Abstract
Arsenic trioxide (As2O3) is a trending subject in recent therapy approaches despite its described toxicity. In this work, we have investigated the use of arsenic trioxide in a murine model of chemically induced inflammatory bowel disease “colitis.” Male mice were randomly separated into four different groups. Controls received vehicle, arsenic group had a daily injection of As2O3 (2.5 mg/kg, i.p.) for 2 days. Colitis was induced through intra-rectal instillation of 4% (v/v) solution of acetic acid in the second day. The treatment group (As2O3 + acetic acid) received the same treatment as the two previous groups. Twenty-four hours after colitis challenge, animals were sacrificed and organs (colons, livers, and kidneys) were taken for analysis. Disease-related macroscopic and microscopic symptoms, as well as histologic observations, showed a high index in the colitis group, which was greatly reduced by the As2O3 pretreatment. Similarly, colon length was reduced during colon inflammation, which was prevented in the presence of As2O3. Inflammatory cells and oxidative stress markers significantly increased during inflammation accompanied by a considerable reduction of antioxidants. As2O3 treatment managed to reverse these observations to normal levels. Mitochondrial implication was observed through mPTP opening phenomena and semi-quantitative cell death estimation. Low-dose As2O3 use as a mean of preventing the acute phase of colitis can be seen as an interesting approach which counts as a great addition to IBD available treatments.
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This work was supported by the DGRSDT (Direction Générale de la Recherche Scientifique et du Développement Technologique), Algiers, Algeria (PNR project, ATRSS/PNR 08/N°305).
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HM, BMAB, AB, and BD conceived and designed the research plan. HM, BMAB, and MF conducted experiments. HM, BMAB, and MF analyzed the data. HM wrote the manuscript. AB and BD supervised the work. All authors read and approved the manuscript.
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All experiments were performed according to the “Ethics Committee for handling laboratory animals” guidelines at the “University of Sciences and Technology Houari Boumediene, Algiers, Algeria.”
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Moulahoum, H., Boumaza, B.M.A., Ferrat, M. et al. Arsenic trioxide ameliorates murine colon inflammation through inflammatory cell enzymatic modulation. Naunyn-Schmiedeberg's Arch Pharmacol 392, 259–270 (2019). https://doi.org/10.1007/s00210-018-1578-1
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DOI: https://doi.org/10.1007/s00210-018-1578-1