Cysteamine-colon and cysteamine-duodenum lesions in rats. Attenuation by gastric pentadecapeptide BPC 157, cimetidine, ranitidine, atropine, omeprazole, sulphasalazine and methylprednisolone

Sikirić, Predrag; Seiwerth, Sven; Grabarević, Željko; Balen, Ivica; Aralica, Gorana; Gjurašin, Miroslav; Komerički, Ljiljana; Perović, Darko; Ziger, Tihomil; Anić, Tomislav; Prkačin, Ingrid; Šeparović, Jadranka; Stančić-Rokotov, Dinko; Lovrić-Benčić, Martina; Mikus, Darko; Silva, Mario; Aralica, Josip; DiBiaggio, Nevena; Šimec, Zoran; Turković, Branko; Rotkvić, Ivo; Miše, Stjepan; Rucman, Rudolf; Petek, Marijan; Sebecic, Bozidar; Ivasovic, Zoran; Boban-Blagaić, Alenka; Sjekavica, Ivo

doi:10.1016/s0928-4257(01)00036-5

Cited by 21 publications

(27 citation statements)

References 33 publications

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“…Finally, pentadecapeptide BPC 157, efficient in therapy of the inflammatory bowel disease (PL14736) (15,16) and intestinal anastomosis healing (13,14), counteracted the colitis induced by a variety of ulcerogens such as cysteamine (27,28), trinitrobenzene sulfonic acid (TNBS) (45,46), iodoacetamide (53). Obviously, all these findings may also help to explain the improvement of colocutaneous fistula healing by BPC 157.…”

Section: Discussionmentioning

confidence: 99%

“…), first application at 30 min after surgery, final 24 h before sacrifice. Alternatively, sulphasalazine (Sigma, St. Louis, MO, USA) (50 mg / kg intraperitoneally, once daily) or 6-α-methylprednisolone (Sigma) (1.0 mg / kg intraperitoneally, once daily) [as described before in colitis-studies (27,28)] were given. Finally, as described previously (4, 17 -19), BPC 157 (10.0 µg/kg) or L-NAME (5.0 mg/kg), L-arginine (200.0 mg / kg), and D-arginine (200.0 mg / kg) (Sigma) were given intraperitoneally alone or in combination (Darginine was not effective, data not shown).…”

Section: Methodsmentioning

confidence: 99%

“…Thus, we studied gastric pentadecapeptide BPC 157 parenteral and peroral therapy in rats with colocutaneous fistulas. For comparison, we used sulphasalazine and 6-α-methylprednisolone [given in the doses previously demonstrated to counteract colitis induced by cysteamine enema (27,28)], as the standard therapy of inflammatory bowel disease (27,28). Interestingly, although the therapies used for pyoderma gangrenosum also include systemic corticosteroids and sulphasalazine (37), the specific sulphasalazine studies on skin wound healing are lacking while 6-α-methylprednisolone suppressed spontaneous healing of open wounds (38).…”

Section: Introductionmentioning

confidence: 99%

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Pentadecapeptide BPC 157, in Clinical Trials as a Therapy for Inflammatory Bowel Disease (PL14736), Is Effective in the Healing of Colocutaneous Fistulas in Rats: Role of the Nitric Oxide-System

et al. 2008

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Abstract. We focused on the therapeutic effect of the stable gastric pentadecapeptide BPC 157 and how its action is related to nitric oxide (NO) in persistent colocutaneous fistula in rats (at 5 cm from anus, colon defect of 5 mm, skin defect of 5 mm); this peptide has been shown to be safe in clinical trials for inflammatory bowel disease (PL14736) and safe for intestinal anstomosis therapy. BPC 157 (10 μg / kg, 10 ng / kg) was applied i) in drinking water until the animals were sacrificed at post-operative day 1, 3, 5, 7, 14, 21, and 28; or ii) once daily intraperitoneally (first application 30 min following surgery, last 24 h before sacrifice) alone or with N G -nitro-L-arginine methyl ester (L-NAME) (5 mg / kg), L-arginine (200 mg/ kg), and their combinations. Sulphasalazine (50 mg / kg) and 6-α-methylprednisolone (1 mg / kg) were given once daily intraperitoneally. BPC 157 accelerated parenterally or perorally the healing of colonic and skin defect, leading to the suitable closure of the fistula, macro / microscopically, biomechanically, and functionally (larger water volume sustained without fistula leaking). L-NAME aggravated the healing failure of colocutaneous fistulas, skin, and colon wounds (L-NAME groups). L-Arginine was effective only with blunted NO generation (L-NAME + L-arginine groups) but not without (L-arginine groups). All of the BPC 157 beneficial effects remained unchanged with blunted NO-generation (L-NAME + BPC 157 groups) and with NO substrate (L-arginine + BPC 157 groups) as well as L-NAME and L-arginine co-administration (L-NAME + L-arginine + BPC 157 groups). Sulphasalazine was only moderately effective, and corticosteroid even had an aggravating effect.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Pentadecapeptide BPC 157, in Clinical Trials as a Therapy for Inflammatory Bowel Disease (PL14736), Is Effective in the Healing of Colocutaneous Fistulas in Rats: Role of the Nitric Oxide-System

et al. 2008

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“…As an antiulcer peptide [17][18][19][20][21][22][23][24][25][26][27][28] it improved healing of intestinal anastomosis and fistula [1,2,28,29], skin [31][32][33][34][35][36][37], and other wounds [38][39][40][41][42][43], and was shown to be both efficient and safe in trials for inflammatory bowel disease (PL14736, Pliva) [44,45]. Likewise, it was found to be more effective both locally and systemically (perorally and parenterally) than standard treatments, e.g., as therapy for gastrointestinal tract ulcers [17,[20][21][22][23][24][25][26][27][28] and other wounds [32][33][34][35][36], intestinal anastomosis [1,2], and gastrocutaneous and colocutaneous fistula …”

Section: Introductionmentioning

confidence: 99%

Gastric Pentadecapeptide BPC 157 and Short Bowel Syndrome in Rats

et al. 2008

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The gastric pentadecapeptide BPC 157, which was shown to be safe as an antiulcer peptide in trials for inflammatory bowel disease (PL14736, Pliva), successfully healed intestinal anastomosis and fistula in rat. Therefore, we studied for 4 weeks rats with escalating short bowel syndrome and progressive weight loss after small bowel resection from fourth ileal artery cranially of ileocecal valve to 5 cm beneath pylorus. BPC 157 (10 microg/kg or 10 ng/kg) was given perorally, in drinking water (12 ml/rat/day) or intraperitoneally (once daily, first application 30 min following surgery, last 24 h before sacrifice). Postoperatively, features of increasingly exhausted presentation were: weight loss appearing immediately regardless of villus height, twofold increase in crypt depth and fourfold increase in muscle thickness within the first week, jejunal and ileal overdilation, and disturbed jejunum/ileum relation. In contrast, constant weight gain above preoperative values was observed immediately with BPC 157 therapy, both perorally and parenterally, and villus height, crypt depth, and muscle thickness [inner (circular) muscular layer] also increased, at 7, 14, 21, and 28 days. Moreover, rats treated with pentadecapeptide BPC 157 showed not different jejunal and ileal diameters, constant jejunum-to-ileum ratio, and increased anastomosis breaking strength. In conclusion, pentadecapeptide BPC 157 could be helpful to cure short bowel syndrome.

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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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Cysteamine-colon and cysteamine-duodenum lesions in rats. Attenuation by gastric pentadecapeptide BPC 157, cimetidine, ranitidine, atropine, omeprazole, sulphasalazine and methylprednisolone

Cited by 21 publications

References 33 publications

Pentadecapeptide BPC 157, in Clinical Trials as a Therapy for Inflammatory Bowel Disease (PL14736), Is Effective in the Healing of Colocutaneous Fistulas in Rats: Role of the Nitric Oxide-System

Pentadecapeptide BPC 157, in Clinical Trials as a Therapy for Inflammatory Bowel Disease (PL14736), Is Effective in the Healing of Colocutaneous Fistulas in Rats: Role of the Nitric Oxide-System

Gastric Pentadecapeptide BPC 157 and Short Bowel Syndrome in Rats

Protective effects of pentadecapeptide BPC 157 on gastric ulcer in rats

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