Stable Gastric Pentadecapeptide BPC 157 Therapy for Monocrotaline-Induced Pulmonary Hypertension in Rats Leads to Prevention and Reversal

Abstract

Background. Monocrotaline selectively injures the lung’s vascular endothelium and induces pulmonary arterial hypertension. The stable gastric pentadecapeptide BPC 157 acts as a prototype cytoprotective agent that maintains endothelium, and its application may be a novel therapy. Besides, BPC 157 prevents and reverses thrombosis formation, maintains platelet function, alleviates peripheral vascular occlusion disturbances, and has anti-arrhythmic and anti-inflammatory effects. Monocrotaline-induced pulmonary arterial hypertension in rats (wall thickness, total vessel area, heart frequency, QRS axis deviation, QT interval prolongation, increase in right ventricle systolic pressure and bodyweight loss) can be counteracted with early or delayed BPC 157 therapy. Methods and Results. After monocrotaline (80 mg/kg subcutaneously), BPC 157 (10 μg/kg or 10 ng/kg, days 1–14 or days 1–30 (early regimens), or days 14–30 (delayed regimen)) was given once daily intraperitoneally (last application 24 h before sacrifice) or continuously in drinking water until sacrifice (day 14 or 30). Without therapy, the outcome was the full monocrotaline syndrome, marked by right-side heart hypertrophy and massive thickening of the precapillary artery’s smooth muscle layer, clinical deterioration, and sometimes death due to pulmonary hypertension and right-heart failure during the 4th week after monocrotaline injection. With all BPC 157 regimens, monocrotaline-induced pulmonary arterial hypertension (including all disturbed parameters) was counteracted, and consistent beneficial effects were documented during the whole course of the disease. Pulmonary hypertension was not even developed (early regimens) as quickly as the advanced pulmonary hypertension was rapidly attenuated and then completely eliminated (delayed regimen). Conclusions. Thus, pentadecapeptide BPC 157 prevents and counteracts monocrotaline-induced pulmonary arterial hypertension and cor pulmonale in rats.

Stable Gastric Pentadecapeptide BPC 157 Therapy for Primary Abdominal Compartment Syndrome in Rats

“…BPC 157 reduces various arrhythmias (i.e., potassium overdose-induced hyperkalemia ( Barisic et al, 2013 ), digitalis ( Balenovic et al, 2009 ), neuroleptics (i.e., prolonged QTc-intervals that may also be centrally related) ( Strinic et al, 2017 ), bupivacaine ( Zivanovic-Posilovic et al, 2016 ), lidocaine ( Lozic et al, 2020 ), and succinylcholine ( Stambolija et al, 2016 )). Likewise, BPC 157 reduces lung congestion after vessel occlusion ( Vukojevic et al, 2018 ; Gojkovic et al, 2020 ; Kolovrat et al, 2020 ; Gojkovic et al, 2021a ; Knezevic et al, 2021a ; Knezevic et al, 2021a ; Gojkovic et al, 2021b ; Knezevic et al, 2021b ; Strbe et al, 2021 ), intratracheal alcohol instillation ( Stancic-Rokotov et al, 2001a ; Stancic-Rokotov et al, 2001b ), and pulmonary hypertension syndrome in chickens ( Grabarevic et al, 1997 ) and in monocrotaline-treated rats ( Udovicic et al, 2021 ). As a recently reviewed subject ( Vukojevic et al, 2022 ), BPC 157 has been shown to reduce brain lesions, trauma-induced brain injury ( Tudor et al, 2010 ), compression-induced spinal cord injury ( Perovic et al, 2019 ), and stroke ( Vukojevic et al, 2020 ).…”

Robert’s Intragastric Alcohol-Induced Gastric Lesion Model as an Escalated General Peripheral and Central Syndrome, Counteracted by the Stable Gastric Pentadecapeptide BPC 157

“…In particular, BPC 157 therapy normalizes the QTc duration in rats treated with neuroleptics, and it prevents and improves chronic heart failure [88,89]. It also improves lung pathology (i.e., pulmonary hypertension syndrome in chickens [91], monocrotaline pulmonary hypertension in rats [92]) and intratracheal HCl instillation-induced lung lesions in rats [93].…”

Over-Dose Lithium Toxicity as an Occlusive-like Syndrome in Rats and Gastric Pentadecapeptide BPC 157

“…In particular, BPC 157 therapy normalizes the QTc duration in rats treated with neuroleptics [ 48 ], and both prevents chronic heart failure and promotes recovery from chronic heart failure [ 93 ]. Similarly, in addition to permanent occlusion of the major vessel-induced lung lesions [ 2 , 3 , 4 , 5 , 6 , 7 , 8 ], and absolute alcohol intragastric instillation occlusion-like peripheral and central syndrome [ 9 ], BPC 157 counteracted the lung pathology that may be induced with pulmonary hypertension syndrome in chickens [ 95 ], or application of monocrotaline in rats [ 96 ] and intratracheal HCl instillation-induced lung lesions in rats [ 97 ]). Regarding the mentioned BPC 157-potassium counteracting relation [ 16 , 52 , 53 ], BPC 157 opposed potassium disturbances both in vivo (a life-saving effect in hyperkalemic rats [ 52 ]) and in vitro [ 52 ], and reduced depolarization by up to 70% compared to controlled hyperkalemic depolarization [ 52 ].…”