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Prolonged severe hypercalcemia induces an acute pancreatitis in rats, and shortening of QT interval and prolongation of PQ interval. The effect of the therapy with stable gastric pentadecapeptide BPC 157 (PL14736)

Prolonged severe hypercalcemia induces an acute pancreatitis in rats, and shortening of QTc interval and prolongation of PQ interval. For counteraction, we propose the stable gastric pentadecapeptide BPC 157 (GEPPPGKPADDAGLV, MW 1419, an anti-ulcer peptide efficient in trials for inflammatory bowel disease (PL 14736, Pliva) and various wound treatment, no toxicity reported) that recovered acute pancreatitis as well as arrhythmias in rats (Dig Dis Sci, 1996, J Pharm Sci, 2003). Materials and methods. Rats received CaCl solution (200 mg or 400 mg/kg i.p.). ECG was continuously recorded, K, Na, Ca, Cl, amylase, CK, LDH serum values assessed at 5, 10, 15, 25, and 60 min, and acute pancreatitis at 60 min (as described (Dig Dis Sci, 1996, J Pharm Sci, 2003, 2007 (in press). BPC 157 (10 mcg/kg, i.p.) was given (i) prophylactically (30 min before CaCl2). Results. Severe hypercalcemia was sustained throughout shortening of QTc interval and prolongation of PQ interval and raise of serum enzymes values (QTc interval, PQ interval, Ca, amylase, CK, LDH:(5 min - 40±2 msec, 50±2 msec, 4, 75 mmol/L, 2605 U/L, 10130 U/L, 3500 U/L), (10 min - 40±2 msec, 60±1 msec, 5, 95 mmol/L, 2810 U/L, 12480 U/L, 4110 U/L), (15 min - 36±2 msec, 75±3 msec, 6, 2 mmol/L, 3330 U/L, 14140 U/L, 5250 U/L), (25 min - 30±3 msec, 80±1 msec, 6, 5 mmol/L, 3480 U/L, 15530 U/L, 5580 u/L), (60 min - 30±1 msec, 100±2 msec, 7, 2 mmol/L, 3620 U/L, 19900 U/L, 6480 U/L )). BPC 157, prophylactically. Severe hypercalcemia was modified, abolished shortening of QTc interval and prolongation of PQ interval and decreased raise of serum enzymes values (QTc interval PQ interval, Ca, amylase, CK, LDH (5 min - 46±2 msec, 58±2 msec, 3, 06 mmol/L, 2110 U/L, 8010 U/L, 1800 U/L), (10 min - 48±3 msec, 60 msec±2 msec, 4, 12 mmol/L, 1900 U/L, 8100 U/L, 2200 U/L), (15 min 40 ±2 msec, 58±4 msec, 5, 2 mmol/L, 2650 U/L, 8500 U/L, 3900 U/L), (25 min 45±2 msec, 63±2 msec, 5, 8 mmol/L, 2750 U/L, 9100 U/L, 4100 U/L), (60 min - 47±3 msec, 60±4 msec, 6, 2mmol/L, 2880 U/L, 10500 U/L, 5700 U/L)). At 60 min acute pancreatitis appeared in controls rats with raised Ca, amylase values. In BPC 157 rats acute pancreatitis was considerably reduced, along with decreased raise of Ca and serum amylase values. Conclusion. Acute CaCl2 bolus induces prolonged hypercalcemia that causes acute pancreatitis along with shortening of QTc interval and prolongation of PQ interval, increased serum enzymes values (i.e., amylase, CK, LDH). BPC 157 medication modified Ca raise after acute CaCl2 bolus and reduced acute pancreatitis, reduced amylase, CK, LDH serum values, and prevented ECG disturbances.

BPC 157; hypercalcemia; pancreatitis; rats

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