Pentadecapeptide BPC 157 Counteracts Failure of Lower Esophageal and Pyloric Sphincter Induced by NSAIDs in Rats

Abstract

The risks of aspirin/NSAIDs to induce esophageal and other GI tract lesions have been documented, whilst their effect on lower esophagea sphincter (LES) and pyloric sphincter (PS) pressure is far less studied. Thereby, we tested in rats various NSAIDs and a safe stable gastric pentadecapeptide BPC 157(GEPPPGKPADDAGLV, MW 1419), LD1 not achieved, since successful in inflammatory bowel disease trials, and counteracts esophagitis, sphincters failure, gastrointestinal ulcer and skin ulcer, gastro- or colo-cutaneous fistulas in rats, and particularly counteracts NSAIDs-lesions(1-6). Diclofenac (DI) (12.5 or 40 mg/kg ip, once daily, for 1, 2 or 3 days), ibuprofen (IB) (400 mg/day/kg for 4 weeks), paracetamol (PA) (150 mg/kg ip, 250 mg/kg ig, 5 g/kg ip once), aspirin (AS) (400 mg/kg i.p. or i.g.), BPC 157 immediately after NSAIDs (10 ug/kg i.p. or i.g.), LES and PS pressure (cm H2O), 10 rats at least per group, assessed as described before (3). NSAIDs (control). Regularly, fall of pressure occurred rapidly and persisted (i.e., DI, 12.5 mg: 30 mins: 45.0±2.5 PS, 55.0±2.5 LES - 3h: 43.8±2.5 PS, 56.0±2.5 LES -41.0±3.0 PS, 48.6±3.5 LES (3 days) ; PA 250 mg ig: 60.0±1.5 PS, 63.0±1.0 LES (15 mins) ; PA 5g ip: 35.0±5.5 PS, 40.0±3.5 LES (3h) ; IB, 4 weeks: 33.0±3.5 PS, 43.0±3.0 LES ; AS 400mg ip, 3h: 60.0±1.5 PS, 62.0±0.5 LES (3h) ; AS 400mg ig, 3h: 58.0±1.5 PS, 61.0±1.0 LES ; BPC 157. Regularly, initial fall of pressure was minimized and pressure values restored to normal values (i.e., DI, 12.5 mg: 30 mins: 66.0±2.5 PS, 70.0±2.5 LES - 3h: 62.8±2.5 PS, 69.0±3.5 LES – 62.2±3.0 PS, 72.6±5.5 LES (3 days) ; PA 250 mg ig: 70.0±1.5 PS, 73.0±1.0 LES (15 mins) ; PA 5g ip: 68.0±5.5 PS, 70.0±2.5 LES (3h) ; IB, 4 weeks: 70.0±5.5 PS, 73.0±6.0 LES ; AS 400mg ip, 3h: 65.0±0.5 PS, 70.0±0.8 LES (3h) ; AS 400mg ig, 3h: 68.0±1.5 PS, 71.0±0.9 LES ; ; (vs. control p<0.05). Finally, these BPC 157 effects correlate with attenuated injuries of liver (PA+BPC157 ; IB+BPC157), stomach (AS+BPC 157, IB+BPC 157, DI+BPC157), and small intestine (DI+BPC157). All tested NSAIDs decrease pressure in LES and PS, whilst BPC 157 counteracts their effects and restored LES and PS function. Literature. 1.Curr Pharm Des. 2010 ; 16:1224-34, 2. Dig Dis Sci. 2009 ; 54:2070-83, 3. J Pharmacol Sci. 2008 ; 108:7-17, 4. Dig Dis Sci. 2009 ; 54:46-56, 5. J Pharmacol Sci. 2007 ; 104:7-18. 6. J Physiol Pharmacol. 2010 ; 61:241-50.