Arsenic trioxide ameliorates murine colon inflammation through inflammatory cell enzymatic modulation
- 27 Downloads
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.
KeywordsArsenic trioxide IBD Colitis Phagocytes Mitochondria
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).
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.
Compliance with ethical standards
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.”
Conflict of interest
The authors declare that they have no conflict of interest.
- Achitei D, Ciobica A, Balan G, Gologan E, Stanciu C, Stefanescu G (2013) Different profile of peripheral antioxidant enzymes and lipid peroxidation in active and non-active inflammatory bowel disease patients. Dig Dis Sci 58:1244–1249. https://doi.org/10.1007/s10620-012-2510-z CrossRefPubMedGoogle Scholar
- Belzacq AS, el Hamel C, Vieira HLA, Cohen I, Haouzi D, Métivier D, Marchetti P, Brenner C, Kroemer G (2001) Adenine nucleotide translocator mediates the mitochondrial membrane permeabilization induced by lonidamine, arsenite and CD437. Oncogene 20:7579–7587. https://doi.org/10.1038/sj.onc.1204953 CrossRefPubMedGoogle Scholar
- Boyer J, Saint-Paul MC, Dadone B, Patouraux S, Vivinus MH, Ouvrier D, Michiels JF, Piche T, Tulic MK (2018) Inflammatory cell distribution in colon mucosa as a new tool for diagnosis of irritable bowel syndrome: a promising pilot study. Neurogastroenterol Motil 30. https://doi.org/10.1111/nmo.13223 CrossRefGoogle Scholar
- Coburn LA, Gong X, Singh K, Asim M, Scull BP, Allaman MM, Williams CS, Rosen MJ, Washington MK, Barry DP, Piazuelo MB, Casero RA, Chaturvedi R, Zhao Z, Wilson KT (2012) L-arginine supplementation improves responses to injury and inflammation in dextran sulfate sodium colitis. PLoS One 7:e33546. https://doi.org/10.1371/journal.pone.0033546 CrossRefPubMedPubMedCentralGoogle Scholar
- Cuzzocrea S, Ayroldi E, di Paola R, Agostini M, Mazzon E, Bruscoli S, Genovese T, Ronchetti S, Caputi AP, Riccardi C (2005) Role of glucocorticoid-induced TNF receptor family gene (GITR) in collagen-induced arthritis. FASEB J 19:1253–1265. https://doi.org/10.1096/fj.04-3556com CrossRefPubMedGoogle Scholar
- Hansen RA, Gartlehner G, Powell GE, Sandler RS (2007) Serious adverse events with infliximab: analysis of spontaneously reported adverse events. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association 5:729–735. https://doi.org/10.1016/j.cgh.2007.02.016 CrossRefGoogle Scholar
- Higgins PD, Skup M, Mulani PM, Lin J, Chao J (2015) Increased risk of venous thromboembolic events with corticosteroid vs biologic therapy for inflammatory bowel disease. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association 13:316–321. https://doi.org/10.1016/j.cgh.2014.07.017 CrossRefGoogle Scholar
- Kandhare AD, Raygude KS, Ghosh P, Ghule AE, Gosavi TP, Badole SL, Bodhankar SL (2012) Effect of hydroalcoholic extract of Hibiscus rosa sinensis Linn. leaves in experimental colitis in rats. Asian Pac J Trop Biomed 2:337–344. https://doi.org/10.1016/S2221-1691(12)60053-7 CrossRefPubMedPubMedCentralGoogle Scholar
- Naranmandura H, Chen X, Tanaka M, Wang WW, Rehman K, Xu S, Chen Z, Chen SQ, Suzuki N (2012) Release of apoptotic cytochrome C from mitochondria by dimethylarsinous acid occurs through interaction with voltage-dependent anion channel in vitro. Toxicol Sci 128:137–146. https://doi.org/10.1093/toxsci/kfs154 CrossRefPubMedGoogle Scholar
- Paul MK, Rajinder K, Mukhopadhyay AK (2008) Characterization of rat liver mitochondrial permeability transition pore by using mitochondrial swelling assay. Afr J Pharm Pharmacol 2:014–021Google Scholar
- Ramasamy S, Nguyen DD, Eston MA, Nasrin Alam S, Moss AK, Ebrahimi F, Biswas B, Mostafa G, Chen KT, Kaliannan K, Yammine H, Narisawa S, Millán JL, Warren SH, Hohmann EL, Mizoguchi E, Reinecker HC, Bhan AK, Snapper SB, Malo MS, Hodin RA (2011) Intestinal alkaline phosphatase has beneficial effects in mouse models of chronic colitis. Inflamm Bowel Dis 17:532–542. https://doi.org/10.1002/ibd.21377 CrossRefPubMedPubMedCentralGoogle Scholar
- Shen ZX, Chen GQ, Ni JH, Li XS, Xiong SM, Qiu QY, Zhu J, Tang W, Sun GL, Yang KQ, Chen Y, Zhou L, Fang ZW, Wang YT, Ma J, Zhang P, Zhang TD, Chen SJ, Chen Z, Wang ZY (1997) Use of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia (APL): II. Clinical efficacy and pharmacokinetics in relapsed patients. Blood 89:3354–3360PubMedGoogle Scholar
- Swirski FK, Nahrendorf M, Etzrodt M, Wildgruber M, Cortez-Retamozo V, Panizzi P, Figueiredo JL, Kohler RH, Chudnovskiy A, Waterman P, Aikawa E, Mempel TR, Libby P, Weissleder R, Pittet MJ (2009) Identification of splenic reservoir monocytes and their deployment to inflammatory sites. Science 325:612–616. https://doi.org/10.1126/science.1175202 CrossRefPubMedPubMedCentralGoogle Scholar
- Zhou XG, Scharf ME, Sarath G, Meinke LJ, Chandler LD, Siegfried BD (2004) Partial purification and characterization of a methyl-parathion resistance-associated general esterase in Diabrotica virgifera virgifera (Coleoptera : Chrysomelidae). Pestic Biochem Physiol 78:114–125. https://doi.org/10.1016/j.pestbp.2003.10.003 CrossRefGoogle Scholar