Cobalt Modulates Healing of Gastric Ulceration in Male Wistar Rats: iNOS/COX-2 Crosstalk

Abstract

Background: Information on the interplay between gastric iNOS and COX-2 expression by Cobalt (CoCl₂) during gastro-protection is unclear.

Objective: Cobalt activities on iNOS and COX-2 interplay was investigated using Reserpine (RGU), and Pyloricligation (PLGU) gastric ulcer models.

Materials and Methods: In RGU, 50 Wistar rats grouped; 1-control, 2-ulcerated untreated (RUU), 3, 4, and 5 were ulcerated pre-treated  with 62mg/kg, 25mg/kg CoCl₂ and 3.6mg/kg omeprazole for 5 days and sacrificed 3 and 8 hours after reserpine administration. In PLGU,  25 Wistar rats grouped; A-25mg/kg Cocl₂, B-62mg/kg Cocl₂, C-Cimetidine (36.88mg/kg), D-ulcerated untreated (UU), and E–control, were  pretreated for 8 days prior 18 hours pyloric-ligation. Thereafter, macroscopic gastric ulceration (GU), biochemical analysis with histology,  and immunohistochemistry were evaluated on excised stomach. Data were expressed as Mean+SEM, and p<0.05 was significant. 

Results:  In RGU model, significant increase in GU score, nitric oxide, lipid peroxidation, and degranulated mast cells but a decrease in sulfhydryl,  hydrogen peroxide levels in RUU by 3H and 8H were ameliorated by CoCl₂. Histology revealed increased degranulated mast cells in the  RUU compared with CoCl₂-treated groups. CoCl₂ treatment significantly decreased gastric acid secretion, ulcer index, parietal cell count,  H+ /K+ATPase and Na⁺ /K+ATPase activities compared with UU. Gastric sulfhydryl, mucin, pepsin, with mucous cell count significantly  increased in CoCl₂-treated groups compared with UU. Gastric iNOS positive reactivity was upregulated while COX-2 positive reactivity was  downregulated in CoCl₂-treated groups compared with UU . 

Conclusion: Cobalt chloride exerted gastrointestinal cytoprotective action  via mast cell stabilization, mucus production, with modulated expressions of gastric iNOS and COX-2 reactivity at the ulcerated site.