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INCISIONAL VENTRAL HERNIA IN RATS, STABLE GASTRIC PENTADECAPEPTIDE BPC 157, L-NAME AND L-ARGININE Alen Pajtak2, Zdenko Bilic2, Fedor Amic2, Domagoj Drmic2, Frane Pamukovic1, Janos Kodvanj1, Sven Seiwerth3, Predrag Sikiric*2 1Faculty of Mechanical Engineering and Naval Architecture, Zagreb, Croatia; 2Pharmacology, School of Medicine, University of Zagreb, Zagreb, Croatia; 3School of Medicine, University of Zagreb, Zagreb, Croatia
Aim. Incisional ventral hernia (IVH) formation has a unique biomechanical disturbance which can be described by “early wound failure” mechanism. Therefore, we suggest that stable gastric pentadecapeptide BPC 157 (used in trials: IBD; now, multiple sclerosis) known to heal various internal and external wounds and muscle injuries and interact with NO-system (Curr Med Chem 2012;19(1):126-32; Curr Pharm Des 2011;17(16):1612-32; Curr Pharm Des 2014;20(7):1126-35) rescues IVH in rats. To demonstrate that that rescue of IVH is also a particular NO-system related effect, NOS-blocker L-NAME and NOS-substrate L-arginine were also given alone and/or combined. Methods. Wistar Albino male rats underwent ingrained method (Ann Surg. 2004 Jul;240(1):179-86.) of early wound failure induction (satisfactory IVH incidence) received medication/kg (BPC 157 (10ug, 0.16ug/mL, 12mL/day/rat, in drinking water), L-NAME (5mg/day), L-arginine (100mg/day) both intraperitoneally, alone and/or combined; or drinking water only (controls)) through 14 days. IVH size, cutaneous wound healing (CVH) quality and intraabdominal adhesions (IA) were scored. Results: IVH size was 6.84.8mm in controls. BPC 157 exhibited size 0.81.9 (vs. control p<0.001). L-NAME treated animals had IVH size 21.610.5 (p=0.0009); L-arginine treated animals had IVH size 24.619.53 (p=0.013). L-NAME+BPC 157 treated animals had IVH size 9.410.5 (p=0.525). L-arginin+BPC 157 treated animals had IVH incidence, size 19.417.5 (p=0.087). L-NAME+L-arginine treated rats had IVH size 21.421.4 (p=0.053); four animals died. L-NAME+L-arginine+BPC 157 treated animals had IVH size 13.115.5 (p=0.254). BPC 157 had positive effect on CVH (p=0.0001) and IA (p<0.0001), while L-NAME and L-arginine had negative impact on IA (p=0.0001; p=0.041) (Fig 1). Conclusion. BPC 157 rescues IVH, while both L-NAME and L-arginine exhibit an opposite harmful effect. However, this beneficial effect of BPC 157 against unusual negative overlapping of L-NAME and L-arginine is also specific aspect of NO-system dual (L-NAME vs. L-arginine) role (vs. combination) (for review see Eur J Pharmacol. 2016 Jan 15;771:211-9.; Curr Pharm Des 2014;20(7):1126-35), where each of these effects is specific (i.e., NO-related). Namely, given together (L-NAME+L-arginine) regularly attenuated or antagonized each other's response. In practice, this means two pharmacologically distinct mechanisms with opposite effects on the same signaling pathway confronted with the regularly unresolvable same physiological failure (IVH growth). Also, in practice, this means two distinct end points, that should be both overwhelmed to achieve presentation seen in rats underwent BPC 157 application. Thus, these findings suggest possible application of BPC 157 in IVH rescue, and this is also a particular NO-system related effect. Back to 2017 Posters |
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