Effect of CCl4 and blocking H2S biosynthesis on oesophageal mucosa rats: model of nonerosive oesophagitis.

Nonerosive esophagitis (NEO) - a chronic inflammatory condition with diagnostic and therapy unclear approaches. The aim of study was to develop the new models of NEO using the chemical ulcerogens: carbon tetrachloride (CCl(4)), hydrogen sulfide (H(2)S). We modified the method of NEO with cytoprotective prostaglandins (COX) and H(2)S biosynthesis carried out on rats, divided into groups: 1st - vehicle (1 ml 0.9% NaCl), CCl(4) (twice 0.3 ml/200g/body weight); the next day 2(nd) - vehicle; 3(rd) - nonselective blocker of COX (naproxen; 30 mg/kg); 4(th) - ATB-346 (H(2)S-releasing naproxen; 43.5 mg/kg, «Antibe Therapeutics», Canada) with per os administration. After H(2)S-biosythesis modification by intraperitoneal administration of cystathionine g-lyase (CSE) inhibitor, DL-propargylglycine (PAG, 25 mg/kg), cystathionine-b-synthetase (CBS) inhibitor, O-carboxymethyl-hydroxylamine hemihydrochloride (CHH, 50 mg/kg) or H(2)S donor NaHS (100 mlmol/kg), stress was inducted by Takagi, 1964. The lower third of EM and esophagogastric junction were estimated via histological score index, IL-17, IL-10 by ELISA. The obtained data indicated the strong cytotoxic influence of CCl(4) on EM, corneal and epithelial layers thickness increasing, muscle plate and submucosal edema disorganization vs control and ATB-346 treatment. Over-expression of IL-17 was achieved using PAG and BCA vs control. WIRS-associated EM injury with blocking CSE, CBS characterized by submucosal oedema, neutophilic infiltration, destructive lesions, HSI rising up to 6 vs control. Increased IL-17 to 65% and decreased IL-10 in 30% vs control. H(2)S plays key role in the integrity of oesophageal mucosa and modification of H(2)S synthesis and CCl(4)-related injury can be novel approach of animal model production NEO, similar to human NERD and will help in its pathogenesis identification and preventive drugs creation.