Pentadecapeptide BPC 157 Therapy in Rats with Cysteamine Induced‐Terminal Ileitis

Abstract

AimWe introduce pentadecapeptide BPC 157 therapy in rats with cysteamine induced‐terminal ileitis, 1 h, 1 month, 2 months. We counteracted gross hyperemia, edema, erosion, bleeding, and, microscopically, significant loss of villous architecture, loss and shortening of villae and severe lymphocytic infiltrate. BPC 157 counteracts various lesions in the whole GI‐tract and free radicals formation (Curr Pharm Des 2018;24:1990–2001), and tested in ulcerative colitis trials and now in multiple sclerosis (Curr Pharm Des 2018;24:1990–2001). Previously, cysteamine, was known to induce gastric acid hypersecretion, as a prototype of duodenal lesion (Lancet 1979 Oct 27;2(8148):880–2). Subsequently, cysteamine induced duodenal lesions after gastrectomy, and applied as an enema, ulcerative colitis in rats. BPC 157 counteracts all of these lesions (Life Sci 1994;54(5):PL63‐8, Dig Dis Sci 1997 May;42(5):1029–37, J Physiol Paris 2001 Jan–Dec;95(1–6):283–8, J Physiol Paris 2001 Jan–Dec;95(1–6):261–70, Eur J Pharmacol 2003 Sep 5;477(1):73–80, J Physiol Pharmacol 2013 Oct;64(5):597–612)MethodsCysteamine (400 mg/kg, 1 ml/rat) was applied in female Albino Wistar rats, 200 g bw into the terminal ileum, 5 cm segment up to ileocecal valve, which was kept gently compressed for 1 min, and then released. Medication (/kg) (BPC 157 (10 μg, 10 ng), or saline (5 ml) (controls)) was applied as an abdominal bath immediately after the end of the cysteamine application procedure, and then if rats were not sacrificed at 1 h, continuously, perorally in drinking water (0.16 μg/ml, 0.16 ng/ml, 12 ml/rat/day) till the end of 1 or 2 months.ResultsFor gross assessment, the hyperemia, edema, erosion and bleeding scores (0–3) were summarized (giving the 0–12 scoring, and assessed as Min/Med/Max). Control rats exhibit the following scoring: 11/11/12 at 1 h, 8/8/9 at 1 month, and 8/8/9 at 2 months. Contrarily, all BPC 157 rats present markedly lower scoring (3/3/4 at 1 h, 0/1/1 at 1 month, and 0/1/1 at 2 months, 10 μg regimen Min/Med/Max, P<0.05, vs. control, at least, while 10 ng regimen shows similar beneficial effect). Microscopically, much like in patients, cysteamine induced terminal ileitis goes with submucosal congestion, significant loss of villous architecture, loss and shortening of villae, lamina propria infiltrated with mild to severe lymphocytic infiltrate much like intraepithelial lymphocytes infiltration and some epithelial elevation from lamina propria. Contrarily, better preservation of mucosal architecture appears in pentadecapeptide BPC 157 treated rats. There is only mild villous edema with capillary congestion and mild lymphocytic infiltrate. No epithelial elevation from lamina propria is found (Fig. 1, Fig. 2, left control, right BPC 157).ConclusionFor further therapy, beneficial effect of the BPC 157 counteracts cysteamine‐terminal ileitis.Support or Funding InformationThis work was supported by the University of Zagreb, Zagreb, Croatia (Grant BM 099).Cysteamine Terminal Ileitis, 1 hourFigure 1