Stable Gastric Pentadecapeptide BPC 157 in Trials for Inflammatory Bowel Disease (PL-10, PLD-116, PL14736, Pliva, Croatia) Heals Ileoileal Anastomosis in the Rat
- 111 Downloads
Gastric pentadecapeptide BPC 157 (BPC 157), which has been shown to be safe in clinical trials for inflammatory bowel disease (PL-10, PLD-116, PL14736, Pliva, Croatia), may be able to cure intestinal anastomosis dehiscence. This antiulcer peptide shows no toxicity, is limit test negative, and a lethal dose is not achieved. It is stable in human gastric juice. In comparison with other standard treatments it is more effective for ulcers and various wounds, and can be used without a carrier needed for other peptides, both locally and systemically (i.e., perorally, parenterally). We studied the effectiveness of BPC 157 for ileoileal anastomosis healing in rats.
We assessed ileoileal anastomosis dehiscence macroscopically, histologically, and biomechanically (volume [ml] infused through a syringe-perfusion pump system (1 ml/10 s), and pressure [mmHg] to leak induction [catheter connected to a chamber and a monitor, at 10 cm proximal to anastomosis]), at 1, 2, 3, 4, 5, 6, 7, and 14 days. BPC 157 (10 µg, 10 ng, 10 pg/kg i.p. (or saline [5 ml/kg]) was first administered after surgery, while it was last given 24 h before either assessment or sacrifice.
Throughout the experiment, both higher doses of BPC 157 were shown to improve all parameters of anastomotic wound healing. The formation of adhesions remained slight, the blood vessels were filled with blood, and a mild intestinal passage obstruction was only temporarily observed. Anastomosis without leakage induces markedly higher volume and pressure values, with a continuous increase toward healthy values. From day 1, edema was markedly attenuated and the number of granulocytes decreased, while from days 4 or 5 necrosis decreased and granulation tissue, reticulin, and collagen formation substantially increased, thus resulting in increased epithelization.
This study showed BPC 157 to have a beneficial effect on ileoileal anastomosis healing in the rat.
Key wordsPentadecapeptide BPC 157 Ileoileal anastomosis healing Rat
Unable to display preview. Download preview PDF.
- 2.Sikiric, P, Seiwerth, S, Grabarevic, Z, Petek, M, Rucman, R, Turkovic, B, et al. 1994The beneficial effect of BPC 157, a 15 amino acid peptide BPC fragment, on gastric and duodenal lesion induced by restraint stress, cysteamine and 96% ethanol in rates. A comparative study with H2 receptor antagonists, dopamine promoters and gut peptidesLife Sci54PL638PubMedCrossRefGoogle Scholar
- 8.Veljaca M, Krnic Z, Brajsa K, Mildner B, Pavic-Saladojev D, Seveljevic-Jaran D, et al. The development of PL 14736 for treatment of inflammatory bowel disease. IUPHAR-GI Section Symposium. Honolulu, Hawaii, 2002;13–15:0–32Google Scholar
- 9.Veljaca, M, Pavic Sladoljev, D, Mildner, B, Brajsa, K, Bubenik, M, Stipanicic, S, et al. 2003Safety, tolerability and pharmacokinetics of PL 14736, a novel agent for treatment of ulcerative colitis, in healthy male volunteersGut51A309Google Scholar
- 10.Xue, XC, Wu, YJ, Gao, MT 2004Study of the protective effects of pentadecapeptide BPC 157 on wounds in small-type pigsChin New Drugs J126024Google Scholar
- 13.Sebecic, B, Nikolic, V, Sikiric, P, Seiwerth, S, Sosa, T, Patrlj, L, et al. 1999Osteogenic effect of gastric pentadecapeptide BPC 157 on the healing of segmental bone defects in rabbits: a comparison with the bone marrow and autologous cortical bone implantationBone24195202PubMedCrossRefGoogle Scholar
- 18.Urist, MR 1995The first three decades of bone morphogenetic proteinOsteologie420723Google Scholar
- 24.Zoricic, I, Sikiric, P, Seiwerth, S 1997Pentadecapeptide BPC 157 beneficially influences the healing of colon-colon anastomoses in ratsMozsik, GNagy, LPar, ARainsford, KD eds. Cell injury and protection in the gastrointestinal trace. From basic sciences to clinical perspectives 1996Kluwer Academic PublishersDordrecht Boston London24958Google Scholar
- 25.Pajic, A, Fattorini, I, Gjurasin, M, Gogolja, D, Vlahovic, T, Vrtar, Z, et al. 2003Gastric pentadecapeptide BPC 157 (PL-10, PL-116) reduces and reverses peritonitis intra-abdominal adhesion in normal and sialoadenectomized rat and abolished mortality in corticosteroid-ratDig Dis Sci481894Google Scholar
- 29.Veljaca, M, Lesch, CA, Sanchez, B, Low, J, Guglietta, A 1995Protection of BPC-15 on TNBS-induced colitis in rats: possible mechanisms of actionGastroenterology108936Google Scholar
- 32.Turkovic, B, Sikiric, P, Seiwerth, S, Mise, S, Anic, T, Petek, M, et al. 2004Stable gastric pentadecapeptide BPC 157 studied for inflammatory bowel disease (PLD-116, PL14736, Pliva) induces nitric oxide synthesisGastroenterology126287Google Scholar
- 34.Lovric-Bencic, M, Sikiric, P, Separovic, J, Seiwerth, S, Rogic, D, Kusec, V, et al. 2004Doxorubicin congestive heart failure-increased big-endothelin 1 plasma concentration. Reversal by amlodipine, losartan and gastric pentadecapeptide BPC 157 in rat and mouseJ Pharmacol Sci951926PubMedCrossRefGoogle Scholar
- 38.Gjurasin, M, Miklic, P, Buljat, G, Perovic, D, Jukic, I, Sikiric, P, et al. 2003Selective healing effect of the gastric pentadecapeptide BPC 157 on injured part of the nerve in subtotal sciatic nerve transectionDig Dis Sci481878Google Scholar