Effects of Diclofenac, L-NAME, L-Arginine, and Pentadecapeptide BPC 157 on Gastrointestinal, Liver, and Brain Lesions, Failed Anastomosis, and Intestinal Adaptation Deterioration in 24 Hour-Short-Bowel Rats

Abstract

Stable gastric pentadecapeptide BPC 157 was previously used to ameliorate wound healing following major surgery and counteract diclofenac toxicity. To resolve the increasing early risks following major massive small bowel resectioning surgery, diclofenac combined with nitric oxide (NO) system blockade was used, suggesting therapy with BPC 157 and the nitric oxide synthase (NOS substrate) L-arginine, is efficacious. Immediately after anastomosis creation, short-bowel rats were untreated or administered intraperitoneal diclofenac (12 mg/kg), BPC 157 (10 μg/kg or 10 ng/kg), L-NG-nitroarginine methyl ester (L-NAME, 5 mg/kg), L-arginine (100 mg/kg) alone or combined, and assessed 24 h later. Short-bowel rats exhibited poor anastomosis healing, failed intestine adaptation, and gastrointestinal, liver, and brain lesions, which worsened with diclofenac. This was gradually ameliorated by immediate therapy with BPC 157 and L-arginine. Contrastingly, NOS-blocker L-NAME induced further aggravation and lesions gradually worsened. Specifically, rats with surgery alone exhibited mild stomach/duodenum lesions, considerable liver lesions, and severe cerebral/hippocampal lesions while those also administered diclofenac showed widespread severe lesions in the gastrointestinal tract, liver, cerebellar nuclear/Purkinje cells, and cerebrum/hippocampus. Rats subjected to surgery, diclofenac, and L-NAME exhibited the mentioned lesions, worsening anastomosis, and macro/microscopical necrosis. Thus, rats subjected to surgery alone showed evidence of deterioration. Furtheremore, rats subjected to surgery and administered diclofenac showed worse symptoms, than the rats subjected to surgery alone did. Rats subjected to surgery combined with diclofenac and L-NAME showed the worst deterioration. Rats subjected to surgery exhibited habitual adaptation of the remaining small intestine, which was markedly reversed in rats subjected to surgery and diclofenac, and those with surgery, diclofenac, and L-NAME. BPC 157 completely ameliorated symptoms in massive intestinal resection-, massive intestinal resection plus diclofenac-, and massive intestinal resection plus diclofenac plus L-NAME-treated short bowel rats that presented with cyclooxygenase (COX)-NO-system inhibition. L-arginine ameliorated only L-NAME-induced aggravation of symptoms in rats subjected to massive intestinal resection and administered diclofenac plus L-NAME.

Stable gastric pentadecapeptide BPC 157 in honeybee (Apis mellifera) therapy, to control Nosema ceranae invasions in apiary conditions

“…Results of this field study demonstrated that BPC 157 administrated via sugar syrup as a food supplement significantly reduced ( (Klicek et al, 2013;Lojo et al, 2016;Sikiric et al, 2001;Veljaca et al, 1995). As indicated previously, BPC 157 has been tested in clinical trials as an agent against ulcerative colitis, but studies have shown its efficacy throughout complete gastrointestinal tract .…”

“…Finally, the conclusive prospect (i.e., BPC 157 application as an innate treatment to successfully oppose invasion with N. ceranae ) is supported by a variety of beneficial effects of BPC 157 noted in colitis lesion studies (Klicek et al., ; Lojo et al., ; Sikiric et al., ; Veljaca et al., ). As indicated previously, BPC 157 has been tested in clinical trials as an agent against ulcerative colitis, but studies have shown its efficacy throughout complete gastrointestinal tract (Sikiric et al., ).…”

Stable Gastric Pentadecapeptide BPC 157, Robert's Stomach Cytoprotection/Adaptive Cytoprotection/Organoprotection, and Selye's Stress Coping Response: Progress, Achievements, and the Future

“…We noted the antagonization of the corresponding alcoholinduced [48][49][50][51][52] and NSAIDs-induced [53][54][55][56][57] stomach lesions, much like the counteraction of the liver and brain lesions, which were induced by alcohol [58][59][60] or NSAIDs. [53][54][55][56][57]61 To emphasize, much like the prototypic acute alcohol-stomach lesion, [48][49][50][51] the beneficial range of the BPC 157 counteracts alcohol in both acute intoxication (protracted drowsiness, increased alcohol level in blood, hypothermia) and chronic intoxication (withdrawal convulsions). 59,60 Likewise, it counteracts consequences of the chronic abuse (drinking alcohol for 3 months) 58 such as chronic gastric lesions 51 or liver lesions with portal hypertension.…”

“…58 For NSAIDsadverse effects (i.e., gastrointestinal, liver and brain injuries), BPC 157 counteraction includes both COX-1 and COX-2 block-ers. [52][53][54][55][56][57]61 BPC 157 reduces bleeding after amputation, and may also counteract aspirin induced prolongation of bleeding and thrombocytopenia. 62,63 An interesting point is that BPC 157 may also prevent and reverse adjuvant arthritis in rats.…”

“…Due to the comparative small size of the rats and large size of the defects, these defects would fairly mimic large fistulas in patients that would hardly heal spontaneously. [82][83][84][85][86][87] A similar demonstration should be the creation of the different gastrointestinal anastomoses 57,[88][89][90][91][92] that would accordingly heal as opposed to commonly poor healing in the corresponding control rats. Thus, the healing of the esophagocutaneous, 82 gastrocutaneous, 83 duodenocutaneous, 84 colocutaneous, 85 vesicovaginalis, 86 and rectovaginalis fistulas, 87 assessed grossly, biomechanically and microscopically means demonstration of the both external and internal fistulas healing [82][83][84][85][86][87] and consequently, the realization of the simultaneous healing of different tissues.…”