Toxicity by NSAIDs. Counteraction by Stable Gastric Pentadecapeptide BPC 157

Abstract

Stable gastric pentadecapeptide BPC 157 is an anti-ulcer peptidergic agent, proven in clinical trials to be both safe in inflammatory bowel disease (PL-10, PLD-116, PL 14736) and wound healing, stable in human gastric juice, with no toxicity being reported. Recently, we claim that BPC 157 may be used as an antidote against NSAIDs. We focused on BPC 157 beneficial effects on stomach, duodenum, intestine, liver and brain injuries, adjuvant arthritis, pain, hyper/hypothermia, obstructive thrombus formation and thrombolysis, blood vessel function, counteraction of prolonged bleeding and thrombocytopenia after application of various anticoagulants and antiplatelet agents and wound healing improvement. The arguments for BPC 157 antidote activity (i.e., the role of BPC 157 in cytoprotection, being a novel mediator of Robert's cytoprotection and BPC 157 beneficial effects on NSAIDs mediated lesions in the gastrointestinal tract, liver and brain and finally, counteraction of aspirin-induced prolonged bleeding and thrombocytopenia) obviously have a counteracting effect on several established side-effects of NSAIDs use. The mentioned variety of the beneficial effects portrayed by BPC 157 may well be a foundation for establishing BPC 157 as a NSAIDs antidote since no other single agent has portrayed a similar array of effects. Unlike NSAIDs, a very high safety (no reported toxicity (LD1 could be not achieved)) profile is reported for BPC 157. Also, unlike the different dosage levels of aspirin, as a NSAIDs prototype, which differ by a factor of about ten, all these beneficial and counteracting effects of BPC 157 were obtained using the equipotent dosage (μg, ng/kg) in parenteral or peroral regimens.

Stable gastric pentadecapeptide BPC 157 in honeybee (Apis mellifera) therapy, to control Nosema ceranae invasions in apiary conditions

“…Several molecular pathways are discussed as possible targets of BPC 157 (Cesarec et al, 2012;Chang, Tsai, Hsu, & Pang, 2014;Chang, Tsai, Lin, Hsu, & Pang, 2011;Hsieh et al, 2017;Huang et al, 2015;Tkalcevic et al, 2007). Thereby, BPC 157 was considered to be suitable for the extension of the beneficial effect to the entire gastrointestinal tract Sikiric et al, 2010Sikiric et al, , 2012Sikiric et al, , 2014Sikiric et al, , 2017Sikiric et al, 2011Sikiric et al, , 2013Sikiric et al, , 2016Duzel et al, 2017).…”

Stable Gastric PentadecapeptideBPC 157, Somatosensory Neurons and Their Protection and Therapeutic Extensions — A Survey

“…With BPC 157 given alone, without a carrier, BPC 157 application strategy (for review see, i. e., (Sikiric et al, 2010(Sikiric et al, , 2011(Sikiric et al, , 2012(Sikiric et al, , 2013(Sikiric et al, , 2014Seiwerth et al, 2014)) considerably overrides the standard peptides and their use with different carriers (i. e., peptide+carrier(s) complex) to establish the therapeutic effect (thereby erroneously) ascribed to the given peptide. Therefore, the activity -methodology dilemma whereby it is difficult to identify the real active part in peptide+carrier complex (peptide, carrier, peptide+carrier complex or neither of them) or specify their particular contribution is not applicable to BPC 157 (for review see, i. e., Urist, 1996).…”

“…Thereby, such kind of pathophysiologic importance along with unlimited applications of BPC 157 regimens contrasts with the evidence for standard peptides providing that regardless commonly acknowledged pathophysiologic importance at least in many occasions they need a carrier (one or more) to become effective and furthermore, that their application prefers to be local, at the site of injury, given into the injury defect (for review see, i. e., (Urist, 1996)). Therefore, pentadecapeptide BPC 157 certainly avoids a common scenario with standard peptides where their limited application in pharmacology could hardly acknowledge their suggested prime physiological importance (Sikiric et al, 2010(Sikiric et al, , 2011(Sikiric et al, , 2012(Sikiric et al, , 2013(Sikiric et al, , 2014Seiwerth et al, 2014)…”

Stable gastric pentadecapeptide BPC 157 can improve the healing course of spinal cord injury and lead to functional recovery in rats

“…The peptide BPC 157 is part of the sequence of the human gastric juice protein BPC and is freely soluble in water and 0.9% NaCl at pH 7.0. BPC 157 was prepared as described previously with 99% high-pressure liquid chromatography (HPLC) purification, expressing 1-des-Gly peptide as an impurity [1][2][3][4][5][6][7][8][9][10][11].…”

“…In comparison, the stable gastric pentadecapeptide BPC 157, an emerging treatment with potential therapeutic applications, appears to be unrestricted by the limitations seen in previous therapies. The stable gastric pentadecapeptide BPC 157, an original cytoprotective antiulcer peptide that is used in ulcerative colitis and recently in a multiple sclerosis trial and that has an LD1 that has not been achieved [1][2][3][4][5][6][7][8][9][10][11], is known to have pleiotropic beneficial effects [1][2][3][4][5][6][7][8][9][10][11] and to interact with several molecular pathways [2,[27][28][29][30][31][32]. BPC 157 has beneficial effects on inflammation, hemorrhage, and edema after traumatic brain injury [33], various severe encephalopathies (which follow gastrointestinal and/or liver lesions), NSAID overdose [34][35][36][37], or insulin overdose seizures [38] and on severe muscle weakness after exposure to the specific neurotoxin cuprizone in a rat multiple sclerosis model [39] or magnesium overdose [40].…”