Stable Gastric Pentadecapeptide BPC 157 Antagonized Local Anesthetic Effect of Lidocaine

We documented that stable gastric pentadecapeptide BPC 157 counteracts convulsions induced by concomitant application of atypical neuroleptic, SSRI and NSAID, risperidone, citalopram and metamizole in rats. BPC 157, LD1 not achieved, was implemented as an anti-ulcer peptide in inflammatory bowel disease trials and now in a multiple sclerosis trial. Previously, BPC 157 counteracts consequences of dopamine (D), receptors blockade (neuroleptics-induced catalepsy, prolonged QT intervals, sphincters dysfunction and gastric lesions), much like over-stimulation (amphetamine acute and chronic disturbances; much like Dreceptors supersensitivity (amphetamine after haloperidol)), nigrostriatal lesions (MPTP Parkinsogenic neurotoxin), D-vesicles depletion (reserpine). Similarly, BPC 157 counteracts immobility more than imipramine in depression-models (Porsolt’s and chronic unpredictable stress-open field) and induces 5-HT release in particular brain areas (nigrostriatum) when given peripherally, acute and chronically. Also, BPC 157 counteracts convulsions induced by various convulsants (picrotoxine, strychnine, bicuculline) much like either with insulin or with paracetamol. we applied (mg/kg) risperidone 2.5 mg/kg, citalopram 2.0 mg/kg and metamizole 2.0 intraperitoneally. Medication (mg/kg), given 15 min before, or immediately after, includes BPC 157(0.01; 0,00001) while control rats received an equivolume of saline (5 mL/kg). Thereafter, at 20 minutes after medication risperidone/citalopram/metamizole rats became markedly sedated. Then, after the next 20 minutes they start with tonic-clonic seizures. The seizure period was lasting for the next 3 hours. Contrarily, either of BPC 157 regimens maintained normal behavior in all rats. BPC 157 exhibits also an anticonvulsant capacity, as well as a particular profile, which could in a therapy of neuroleptic, SSRI and NSAID intoxication

Suprahepatic inferior caval vein occlusion induced portal and caval hypertension, aortic hypotension and esophageal bleeding. therapy with pentadecapeptide BPC 157

Pentadecapeptide BPC 157 is intraduced as therapy in a suprahepatic inferior caval vein (ICV) occlusion 15 min, 24h, 48h after complete ICV ligation. Suprahepatic ICV complications that were counteracted by BPC 157 included esophageal bleeding, severe portal and caval hypertension, and aortal hypotension. Likewise, BPC 157 counteracts the lesions in the whole GI-tract. Medication (BPC 157 (10 μg/kg, 10 ng/kg), or saline (5 ml/kg) (controls)) was applied as an abdominal bath immediately after ICV occlusion. ICV occlusion produced severe esophageal bleeding in all controls, along with microscopy findings. Contrarily, given in ischemic period, BPC 157 counteracts severe esophageal bleeding and maintained grossly intact esophageal mucosa . In rats with ICV occlusion, assessment of portal (PV), caval (ICV) and aortal (AA) pressure showed huge portal hypertension and more caval hypertension, along with mild aortic hypotension (15 min: 68±4 PV, 45±4 ICV, 73±3 AA; 24 h: 56±5 PV, 49±5 ICV, 35±3 AA; 48 h 30±3 PV, 48±5 ICV, 39±3 AA-ligation period). Contrarily, BPC 157 in rats with suprahepatic ICV occlusion markedly counteracted portal and caval hypertension, and arterial hypotension (10 μg/kg bath 15 min: 3±1 PV, 9±1 ICV, 117±5 AA; 24 h: 5±1 PV, 9±1 ICV, 67±5 AA; 48 h: 5±1 PV, 9±1 ICV, 70±6 AA), 10 ng/kg bath produced similar results. BPC 157 therapy successfully counteracts the adverse effects of the suprahepatic ICV occlusion

Portal triad obstruction and reperfusion in rats –the effect of BPC 157

To investigate effects of pentadecapeptide BPC 157 therapy in temporary portal triad obstruction – PTO (hepatic artery, portal vein, common bile duct, 30 min in rats), and in reperfusion period thereafter, during 15 min and 24 h. BPC 157 (10 μg/kg, 10 ng/kg), or saline (5 ml/kg) was applied as a bath at the hepatoduodenal ligament area immediately after portal triad clamping or at the same area at 1 min or at 24 h reperfusion time. A period of 30 min of PTO much like reperfusion during 15 min and 24 h regularly produced severe hemorrhagic congestion (scored 0-4) of the stomach, duodenum, jejunum, cecum, colon, and esophageal bleeding in all controls. Contrarily, given either in ischemia period or in reperfusion period, BPC 157 counteracts severe hemorrhagic congestion in all organs, counteracts esophageal bleeding and maintained grossly intact esophageal mucosa. BPC 157 promptly induced effective shunting (venography in portal vein below ligation, portal vein-superior mesenteric vein-inferior mesenteric vein-rectal veins-left iliac vein-inferior caval vein). BPC 157, since attenuates portal hypertension in PTO-period, and completely eliminates pre-existing portal hypertension in post-PTO-period resulting in the values much like in the normal rats. PTO induced esophageal bleeding and severe hemorrhagic congestion in stomach, duodenum, jejunum, cecum and colon. BPC 157 counteracts these complications along with portal hypertension. Pringle maneuver and its consequences may have BPC 157 application as a successful therapy

BPC 157 pentadecapepide attenuates acute renal ischemia injury, prevents ensuing hemodynamic disturbances, peaked and inverted p waves, and gastrointestinal lesions

We focused on the effects of BPC 157 on acute unilateral renal ischemia in rats, subsequent severe portal (PV) and inferior vena cava (IVC) hypertension and thrombosis, abdominal aorta (AA) hypotension, peaked or inverted P waves and gastrointestinal lesions. Medication (/kg) (BPC 157 (10 μg)(treated group) or saline (5 ml)(control group)) was applied as an abdominal bath immediately after the right renal artery was ligated. 10min, 1h, and 24h after ligation electrocardiography, USB microcamera recording, intravascular cannulation, and thrombi extraction was performed. Control rats exhibited PV and IVC hypertension, aortic hypotension (mmHg) (10min: 32±2 PV, 24±4 IVC, 75±2 AA; 1h: 43±4 PV, 46±3 IVC, 73±4 AA; 24h: 30±2 PV, 34±1 IVC, 86±3 AA) and thrombosis (thrombus weight, mg) (10min: 1.3±0.3 IVC, 3.5±0.4 PV; 1h: 15.1±0.5 IVC, 5.4±0.2 PV; 24h: 16.3±1.5 IVC, 6.1±0.9 PV). Treated group showed improved pressure values (10min: 4±1 PV, 8±1 IVC, 84±3 AA; 1h: 18±2 PV, 6±1 IVC, 92±3 AA; 24h: 5±1 PV, 10±1 IVC, 97±2 AA) and milder thrombosis (10min: no thrombi; 1h: 7.7±0.3 IVC, 2.3±0.2 PV; 24h: 11.6±0.5 IVC, 3.2±0.2 PV). Control rats exhibited peaked (10 min, 1h) or inverted (24h) P waves, gastric and intestinal lesions (24h) and complete renal infarction (24h), whereas the treated rats exhibited no P wave abnormalities, significantly mitigated gastrointestinal lesions (24h) and only partial renal infarction (24h). BPC 157 therapy reduces the severity of renal ischemia injury, counteracts hemodynamic disturbances, P wave abnormalities and gastrointestinal lesions that follow

BPC 157 pentadecapepide attenuates acute renal ischemia injury, prevents ensuing hemodynamic disturbances, peaked and inverted p waves, and gastrointestinal lesions

We focused on the effects of BPC 157 on acute unilateral renal ischemia in rats, subsequent severe portal (PV) and inferior vena cava (IVC) hypertension and thrombosis, abdominal aorta (AA) hypotension, peaked or inverted P waves and gastrointestinal lesions. Medication (/kg) (BPC 157 (10 μg)(treated group) or saline (5 ml)(control group)) was applied as an abdominal bath immediately after the right renal artery was ligated. 10min, 1h, and 24h after ligation electrocardiography, USB microcamera recording, intravascular cannulation, and thrombi extraction was performed. Control rats exhibited PV and IVC hypertension, aortic hypotension (mmHg) (10min: 32±2 PV, 24±4 IVC, 75±2 AA; 1h: 43±4 PV, 46±3 IVC, 73±4 AA; 24h: 30±2 PV, 34±1 IVC, 86±3 AA) and thrombosis (thrombus weight, mg) (10min: 1.3±0.3 IVC, 3.5±0.4 PV; 1h: 15.1±0.5 IVC, 5.4±0.2 PV; 24h: 16.3±1.5 IVC, 6.1±0.9 PV). Treated group showed improved pressure values (10min: 4±1 PV, 8±1 IVC, 84±3 AA; 1h: 18±2 PV, 6±1 IVC, 92±3 AA; 24h: 5±1 PV, 10±1 IVC, 97±2 AA) and milder thrombosis (10min: no thrombi; 1h: 7.7±0.3 IVC, 2.3±0.2 PV; 24h: 11.6±0.5 IVC, 3.2±0.2 PV). Control rats exhibited peaked (10 min, 1h) or inverted (24h) P waves, gastric and intestinal lesions (24h) and complete renal infarction (24h), whereas the treated rats exhibited no P wave abnormalities, significantly mitigated gastrointestinal lesions (24h) and only partial renal infarction (24h). BPC 157 therapy reduces the severity of renal ischemia injury, counteracts hemodynamic disturbances, P wave abnormalities and gastrointestinal lesions that follow

Pentadecapeptide BPC 157 Counteracts the Adverse Effects of Lithium Overdose in Rats

INTRODUCTION We sought to determine whether stable gastric pentadecapeptide BPC 157 mitigates lithium intoxication in rats. METHODS: Lithium was applied at 500 mg/kg/day, intraperitoneally, once daily throughout 3 subsequent days. Medication used (in mg/kg) for the treatment group includes BPC 157 (0.01; 0.00001), L-NAME (5.0), L-arginine (100.0), applied alone and/or together, while control group rats received an equivolume of saline solution (5 mL/kg). At 20 minutes after drug application, we assessed muscular weakness (score 1-5) during the following 8 minutes. Then, for the next 5 minutes, we recorded an ECG. At 3 hours after that, the brain, the heart, the quadriceps muscle and the diaphragm muscle were used for histopathological analysis. RESULTS Consistently, lithium produced severe intoxication syndrome (muscular weakness and prostration, reduced quadriceps muscle fibers and diaphragm, myocardial infarction, and edema of various brain areas, most prominently in the cerebral cortex). The effects worsening with subsequent applications. L-NAME and L-arginine, given separately, both induced severe aggravation. This aggravation disappeared when L-NAME and L-arginine were given together. Contrarily, when given alone or together with NO-agents, BPC 157 reduced muscular weakness and prostration and muscle damage and mitigated lithium induced myocardial damage. BPC 157 reduced nerve damage and brain edema. CONCLUSION BPC 157 could be used as therapy for lithium intoxication

Spinal instability in rats counteracted by pentadecapeptide BPC 157

To induce spinal instability, we focused on bilateral facetectomy in rats and possible therapeutic benefit with the stable gastric pentadecapeptide BPC 157 given in the drinking water. Male Albino Wistar rats (12 weeks aged, 350-400 g b.w.), 4 rats per group, were used in the experiment. In this study, the bilateral paravertebral muscles attached to the L3–L4 segment were peeled from the lumbar spine to expose the posterior bony elements. The rats then underwent complete resection of bilateral L3–L4 facet joints without neural tissue injuries. After that, muscle and skin incsion were closed and animals returned to cages in pairs. The medication was administrated through drinking water (BPC 157 10 ng/kg, 0.16 ng/mL, 12 ml/rat/day), while controls received drinking water only. Next eight weeks we recorded and measured paw parameters (the lenght between left and right front and back paws) in control, treated and healthy rats. Radiological analysis was also performed. The paw parametars have shown that the front paws in the control group were approximately 35% and the back paws were 13% wider than in helathy rats. Contrarily, the front paws in medicated rats were only 9% and the back paws were only 4% wider than in healthy ones. Radiological assesment of rats spines acquired at 1 week or 8 weeks was conducted and BPC 157 drinking animals had higher bone density overall. BPC 157 improves damage caused by spine instability and it can be potentially used as a treatment for chronic back pain

Splenectomy induced portal and caval hypertension, aortic hypotension, venous thrombosis, peaked p waves, and tachycardia. therapy with pentadecapeptide BPC 157

We introduce BPC 157 therapy for a cluster of complications taking place after splenectomy in rats, including portal vein (PV), inferior vena cava (IVC), superior mesenteric vein (SMV) and lienal vein (LV) thrombosis, severe venous hypertension (PV, IVC), abdominal aorta (AA) hypotension, peaked P waves and tachycardia. Medication (/kg) (BPC 157 (10 μg)(treated group) or saline (5 ml)(control group)) was applied as an abdominal bath immediately after splenectomy. 10min, 3h, and 24h after splenectomy rats were assessed via electrocardiography, USB microcamera, intravascular cannulation, and thrombi extraction. Splenectomized rats exhibited PV and IVC hypertension, aortic hypotension (mmHg) (10min: 65±4 PV, 46±4 IVC, 71±3 AA; 3h: 42±4 PV, 61±4 IVC, 70±3 AA; 24h: 38±4 PV, 47±4 IVC, 68±3 AA) and thrombosis (thrombus weight, mg) (10min: 9.5±0.5 IVC, 6.6±0.9 PV, 4.8±0.9 SMV, 1.3±0.6 LV; 3h: 10.1±0.5 IVC, 5.3±0.8 PV, 19.2±0.9 SMV, 1.0±0.6 LV; 24h: 33.8±2.5 IVC, 27.5±2.9 PV, 8.8±0.9 SMV, 3.8±0.6 LV). BPC 157 normalised blood pressure (10min: 29±4 PV, 20±4 IVC, 87±3 AA; 3h: 20±4 PV, 17±4 IVC, 81±3 AA; 24h: 12±4 PV, 20±4 IVC, 82±3 AA) and reduced thrombosis (10min: 2.9±0.5 IVC, 2.6±0.9 PV, 3.2±0.3 SMV, 0.5±0.2 LV; 3h: 6.3±0.5 IVC, 2.3±0.5 PV, 5.9±0.9 SMV, 0.6±0.2 LV, 24h: 12.2±2.5 IVC, 1.9±0.5 PV, 4.8±0.9 SMV, 2.0±0.6 LV). Control group presented with peaked P waves, tachycardia and PV/SMV congestion, whereas the treated group showed none of the aforementioned phenomena. BPC 157 therapy counteracts hemodynamic disturbances, peaked P waves, and tachycardia as post-splenectomy complications

Splenectomy induced portal and caval hypertension, aortic hypotension, venous thrombosis, peaked p waves, and tachycardia. therapy with pentadecapeptide BPC 157

We introduce BPC 157 therapy for a cluster of complications taking place after splenectomy in rats, including portal vein (PV), inferior vena cava (IVC), superior mesenteric vein (SMV) and lienal vein (LV) thrombosis, severe venous hypertension (PV, IVC), abdominal aorta (AA) hypotension, peaked P waves and tachycardia. Medication (/kg) (BPC 157 (10 μg)(treated group) or saline (5 ml)(control group)) was applied as an abdominal bath immediately after splenectomy. 10min, 3h, and 24h after splenectomy rats were assessed via electrocardiography, USB microcamera, intravascular cannulation, and thrombi extraction. Splenectomized rats exhibited PV and IVC hypertension, aortic hypotension (mmHg) (10min: 65±4 PV, 46±4 IVC, 71±3 AA; 3h: 42±4 PV, 61±4 IVC, 70±3 AA; 24h: 38±4 PV, 47±4 IVC, 68±3 AA) and thrombosis (thrombus weight, mg) (10min: 9.5±0.5 IVC, 6.6±0.9 PV, 4.8±0.9 SMV, 1.3±0.6 LV; 3h: 10.1±0.5 IVC, 5.3±0.8 PV, 19.2±0.9 SMV, 1.0±0.6 LV; 24h: 33.8±2.5 IVC, 27.5±2.9 PV, 8.8±0.9 SMV, 3.8±0.6 LV). BPC 157 normalised blood pressure (10min: 29±4 PV, 20±4 IVC, 87±3 AA; 3h: 20±4 PV, 17±4 IVC, 81±3 AA; 24h: 12±4 PV, 20±4 IVC, 82±3 AA) and reduced thrombosis (10min: 2.9±0.5 IVC, 2.6±0.9 PV, 3.2±0.3 SMV, 0.5±0.2 LV; 3h: 6.3±0.5 IVC, 2.3±0.5 PV, 5.9±0.9 SMV, 0.6±0.2 LV, 24h: 12.2±2.5 IVC, 1.9±0.5 PV, 4.8±0.9 SMV, 2.0±0.6 LV). Control group presented with peaked P waves, tachycardia and PV/SMV congestion, whereas the treated group showed none of the aforementioned phenomena. BPC 157 therapy counteracts hemodynamic disturbances, peaked P waves, and tachycardia as post-splenectomy complications

BPC 157 given during reperfusion counteracts portal hypertension, caval hypertension, and aortal hypotension in rats with prior portal triad obstruction

Reperfusion provokes major disturbances after the Pringle maneuver. We demonstrated the usefulness of the stable gastric pentadecapeptide BPC 157 as therapy for the hemodynamic disturbances after the Pringle maneuver, a temporary portal triad obstruction (PTO) (hepatic artery, portal vein, common bile duct occlusion for 30 min), with BPC 157 given during reperfusion, in the post-PTO period. In deeply anesthetized and laparatomized rats that had a PTO, the recording lasted 5 minutes with a cannula connected to a pressure transducer, inserted into the portal vein, inferior caval vein and abdominal aorta at the level of its bifurcation at 24 h of reperfusion time. BPC 157 or saline was applied as an abdominal bath in rats that had a PTO, in the post-PTO-period, at 1 min or at 24 h reperfusion time. When BPC 157 was given in circumstances of portal and caval hypertension, and arterial hypotension, disturbances were completely eliminated. This presents a potential therapeutic advantage. Thereby, whithout therapy, the pressure of both the portal and the caval system remains elevated after removal of the portal clamp. Thus, the effectiveness of the therapy, when given at distinctive points during reperfusion, appears as conclusive evidence of its efficacy. BPC 157 therapy mitigates the whole syndrome, involving the course of an even more complex model that should include rats clamped by the hepatic artery, portal vein, and bile duct vs. rats that used to have a clamped portal triad and later underwent reperfusion