Stable Gastric Pentadecapeptide BPC 157 Heals Established Vesicovaginal Fistula and Counteracts Stone Formation in Rats

Abstract

With the stable gastric pentadecapeptide BPC 157 therapy known to heal various both external and internal rat fistulas, we attempt to approach vesicovaginal fistula, continuous urine leaking through vagina, bladder stones, and a possible therapy solution among rats with well-formed 2 week-fistulas (vaginal/vesical 4 mm large defects) started with delayed therapy. Subsequent control fistula course (the subsequent 1, 2, 4, and 6 weeks) since beginning revealed the failed healing, fistula leaking, adhesions, urinary leaking through vagina, failed epithelization, collagenization, granulation tissue and neovascularization, increased inflammation, and necrosis. Thereby, the later intervals revealed the persistent inability to sustain even minimal volume, vesical, and vaginal defects and stone formation at the end of the experiment (fistula-time day 56). BPC 157 therapy (10 µg/kg, 10 ng/kg, intraperitoneally once time daily or perorally in drinking water until sacrifice) was initiated with a considerable delay (at 2 weeks after fistula formation). Already within 1 week therapy, all BPC 157 regimens stopped urinary leaking through vagina, reversed the otherwise resistant poor healing course to the increased epithelization, collagenization, granulation tissue and neovascularization, decreased inflammation, and decreased necrosis. Thereby, at later intervals, all BPC 157 rats exhibited a five times larger volume that can be sustained before leaking as in healthy, vesical, and vaginal defects completely closed and no stone formation. Thus, macro/microscopic and functional recovery, and counteracted stone formation. Concluding, BPC 157 therapy’s beneficial effects resulted in healing and no stone formation, with µg- and ng-regimens, either given daily perorally in drinking water or intraperitoneally.

Stable Gastric Pentadecapeptide BPC 157 as Useful Cytoprotective Peptide Therapy in the Heart Disturbances, Myocardial Infarction, Heart Failure, Pulmonary Hypertension, Arrhythmias, and Thrombosis Presentation

“…BPC 157 therapy might have a particular effect on other smooth muscles. During sick conditions, BPC 157 therapy might have a particularly beneficial effect on many sphincters (lower esophageal sphincter, pyloric sphincter [ 67 , 101 , 170 , 172 , 173 , 174 , 175 , 176 , 177 , 178 ], pupil [ 26 , 179 ], urinary sphincter [ 62 , 180 , 181 ]) and might recover their distinctive functions. This particular effect might suggest a distinctive therapy effect depending on the injury condition, along with the general agenda of the cytoprotection concept (i.e., maintained cell integrity against different noxious agents’ injurious effect) (for review, see, i.e., [ 2 , 3 , 4 , 5 , 6 , 7 , 8 ]).…”

“…Moreover, in a more general view, decisive for the maintenance of muscle contractility and heart function, the counteraction of arrhythmias as an interaction of several changes in the fundamental electrophysiological properties of cardiac muscle fibers might also consider the additional BPC 157 therapy effect. These might be the simultaneous beneficial recovery of the disabled striated muscle function [ 67 , 68 , 69 , 71 , 72 , 111 , 112 , 113 , 114 , 115 ] as well as recovery of the disabled smooth muscle [ 101 , 170 , 172 , 173 , 174 , 175 , 176 , 177 , 178 , 179 , 180 , 181 ], effectively working through hyperkalemic [ 67 , 68 ] and hypokalemic [ 69 ] conditions. Evidently, BPC 157 therapy annihilated lethal outcomes in both hyperkalemia [ 67 ] and hypokalemia [ 69 ]).…”

Stable Gastric Pentadecapeptide BPC 157 and Striated, Smooth, and Heart Muscle

“…Finally, tumor-cachexia was counteracted [ 10 ]. Additionally, the reported evidence included the maintenance and recovery of the smooth muscle function (i.e., various sphincter functions) [ 73 , 91 , 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 , 115 , 116 , 117 , 118 , 119 , 120 , 121 ], and the heart muscle [ 6 , 54 , 72 , 74 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 105 , 106 , 121 , 122 , 123 ]. Thus, in general, this resolved multitude might be the result of the multimodal muscle–axis impact.…”

“…It might be that the particular effect of BPC 157 in electrolyte disturbances (i.e., hyperkalemia, hypokalemia, hypermagnesemia, and hyperlithemia [ 19 , 55 , 80 , 105 , 106 ]), and membrane potential [ 19 , 103 , 105 , 106 , 122 ], might confirm the particular effect of BPC 157 on the smooth muscle, and vice versa. Particular sphincters (lower esophageal sphincter, pyloric sphincter [ 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 , 115 ], pupil [ 73 , 116 ], urinary sphincter [ 91 , 117 , 118 ]) with distinctive functions, are all affected in the same way during conditions of sickness and the recovery of disabled function. This particular effect might suggest a distinctive therapy effect depending on the injury condition, along with the general content of the cytoprotection concept (i.e., maintained cell integrity against different noxious agents’ injurious effects) (reviewed elsewhere, see [ 1 , 3 , 4 , 5 , 6 , 8 , 9 , 32 , 33 , 34 , 92 ]).…”

“…Furthermore, the literature also focused on the succinylcholine-induced neuromuscular junction blockade [ 102 ], local anesthesia [ 103 , 104 ] (i.e., via lidocaine intraplantar application and axillary and spinal (L4-L5) intrathecal block [ 103 ]), electrolytes disturbances [ 19 , 55 , 80 , 105 , 106 ], neuroleptics dopamine blockade [ 26 , 51 , 54 , 55 ], NO-system blockade [ 26 ], alcohol intoxication [ 22 ], serotonin syndrome [ 25 ], particular neurotoxins (inducing Parkinson-like disturbances in mice [ 30 ] or multiple sclerosis-like disturbances in rats [ 31 ]), and tumor cachexia [ 10 ]. These intriguing relations might also include, besides the striated muscle, the smooth muscle (i.e., various sphincter functions) [ 73 , 91 , 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 , 115 , 116 , 117 , 118 , 119 , 120 , 121 ], and the heart muscle [ 6 , 54 , 72 , 74 , 76 , 77 , 78 , 79 , 80 ,…”