Haloperidol-stomach lesions attenuation by pentadecapeptide BPC 157, omeprazole, bromocriptine, but not atropine, lansoprazole, pantoprazole, ranitidine, cimetidine and misoprostol in mice

Bilic, Ivanka; Zoricic, Ivan; Anić, Tomislav; Šeparović, Jadranka; Stančić-Rokotov, Dinko; Mikus, Darko; Buljat, Gojko; Ivanković, Davor; Aralica, Gorana; Prkačin, Ingrid; Perović, Darko; Miše, Stjepan; Rotkvić, Ivo; Petek, Marijan; Rucman, Rudolf; Seiwerth, Sven; Sikirić, Predrag

doi:10.1016/s0024-3205(00)01025-0

Cited by 25 publications

(29 citation statements)

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“…So they believed that BPC 157 had a modulatory effect on dopamine system [20] . In a haloperidol-induced gastric lesion model, both dopamine agonists (i.e., bromocriptine, amantadine) and gastric pentadecapeptide BPC 157 could antagonize these lesions, but other antiulcer agents (atropine, pirenzepine, misoprostol, pantoprazole, lansoprazole, cimetidine and ranitidine) were not as effective [10] . Besides, a particular interaction of BPC 157 with central dopamine system was also shown in other experimental models (i.e., protection of stress ulcers).…”

Section: Discussionmentioning

confidence: 97%

“…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%

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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: 97%

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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“…We are aware that the dose of 100 mg/kg pantoprazole per day is substantially higher than the doses given in daily clinical practice in humans. However, in experimental studies, in particular in proofof-principle studies, doses of pantoprazole ranging between 1 and 300 mg/kg/day are reported in mice and rats [13,14]. Accordingly, we chose a dose of 100 mg/kg/day in the present study.…”

Section: Animals and Specimensmentioning

confidence: 99%

Pantoprazole, a Proton Pump Inhibitor, Delays Fracture Healing in Mice

et al. 2012

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Proton pump inhibitors (PPIs), which are widely used in the treatment of dyspeptic problems, have been shown to reduce osteoclast activity. There is no information, however, on whether PPIs affect fracture healing. We therefore studied the effect of the PPI pantoprazole on callus formation and biomechanics during fracture repair. Bone healing was analyzed in a murine fracture model using radiological, biomechanical, histomorphometric, and protein biochemical analyses at 2 and 5 weeks after fracture. Twenty-one mice received 100 mg/kg body weight pantoprazole i.p. daily. Controls (n = 21) received equivalent amounts of vehicle. In pantoprazole-treated animals biomechanical analysis revealed a significantly reduced bending stiffness at 5 weeks after fracture compared to controls. This was associated with a significantly lower amount of bony tissue within the callus and higher amounts of cartilaginous and fibrous tissue. Western blot analysis showed reduced expression of the bone formation markers bone morphogenetic protein (BMP)-2, BMP-4, and cysteine-rich protein (CYR61). In addition, significantly lower expression of proliferating cell nuclear antigen indicated reduced cell proliferation after pantoprazole treatment. Of interest, the reduced expression of bone formation markers was associated with a significantly diminished expression of RANKL, indicating osteoclast inhibition. Pantoprazole delays fracture healing by affecting both bone formation and bone remodeling.

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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%

“…In the meanwhile, both prophylactic and therapeutic effects in various gastrointestinal lesions models were further elaborated (Bedekovic et al, 2003;Bilic et al, 2001;Petrovic et al, 2006;Stancic-Rokotov et al, 2001a, b;Sikiric et al, 2001bSikiric et al, , c, 2003Prkacin et al, 2001a, b;Xue et al, 2004b). Indicative for further ulcerative colitis therapy, BPC 157, unlike sulphasalazine, not only attenuates lesions (Sikiric et al, 1993b;Veljaca et al, 1994), but prevents recidive in cysteamine-chronic colitis model (Sikiric et al, 2001b, c).…”

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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Haloperidol-stomach lesions attenuation by pentadecapeptide BPC 157, omeprazole, bromocriptine, but not atropine, lansoprazole, pantoprazole, ranitidine, cimetidine and misoprostol in mice

Cited by 25 publications

References 0 publications

Protective effects of pentadecapeptide BPC 157 on gastric ulcer in rats

Protective effects of pentadecapeptide BPC 157 on gastric ulcer in rats

Pantoprazole, a Proton Pump Inhibitor, Delays Fracture Healing in Mice

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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