Molecular Dissection of the Arsenic-Induced Leukocyte Incursion into the Inflamed Thymus and Spleen and Its Amelioration by Co-supplementation of L-Ascorbic Acid and α-Tocopherol.

Arsenic, a surreptitious presence in our environment, perpetuates a persistent global menace with its deleterious impacts. It possesses the capability to trigger substantial immunosuppression by instigating inflammation in critical organs like the thymus and spleen. L-Ascorbic acid (L-AA) exhibits robust immunoregulatory prowess by orchestrating the epigenetic terrain through TET and JHDM pathways. Conversely, α-tocopherol (α-T) demonstrates the capacity to dampen the production of pro-inflammatory cytokines by modulating the PI3K-Akt axis. Given these insights, this inquiry embarks on exploring the mitigative potential of L-AA and α-T co-supplementation at the transcriptome level within leukocytes under arsenic exposure. Concurrently, the research endeavours to unravel the potent anti-inflammatory effects of administering α-T and L-AA, alleviating inflammation within the spleen and thymus amidst arsenic-induced insult and delving deeply into their immunomodulatory mechanisms. The rats were randomly allocated into eight distinct groups for subsequent experimentation: (I) the control group was administered solely with distilled water as the vehicle (control); (II) NaAsO-treated group (As); (III) NaAsO treated along with L-ascorbic acid and α-tocopherol supplemented group (As + L-AA + α-T); (IV) L-ascorbic acid and α-tocopherol supplemented group (L-AA + α-T); (V) NaAsO treated along with L-ascorbic acid supplemented group (As + L-AA); (VI) only L-ascorbic acid supplemented group (L-AA); (VII) NaAsO treated along with α-tocopherol supplemented group (As + α-T); (VIII) only α-tocopherol supplemented group (α-T). Rats treated with NaAsO exhibited an increased neutrophil count in their bloodstream, as revealed by a comprehensive transcriptomic analysis showcasing heightened expressions of ItgaM, MMP9, and Itga4 within circulating leukocytes under arsenic exposure. Concurrently, arsenic heightened the expression of pro-inflammatory cytokines within the thymus and spleen. This elevated cytokine activity promoted the upregulation of ICAM-1 on vascular endothelial cells, facilitating the infiltration of Ly6g + leukocytes into the afflicted thymus and spleen. Remarkably, the combination of L-AA acid and α-T demonstrated substantial therapeutic efficacy, adeptly reducing the influx of Ly6g + leukocytes into these immune sites and subsequent reduction of excessive collagen deposition. The dynamic duo of L-AA and α-T achieved this amelioration by suppressing the expression of ItgaM, MMP9, and Itga4 mRNA within circulating leukocytes and moderating tissue levels of pro-inflammatory cytokines in arsenic-exposed thymus and spleen.