BPC 157's effect on healing

International journal of scientific research, 2019

Surgeons concern for complications and outcomes of gastrointestinal tract surgery, especially in patients who has received intraluminal contrast media before surgery. As of now in most of the diagnostic radiology, non ionic contrast agents have replaced barium sulphate as contrast medium of choice but still barium sulphate is being used as contrast medium at primary and secondary care centers. Therefore we conducted this experimental study to compare the effect of barium sulphate and gastrogran dye on intraluminal wound healing in the gastrointestinal tract of albino rats particularly in context of macroscopic and histological ndings. Materials and Methods: This experimental study with prior approval of animal ethics committee was conducted in the department of general surgery at NSCB Medical College, Jabalpur, India. 45 Albino Rats were divided into 3 study groups (n= 15) and as per xed protocol, linear incision was made on the anti mesenteric border of colon. O.5 ml of NS, Barium sulphate and gastrogran was instilled intraluminaly in Group A, B and C subsequently. Post instillation, colon was repaired transeversally with full thickness vicryl 6-0 sutures. Half of the rats from each group were sacriced on POD 7 and rest on POD 21. After macroscopic examination, repaired area of bowel was taken out for histological assessment and the HPR were graded as per 'tissue morphological score ' Shackleton KL et al [1]. Results: 50 % of survived rats in each group were sacriced and analyzed as per tissue morphology score on POD 7. The tissue morphological score is based on neutrophillic inltration, lymphocytic inltration, collagen formation, granuloma formation and mucosal continuity. Mucosal continuity is a major determinant of wound healing and the best mucosal continuity was noted in-group C. About 90% cases of gastrogran dye group showed good mucosal continuity in comparison to 60 % cases of barium group. On POD 21, the ndings of all the three groups were similar. Conclusion: Gastrogran (Non Ionic contrast) group showed good tissue healing in early phases with less complications. It is a better contrast medium as compared to barium sulphate. On the other hand, Barium sulphate resulted in more complications like adhesion and pus pocket formation.

Burns, 2001

The effects of the gastric pentadecapeptide BPC 157 were investigated when administered topically or systemically in burned mice. This agent is known to have a beneficial effect in a variety of models of gastrointestinal lesions, as well as on wound or fracture healing. Deep partial skin thickness burns (1.5 × 1.5 cm) covering 20% of total body area, were induced under anesthesia on the back of mice by controlled burning and gastric lesions were assessed 1, 2, 3, 7, 14 and 21 days following injury. The first application of BPC 157 was immediately following burning, and thereafter, once daily, until 24 h before sacrifice. In the initial experiments, exposure to direct flame for 5 s, the BPC 157 was applied at 10 mg or 10 ng/kg b.w. intraperitoneally (i.p.) by injection or alternatively, topically, at the burn, as a thin layer of cream (50 mg of BPC 157 dissolved in 2 ml of distilled water was mixed with 50 g of commercial neutral cream (also used as local vehicle-control)), while silver sulfadiazine 1% cream was a standard agent acting locally. Others received no local medication: they were treated i.p. by injection of distilled water (distilled water-control) or left without any medication (control). In subsequent experiments involving deeper burns (direct flame for 7 s), BPC 157 creams (50 mg, 5 mg, 500 ng, 50 ng or 5 ng of BPC 157 dissolved in 2 ml of distilled water was mixed with 50 g of commercial neutral cream), or vehicle as a thin layer of cream, were applied topically, at the burn. Compared with untreated controls, in both experiments, in the BPC 157 cream-treated mice all parameters of burn healing were improved throughout the experiment: less edema was observed and inflammatory cell numbers decreased. Less necrosis was seen with an increased number of capillaries along with an advanced formation of dermal reticulin and collagen fibers. An increased number of preserved follicles were observed. Two weeks after injury, BPC 157 cream-treated mice completely reversed the otherwise poor re-epithelization ratio noted in the untreated control or mice treated with vehicle only. Tensiometry investigation showed an increased breaking strength and relative elongation of burned skin, while water content in burned skin decreased. This was, however, not the case with the vehicle or silver sulfadiazine. Relative to the control values, in silver sulfadiazine cream-treated mice, only collagen fiber formation was increased, in addition to a decreased inflammatory cell number. Relative to control values, BPC 157 given i.p. decreased the number of inflammatory cells, lowered water content in burned skin, and raised breaking strength and relative elongation of burned skin during tensiometry. Through the experimental period, gastric lesions were continuously noted in all thermally injured mice left without local medication and they were consistently attenuated only by BPC 157 treatments: either given i.p. (at either dose), or given locally (at either concentration). Other treatments (i.e. local treatment with silver sulfadiazine cream or neutral cream in mice subjected for 5 s to direct flame), led to only poor, if any attenuation. This stable gastric pentadecapeptide appears to be active and gives a stimulation to burn healing at the defect site. The agent may act by causing an upregulation of the growth factors, as well as influencing other local factors.

Journal of Physiology-Paris, 1999

A clear protection of the gastrointestinal tract and an evident anti-inflammatory effect were shown for a novel stomach pentadecapeptide BPC 157 (i.p./i.g.) in comparison with several reference standards in various ulcer models along with a protection of endothelium and particular interaction with the NO-system. Thus, we evaluated whether this pentadecapeptide along with other gastroprotective agents could affect angiogenesis and the healing process in vivo using a procedure initially described by Szabo and co-workers. In each rat, two sterile sponges (1

Surgery Today, 2008

Purpose. Stable gastric pentadecapeptide BPC 157 accelerates the healing of a transected Achilles tendon and a transected quadriceps muscle. It may also be of clinical relevance as a systemic and local peptide treatment for crush injury of a major muscle, such as gastrocnemius muscle complex. BPC 157 is effective without a carrier, and it is presently undergoing trials for infl ammatory bowel disease, and no toxicity has so far been reported. Methods. In crushed rats (force delivered 0.727 Ns/cm 2), BPC 157 was applied either intraperitoneally or locally, as a thin cream layer, immediately after injury (sacrifi ce at 2 h), and once a day for 14 days. Results. BPC 157 improved muscle healing, macroscopically (less hematoma and edema, no post-injury leg contracture), microscopically, functionally, and also based on enzyme activity (creatine kinase, lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase). Conclusion. BPC 157, at all investigated intervals, given locally or intraperitoneally, accelerated post-injury muscle healing and also helped to restore the full function.

Journal of Investigative Surgery, 2004

Wound contraction is a clinically important biological process because it frequently results in contractures, strictures, and stenosis. If collagen synthesis could be altered to minimize the contracture, then the outcome could be improved. Lathyrism produces poorly cross-linked collagen in healing anastomosis, keeping a larger portion of the synthesized collagen soluble. Ultimately, the amount of contracting collagen is reduced, lowering the bulk and lessening the contracture. The aim of this study was to observe the effects of a lathyrogen, beta-aminopropionitrile (BAPN), on the healing of colonic anastomosis. Thirty rats were divided into three groups. Colostomy and anastomosis were performed on all rats. Intraperitoneal saline solution (control) and either intraperitoneal (ip) or oral (po) BAPN were administered. The rats were killed 1 week later. Anastomotic healing was assessed by bursting pressure and the hydroxyproline content of the anastomotic tissues. Granulation tissue thickness, number of fibroblasts, inflammatory cells, and growing capillaries in granulation tissue per unit area were determined. Collagen fibril diameters were estimated, and spatial arrangements of fibrils were examined by an electron microscope. All results were evaluated by Mann-Whitney U-test. The analyses of anastomotic tissues from BAPN-treated rats showed a significantly reduced mean bursting pressure (158.9 ± 12.3, 171.3 ± 13.9, ip and po, respectively), hydroxyproline content (8.9 ± 2.6, 10.1 ± 2.7), granulation tissue thickness (24.3 ± 2.6, 16.1 ± 5.2), number of inflammatory cells (37.8 ± 4.3, 25 ± 4.3), fibroblasts (3.2 ± 1.1, 2.8 ± 0.7), and a significantly reduced collagen fiber diameter (15 ± 2, 20 ± 3) compared with those of control group (236.9 ± 9, 14 ± 4.4, 26.8 ± 4.8, 39 ± 2.6, 6.9 ± 1.1, and 35 ± 5, respectively). As a result, collagen fibers were flimsy, and lost their regular parallel alignment in the BAPN groups. On the other hand, a number of growing capillaries were found to be significantly increased in these groups (16.5 ± 1.1, 18.2 ± 0.7)

PLOS ONE, 2015

Strategies for skin regeneration have been developed to provide effective treatment for cutaneous wounds and disease. Dermal substitutes have been used to cover the lesion to facilitate cell colonization, thereby promoting dermal regeneration. However, very little is known about Pelnac matrix especially at histological level. Therefore, the present work carried out an experimental in vivo comparative analysis between Pelnac and Integra, the most used dermal templates, in a mouse model of full-thickness skin wounds. Histological sections performed at the 3 rd , 6 th and 9 th days after surgery were analyzed with regard to inflammatory response and vascularization. Both templates were completely incorporated in all animals at the end of the analyzed period. Pelnac-treated animals displayed reduced granulation tissue during the first 6 days of treatment compared to the animals treated with Integra at the same time period. The number of inflammatory cells (neutrophils) was similar in both groups during the period, significantly reducing at the end of inflammatory phase (9 th day of treatment) consistent with the progression of healing process. In addition, the density of blood vessels was also statistically similar in both matrices. Therefore, the two dermal templates displayed comparable biological behavior in tissue repair. It is noteworthy that this is the first experimental study comparing Pelnac and Integra dermal templates with focus on full-thickness skin wounds.

Journal of physiology and pharmacology: an official journal of the Polish Physiological Society

While very rarely reported, duodenocutanenous fistula research might alter the duodenal ulcer disease background and therapy. Our research focused on rat duodenocutaneous fistulas, therapy, stable gastric pentadecapeptide BPC 157, an anti-ulcer peptide that healed other fistulas, nitric oxide synthase-substrate L-arginine, and nitric oxide synthaseinhibitor L-nitro-arginine methyl ester (L-NAME). The hypothesis was, duodenal ulcer-healing, like the skin ulcer, using the successful BPC 157, with nitric oxide-system involvement, the "wound healing-therapy", to heal the duodenal ulcer, the fistula-model that recently highlighted gastric and skin ulcer healing. Pressure in the lower esophageal and pyloric sphincters was simultaneously assessed. Duodenocutaneous fistula-rats received BPC 157 (10 µg/kg or 10 ng/kg, intraperitoneally or perorally (in drinking water)), L-NAME (5 mg/kg intraperitoneally), L-arginine (100 mg/kg intraperitoneally) alone and/or together, throughout 21 days. Duodenocutaneous fistula-rats maintained persistent defects, continuous fistula leakage, sphincter failure, mortality rate at 40% until the 4 th day, all fully counteracted in all BPC 157-rats. The BPC 157-rats experienced rapidly improved complete presentation (maximal volume instilled already at 7 th day). L-NAME further aggravated the duodenocutaneous fistula-course (mortality at 70% until the 4 th day); L-arginine was beneficial (no mortality; however, maximal volume instilled not before 21 th day). L-NAME-worsening was counteracted to the control level with the L-arginine effect, and vice versa, while BPC 157 annulled the L-NAME effects (L-NAME + L-arginine; L-NAME + BPC 157; L-NAME + L-arginine + BPC 157 brought below the level of the control). It is likely that duodenocutaneous fistulas, duodenal/skin defect simultaneous healing, reinstated sphincter function, are a new nitric oxide-system related phenomenon. In conclusion, resolving the duodenocutanenous fistulashealing, nitric oxide-system involvement, should illustrate further wound healing therapy to heal duodenal ulcers.

Journal of Orthopaedic Research, 2003

In studies intended to improve healing of transected Achilles tendon, effective was a stable gastric pentadecapeptide BPC 157 (GEPPPGKPADDAGLV, M.W. 1419). Currently in clinical trials for inflammatory bowel disease (PLD-I 16, PL 14736, Pliva), it ameliorates internal and external wound healing. In rats, the right Achilles tendon transected (5 mm proximal to its calcaneal insertion) presents with a large tendon defect between cut ends. Agents (ikg b.w., i.p., once time daily) (BPC 157 (dissolved in saline, with no carrier addition) ( 10 pg. 10 ng or 10 pg) or saline (5.0 ml)), were firstly applied at 30 min after surgery, the last application at 24 h before autopsy. Achilles functional index (AFI) was assessed once time daily. Biomechanical, microscopical and macroscopicdl assessment was on day 1. 4, 7, 10 and 14. Controls generally have severely compromised healing. In comparison, pentadecapeptide BPC 157 fully improves recovery: (i) biomechanically, increased load of failure, load of Failure per area and Young's modulus of elasticity; (ii) functionally, significantly higher AFI-values; (iii) microscopically, more mononuclears and less granulocytes, superior formation of fibroblasts, reticulin and collagen; (iv) macroscopically, smaller size and depth of tendon defect, and subsequently the reestablishment of full tendon integrity. Likewise, unlike TGF-P, pentadecapeptide BPC 157, presenting with no effect on the growth of cultured cell of its own, consistently opposed 4-hydroxynonenal (HNE), a negative modulator of the growth. HNE-effect is opposed in both combinations: BPC 157 + HNE (HNE growth inhibiting effect reversed into growth stimulation of cultured tendocytes) and HNE + BPC 157(abolished inhibiting activity of the aldehyde), both in the presence of serum and serum deprived conditions. In conclusion, these findings, particularly, Achilles tendon transection fully recovered in rats, peptide stability suitable delivery, usefully favor gastric pentadecapeptide BPC 157 in future Achilles tendon therapy.

Gene Reports, 2019

Background: The effect of delivered bromine vapor and also bromine substitutions are shown to play an important role in anti-inflammatory activity. The present study encompasses a broad in vivo study to size up healing activity of a novel dibromide substituted Schiff based compound against cutaneous wound model in Sprague Dawley (SD) rats. Methodology/principal findings: 2, 2′-[1, 2-Cyclohexanediylbis(nitriloethylidyne)] bis[4-bromophenol], CNBP, is synthesized through a Schiff base reaction applying the related ketone and diamine as the initiators. Four groups of six in each male SD rats are divided as negative group which are treated with gum acacia, positive control animals which are treated with topical dosage of Intrasite gel, and testing groups treated with low (10 mg/kg) and high (20 mg/kg) doses of CNBP. The excisional wounds are created on the posterior neck area of each group and the wound closure percentage was measured in the two separated days of the experiment. Moreover, the histopathological evaluation and determination of activities of superoxide dismutase (SOD), catalase (CAT), peroxidase (GPx), and malondialdehyde (MDA) of the skin sections are performed. Furthermore, the immunohistochemistry consists of the evaluation of Hsp70 and BAX proteins. Conclusions/significance: The wound closure percentage showed a significant increase in high dose CNBP-treated group compared to the negative control. Histopathological evaluation of the skin sections showed that granulation tissue contained more proliferating fibroblast, collagen deposition, angiogenesis, and also less inflammatory cells in the high dose CNBP-treated group compared to the normal rats. In the treated groups with CNBP, SOD, CAT, and GPx activities were found significantly higher, however, the MDA level was shown to be lower (*P < 0.05; **P < 0.01; ***P < 0.001) than the negative control. At the molecular level, CNBP (20 mg/ ml, HD) improved wound-healing process via down and up regulation of Bax and Hsp70 protein, respectively at the wound site.

European Journal of Pharmacology, 2016

To establish the effects of BPC 157 on the healing of rat colovesical fistulas, Wistar Albino male rats were randomly assigned to different groups. BPC 157, a stable gastric pentadecapeptide, has been used in clinical applications-specifically, in ulcerative colitis-and was successful in treating both external and internal fistulas. BPC 157 was provided daily, perorally, in drinking water (10 µg/kg, 12 ml/rat/day) until sacrifice or, alternatively, 10 µg/kg or 10 ng/kg intraperitoneally, with the first application at 30 min after surgery and the last at 24 h before sacrifice. Controls simultaneously received an equivolume of saline (5.0 ml/kg ip) or water only (12 ml/rat/day). Assessment (i.e., colon and vesical defects, fistula leaking, fecaluria and defecation through the fistula, adhesions and intestinal obstruction as healing processes) took place on days 7, 14 and 28. Control colovesical fistulas regularly exhibited poor healing, with both of the defects persisting; continuous fistula leakage; fecaluria and defecation through the fistula; advanced adhesion formation; and intestinal obstruction. By contrast, BPC 157 given perorally or intraperitoneally and in µg-and ng-regimens rapidly improved the whole presentation, with both colon and vesical defects simultaneously ameliorated and eventually healed. The maximal instilled volume was continuously raised until it reached the values of healthy rats, there were no signs of fecaluria and no defecation through the fistula, there was counteraction of advanced adhesion formation or there was an intestinal obstruction. In conclusion, BPC 157 effects appear to be suited to inducing full healing of colocutaneous fistulas in rats.

2021

Since antiquity, wounds have inflicted enormous pain and suffering to mankind. Amelioration of this pain, faster healing was a daunting task for us from ancient times. The process of wound healing is complex and tightly regulated which mainly affect certain tissues of the bodyprimarily including the skin. It is of paramount importance as it concerns reinstating the integrity of the skin tissues. The cascade of recovery of the wounds may be affected due to a plethora of disease processes, which is further known to induce considerable distress and perturbation to the patients. Medical science has been keen on understanding the mechanism of wound healing and has used many medicaments to help reduce the duration of relapse or recovery. The treatment methods span from the usage of many phytoconstituents to the modern regimen of using novel formulations. The aim of this article is therefore to review the recent biotechnological interventions along with novel treatment regimen that have be...

Journal of investigative surgery : the official journal of the Academy of Surgical Research, 2018

Wound healing consists of a sequence of complex molecular and cellular events. Collagen is composed mainly of proline and hydroxyproline. Proline and hydroxyproline constitute 1/3 of the amino acids in collagen, which makes up approximately 30% of the proteins within the body. The hydroxylation of proline found in collagen determines the stability of the triple helical structure of collagen. In this study, we examined the effects of local and systemic administration of proline on wound healing. 24 female Sprague-Dawley rats were used in the study and divided into three groups. Group 1: The defect created in the backs of the subjects was left to secondary healing. Group 2: 200 µl proline per day was administered topically for 30 days on the defect in the backs of the subjects. Group 3: 200 µl per day was administered intraperitoneally for 30 days on the defect in the backs of the subjects. On day 21, there was a statistically significant difference between the groups in terms of the ...

Transplantation Direct, 2016

Background. Immunosuppressant agents are inevitable for solid organ recipients, but may have a negative effect on wound healing that is difficult to measure because of clinical use of a polydrug regime. The evidence on mycophenolate mofetil (MMF) is scarce and contradictory. This study aims to investigate the effect of MMF administration on wound healing. Methods. Ninety-six male Wistar rats divided into 4 groups underwent anastomotic construction in ileum and colon at day 0. Three groups received daily oral doses of 20 or 40 mg/kg MMF or saline (control group) from day 0 until the end of the experiment. Half of each group was analyzed after 3 days and half after 7 days. Another group started the medication 3 days after the laparotomy and was analyzed after 7 days, half of this group received 20 mg/kg and half 40 mg/kg MMF. Wound strength in anastomoses and in the abdominal wall was measured using bursting pressure, breaking strength, and histology. Trough levels were measured. Results. Significant differences in wound strength were seen in ileum tissue after 3 days, which surprisingly showed a stronger anastomosis in the experimental groups. Bursting pressure as well as breaking strength was higher in the low-dose and highdose MMF group compared with the control group. A negative effect was measured in abdominal wall tissue for the highest-dose group, which disappeared when the medication was delayed for 3 days. Histology showed poorer bridging of the submucosal layer and more polymorphonuclear cell infiltration in the ileum specimens of the control group compared with the treatment groups. Conclusions. As a single agent in a preclinical wound healing model in the rat, MMF has no negative effect on healing of bowel anastomoses but might have a negative effect on the healing of abdominal wall.

Plastic Surgery International, 2013

Background. Complements C3 and C5 have independently been shown to augment and increase wound healing and strength. Our goal was to investigate the combinatorial effect of complements C3 and C5 on wound healing. Methods. Each rat served as its own control where topical collagen was applied to one incision and 100 nM of C3 and C5 in collagen vehicle was applied to the other incision (n=6). To compare between systemic effects, a sham group of rats (n=6) was treated with collagen alone on one wound and saline on the other. At day 3, the tissue was examined for maximal breaking strength (MBS) and sectioned for histological examination. Results. There was a statistically significant 88% increase in MBS with the topical application of C3C5 when compared to sham wounds (n&lt;0.05). This was correlated with increased fibroblast and collagen deposition in the treated wounds. Furthermore, there appeared to be an additive hemostatic effect with the C3C5 combination. Conclusions. The combinatio...