Arsenic trioxide ameliorates murine colon inflammation through inflammatory cell enzymatic modulation

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.