Gastric Pentadecapeptide BPC 157 and Short Bowel Syndrome in Rats

Abstract

The gastric pentadecapeptide BPC 157, which was shown to be safe as an antiulcer peptide in trials for inflammatory bowel disease (PL14736, Pliva), successfully healed intestinal anastomosis and fistula in rat. Therefore, we studied for 4 weeks rats with escalating short bowel syndrome and progressive weight loss after small bowel resection from fourth ileal artery cranially of ileocecal valve to 5 cm beneath pylorus. BPC 157 (10 microg/kg or 10 ng/kg) was given perorally, in drinking water (12 ml/rat/day) or intraperitoneally (once daily, first application 30 min following surgery, last 24 h before sacrifice). Postoperatively, features of increasingly exhausted presentation were: weight loss appearing immediately regardless of villus height, twofold increase in crypt depth and fourfold increase in muscle thickness within the first week, jejunal and ileal overdilation, and disturbed jejunum/ileum relation. In contrast, constant weight gain above preoperative values was observed immediately with BPC 157 therapy, both perorally and parenterally, and villus height, crypt depth, and muscle thickness [inner (circular) muscular layer] also increased, at 7, 14, 21, and 28 days. Moreover, rats treated with pentadecapeptide BPC 157 showed not different jejunal and ileal diameters, constant jejunum-to-ileum ratio, and increased anastomosis breaking strength. In conclusion, pentadecapeptide BPC 157 could be helpful to cure short bowel syndrome.

Pentadecapeptide BPC 157 and its effects on a NSAID toxicity model: Diclofenac-induced gastrointestinal, liver, and encephalopathy lesions

“…A well-balanced effect that affects all of the organs equally may define the same effective counteracting dosage range for all combined organs, including the stomach, intestine, liver and brain lesions in the present study. In particular, due to the gastrointestinal (Sikiric et al 2010(Sikiric et al , 1996(Sikiric et al , 1997a(Sikiric et al ,b, 2001Klicek et al 2008;Skorjanec et al 2009;Sever et al 2009;Prkacin et al 2001a), liver (Ilic et al 2010(Ilic et al , 2009Sikiric et al 1993b;Prkacin et al 2001b) and brain (Blagaic et al 2004;Boban Blagaic et al 2005;Tohyama et al 2004;Jelovac et al 1998Jelovac et al , 1999Sikiric et al 1999;Tudor et al 2010) injuries as well as due to the gastric-liver-brain triad lesions after insulin overdose, the breakdown of liver glycogen occurs with profound hypoglycemia (Ilic et al 2009). …”

“…BPC 157 has been shown to counteract the liver changes induced by chronic ethanol administration (Prkacin et al 2001b), portal hypertension (Prkacin et al 2001b) and gastric lesions (Ilic et al 2009;Prkacin et al 2001a). BC157 also has been shown to reduce damage to the duodenum and colon induced by cysteamine administration (Sikiric et al 2010(Sikiric et al , 2001, and it has been demonstrated to have a prominent angiogenic effect during the healing of different types of tissues (Sikiric et al 2010(Sikiric et al , 2003(Sikiric et al , 2003Klicek et al 2008;Skorjanec et al 2009;Sever et al 2009;Tkalcevic et al 2007;Krivic et al 2006;Novinscak et al 2008;Cerovecki et al 2010). In addition, besides stimulating the expression of the egr-1 gene, BPC 157 has been shown to stimulate the expression of the egr-1 repressor nerve growth factor 1-A binding protein-2 (nab2) (Tkalcevic et al 2007).…”

“…It is likely that BPC in both the upper and lower gastrointestinal tract (Sikiric et al 2010(Sikiric et al , 1996(Sikiric et al 1997a(Sikiric et al ,b, 2001Klicek et al 2008;Skorjanec et al 2009;Sever et al 2009) that is stable in human gastric juice and was proven to be effective in inflammatory bowel disease trials (PL 14736) (for review see Sikiric et al 2010) and for various wound treatments (Skorjanec et al, 2009;Sever et al 2009, Sikiric et al 2003Tkalcevic et al 2007) with no toxicity reported (for review see Sikiric et al 2010). It may also affect many disturbances of the central nervous system (Blagaic et al 2004;Boban Blagaic et al 2005;Tohyama et al 2004;Jelovac et al 1998Jelovac et al , 1999Sikiric et al 1999;Tudor et al 2010) and contain various hepatoprotective effects (Ilic et al 2010(Ilic et al , 2009Sikiric et al 1993a;Prkacin et al 2001b).…”

Stable Gastric Pentadecapeptide BPC 157: Novel Therapy in Gastrointestinal Tract

“…Providing that pentadecapeptide BPC 157 was so far tested only in inflammatory bowel disease patients [1][2][3][4][5][6], the BPC 157 intestinal protection [i.e., 16,31,33,[35][36][37][38][39], Table 5, may be particularly interesting.…”

“…Likewise, BPC 157 was shown to be highly effective in counteracting severe inflammatory bowel disease complications [37][38][39], efficacious in healing of the intestinal anastomosis [37,39,60], colon-colon [61], ileo-ileal [37] and jejuno-ileal termino-terminal anastomosis [39]. BPC 157 increases adaptative capability of the remaining intestine in all intestinal layers, fully reverses short-bowel syndrome in rats after massive intestine resection, reduces body weight loss postoperatively, induces consistent body weight gain and finally reaches the weight increase of rats with intact intestine [39]. Most importantly, providing all these findings together, the prominent healing effect of BPC 157 regimens in colocutaneous fistulas shown to be NO-system dependent [38], may also be likely valid in colocutaneous healing patients.…”