Thioredoxin 1 and Thioredoxin Reductase 1 Redox System Is Dysregulated in Neutrophils of Subjects with Autism: In Vitro Effects of Environmental Toxicant, Methylmercury Article Swipe
Samiyah Alshehri
,
Sheikh F. Ahmad
,
Norah A. Albekairi
,
Sana S. Alqarni
,
Naif O. Al‐Harbi
,
Laila Al‐Ayadhi
,
Sabry M. Attia
,
Ali S. Alfardan
,
Saleh A. Bakheet
,
Ahmed Nadeem
·
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.3390/toxics11090739
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.3390/toxics11090739
Autism spectrum disorder (ASD) is a complex developmental disorder in children that results in abnormal communicative and verbal behaviors. Exposure to heavy metals plays a significant role in the pathogenesis or progression of ASD. Mercury compounds pose significant risk for the development of ASD as children are more exposed to environmental toxicants. Increased concentration of mercury compounds has been detected in different body fluids/tissues in ASD children, which suggests an association between mercury exposure and ASD. Thioredoxin1 (Trx1) and thioredoxin reductase1 (TrxR1) redox system plays a crucial role in detoxification of oxidants generated in different immune cells. However, the effect of methylmercury and the Nrf2 activator sulforaphane on the Trx1/TrxR1 antioxidant system in neutrophils of ASD subjects has not been studied previously. Therefore, this study examined the effect of methylmercury on Trx1/TrxR1 expression, TrxR activity, nitrotyrosine, and ROS in neutrophils of ASD and TDC subjects. Our study shows that Trx1/TrxR1 protein expression is dysregulated in ASD subjects as compared to the TDC group. Further, methylmercury treatment significantly inhibits the activity of TrxR in both ASD and TDC groups. Inhibition of TrxR by mercury is associated with upregulation of the Trx1 protein in TDC neutrophils but not in ASD neutrophils. Furthermore, ASD neutrophils have exaggerated ROS production after exposure to methylmercury, which is much greater in magnitude than TDC neutrophils. Sulforaphane reversed methylmercury-induced effects on neutrophils through Nrf2-mediated induction of the Trx1/TrxR1 system. These observations suggest that exposure to the environmental toxicant methylmercury may elevate systemic oxidative inflammation due to a dysregulated Trx1/TrxR1 redox system in the neutrophils of ASD subjects, which may play a role in the progression of ASD.
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- Type
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- Language
- en
- Landing Page
- https://doi.org/10.3390/toxics11090739
- https://www.mdpi.com/2305-6304/11/9/739/pdf?version=1693279812
- OA Status
- gold
- Cited By
- 8
- References
- 67
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4386246191
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Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W4386246191Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.3390/toxics11090739Digital Object Identifier
- Title
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Thioredoxin 1 and Thioredoxin Reductase 1 Redox System Is Dysregulated in Neutrophils of Subjects with Autism: In Vitro Effects of Environmental Toxicant, MethylmercuryWork title
- Type
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articleOpenAlex work type
- Language
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enPrimary language
- Publication year
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2023Year of publication
- Publication date
-
2023-08-29Full publication date if available
- Authors
-
Samiyah Alshehri, Sheikh F. Ahmad, Norah A. Albekairi, Sana S. Alqarni, Naif O. Al‐Harbi, Laila Al‐Ayadhi, Sabry M. Attia, Ali S. Alfardan, Saleh A. Bakheet, Ahmed NadeemList of authors in order
- Landing page
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https://doi.org/10.3390/toxics11090739Publisher landing page
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https://www.mdpi.com/2305-6304/11/9/739/pdf?version=1693279812Direct link to full text PDF
- Open access
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YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
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https://www.mdpi.com/2305-6304/11/9/739/pdf?version=1693279812Direct OA link when available
- Concepts
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Methylmercury, Thioredoxin, Thioredoxin reductase, Toxicant, Chemistry, Autism spectrum disorder, Oxidative stress, Autism, Immunology, Biology, Biochemistry, Medicine, Environmental chemistry, Toxicity, Psychiatry, Bioaccumulation, Organic chemistryTop concepts (fields/topics) attached by OpenAlex
- Cited by
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8Total citation count in OpenAlex
- Citations by year (recent)
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2025: 4, 2024: 4Per-year citation counts (last 5 years)
- References (count)
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67Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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