observed conflicting results suggesting no association of CNTNAP2 with ASD, other investigations correlated this gene with autism. In addition, CNTNAP2 mediated signaling is generally considered to play a role in neurological disorders due to its critical role in neurodevelopment, neurotransmission, and synaptic plasticity. In this investigation, we studied BBB integrity and oxidative stress in Cntnap2−/− rats. We observed that the BBB permeability was significantly increased in Cntnap2−/− rats compared to littermate wild-type (WT) animals as determined by FITC-dextran and Evans blue assay. High levels of thiobarbituric acid reactive substances and lower amounts of reduced glutathione were observed in brain homogenates of Cntnap2−/− rats, suggesting oxidative stress. Brain sections from Cntnap2−/− rats showed intense inducible nitric oxide synthase immunostaining, which was undetectable in WT animals. Quantification of nitric oxide in brain homogenates revealed significantly high levels in Cntnap2−/− rats compared to the control group. As increased permeability of the BBB and oxidative stress have been observed in ASD individuals, our results suggest that Cntnap2−/− rats have a high construct and face validity and can be explored to develop effective therapeutic modalities.

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Section: Discussionmentioning

confidence: 99%

“…Under pathological conditions such as infection, trauma, or ischemic insult, iNOS can be expressed in the brain and regulate the level of NO [ 45 , 48 , 49 ]. Elevated NO production has been observed in urine, saliva, plasma, and serum samples from individuals with ASD [ 50 , 51 ].…”

Section: Introductionmentioning

confidence: 99%

Altered Blood Brain Barrier Permeability and Oxidative Stress in Cntnap2 Knockout Rat Model

Memis

Mittal

Furar

et al. 2022

JCM

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“…Additionally, higher levels of the NO metabolite nitrite were reported in saliva from 126 ASD children compared with 129 neurotypical children (FD = 1.87; p < 0.0001). [8] The James laboratory at Arkansas Children's Research Institute demonstrated nitrosative stress (as indexed by 3-Nitrotyrosine) in ASD plasma, [9] post-mortem brain tissue [10] and lymphoblastoid cell lines (LCLs) [11] as early as 2012. Nitrosative stress markers were associated with a decreased (unfavorable) glutathione redox ratio which the James laboratory previously demonstrated to be a key metabolic abnormality associated with ASD and impaired methylation capacity in 2004.…”

Section: Doi: 101002/advs202304439mentioning

confidence: 99%

“…[ 7 ] Additionally, higher levels of the NO metabolite nitrite were reported in saliva from 126 ASD children compared with 129 neurotypical children (FD = 1.87; p < 0.0001). [ 8 ]…”

mentioning

confidence: 99%

Nitrosative Stress in Autism: Supportive Evidence and Implications for Mitochondrial Dysfunction

Frye,

Rose,

Voinsky

et al. 2024

Advanced Science

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A recent study by the Amal team published in this journal in May 2023 proved for the first time the link of nitric oxide (NO) with autism spectrum disorder (ASD), thereby opening new venues for the potential use of neuronal nitric oxide synthase (nNOS) inhibitors as therapeutics for improving the neurological and behavioral symptoms of ASD. The authors conclude that their findings demonstrate that NO plays a significant role in ASD. Indeed, earlier studies support elevated NO and its metabolites, nitrite, and peroxynitrite, in individuals diagnosed with ASD. Dysregulated NOS activity may underlie the well‐documented mitochondrial dysfunction in a subset of individuals with ASD. Strategies for treating ASD shall also consider NO effects on mitochondrial respiration in modulating NOS activity. Further experimental evidence and controlled clinical trials with NOS modifiers are required for assessing their therapeutic potential for individuals with ASD.

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“…Additionally, a positive correlation between salivary nitrite and serum nitrate was observed only in children with ADS, but not in the ND group. This preliminary study lays the groundwork for future studies investigating saliva as a noninvasive diagnostic fluid for ASD, as well as the role of NO in autism diagnosis and therapy [ 81 ].…”

Section: Direct Additives In Children’s Nutritionmentioning

confidence: 99%

Additives in Children’s Nutrition—A Review of Current Events

Savin

Vrkatić

Dedić

et al. 2022

IJERPH

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Additives are defined as substances added to food with the aim of preserving and improving safety, freshness, taste, texture, or appearance. While indirect additives can be found in traces in food and come from materials used for packaging, storage, and technological processing of food, direct additives are added to food with a special purpose (canning). The use of additives is justified if it is in accordance with legal regulations and does not pose a health or danger to consumers in the prescribed concentration. However, due to the specificity of the child’s metabolic system, there is a greater risk that the negative effects of the additive will manifest. Considering the importance of the potential negative impact of additives on children’s health and the increased interest in the control and monitoring of additives in food for children, we have reviewed the latest available literature available through PubMed, Scopus, and Google Scholar. Expert data were taken from publicly available documents published from January 2010 to April 2022 by internationally recognized professional organizations. It was found that the most frequently present additives in the food consumed by children are bisphenols, phthalates, perfluoroalkyl chemicals, perchlorates, pesticides, nitrates and nitrites, artificial food colors, monosodium glutamate, and aspartame. Increasing literacy about the presence and potential risk through continuous education of parents and young people as well as active monitoring of newly registered additives and harmonization of existing legal regulations by competent authorities can significantly prevent the unwanted effects of additives on children’s health.

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Saliva nitrite is higher in male children with autism spectrum disorder and positively correlated with serum nitrate

Cited by 5 publications

References 77 publications

Altered Blood Brain Barrier Permeability and Oxidative Stress in Cntnap2 Knockout Rat Model

Altered Blood Brain Barrier Permeability and Oxidative Stress in Cntnap2 Knockout Rat Model

Nitrosative Stress in Autism: Supportive Evidence and Implications for Mitochondrial Dysfunction

Additives in Children’s Nutrition—A Review of Current Events

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