Revised Roberts Cytoprotection and Adaptive Cytoprotection and Stable Gastric Pentadecapeptide BPC 157. Possible Significance and Implications for Novel Mediator

Abstract

The significance of cytoprotection and adaptive cytoprotection and the peptides importance remained to be not completely determined. 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, and stable in human gastric juice, with no toxicity being reported. It has a prominent effect on alcohol- lesions (i.e., induced acutely and chronically) and non-steroidal anti-inflammatory drugs-lesions (while interestingly BPC 157 may both prevent and reverse adjuvant arthritis). To review the importance of BPC 157, this review focused on Robert's cytoprotection concept described in rat stomach, reviewing our evidence that may resolve whether the cytoprotection and adaptive cytoprotection is an uniform phenomenon or not; whether the phenomenon or phenomena are endogenous or not, depending on nature of the irritants (mild or strong); whether this may contribute to stomach mucosa defense either when threaten by various ulcerogens or afforded by various antiulcer agents; whether these phenomena are uniform in whole gastrointestinal tract or not; whether they are interrelated or not. Finally, the importance of the cytoprotection phenomena and cytoprotection activity for skin wound healing, and wound healing in general was challenged. Thereby, this review focused on BPC 157 role in cytoprotection and adaptative cytoprotection suggesting that it may be the essential endogenous mediator able to mediate both cytoprotective and adaptive cytoprotective response in stomach and the whole gastrointestinal tract with significant importance in wound healing as well.

Pentadecapeptide BPC157 reduces bleeding and thrombocytopenia after amputation in rats treated with heparin, warfarin, L-NAME and L-arginine

“…BPC 157 has been shown to exert beneficial effects against different pathological conditions [1,2,10-26], it induced gastroprotective, analgesic and anti-inflammatory wound healing effects [1,2,10-17], also effective against experimental colitis [10][11][12][13][14][15][16] and showing a particular interaction with the NO-system [14,15,[18][19][20][21][22][23][24][25][26]. Recently, we demonstrated the effect of BPC 157 against bleeding/thrombocytopenia after amputation, with or without anticoagulant and aspirin administration and abdominal aorta anastomotic site-thrombosis [1,2].…”

“…Possibly, the consistent endothelium protection during advanced healing processes in different wounds of various tissues, including blood vessels [1,2,[10][11][12][13][14][15][16][17], associated with the counteraction of the L-NAME-induced disturbances as well as the counteraction of the L-arginineinduced disturbances, obtained with the same BPC 157 dose range [14,15,[18][19][20][21][22][23][24][25][26], should likely compete with the prominent endothelium effect of the heparin-impaired endothelial nitric oxide (NO) synthesis [36] as well as warfarin endothelium damage [37]. Finally, as emphasized, BPC 157 beneficial effects include stimulation of egr-1 gene and its co-repressor gene naB2 [17], also responsible for cytokine and growth factor generation and thereby, early extracellular matrix (collagen) and blood vessel formation [17].…”

“…To counteract the consequences of L-NAME and/or L-arginine administration with the disturbed hemostasis, we administered the stable gastric pentadecapeptide BPC 157 [1,2,[10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] not only due to its special effect on hemostasis [1,2], but also owing to a particular beneficial combining [1,2,[10][11][12][13][14], wound healing capacity [1,2,[10][11][12][13][14][15][16][17] and particular interaction with NO-system [14,15,[18][19][20][21][22][23][24][25][26]. Previously, BPC 157 as an originally anti-...…”

“…Previously, BPC 157 as an originally anti-ulcer peptide was implemented in inflammatory bowel disease trials [10][11][12][13][14][15], and now multiple sclerosis [16], lethal dose (LD1) could be not achieved [10][11][12][13][14][15][16]. As mentioned, this unusual combining effect in hemostasis was recently evidenced with bleeding/thrombocytopenia after amputation, with or without anticoagulant and aspirin administration, abdominal aorta anastomotic site-thrombosis, both being counteracted [1,2].…”

“…Wound healing capacity in different tissues [1,2,[10][11][12][13][14][15][16][17] (including blood vessels) (i.e., stimulation of the early growth response 1 (egr-1) gene and its co-repressor nerve growth factor 1-A binding protein-2 (naB2) [17] also responsible for cytokine and growth factor generation and thereby, early extracellular matrix (collagen) and blood vessel formation [17]) and endothelium protection [1,2,14,15] were implicated in these counteracting effects.…”