Protection of BPC-15 on TNBS-induced colitis in rats: Possible mechanisms of action

Veljača, Marija; Lesch, Charles; Sánchez, Belén Sabio; Low, John N.; Guglietta, Antonio

doi:10.1016/1043-6618(95)86312-5

Cited by 8 publications

(9 citation statements)

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“…28,29) Reduction of this enzyme activity can be interpreted as a manifestation of the anti-inflammatory property of a given compound. 25) Colonic tissue MPO activity, markedly elevated in TNBS control animals, was significantly decreased in rats pretreated with coumarin (5 mg/kg) and 4-hydroxycoumarin (25 mg/kg), suggesting an anti-inflammatory activity of these coumarins.…”

Section: Discussionmentioning

confidence: 99%

“…The lack of an effect on this ratio can be explained based on the severe and too extensive colonic damage induced by TNBS/ethanol, which is difficult to overcome by pharmacological treatment as has been previously suggested. 25) On the other hand, the preventative effect of 4-hydroxycoumarin (25 mg/kg) in the acute colitis was associated with decrease of the colonic weight/length ratio. The anti-inflammatory activity of coumarin (5, 25 mg/kg) and 4-hydroxycoumarin (50 mg/kg) in the acute colitis was also related to decrease of the incidence of diarrhoea, thus indicating a restoration of the absorptive ability of the colon which is profoundly altered as a consequence of the inflammatory process.…”

Section: Discussionmentioning

confidence: 99%

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Intestinal Anti-inflammatory Activity of Coumarin and 4-Hydroxycoumarin in the Trinitrobenzenesulphonic Acid Model of Rat Colitis

Luchini

Rodrigues-Orsi

Cestari

et al. 2008

Biological & Pharmaceutical Bulletin

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Coumarins represent an important class of phenolic compounds with multiple biological activities, including inhibition of lipidic peroxidation and neutrophil-dependent anion superoxide generation, anti-inflammatory and immunosuppressor actions. All of these proprieties are essential for that a drug may be used in the treatment of inflammatory bowel disease. The present study examined intestinal anti-inflammatory activity of coumarin and its derivative, the 4-hydroxycoumarin on experimental ulcerative colitis in rats. This was performed in two different experimental settings, i.e. when the colonic mucosa is intact or when the mucosa is in process of recovery after an initial insult. The results obtained revealed that the coumarin and 4-hydroxycoumarin, at doses of 5 and 25 mg/kg, significantly attenuated the colonic damage induced by trinitrobenzenesulphonic acid (TNBS) in both situations, as evidenced macroscopically, microscopically and biochemically. This effect was related to an improvement in the colonic oxidative status, since coumarin and 4-hydroxycoumarin prevented the glutathione depletion that occurred as a consequence of the colonic inflammation.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Intestinal Anti-inflammatory Activity of Coumarin and 4-Hydroxycoumarin in the Trinitrobenzenesulphonic Acid Model of Rat Colitis

Luchini

Rodrigues-Orsi

Cestari

et al. 2008

Biological & Pharmaceutical Bulletin

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“…62,63], and reduced levels of leukotriene B4 (LTB4), thromboxane B2 (TXB2), and myeloperoxidase (MPO) in both serum and inflamed tissues [62,63]. With respect to BPC 157's recent use in inflammatory bowel disease patients [19][20][21], this may be beneficial, considering the highly increased incidence of fistulas in patients with corticosteroid-resistant inflammatory bowel disease [64].…”

Section: Atropinementioning

confidence: 98%

Therapy for Unhealed Gastrocutaneous Fistulas in Rats as a Model for Analogous Healing of Persistent Skin Wounds and Persistent Gastric Ulcers: Stable Gastric Pentadecapeptide BPC 157, Atropine, Ranitidine, and Omeprazole

et al. 2008

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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%

“…13). Importantly, pentadecapeptide BPC 157's beneficial effect on both the wound and mucosa healing reduces the number of inflammatory cells (8,9,44) and levels of leukotriene B 4 (LTB 4 ), thromboxane B 2 (TXB 2 ), and myeloperoxidase (MPO) in the serum and inflamed tissues (45,46). Together, these could significantly affect the afferent nerve function (47).…”

Section: Discussionmentioning

confidence: 99%

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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Protection of BPC-15 on TNBS-induced colitis in rats: Possible mechanisms of action

Cited by 8 publications

References 0 publications

Intestinal Anti-inflammatory Activity of Coumarin and 4-Hydroxycoumarin in the Trinitrobenzenesulphonic Acid Model of Rat Colitis

Intestinal Anti-inflammatory Activity of Coumarin and 4-Hydroxycoumarin in the Trinitrobenzenesulphonic Acid Model of Rat Colitis

Therapy for Unhealed Gastrocutaneous Fistulas in Rats as a Model for Analogous Healing of Persistent Skin Wounds and Persistent Gastric Ulcers: Stable Gastric Pentadecapeptide BPC 157, Atropine, Ranitidine, and Omeprazole

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

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