engleski

Esophageal Cytoprotection in Rats. Stable Gastric Pentadecapeptide BPC 157 and Omeprazole

Abstract Aim Up to now, esophagus, as a direct target, is not particularly concerned in stomach cytoprotection studies performed with direct instillation of the nocuous agent in the rat stomach (Curr Pharm Des 2010 ; 16(10):1224–34). Therefore, using intraesophageal administration of various nocuous irritants, and then, intraesophageal administration of medication in rats, we hypothesize the stable gastric pentadecapeptide BPC 157 to induce direct cytoprotection in esophagus. BPC 157 was originally an anti-ulcer peptide used in trials for ulcerative colitis and now is in trials for the treatment of multiple sclerosis that largely interacts with NO-system (Curr Pharm Des 2014 ; 20(7):1126–35) and thought to be novel mediator of Robert's cytoprotection in rat stomach studies, known to exert an immediate endothelium protection alongside with mucosal protection in stomach, known to counteract variously induced gastrointestinal lesions in various species, and thereby suited for the necessary generalization of the concept of the stomach cytoprotection to the entire gastrointestinal tract, and to the esophagus, in particular (Curr Pharm Des. 2014 ; 20(7):1126–35). Materials and methods Male Wistar Albino rats, randomly assigned, underwent to various nocuous agents (10% NaOH ; 3.65% HCl ; 96% alcohol) application at the cervical part of the esophagus, 0.5ml/rat, close to pharyngoesophageal junction, received immediately thereafter medication at the same esophageal site (/kg, 0.5ml/rat, stable gastric pentadecapeptide BPC 157 10μg, or omeprazole 10 mg or saline (control)). Esophageal lesions were assessed (expressed as % of total esophageal area, means±SD, as described before (Life Sci 1994 ; 54(5):PL63-8) and confirmed using VAMS software (Zagreb, Croatia), specimens proceded for histology assessment) immediately after sacrifice at 1min or 1h or 24h thereafter. Both agents were given in dose-regimen known to produce a cytoprotective effect in the stomach. Results Strong base or strong acid, or strong alcohol, all produced immediately huge esophageal lesions, while some of them progressively were further enlarged (1min–1h–24h) (60±5–80±5–90±8 (NaOH) ; 70±5–73±7–70±8 (HCl) ; 50±5–55±6–51±7 (alcohol). Pentadecapeptide BPC 157 consistently reduced all of these lesions (27±5–38±4–42±5 (NaOH) ; 30±8– 28±5–18±5 (HCl) ; 12±5–16±5–14±5 (alcohol). Omeprazole might only postpone these lesions development (34±5–70±10–80±9 (NaOH) ; 52±5–71±9– 78±11 (HCl) ; 40±5–56±8–53±9 (alcohol). Histology assessment was along with these findings. Conclusion BPC 157 might act as a cytoprotective agent also in the esophagus, and exert an immediate cytoprotection while in esophagus. By contrast, omeprazole, known as a PPI prototype, delays these lesions cours, but exhibits a more limited effect, that was seen only at the very early interval, and thereby, less cytoprotective effectiveness while in the esophagus. Support or Funding Information University of Zagreb, Zagreb, Croatia (Grant number BM099)

BPC 157, Omeprazole

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