Evaluation of the effects of rofecoxib and nitric oxide-releasing aspirin on stress-induced gastric ulcers in rats

ABSTRACT

The study was conducted to investigate possible mechanisms of the protective actions of rofecoxib [a selective COX-2 inhibitor] and nitric oxide-releasing aspirin [NO-aspirin] against experimentally induced gastric lesions in rats. The rats were randomly assigned to vehicle [carboxymethylcellulose], rofecoxib [5 mg/Kg] and NO-aspirin [55mg/Kg]-pretreated groups, in addition to the non-stressed control group. Gastric lesions were induced by exposing the rats to 3 hrs cold restraint stress [CRS] and ulcer indices were determined. Gastric juice parameters [pH, free and total acid output, mucin and pepsin concentrations] were determined. The stomachs were used for determination of gastric mucosal level of lipid peroxides as well as total nitrites. Results showed that both rofecoxib and NO-aspirin displayed protective effects against lesions formation. Pretreatment with both drugs significantly lowered gastric acid secretion, mucin and pepsin concentrations as well as mucosal levels of lipid peroxides and total nitrites compared to CRS rats. This protection was possibly mediated through lowering of gastric juice acid secretion and proteolytic activity and increasing mucin concentration as well as free radical scavenging and reduction of the detrimental increase of nitric oxide during CRS