Arsenic trioxide exposure accelerates colon preneoplasic aberrant crypt foci induction regionally through mitochondrial dysfunction

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dc.contributor.authorMoulahoum, Hichem
dc.contributor.authorBoumaza, Betkacem Mohamed Amine
dc.contributor.authorFerrat, Meriem
dc.contributor.authorDjerdjouri, Bahia
dc.date.accessioned2019-10-27T10:42:05Z
dc.date.available2019-10-27T10:42:05Z
dc.date.issued2018
dc.departmentEge Üniversitesien_US
dc.description.abstractArsenic poisoning is a worldwide problem. Thus, we studied the effects of arsenic trioxide (ATO) administration on a 1,2-dimethylhydrazine (DMH)-induced preneoplasic colon carcinogenesis model. Mice were separated into four study groups; the control group received only vehicles. The ATO group received daily a 2.5 mg kg(-1) dose for 4 weeks. The DMH group received DMH (20 mg kg(-1)) twice in two weeks. The third group (D-ATO) had the same as the DMH group with ATO administration starting at week 10. At the end of 14 weeks, colons from sacrificed mice were taken, segmented into distal and proximal and subjected to aberrant crypt foci (ACF), aberrant crypt (AC) counting, alcian blue, H&E and Hoechst histological study and lastly oxidative stress marker analysis as well as mitochondrial swelling assessment. Data showed a significant increase in ACF and AC after DMH treatment, which was further increased after ATO addition. A perturbed histological structure was observed and loss of mucin producing cells in the colon tissue was observed. An important impact on the distal colon compared to the proximal one was noticed. The oxidative stress balance showed a similar pattern with an increase in MPO, NO/L-ornithine balance and MDA, while a decrease was observed in the antioxidant enzymes (CAT, SOD and GSH). In all parameters analyzed, the distal colons showed higher values than proximal. Furthermore, histological cell death analysis in combination with mitochondrial permeability pore opening suggested ATO contribution in the pathological effect. Our study has shown that ATO administration accelerated colon cancer development suggesting the heaviness of such treatments and the need to explore combinations and cycle type formulas.en_US
dc.description.sponsorshipProgramme National de Recherche en Sciences Fondamentales, 2011, DGRSDT (Direction Generale de la Recherche Scientifique et du Developpement Technologique) Algiers, Algeria [305]; Agence Universitaire de la Francophonie bureau Europe centrale et orientale (AUF-Beco), Romaniaen_US
dc.description.sponsorshipThis work was supported by the "Programme National de Recherche en Sciences Fondamentales", 2011, DGRSDT (Direction Generale de la Recherche Scientifique et du Developpement Technologique) Algiers, Algeria under the reference ATRSS/PNR 08/No 305. We gratefully acknowledge the financial support from the Agence Universitaire de la Francophonie bureau Europe centrale et orientale (AUF-Beco), Romania.en_US
dc.identifier.doi10.1039/c7tx00213ken_US
dc.identifier.endpage190en_US
dc.identifier.issn2045-452X
dc.identifier.issn2045-4538
dc.identifier.issue2en_US
dc.identifier.pmid30090573en_US
dc.identifier.scopusqualityQ3en_US
dc.identifier.startpage182en_US
dc.identifier.urihttps://doi.org/10.1039/c7tx00213k
dc.identifier.urihttps://hdl.handle.net/11454/30610
dc.identifier.volume7en_US
dc.identifier.wosWOS:000436017700004en_US
dc.identifier.wosqualityQ4en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherRoyal Soc Chemistryen_US
dc.relation.ispartofToxicology Researchen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.titleArsenic trioxide exposure accelerates colon preneoplasic aberrant crypt foci induction regionally through mitochondrial dysfunctionen_US
dc.typeArticleen_US

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