Salutary effect of gastric pentadecapeptide BPC 157 in two different stress urinary incontinence models in female rats

Jandrić, Ivan; Vrčić, Hrvoje; Balen, Marica Jandrić; Kolenc, Danijela; Brčić, Luka; Radic, Bozo; Drmic, Domagoj; Seiwerth, Sven; Sikirić, Predrag

doi:10.12659/msmbr.883828

Cited by 18 publications

(22 citation statements)

References 48 publications

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“…Previously, we demonstrated that BPC 157 maintains sphincter function (lower esophageal, pyloric[17,18,20-23], urethral[24], and pupil[25]). Specifically, simultaneous lower esophageal and pyloric sphincter function assessment, as a hallmark of reinstated function and tissue integrity[17,18,20-23], demonstrates that when there are more lesions present, the sphincter pressure is lower[17,18,20-23].…”

Section: Discussionmentioning

confidence: 99%

Esophagogastric anastomosis in rats: Improved healing by BPC 157 and L-arginine, aggravated by L-NAME

Djaković¹,

Djaković²,

Cesarec³

et al. 2016

WJG

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AIMTo cure typically life-threatening esophagogastric anastomosis in rats, lacking anastomosis healing and sphincter function rescue, in particular.METHODSBecause we assume esophagogastric fistulas represent a particular NO-system disability, we attempt to identify the benefits of anti-ulcer stable gastric pentadecapeptide BPC 157, which was in trials for ulcerative colitis and currently for multiple sclerosis, in rats with esophagocutaneous fistulas. Previously, BPC 157 therapies have promoted the healing of intestinal anastomosis and fistulas, and esophagitis and gastric lesions, along with rescued sphincter function. Additionally, BPC 157 particularly interacts with the NO-system. In the 4 d after esophagogastric anastomosis creation, rats received medication (/kg intraperitoneally once daily: BPC 157 (10 μg, 10 ng), L-NAME (5 mg), or L-arginine (100 mg) alone and/or combined or BPC 157 (10 μg, 10 ng) in drinking water). For rats underwent esophagogastric anastomosis, daily assessment included progressive stomach damage (sum of the longest diameters, mm), esophagitis (scored 0-5), weak anastomosis (mL H2O before leak), low pressure in esophagus at anastomosis and in the pyloric sphincter (cm H2O), progressive weight loss (g) and mortality. Immediate effect assessed blood vessels disappearance (scored 0-5) at the stomach surface immediately after anastomosis creation.RESULTSBPC 157 (all regimens) fully counteracted the perilous disease course from the very beginning (i.e., with the BPC 157 bath, blood vessels remained present at the gastric surface after anastomosis creation) and eliminated mortality. Additionally, BPC 157 treatment in combination with L-NAME nullified any effect of L-NAME that otherwise intensified the regular course. Consistently, with worsening (with L-NAME administration) and amelioration (with L-arginine), either L-arginine amelioration prevails (attenuated esophageal and gastric lesions) or they counteract each other (L-NAME + L-arginine); with the addition of BPC 157 (L-NAME + L-arginine + BPC 157), there was a marked beneficial effect. BPC 157 treatment for esophagogastric anastomosis, along with NOS-blocker L-NAME and/or NOS substrate L-arginine, demonstrated an innate NO-system disability (as observed with L-arginine effectiveness). BPC 157 distinctively affected corresponding events: worsening (obtained with L-NAME administration that was counteracted); or amelioration (L-arginine + BPC 157-rats correspond to BPC 157-rats).CONCLUSIONInnate NO-system disability for esophagogastric anastomoses, including L-NAME-worsening, suggests that these effects could be corrected by L-arginine and almost completely eliminated by BPC 157 therapy.

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Section: Discussionmentioning

confidence: 99%

Esophagogastric anastomosis in rats: Improved healing by BPC 157 and L-arginine, aggravated by L-NAME

Djaković¹,

Djaković²,

Cesarec³

et al. 2016

WJG

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“…Also, a similar protocol was successful in the therapy of the other fistulas, that is, gastrocutaneous ( Skorjanec et al, 2009 ), esophagocutaneous ( Cesarec et al, 2013 ), duodenocutaneous ( Skorjanec et al, 2015 ), vesicovaginal ( Grgic et al, 2016 ), and rectovaginal ( Baric et al, 2016 ) in rats. Noteworthy, as shown in separate studies, BPC 157 counteracts the known lesions in the skin ( Seiwerth et al, 1997 ; Mikus et al, 2001 ; Sikiric et al, 2003 ; Xue et al, 2004a ; Bilic et al, 2005 ; Seveljevic-Jaran et al, 2006 ; Tkalcevic et al, 2007 ; Huang et al, 2015 ), stomach ( Sikiric et al, 1997a ; Petek et al, 1999 ; Mikus et al, 2001 ; Xue et al, 2004b ; Becejac et al, 2018 ; Ilic et al, 2009 ; Ilic et al, 2011a ), duodenum ( Sikiric et al, 1994 ; Sikiric et al, 1997b ; Sikiric et al, 2001 ; Bedekovic et al, 2003 ; Amic et al, 2018 ), esophagus ( Sikiric et al, 1999b ; Petrovic et al, 2006 ; Dobric et al, 2007 ; Djakovic et al, 2016 ), colon ( Sikiric et al, 2001 ; Klicek et al, 2013 ), rectum ( Sikiric et al, 2001 ; Klicek et al, 2013 ), bladder ( Sucic et al, 2019 ), and vagina ( Jandric et al, 2013 ), whereas the fistula studies show an additional combining healing effect, providing different combinations of the lesions that were simultaneously included ( Figures 3 , 4 ), thereby a proof of the concept for a quite general healing effect ( Klicek et al, 2008 ; Skorjanec et al, 2009 ; Cesarec et al, 2013 ; Skorjanec et al, 2015 ; Baric et al, 2016 ; Grgic et al, 2016 ; Sikiric et al, 2020a ). A particular relationship was established with the NO-system, and the advantage of the BPC 157 over the corresponding standard agents (i.e., corticosteroids, sulfasalazine, H2 blockers, anticholinergics, and proton pump inhibitors) which showed only weak, if any, effect on these fistulas closing (…”

Section: Background or Overviewmentioning

confidence: 99%

Stable Gastric Pentadecapeptide BPC 157 and Wound Healing

et al. 2021

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Significance: The antiulcer peptide, stable gastric pentadecapeptide BPC 157 (previously employed in ulcerative colitis and multiple sclerosis trials, no reported toxicity (LD1 not achieved)), is reviewed, focusing on the particular skin wound therapy, incisional/excisional wound, deep burns, diabetic ulcers, and alkali burns, which may be generalized to the other tissues healing.Recent Advances: BPC 157 has practical applicability (given alone, with the same dose range, and same equipotent routes of application, regardless the injury tested).Critical Issues: By simultaneously curing cutaneous and other tissue wounds (colocutaneous, gastrocutaneous, esophagocutaneous, duodenocutaneous, vesicovaginal, and rectovaginal) in rats, the potency of BPC 157 is evident. Healing of the wounds is accomplished by resolution of vessel constriction, the primary platelet plug, the fibrin mesh which acts to stabilize the platelet plug, and resolution of the clot. Thereby, BPC 157 is effective in wound healing much like it is effective in counteracting bleeding disorders, produced by amputation, and/or anticoagulants application. Likewise, BPC 157 may prevent and/or attenuate or eliminate, thus, counteract both arterial and venous thrombosis. Then, confronted with obstructed vessels, there is circumvention of the occlusion, which may be the particular action of BPC 157 in ischemia/reperfusion.Future Directions: BPC 157 rapidly increases various genes expression in rat excision skin wound. This would define the healing in the other tissues, that is, gastrointestinal tract, tendon, ligament, muscle, bone, nerve, spinal cord, cornea (maintained transparency), and blood vessels, seen with BPC 157 therapy.

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“…In relation to the improved sphincter function and smooth muscle function, BPC 157 may additionally rescue the function of other failed sphincters as well [66]. This BPC 157 effect may lead to strands of newly formed muscle after intestinal anastomosis, increased anastomotic strength (and thereby, improved ileo-ileal anastomosis healing) [37,39,61] and a particular increase of muscle thickness (inner (circular) muscular layer) (more than villus height and crypt depth increased) after massive intestine resection [39].…”

Section: Mechanism Implicationsmentioning

confidence: 99%

Stable Gastric Pentadecapeptide BPC 157: Novel Therapy in Gastrointestinal Tract

Sikirić¹,

Seiwerth²,

Rucman³

et al. 2011

CPD

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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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Salutary effect of gastric pentadecapeptide BPC 157 in two different stress urinary incontinence models in female rats

Cited by 18 publications

References 48 publications

Esophagogastric anastomosis in rats: Improved healing by BPC 157 and L-arginine, aggravated by L-NAME

Esophagogastric anastomosis in rats: Improved healing by BPC 157 and L-arginine, aggravated by L-NAME

Stable Gastric Pentadecapeptide BPC 157 and Wound Healing

Stable Gastric Pentadecapeptide BPC 157: Novel Therapy in Gastrointestinal Tract

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