Gastric mucosal lesions induced by complete dopamine system failure in rats. The effects of dopamine agents, ranitidine, atropine, omeprazole and pentadecapeptide BPC 157

Sikirić, P.; Šeparović, Jadranka; Buljat, Gojko; Anić, Tomislav; Stančić-Rokotov, Dinko; Mikus, Darko; Duplančić, Božidar; Marović, Anton; Zoricic, Ivan; Prkačin, Ingrid; Lovrić-Benčić, Martina; Aralica, Gorana; Ziger, Tihomil; Perović, Darko; Jelovac, Nikola; Dodig, Goran; Rotkvić, Ivo; Miše, Stjepan; Seiwerth, Sven; Turković, Branko; Grabarević, Željko; Petek, Marijan; Rucman, Rudolf

doi:10.1016/s0928-4257(00)00147-9

Cited by 25 publications

(32 citation statements)

References 23 publications

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“…On the other hand, BPC 157 was also effective. This result showed that BPC 157 might not act directly through dopamine system, but through a corresponding system parallel to dopamine system, and it might still function despite the extensive inhibition of endogenous dopamine system activity [22] . Considering the indicated GABA (gamma-amino butyric acid)/ dopamine system interactions, besides an anti-anxiety effect [14] , BPC 157 might act through GABA.…”

Section: Discussionmentioning

confidence: 95%

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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Section: Discussionmentioning

confidence: 95%

Protective effects of pentadecapeptide BPC 157 on gastric ulcer in rats

Xue¹,

Wu²,

Gao³

et al. 2004

WJG

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“…Thereby, besides counteraction of alcohol, acute and chronic lesion [11,13,19,25,26], and thereby cytoprotective and adaptive cytoprotective BPC 157 activity (noted also in vitro studies [17,18]), even in the long-term [11,13,19,25,26] (although BPC 157 inhibits also pylorus-ligation-induced gastric lesions [29]), BPC 157 may counteract haloperidol-, reserpine-, MPTP-lesions [21][22][23][24], and thereby, dopamine system disturbances (we evidenced that BPC 157 particularly affects substantia nigra by alpha-[14C]methyl-L-tryptophan (alpha-MTrp) autoradiographic method [51]), various NSAIDs-lesions, and in turn, PGs-system failure [16,32], capsaicin-lesions [13], and consequently, somatosensory neuron failure. Interestingly, BPC 157 also antagonized rat adjuvant arthiritis [16] and capsaicin-nasal lesions [52].…”

Section: Stomachmentioning

confidence: 99%

Stable Gastric Pentadecapeptide BPC 157: Novel Therapy in Gastrointestinal Tract

Sikirić¹,

Seiwerth²,

Rucman³

et al. 2011

CPD

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200

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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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“…Also, the function of afferent nerve system that closely collaborates with NO-system (Holzer, 1991) is signifi cantly recovered by this pentadecapeptide in capsaicin studies (Sikiric et al, 1993a(Sikiric et al, , 1996aKalogjera et al, 1997). Finally, this peptide recovers the blockade of central dopamine system (induced by haloperidol, centrally acting dopamine receptor antagonist) (Jelovac et al, 1999a;Bilic et al, 2001;Sikiric et al, 2000a). This is important since central dopamine system breakdown is responsible for gastrointestinal ulcer development, and haloperidol produces perforate ulcers in patients (Szabo and Neumeyer, 1983).…”

Section: Introductionmentioning

confidence: 99%

“…This is important since central dopamine system breakdown is responsible for gastrointestinal ulcer development, and haloperidol produces perforate ulcers in patients (Szabo and Neumeyer, 1983). BPC 157 effect opposes other lesions, induced by central dopamine system disturbances, like neurotoxin MPTP (affecting substantia nigra) , and reserpine (vesicles depletion) (Sikiric et al, 2000a). Besides, after either acute or chronic peripheral administration of BPC 157, highly specifi c alpha-methyl-Ltryptophan autoradiographic measurements showed affected central nervous system neurotransmitters synthesis and function in specifi c regions (an increased 5-HT synthesis in rat substantia nigra's (compacta and reticulate) structure (Tohoyama et al, 2004).…”

Section: Introductionmentioning

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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Gastric mucosal lesions induced by complete dopamine system failure in rats. The effects of dopamine agents, ranitidine, atropine, omeprazole and pentadecapeptide BPC 157

Cited by 25 publications

References 23 publications

Protective effects of pentadecapeptide BPC 157 on gastric ulcer in rats

Protective effects of pentadecapeptide BPC 157 on gastric ulcer in rats

Stable Gastric Pentadecapeptide BPC 157: Novel Therapy in Gastrointestinal Tract

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.

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