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Co-administration of L-Ascorbic Acid and α-Tocopherol Alleviates Arsenic-Induced Immunotoxicities in the Thymus and Spleen by Dwindling Oxidative Stress-Induced Inflammation

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Abstract

Herein, we investigated whether L-ascorbic acid (L-AA) and α-tocopherol (α-T) co-administration has the potential to alleviate arsenic-induced immunotoxicities in the thymus, spleen, and circulating leukocytes. Forty-eight adult male Wistar rats were randomly divided into four groups before the treatment: group I (control); group II (sodium arsenite, 3 mg/kg/day/rat); group III (sodium arsenite + L-AA (200 mg/kg/day/rat) and α-T (400 mg/kg/day/rat)); group IV (L-AA and α-T). The result showed that sodium arsenite exposure (consecutive 30 days) caused weight reduction, structural alterations in the thymus and spleen, accompanied by a decrease in thymocyte and splenocyte count. Decreased superoxide dismutase and catalase activity, increased malondialdehyde and protein–carbonyl content, reduced Nrf2 and Bcl2 expression, and increased p-ERK, NF-kβ, Bax, and cleaved-caspase-3 expression were also observed in the thymus and spleen of arsenic-exposed rats. Enhanced plasma ACTH and corticosterone, ROS-induced apoptosis of lymphocytes were also observed. L-AA and α-T co-administration has the potential to abrogate the deleterious impact of arsenic on the thymus, spleen, and circulating lymphocytes. Whole transcriptome analysis of leukocytes revealed that arsenic treatment augmented the expression of Itga4, Itgam, and MMP9 genes, which might help in transient migration of the leukocytes through the endothelial cell layer. Co-administration with L-AA and α-T maintained Itga4, Itgam, and MMP9 gene expression within leukocytes at a lower level.

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The data that supports the finding of the study are available from the corresponding author upon reasonable request.

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Funding

This work was supported by a grant from the research programme (No: 5/8–4/17/Env/2020-NCD-II) funded by the Indian Council of Medical Research (ICMR), Department of Health Research, Ministry of Health and Family welfare, Government of India (New Delhi, India). We are also grateful to DST-FIST, Government of India (DLS[SR/FST/LSI-560/2013(C)]) and DBT-BUILDER (BT/INF/22/SP45088/2022).

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Jeet Maity: conceptualisation, data curation, analysis, investigation, validation, writing — original draft. Priyankar Pal: data curation. Prabir Kumar Mukhopadhyay and Ranjana Pal: conceptualisation, funding acquisition, project administration, resources, validation.

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Correspondence to Prabir Kumar Mukhopadhyay.

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Maity, J., Pal, P., Pal, R. et al. Co-administration of L-Ascorbic Acid and α-Tocopherol Alleviates Arsenic-Induced Immunotoxicities in the Thymus and Spleen by Dwindling Oxidative Stress-Induced Inflammation. Biol Trace Elem Res 202, 2199–2227 (2024). https://doi.org/10.1007/s12011-023-03841-7

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