Metabolic reprogramming in the arsenic carcinogenesis

Ruan, Yihui; Fang, Xin; Guo, Tingyue; Liu, Yiting; Yu, Huimei; Wang, Xuening; Hu, Yuxin; Gao, Lanyue; Li, Yongfang; Pi, Jingbo; Xu, Yuanyuan

doi:10.1016/j.ecoenv.2021.113098

Cited by 13 publications

(1 citation statement)

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“…Moreover, a principal environmental concern is increasing arsenic contamination in groundwater sources [ 4 ]. The use of contaminated water increases the susceptibility to several autoimmune-related diseases and cancers [ 5 , 6 , 7 ]. The US National Research Council has noted that as many as 1 in 100 additional cancer deaths could be expected from a lifetime exposure to arsenic-contaminated drinking water containing 50 μg/mL [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

Route of Arsenic Exposure Differentially Impacts the Expression of Genes Involved in Gut-Mucosa-Associated Immune Responses and Gastrointestinal Permeability

Gokulan

Mathur

Kumar

et al. 2023

IJMS

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First-pass metabolism alters arsenic biotransformation and its immunomodulatory activities. This study aims to determine the mRNA expression of intestinal-immunity- and permeability-associated genes, levels of cytokine/chemokines and levels of immunoglobulin isotypes when CD-1 mice were exposed to a single dose of intravenous (IV) sodium arsenite (50 µg/kg body weight (BW)) and to compare these responses to exposure via oral gavage (OG) (50 µg/kg BW). Samples were collected at 1, 4, 24 and 48 h post IV exposure and 24 and 48 h post OG. Sodium arsenite IV exposure led to a transient modulation of mRNA expression and protein levels of immunity-related genes involved in inflammation/apoptotic pathways and production of cytokines/chemokines, whereas it also led to downregulated expression of genes encoding tight junction, focal adhesion, and gap junction proteins, which are responsible for maintaining cell permeability. Oral exposure perturbed fewer cell-permeability-related genes at 24 and 48 h post exposure. At 24 h post exposure, OG decreased IgA and IgG2b levels; however, IV exposure significantly increased IgG2b, IgG3 and IgA in ileal tissue. Earlier, we showed significant downregulation of mRNA expression of genes involved in the immune-related pathways during OG in the intestinal mucosa of the same animals. Cumulatively, these results provide evidence that the exposure route of a xenobiotic can differentially impact the intestinal responses due to the impact of first-pass metabolism.

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