Pentadecapeptide BPC 157 attenuates gastric lesions induced by alloxan in rats and mice

Petek, Marijan; Sikirić, P.; Anić, Tomislav; Buljat, Gojko; Šeparović, Jadranka; Stančić-Rokotov, Dinko; Seiwerth, Sven; Grabarević, Željko; Rucman, Rudolf; Mikus, Darko; Zoricic, Ivan; Prkačin, Ingrid; Sebecic, Bozidar; Ziger, Tomislav; Corić, V.; Turković, Branko; Aralica, Gorana; Rotkvić, Ivo; Miše, Stjepan; Hahn, Vladimir

doi:10.1016/s0928-4257(99)00120-5

Cited by 8 publications

(8 citation statements)

References 15 publications

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“…Thus, it may be that BPC 157 as a cytoprotective agent [1][2][3][4] essentially combines the processes responsible for both stomach and skin ulcer healing [25]. Therefore, it may have an exceptionally wide range of beneficial effects against different gastric lesion models [1][2][3][4], gastric acid non-dependent, gastric acid dependent, besides the models commonly thought to be prostaglandin related [1][2][3][4][6][7][8]24,26] and in turn, with PGs-system failure [1][2][3][4] in the models that implicate dopamine [27][28][29][30], glucose (hyperglycemia or hypoglycemia) [31,32], as well as those that involve NO-system disbalance [33]. Therefore, besides NSAIDscounteraction, on the base of counteraction of acute and chronic alcohol lesions [22][23][24][33][34][35], the cytoprotective and adaptive cytoprotective BPC 157 activities (noted also in vitro studies [36,37]) even in the longer-term [22][23][24][33][34][35], are obviously a part of a larger array of beneficial effects of BPC 15...…”

Section: Toxicity By Nsaidsmentioning

confidence: 99%

“…Interestingly, the beneficial effect against gastric lesions is in conjunction with the antagonization of central dopamine system disturbances [27][28][29][30]39]. BPC 157 also antagonizes alloxan-gastric lesions [32] as well as heals the diabetic alloxan skin ulcer [40] and also, given in the same dose, counteracts insulin-over-dose-gastric lesions and convulsions [31]. BPC 157 counteracts capsaicingastric lesions [24] and capsaicin-nasal lesions [41] and consequently, somatosensory neuron failure [24].…”

Section: Toxicity By Nsaidsmentioning

confidence: 99%

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Toxicity by NSAIDs. Counteraction by Stable Gastric Pentadecapeptide BPC 157

Sikirić

Seiwerth²,

Rucman³

et al. 2012

CPD

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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 ( g, ng/kg) in parenteral or peroral regimens.

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Section: Toxicity By Nsaidsmentioning

confidence: 99%

Section: Toxicity By Nsaidsmentioning

confidence: 99%

Toxicity by NSAIDs. Counteraction by Stable Gastric Pentadecapeptide BPC 157

Sikirić

Seiwerth²,

Rucman³

et al. 2012

CPD

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“…Originally, the organoprotective agents (prostaglandins, somatostatin previously had cytoprotective effect on alcohol-gastric lesion) show benefi cial activity only when given prophylactically against acute pancreatitis or liver lesion (Szabo and Usadel, 1982;Robert et al, 1989). Noteworthy, in those disturbances (pancreas and liver lesions), pentadecapeptide BPC 157 acts both prophylactically and therapeutically (Petek et al, 1999;Sikiric et al, 1993cSikiric et al, , 1996bPrkacin et al, 2001bPrkacin et al, , 2002.…”

Section: Therapeutic Potential Of Gastric Pentadecapeptide Bpc 157 Asmentioning

confidence: 99%

Stable gastric pentadecapeptide BPC 157 in trials for inflammatory bowel disease (PL-10, PLD-116, PL 14736, Pliva, Croatia). Full and distended stomach, and vascular response.

et al. 2006

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Gastric pentadecapeptide BPC 157 (GEPPPGKPADDAGLV, M.W. 1419, safe in clinical trials for inflammatory bowel disease (PL 10, PLD 116, PLD 14736, Pliva, Croatia)) has a particular cytoprotective/adaptive cytoprotective activity. The cytoprotective/adaptive cytoprotection researches largely neglect that stomach distension could per se jeopardize the mucosal integrity, with constantly stretched mucosa and blood vessels, and sphincters more prone for reflux induction. After absolute alcohol instillation in fully distended rat stomach, gastric, esophageal and duodenal lesions occur. Throughout next 3 min, left gastric artery blood vessels clearly disappear at the serosal site, indicative for loss of vessels both integrity and function. Contrary, constant vessels presentation could predict the beneficial effect of applied agent. After pentadecapeptide BPC 157 instillation into the stomach the vessels presentation remains constant, and lesions of stomach, esophagus, and duodenum are inhibited. Standards (atropine, ranitidine, omeprazole) could only slightly improve the vessels presentation compared to control values, and they have only a partial effect on the lesions. In this review we emphasize BPC 157 unusual stability, and some of its important effects: effectiveness against various lesions in gastrointestinal tract, on nitric oxide (NO)-system, and NO-agents effects, on somatosensory neurons, salivary glands function, recovery of AMP-ADP-ATP system, endothelium protection, effect on endothelin, and on angiogenesis promotion. It also antagonizes other alcohol effects, including acute and chronic intoxication. Given peripherally, it counteracts the consequence of central dopamine system disturbances (receptor blockade), and induces serotonin release in substantia nigra. Therapeutic potential of BPC 157 as a cytoprotective agent is also seen in its capability to heal various wounds. Given directly into the stomach, BPC 157 instantly recovers disturbed lower esophageal and pyloric sphincter pressure in rats after 12-20 months of untreated esophagitis. All these could be suggestive for its role as a natural protectant in gastric juice with particular function throughout stomach distension.

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“…Although the detailed mechanism is poorly understood, BPC 157 appears to be beneficial to almost all organ systems in many species when very low dosages (mostly mg/kg and ng/kg) are used. It has many functions such as attenuating liver, lung, colon and gastric lesions [3][4][5][6][7][8][9][10][11][12][13] , displaying anti-anxiety and antidepressant effects [14,15] , improving angiogenesis and wound healing [8,16,17] , reversing MPTP-motor abnormalities in Parkinson's disease models [11] , having mucosal protective and anti-inflammatory effects [10,18,19] , particularly affecting dopamine systems [20] , and persistent activity [6,21] . All these findings showed that BPC 157 could be a useful prototype of a new class of drugs and organ protective agents.…”

Section: Introductionmentioning

confidence: 99%

Protective effects of pentadecapeptide BPC 157 on gastric ulcer in rats

Xue¹,

Wu²,

Gao³

et al. 2004

WJG

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AIM:To investigate the protective effects of gastric pentadecapeptide BPC 157 on acute and chronic gastric ulcers in rats and to compare the results in therapy of human gastric ulcers by different administration methods. METHODS:Gastric pentadecapeptide BPC 157 was administered (initial single or continuous administration) into rats either intragastrically or intramuscularly before (induced acute gastric ulcer) or after (induced chronic gastric ulcer) the applications of inducing agents, and each animal was sacrificed to observe the protective effects of BPC 157 on gastric ulcers. RESULTS:Both intramuscular (im) and intragastric (ig) administration of BPC 157 could apparently reduce the ulcer area and accelerate the healing of induced ulcer in different models and the effect of im administered BPC 157 was better than that of ig. The rats treated with higher dosages (400 ng/kg, 800 ng/kg) of BPC 157 (im and ig) showed significantly less lesion (P<0.01 vs excipient or saline control), the inhibition ratio of ulcer formation varied between 45.7% and 65.6%, from all measurements except 400 ng/kg BPC 157 in pylorus ligation induced model (P<0.05), in which the inhibition rate was 54.2%. When im administered (800 ng/kg BPC 157) in three models, the inhibition ratio of ulcer formation was 65.5%, 65.6% and 59.9%, respectively, which was better than that of famotidine (its inhibition rate was 60.8%, 57.2% and 34.3%, respectively). Continuous application of BPC 157 (in chronic acetate induced gastric ulcer) could accelerate rebuilding of glandular epithelium and formation of granulation tissue (P<0.05 at 200 ng/kg and P<0.01 at 400 ng/kg and 800 ng/kg vs excipient or saline control). CONCLUSION:Both im and ig administered gastric pentadecapeptide BPC 157 can apparently ameliorate acute gastric ulcer in rats and antagonize the protracted effect of acetate challenge on chronic ulcer. The effect of im administration of BPC 157 is better than that of ig, and the effective dosage of the former is lower than that of the latter.

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Pentadecapeptide BPC 157 attenuates gastric lesions induced by alloxan in rats and mice

Cited by 8 publications

References 15 publications

Toxicity by NSAIDs. Counteraction by Stable Gastric Pentadecapeptide BPC 157

Toxicity by NSAIDs. Counteraction by Stable Gastric Pentadecapeptide BPC 157

Stable gastric pentadecapeptide BPC 157 in trials for inflammatory bowel disease (PL-10, PLD-116, PL 14736, Pliva, Croatia). Full and distended stomach, and vascular response.

Protective effects of pentadecapeptide BPC 157 on gastric ulcer in rats

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