Stable Gastric Pentadecapeptide BPC 157 May Counteract Myocardial Infarction Induced by Isoprenaline in Rats

Abstract

We revealed that the stable gastric pentadecapeptide BPC 157, a useful peptide therapy against isoprenaline myocardial infarction, as well as against isoprenaline myocardial reinfarction, may follow the counteraction of the recently described occlusion-like syndrome, induced peripherally and centrally, which was described for the first time in isoprenaline-treated rats. BPC 157 (10 ng/kg, 10 µg/kg i.p.), L-NAME (5 mg/kg i.p.), and L-arginine (200 mg/kg i.p.) were given alone or together at (i) 30 min before or, alternatively, (ii) at 5 min after isoprenaline (75 or 150 mg/kg s.c.). At 30 min after isoprenaline 75 mg/kg s.c., we noted an early multiorgan failure (brain, heart, lung, liver, kidney and gastrointestinal lesions), thrombosis, intracranial (superior sagittal sinus) hypertension, portal and caval hypertension, and aortal hypotension, in its full presentation (or attenuated by BPC 157 therapy (given at 5 min after isoprenaline) via activation of the azygos vein). Further, we studied isoprenaline (75 or 150 mg/kg s.c.) myocardial infarction (1 challenge) and reinfarction (isoprenaline at 0 h and 24 h, 2 challenges) in rats (assessed at the end of the subsequent 24 h period). BPC 157 reduced levels of all necrosis markers, CK, CK-MB, LDH, and cTnT, and attenuated gross (no visible infarcted area) and histological damage, ECG (no ST-T ischemic changes), and echocardiography (preservation of systolic left ventricular function) damage induced by isoprenaline. Its effect was associated with a significant decrease in oxidative stress parameters and likely maintained NO system function, providing that BPC 157 interacted with eNOS and COX2 gene expression in a particular way and counteracted the noxious effect of the NOS-blocker, L-NAME.

Therapy Effect of the Stable Gastric Pentadecapeptide BPC 157 on Acute Pancreatitis as Vascular Failure-Induced Severe Peripheral and Central Syndrome in Rats

“…As a cause-effect relation, vascular failure may occur even before full acute pancreatitis presentation with a severe occlusion-like syndrome, peripherally and centrally. Essentially (i.e., providing a common vascular disability point), this might correspond to the previously described syndrome commonly seen with an endothelium-damaging agent overdose, alcohol [ 25 ], lithium [ 24 ], myocardial infarction [ 23 ], and maintained intra-abdominal hypertension, grade III and IV [ 22 ], as well as corresponding to the described occlusion syndrome with major vessel occlusion, peripherally [ 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 ] or centrally [ 20 ]. Of note, all of these disturbances were consistently attenuated with the application of BPC 157 therapy and activation of the collateral pathways, relayed on the given injury [ 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 ].…”

“…Essentially (i.e., providing a common vascular disability point), this might correspond to the previously described syndrome commonly seen with an endothelium-damaging agent overdose, alcohol [ 25 ], lithium [ 24 ], myocardial infarction [ 23 ], and maintained intra-abdominal hypertension, grade III and IV [ 22 ], as well as corresponding to the described occlusion syndrome with major vessel occlusion, peripherally [ 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 ] or centrally [ 20 ]. Of note, all of these disturbances were consistently attenuated with the application of BPC 157 therapy and activation of the collateral pathways, relayed on the given injury [ 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 ]. As a particular therapy effect, the BPC 157 regimen was given as intragastric bolus, or continuously orally in drinking water, starting in the early or late advanced injury course (for review, see, i.e., [ 1 , 2 , 3 , 4 , 5 , 6 , 7 ]).…”

“…Therapeutically, BPC 157 exhibited particular recovering vascular effects when confronted with various intentionally induced severe vascular disturbances (i.e., major vessel occlusion [ 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 ], peripheral [ 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 ] and central [ 20 , 21 ], vessel compression (intra-abdominal hypertension) [ 22 ], endothelium-damaging agents [ 23 , 24 , 25 ] and procedures [ 26 , 27 , 28 ]). BPC 157 cured the bile duct ligation-induced acute pancreatitis and its concomitant gastrointestinal disturbances [ 29 , 30 ], and prevented and reversed bile duct ligation-induced liver cirrhosis [ 31 ] in rats.…”

“…BPC 157 cured the bile duct ligation-induced acute pancreatitis and its concomitant gastrointestinal disturbances [ 29 , 30 ], and prevented and reversed bile duct ligation-induced liver cirrhosis [ 31 ] in rats. Considering the previous therapy effect in rats with vascular disturbances [ 14 , 15 , 16 , 20 , 22 , 23 , 24 , 25 ] as well as in bile duct-ligated rats [ 29 , 30 , 31 ], this novel study analyzing acute pancreatitis/vascular disturbances shows the particularities of bile duct ligation-induced vascular failure. As a cause-effect relation, vascular failure may occur even before full acute pancreatitis presentation with a severe occlusion-like syndrome, peripherally and centrally.…”

“…The recognition of the cytoprotection maxim endothelium maintenance→ epithelium maintenance is potentially an essential but unresolved active key of Robert’s and Szabo’s cytoprotection concept, although they were overwhelmingly focused on stomach cytoprotection [ 32 , 33 , 34 ]. Recently, in these terms (activation of the collateral pathways, relayed on the given injury) [ 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 ], we reviewed the greater pleiotropic cytoprotection potential of the stable gastric pentadecapeptide BPC 157 as a novel cytoprotection mediator largely involved in healing (for review, see i.e., [ 1 , 2 , 3 , 4 , 5 , 6 ]), inside and outside the gastrointestinal tract (i.e., BPC 157 counteracted leaky gut (for review, see i.e., [ 4 ]). Special areas of therapy could be the bile duct ligation-induced disturbances [ 29 , 30 , 31 ].…”