Apoptosis in the gastric ulceration "shay rat model” : role of IL-6 modulation by the cytoprotectant copper-glycinate and-nicotinate complexes

الملخص EN

So far, the mechanism (s) of the very promising gastric antiulcerogenic acting: copper-nictitate and copper-glaciate complexes is not yet completely understood.

It could be hypothesized that modulation of IL-6 and apoptosis may elucidate one aspect of a common mechanism(s) of their action.

“Shay Rat” pyloric ligation gastric ulcer model was utilized in this study.

Total IL-6 in gastric juice and blood serum was measured by an ELISA assay.

Total DNA content and its percentage of fragmentation in gastric juice and Caspase-3 activity in the non glandular stomach mucosal scraping were measured colorimetrically in the four studied groups (I : control ulcerated untreated ; II : ulcerated –treated with copper-glaciate, III : ulcerated treated with copper-nictitate and, IV : ulcerated treated with Omeprazole therapeutic control ,16 rats each).

There were highly significant reduction in the levels of each of IL-6 in gastric juice, serum of treated rats (P < 0.001), fragmented DNA, and correlating reduction in the caspase-3 activity (P < 0.001) amongst the different treatments compared to untreated rats.

Histopathological examination revealed discontinuation of the lining epithelium by aggregated lymph follicles and/or inflammatory cells infiltration ,dilated and congested blood vessels and apoptotic changes affecting epithelial cells mainly, all significantly but differentially prevented by treatments.

This study showed for the first time that gastric ulceration augmented IL-6 and promoted caspase-3 activity as a marker for apoptosis confirmed by DNA fragmentation and histopathology in the used “Shay Rat” gastric ulcer model .All parameters were greatly alleviated by treatments, with stronger equipotent ability for each of the copper complexes used compared to the clinical gold-standard treatment of the disease, omeprazole.