Intestinal homeostasis disruption in mice chronically exposed to arsenite-contaminated drinking water

Domene, Adrián; Orozco, H.; Rodríguez-Viso, Pilar; Monedero, Vicente; Zúñiga, Manuel; Vélez, Dinoraz; Devesa, Vicenta

doi:10.1016/j.cbi.2023.110404

Cited by 10 publications

(12 citation statements)

References 78 publications

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“…Gene expression data show a reduction in the number of transcripts of the major mucin of the colonic mucus layer. As observed in As(III)-treated animals, this reduction is associated with a reduction of the population of mucus-secreting cells. Exposure to As(V) could affect the differentiation of stem cells into the secretory lineage, as seen in As(III)-treated mice, which would explain the observed reduced number of mucus-secreting cells (Figure ).…”

Section: Discussionsupporting

confidence: 58%

“…A differential toxic effect of both forms of inorganic As is observed at the gut microbiota level. Treatment of mice with As(III) affects the abundance of some taxa, although the composition of the microbiota is not altered . In the analysis of alpha diversity, differences in the effect of exposure to each of the arsenical forms were observed.…”

Section: Discussionmentioning

confidence: 97%

“…By contrast, although treatment with 15 mg/L As(V) resulted in increased oxidative stress (Figure 1A−C), some degree of leukocyte infiltration (Figure 3A,B) and downregulation of proteins of the junctional complex and the mucus layer (Table 2), it did not significantly affect intestinal permeability (Figure 9). Previous in vitro studies have shown that As(V) does not exert an effect on intestinal monolayers as relevant as As(III); 42 however, in this study, exposure to As(V) generates a similar effect as As(III) 18 in many of the toxicological endpoints analyzed. Transformations of As(V) as it passes through the digestive tract might partly explain the differences between in vitro and in vivo assays.…”

Section: Discussionmentioning

confidence: 99%

“…Standards solutions were derivatized under the same conditions as those applied to feces samples. The analytical features of the method were reported previously …”

Section: Materials and Methodsmentioning

confidence: 99%

“…The analytical features of the method were reported previously. 18 2.5. Evaluation of the Intestinal Mucosa Structure.…”

Section: T H Imentioning

confidence: 99%

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Impact of Chronic Exposure to Arsenate through Drinking Water on the Intestinal Barrier

Domene,

Orozco,

Rodríguez-Viso

et al. 2023

Chem. Res. Toxicol.

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Chronic exposure to inorganic arsenic (As) [As(III) + As(V)], which affects millions of people, increases the incidence of some kinds of cancer and other noncarcinogenic pathologies. Although the oral pathway is the main source of exposure, in vivo studies conducted to verify the intestinal toxicity of this metalloid are scarce and are mainly focused on evaluating the toxicity of As(III). The aim of this study was to evaluate the effect of chronic exposure (6 months) of BALB/c mice to As(V) (15–60 mg/L) via drinking water on the different components of the intestinal barrier and to determine the possible mechanisms involved. The results show that chronic exposure to As(V) generates a situation of oxidative stress (increased lipid peroxidation and reactive species) and inflammation (increased contents of several proinflammatory cytokines and neutrophil infiltrations) in the intestinal tissues. There is also evidence of an altered expression of constituent proteins of the intercellular junctions (Cldn1, Cldn3, and Ocln) and the mucus layer (Muc2) and changes in the composition of the gut microbiota and the metabolism of short-chain fatty acids. All of these toxic effects eventually may lead to the disruption of the intestinal barrier, which shows an increased paracellular permeability. Moreover, signs of endotoxemia are observed in the serum of As(V)-treated animals (increases in lipopolysaccharide-binding protein LBP and the proinflammatory cytokine IL-1β). The data obtained suggest that chronic exposure to As(V) via drinking water affects the intestinal environment.

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Section: Discussionsupporting

confidence: 58%

Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

“…Standards solutions were derivatized under the same conditions as those applied to feces samples. The analytical features of the method were reported previously …”

Section: Materials and Methodsmentioning

confidence: 99%

“…The analytical features of the method were reported previously. 18 2.5. Evaluation of the Intestinal Mucosa Structure.…”

Section: T H Imentioning

confidence: 99%

See 3 more Smart Citations

Impact of Chronic Exposure to Arsenate through Drinking Water on the Intestinal Barrier

Domene,

Orozco,

Rodríguez-Viso

et al. 2023

Chem. Res. Toxicol.

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Ferulic Acid Inhibits Arsenic‐Induced Colon Injury by Improving Intestinal Barrier Function

Wang,

Hong,

et al. 2024

Environmental Toxicology

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The prolonged exposure to arsenic results in intestinal barrier dysfunction, which is strongly concerned with detrimental processes such as oxidative stress and the inflammatory response. Ferulic acid (FA), as a phenolic acid, possesses the capability to mitigate arsenic‐induced liver damage and cardiotoxic effects dependent on inhibition of oxidative stress and inflammatory responses. FA can mitigate testicular tissue damage and alveolar epithelial dysfunction, the mechanism of which may rely on nuclear factor erythroid 2‐related factor 2/heme oxygenase 1 (Nrf2/HO‐1) activation and nuclear factor‐kappa B (NF‐κB) pathway blocking. Based on the antioxidant and anti‐inflammatory properties of FA, we speculated that FA might have the potential to inhibit arsenic‐induced intestinal damage. To confirm this scientific hypothesis, mice exposed to sodium arsenite were treated with FA to observe colonic histopathology and TJ protein levels, and oxidative stress and TJ protein levels in Caco‐2 cells exposed to sodium arsenite were assessed after FA intervention. In addition, molecular levels of NF‐κB and Nrf2/HO‐1 pathway in colon and Caco‐2 cells were also detected. As shown in our data, FA inhibited arsenic‐induced colon injury, which was reflected in the improvement of mucosal integrity, the decrease of down‐regulated expression of tight junction (TJ) proteins (Claudin‐1, Occludin, and ZO‐1) and the inhibition of oxidative stress. Similarly, treatment with FA attenuated the inhibitory effect of arsenic on TJ protein expression in Caco‐2 cells. In addition to suppressing the activation of NF‐κB pathway, FA retrieved the activation of Nrf2/HO‐1 pathway in colon and intestinal epithelial cells induced by arsenic. In summary, our findings propose that FA has the potential to mitigate arsenic‐induced intestinal damage by preserving the integrity of intestinal epithelial TJs and suppressing oxidative stress. These results lay the groundwork for the potential use of FA in treating colon injuries caused by arsenic.

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Urea cycle promotion via ammonia-upregulated CPS1 is involved in arsenite-induced pulmonary fibrosis through enhancing collagen synthesis

Xie,

Wang,

Chen

et al. 2024

Chemico-Biological Interactions

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Intestinal homeostasis disruption in mice chronically exposed to arsenite-contaminated drinking water

Cited by 10 publications

References 78 publications

Impact of Chronic Exposure to Arsenate through Drinking Water on the Intestinal Barrier

Impact of Chronic Exposure to Arsenate through Drinking Water on the Intestinal Barrier

Ferulic Acid Inhibits Arsenic‐Induced Colon Injury by Improving Intestinal Barrier Function

Urea cycle promotion via ammonia-upregulated CPS1 is involved in arsenite-induced pulmonary fibrosis through enhancing collagen synthesis

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