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Therapy with gastric pentadecapeptide BPC 157 (PL14736) and L-NAME in short bowel syndrome and entero-enteral anastomosis healing in rats

Gastric pentadecapeptide BPC 157 (BPC 157), safe in trials for inflammatory bowel disease (IBD) (PL14736 Pliva)(Gastroenterology, 2005), could also be useful in IBD complications. It successfully heals the intestinal anastomosis in rats (Surg Today, 2007) and has a therapeutic effect on the short-bowel syndrome that compromises nutritional status and healing process (Dig Dis Sci, 2008). Also, it interacts with the NO-system and counteracts the effects of NOS-inhibition, induced by application of NOS-inhibitor, N-G-nitro-L-arginine-methyl ester (L-NAME) (Eur J Pharmacol, 1997, J Pharm Sci, 2008). Thereby, this study investigates whether the therapeutic effect of the pentadecapeptide BPC 157 on the short-bowel syndrome could be abolished by L-NAME application. Extensive small bowel resection (from the 4th ileal artery cranially of the ileocecal valve to 5 cm underneath the pylorus) and entero-enteral anastomosis were carried out in male rats as described before (Surg Today, 2007, Gastroenterology, 2007) Medication (BPC 157 (10 µg, 10 ng, 10 pg), L-NAME (5 mg) or an equivolume of saline (5 ml) was given once daily, i.p. (/kg), first application 30 min following surgery, last 24 h before sacrifice (at the post-operative day 1, 3, 5, 6, 7, 14). The assessment includes macroscopic presentation (body weight, mass of small intestine (3 cm cranially to 3 cm caudally from anastomosis), diameter measurements (jejunal, ileal and anastomosis diameter), biomechanical presentation (the volume (ml) instilled through a syringe-perfusion pump system (1ml /10 sec)) to the induction of leakage), microscopic presentation (Surg Today, 2007, Dig Dis Sci, 2008). A severe bowel syndrome was observed (severe body weight loss, jejunal diameter increase, a small volume (2-3 ml) before leakage, particularly decreased height of the villi distal to anastomosis). This was completely counteracted by both pentadecapeptide BPC 157 regimens. Weight gain to healthy values along with markedly higher volume values (4-6 ml) was obtained without leakage. Anastomosis healing is improved (edema markedly attenuated, granulocyte number decreased, necrosis attenuated, granulation tissue, reticulin and collagen formation markedly increased, and finally epithelization increased). All measured diameters were similar to diameter of healthy animals, the height of the villi distal to the anastomosis were higher than in controls. BPC 157 therapeutic effect could be not abolished by L-NAME application. Alone, L-NAME application aggravated short bowel syndrome. Short bowel syndrome and entero-enteral anastomosis healing may be a particular target for therapy with BPC 157.

BPC 157; L-NAME; short bowel syndrome

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