No abstract

Arsenic 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 dose for 4 weeks. The DMH group received DMH (20 mg kg) 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.

This study investigated the potential of gadolinium chloride (GdCl 3 ), an inhibitor of kupffer cells on the myeloperoxidase (MPO) function, both in vivo on colon inflammation model and in vitro on thioglycollate-elicited peritoneal neutrophils. Colon inflammation was induced in mice (n = 7) by 4% acetic acid (AA) enema. GdCl 3 (10 mg/kg) treatment was given 24 h before AA challenge. Clinical changes during the protocol were scored. Colons were segmented into distal and proximal parts for histological and biochemical assessment. Furthermore, myeloperoxidase (MPO) enzymes were extracted and analyzed by western blot. Short-term GdCl 3 treatment inhibited dose-dependently superoxide anion (O 2 •− ), alkaline phosphatase (ALP), and MPO release and promoted neutrophil apoptosis. In vivo, low-dose GdCl 3 improved colitis scores and inhibited acute phagocyte recruitment and colon damage within the mucosa as revealed by the decrease in MPO, nitric oxide (NO), and malondialdehyde (MDA) levels. At the same time, GdCl 3 restored catalase (CAT), superoxide dismutase (SOD) activities, and reduced glutathione (GSH) levels, thus reversing the MDA/GSH ratio in both distal and proximal colons. Compared to proximal, distal colon was more altered and displayed higher pathological manifestations. Lastly, the induction of apoptosis and regulation of the major nitrosative and oxidative functions of neutrophils by GdCl 3 suggests its consideration as a beneficial tool in attenuating colon inflammation.

No abstract