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Effect of CCl4 and Blocking H2S Biosynthesis on Oesophageal Mucosa Rats: Model of Nonerosive Oesophagitis

Effect of CCl4 and Blocking H2S Biosynthesis on Oesophageal Mucosa Rats: Model of Nonerosive Oesophagitis

Dzvenyslava Khyrivska, Nazar Hrytsevych, Nazar Bula, Irena Pshyk-Titko, Maryana Savytska, Oksana Zayachkivska, Elena Havryluk

Folia Med Cracov. 2014;54(4):79-90.

PMID: 25891244

Abstract:

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP2921144	O-(Carboxymethyl)hydroxylamine hemihydrochloride		2921-14-4	Price

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