Peptide therapy with pentadecapeptide BPC 157 in traumatic nerve injury

Gjurašin, Miroslav; Miklić, Pavle; Župančić, Božidar; Perović, Darko; Žarković, Kamelija; Brčić, Luka; Kolenc, Danijela; Radic, Bozo; Seiwerth, Sven; Sikirić, Predrag

doi:10.1016/j.regpep.2009.11.005

Cited by 37 publications

(51 citation statements)

References 42 publications

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“…Since the very beginning, stable gastric pentadecapeptide BPC 157 signiﬁcantly improved all parameters of anastomotic wound healing in rats with esophagogastric anastomosis, as has previously been shown with various intestinal anastomoses[10-14] (note BPC 157 also improves the blood vessel and peripheral nerve anastomoses[63,64]), and with both external and internal fistulas[7,15-19], which were originally created as the surgical anastomoses between various tissues[7,15-19]. As a result, BPC 157 especially improves the anastomotic strength.…”

Section: Discussionmentioning

confidence: 87%

Esophagogastric anastomosis in rats: Improved healing by BPC 157 and L-arginine, aggravated by L-NAME

Djaković¹,

Djaković²,

Cesarec³

et al. 2016

WJG

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AIMTo cure typically life-threatening esophagogastric anastomosis in rats, lacking anastomosis healing and sphincter function rescue, in particular.METHODSBecause we assume esophagogastric fistulas represent a particular NO-system disability, we attempt to identify the benefits of anti-ulcer stable gastric pentadecapeptide BPC 157, which was in trials for ulcerative colitis and currently for multiple sclerosis, in rats with esophagocutaneous fistulas. Previously, BPC 157 therapies have promoted the healing of intestinal anastomosis and fistulas, and esophagitis and gastric lesions, along with rescued sphincter function. Additionally, BPC 157 particularly interacts with the NO-system. In the 4 d after esophagogastric anastomosis creation, rats received medication (/kg intraperitoneally once daily: BPC 157 (10 μg, 10 ng), L-NAME (5 mg), or L-arginine (100 mg) alone and/or combined or BPC 157 (10 μg, 10 ng) in drinking water). For rats underwent esophagogastric anastomosis, daily assessment included progressive stomach damage (sum of the longest diameters, mm), esophagitis (scored 0-5), weak anastomosis (mL H2O before leak), low pressure in esophagus at anastomosis and in the pyloric sphincter (cm H2O), progressive weight loss (g) and mortality. Immediate effect assessed blood vessels disappearance (scored 0-5) at the stomach surface immediately after anastomosis creation.RESULTSBPC 157 (all regimens) fully counteracted the perilous disease course from the very beginning (i.e., with the BPC 157 bath, blood vessels remained present at the gastric surface after anastomosis creation) and eliminated mortality. Additionally, BPC 157 treatment in combination with L-NAME nullified any effect of L-NAME that otherwise intensified the regular course. Consistently, with worsening (with L-NAME administration) and amelioration (with L-arginine), either L-arginine amelioration prevails (attenuated esophageal and gastric lesions) or they counteract each other (L-NAME + L-arginine); with the addition of BPC 157 (L-NAME + L-arginine + BPC 157), there was a marked beneficial effect. BPC 157 treatment for esophagogastric anastomosis, along with NOS-blocker L-NAME and/or NOS substrate L-arginine, demonstrated an innate NO-system disability (as observed with L-arginine effectiveness). BPC 157 distinctively affected corresponding events: worsening (obtained with L-NAME administration that was counteracted); or amelioration (L-arginine + BPC 157-rats correspond to BPC 157-rats).CONCLUSIONInnate NO-system disability for esophagogastric anastomoses, including L-NAME-worsening, suggests that these effects could be corrected by L-arginine and almost completely eliminated by BPC 157 therapy.

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Section: Discussionmentioning

confidence: 87%

Esophagogastric anastomosis in rats: Improved healing by BPC 157 and L-arginine, aggravated by L-NAME

Djaković¹,

Djaković²,

Cesarec³

et al. 2016

WJG

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“…In analogy to improve sphincter function, in quadriceps muscle or gastrocnemius muscle complex injuries, BPC 157 increases muscle function and healing, after a complete transection or major crush [67][68][69]. In addition, these effects of BPC 157 [67][68][69] occur concurrently with its marked neuroprotective capability [70,71], and are along with counteracted doxorubicineheart failure and arrhythmias [72,73]. Also, pentadecapeptide BPC 157 given peripherally could affect sphincter function through serotonin [51,74] or dopamine (presenting in the same dose-range BPC 157 prevented/ reversed catalepsy or stereotypy and all concomitant gastrointestinal lesions) [21][22][23][24].…”

Section: Mechanism Implicationsmentioning

confidence: 99%

Stable Gastric Pentadecapeptide BPC 157: Novel Therapy in Gastrointestinal Tract

Sikirić¹,

Seiwerth²,

Rucman³

et al. 2011

CPD

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Stable gastric pentadecapeptide BPC 157 is an anti-ulcer peptidergic agent, safe in inflammatory bowel disease clinical trials (GEPPPGKPADDAGLV, M.W. 1419, PL 14736) and wound healing, stable in human gastric juice and has no reported toxicity. We focused on BPC 157 as a therapy in peridontitis, esophagus, stomach, duodenum, intestine, liver and pancreas lesions. Particularly, it has a prominent effect on alcohol-lesions (i.e., acute, chronic) and NSAIDs-lesions (interestingly, BPC 157 both prevents and reverses adjuvant arthritis). In rat esophagitis and failed function of both lower esophageal sphincter (LES) and pyloric sphincters (PS), BPC 157 increased pressure in both sphincters till normal and reduced esophagitis. However, in healthy rats, it may decrease (PS) or increase (LES) the pressure in sphincters. It has strong angiogenic potential, it acts protectively on endothelium, prevents and reverses thrombus formation after abdominal aorta anastomosis, affects many central disturbances (i.e., dopamine and 5-HT system), the NO-system (either L-arginine and L-NAME effects), endothelin, acts as a free radical scavenger (counteracting CCl4-, paracetamol-, diclofenac-injuries) and exhibits neuroprotective properties. BPC 157 successfully heals the intestinal anastomosis, gastrocutaneous, duodenocutaneous and colocutaneous fistulas in rats, as well as interacting with the NO-system. Interestingly, the fistula closure was achieved even when the BPC 157 therapy was postponed for one month. In short-bowel syndrome escalating throughout 4 weeks, the constant weight gain above preoperative values started immediately with peroral and parental BPC 157 therapy and the villus height, crypth depth and muscle thickness (inner (circular) muscular layer) additionally increased. Thus, BPC 157 may improve gastrointestinal tract therapy.

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“…Further, this analogy actually conveys in mentioned NO-system-terms cardiac muscle (decreased extracellular potassium: myocardial hyperexcitability with the potential to develop re-entrant arrhythmias) and skeletal muscle (decreased potassium levels in the extracellular space: hyperpolarization of the resting membrane potential, a greater than normal stimulus for depolarization of the membrane in order to initiate an action potential) [24]. In support, presenting the general significance of skeletal muscle for plasma potassium homeostasis [31], BPC 157's heart effect [9,10,27] are along with prominent neuroprotective effect [33,34], marked increase of the healing rate of severely damaged skeletal muscles and recovering of their function [35][36][37].…”

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confidence: 99%

Mortal Furosemide-Hypokalemia-Disturbances in Rats NO-System Related Shorten Survival by L-NAME. Therapy Benefit with BPC 157 Peptide More Than With L-Arginine

Balenovic¹,

Barišić²,

Prkačin³

et al. 2012

J Clin Exp Cardiolog

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Background: We focused on NO-system-relations (worsening/amelioration) of furosemide (100 mg/kg intraperitoneally)-diuresis-hypokalemia mortal course in rats and beneficial effect of BPC 157 therapy. Methods:Electrocardiographically 90-150 min post-furosemide application duration of PR, RR, QRS, QT intervals, P, R, S, T waves and its amplitude as well were analysed along with appearance of AV block, ventricular premature beats, ventricular tachycardia. Clinically, skeletal muscle myoclonal activity and lethality at 150 min were also analysed.Results: All NO-system-related agents (alone and/or combined, before/after furosemide) not changed hypokalemia and all averted to some extent furosemide-forced diuresis. NOS-blocker, L-NAME (5 mg/kg intraperitoneally) accelerated mortality, aggravated cardiac and extra-cardiac manifestations, thereby, NO-systemrelated. Prevented hypokalemia-mortality was with NO-precursor L-arginine (100 mg/kg intraperitoneally) and stable gastric pentadecapeptide BPC 157 (10 ug, 10 ng/kg intraperitoneally/intragastrically). Specifically, BPC 157 showed most complete benefit. i. BPC 157 given 15 min before furosemide. All BPC 157 regimens maintained sinus rhythm, had no ventricular premature beats, ventricular tachycardia, AV block, no prolongation of intervals and waves without reduction of amplitude. ii. BPC 157 given 90 min after furosemide (with hypokalemia, 3 rd grade AV block and/ or ventricular tachycardia being present). Within 5-10 minutes, BPC 157 regimens normalized P, R, S, T waves, PR, RR, QRS, QT interval duration, R, S, T wave amplitude, total AV block and terminated ventricular tachycardia. Likewise, BPC 157 eliminated skeletal muscle myoclonus. Conclusion:L-NAME/L-arginine was mutual counteraction while BPC 157 completely eliminated L-NAME (arrhythmias, myoclonus, mortality), without an additive benefit when combined with L-arginine. Thus, we showed potentially effective therapeutic interventions for acute hypokalemia.Mortal Furosemide-Hypokalemia-Disturbances in Rats NO-System Related Shorten Survival by L-NAME. Therapy Benefit with BPC 157 Peptide More Than With L-Arginine Keywords: Pentadecapeptide BPC 157; L-NAME; L-arginine; Hypokalemic lethal outcome; Arrhythmia; Rats Introduction NO-system is proposed as endogenous cardioprotectant and antifibrillatory factor [1,2]. Diuretic-hypokalemia is an increasingly common cause of arrhythmias [3]. Therefore, we attempted to define hypokalemia and/or hypokalemia disturbances as particular disturbances related to NO-system and possible therapeutic value of NOsystem-related agents: NO-synthase (NOS)-blocker, L-NAME, NOSsubstrate, L-arginine, and, particularly, stable gastric pentadecapeptide BPC 157 [4][5][6]. In this, we focused on so far not demonstrated with L-NAME/L-arginine application [1,2] NO-system-relations in mortal furosemide-diuresis-hypokalemia course; -ECG changes, carefully analyzed in rats [7] (prolongation of P, R, S, T waves and PR, RR, QRS, QT interval duration, and reduced amplitude of R, S, T wave (alt...

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Peptide therapy with pentadecapeptide BPC 157 in traumatic nerve injury

Cited by 37 publications

References 42 publications

Esophagogastric anastomosis in rats: Improved healing by BPC 157 and L-arginine, aggravated by L-NAME

Esophagogastric anastomosis in rats: Improved healing by BPC 157 and L-arginine, aggravated by L-NAME

Stable Gastric Pentadecapeptide BPC 157: Novel Therapy in Gastrointestinal Tract

Mortal Furosemide-Hypokalemia-Disturbances in Rats NO-System Related Shorten Survival by L-NAME. Therapy Benefit with BPC 157 Peptide More Than With L-Arginine

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