NO system dependence of atropine-induced mydriasis and L-NAME- and L-arginine-induced miosis: Reversal by the pentadecapeptide BPC 157 in rats and guinea pigs

Kokot, Antonio; Zlatar, Mirna; Stupnišek, Mirjana; Drmic, Domagoj; Radić, Radivoje; Včev, Aleksandar; Seiwerth, Sven; Sikirić, Predrag

doi:10.1016/j.ejphar.2015.12.016

Cited by 29 publications

(89 citation statements)

References 32 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%

“…BPC 157, a peptide, is part of the sequence of human gastric juice protein BPC, and it is freely soluble in water at pH 7.0 and saline. The peptide was prepared, as described previously[15-25], with 99% high pressure liquid chromatography (HPLC) purity, expressing 1-des-Gly peptide as an impurity. L-NAME (Sigma, United States) and L-arginine (Sigma, United States) were used accordingly[1,5,7,17-19,45-51].…”

Section: Methodsmentioning

confidence: 99%

“…Together, intestinal anastomosis[10-14] and fistulas[15-20] healing, esophagitis and gastric lesion healing, alongside with rescued sphincter function[10,11,17,18,20-25] could certainly improve the possible curative peptides therapy for rat esophagogastric anastomosis. Until now, only to improve anastomosis healing, tested were keratinocyte growth factor-2 (KGF-2) (shown to be ineffective given intraperitoneally)[26] (regardless to therapeutic efficacy of a mutant of KGF-2 on trinitrobenzene sulfonic acid-induced rat model of Crohn’s disease[27]) and FGF-beta (effective given topically[28]).…”

Section: Introductionmentioning

confidence: 99%

“…As a result, these standard peptide growth factors[26,28] only support the particular perilous course of the esophagogastric anastomosis and show little improvement in rats[29,30]. On the other hand, these combined BPC 157 effects may be more useful for both anastomosis healing and sphincter function rescue[10-14,17,18,20-25]. As a result, the esophagogastric anastomosis healing should both resist leakage and maintain some “sphincter” function at the anastomosis site.…”

Section: Introductionmentioning

confidence: 99%

“…For practical purposes, the stable gastric pentadecapeptide BPC 157, was given daily, intraperitoneally or orally, in drinking water, using the previous efficacious regimens[7,15-25]. In addition to these effects, the possible simultaneous healing (stable gastric pentadecapeptide BPC 157, along with both NOS-blockade, L-NAME, and NOS-substrate L-arginine application[1]) would define the esophagogastric anastomosis healing, define esophagitis and gastric defects healing, rescue “sphincter” pressure at the site of anastomosis and preserve pyloric sphincter pressure, as a new NO-system related phenomenon.…”

Section: Introductionmentioning

confidence: 99%

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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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