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

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

The effect of pentadecapeptide BPC 157 on high-fat diet induced hypertension in rat

Hyperlipidaemia, hypercholesterolaemia and hypertriglyceridaemia are known as factors that increas blood pressure and risk of cardiovascular complications. We wanted to examine effects of pentadecapeptide BPC 157 on high-fat diet induced hypertension in rats. 4 Male Winstar Albino rats (240g) 4 months old, were used in this study. 2 rats per each group were fed with fat (white bacon) for 4 weeks. Control group was given water p.o. ad libitum while BPC group was given (10ng/kg) of pentadecapeptide BPC 157 per liter solution p.o. ad libitum. Blood pressure was measured using noninvasive tail cuff method every day for 4 weeks period. Systolic blood pressure increased in both groups but increase in control groups was significantly higher then in BPC 157 threated group (CON day 0. = 158 mmHg, BPC day 0. = 155 mmHg; CON day 25. = 205 mmHg, BPC day 25. = 165 mmHg) .Drop of blood pressure in first few days can be attributed to adapting on the new food that was given to rats. Feeding rats with a high-fat diet is known to produce changes of which one of the consequence is increased blood pressure or hypertension. We proved that pentadecapeptide BPC 157 decreases systolic blood pressure induced by fat diet

Pentadecapeptide BPC 157 therapy in rats with cysteamine induced-terminal ileitis

We introduce pentadecapeptide BPC 157 therapy in rats with cysteamine induced-terminal ileitis 1h/1month/2months. We counteracted gross hyperemia, edema, erosion, bleeding, microscopically significant loss of villous architecture, loss and shortening of villae and severe lymphocytic infiltrate. Pentadecapeptide counteracts various lesions in the whole GI-tract and free radical formation, and tested in ulcerative colitis trials and now in multiple sclerosis. Cysteamine was known to induce gastric-acid hypersecretion as a prototype of duodenal lesion. Cysteamine induced duodenal lesions after gastrectomy, and applied as an enema, ulcerative colitis in rats Cysteamine was applied in female Albino Wistar rats into the terminal ileum, 5 cm segment up to ileocecal valve, which was kept gently compressed for 1 min, and then released. Medication(BPC, or saline (controls)) was applied as an abdominal bath immediately after the end of the cysteamine application procedure, and then if rats were not sacrificed at 1 h, continuously, perorally in drinking water till the end of 1 or 2 months The hyperemia, edema, erosion and bleeding scores were summarized. Microscopically, cysteamine induced terminal ileitis presents with: submucosal congestion, significant loss of villous architecture, loss and shortening of villae and lamina propria infiltrated with mild to severe lymphocytic infiltrate, much like intraepithelial lymphocyte infiltration and some epithelial elevation from lamina propria. Better preservation of mucosal architecture appears in pentadecapeptide treated rats. There is only mild villous edema with capillary congestion and mild lymphocytic infiltrate. No epithelial elevation from lamina propria For further therapy, beneficial effect of the BPC counteracts cysteamine- terminal ileitis

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

Complications of portal triad obstruction and reperfusion in rats. pentadecapeptide BPC 157 counteracts venous and arterial thrombosis and arrhythmias

We wanted to explore effect of pentadecapeptide BPC 157 therapy in temporary portal triad obstruction (PTO) (hepatic artery (HA), portal vein (PV), bile duct occlusion for 30 min in rats), and in reperfusion period in post-PTO-period on the counteraction of the Pringle maneuver complications (cloth formation in the PV, superior mesenteric vein (SMV), lienal vein (LV), inferior caval vein (ICV) HA, peaked P wave and tachycardia). Medication (BPC 157 (10 μg/kg, 10 ng/kg), or saline (5 ml/kg) (controls)) was applied as a bath at the clamped area after portal triad clamping in rats with PTO or at the area that used to be clamped at 1 min or at 24 h reperfusion time. A period of 30 min of PTO produced thrombosis in the ICV, PV, SMV, LV and HA. In BPC 157 treated rats, the weights of the formed clots were smaller. PTO rats exhibited peaked P wave values and tachycardia which were absent in BPC 157-treated rats. Rats in post-PTO-period, during reperfusion exhibited peaked P wave values and tachycardia. Applications of BPC 157 (given at 1 min or at 24 h reperfusion time) resulted in the absence of the peaked P waves. Tachycardia was also affected; sinus rhythm appeared in a normal range of heart frequency. Confronted with Pringle maneuver and its consequences, BPC 157 therapy distinctively mitigates the whole syndrome, involving the counteraction of the course of the thrombosis in both veins and arteries, and ECG acute right ventricular overload

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

The effect of pentadecapeptide BPC 157 on high-fat diet induced hypertension in rat

Hyperlipidaemia, hypercholesterolaemia and hypertriglyceridaemia are known as factors that increas blood pressure and risk of cardiovascular complications. We wanted to examine effects of pentadecapeptide BPC 157 on high-fat diet induced hypertension in rats. 4 Male Winstar Albino rats (240g) 4 months old, were used in this study. 2 rats per each group were fed with fat (white bacon) for 4 weeks. Control group was given water p.o. ad libitum while BPC group was given (10ng/kg) of pentadecapeptide BPC 157 per liter solution p.o. ad libitum. Blood pressure was measured using noninvasive tail cuff method every day for 4 weeks period. Systolic blood pressure increased in both groups but increase in control groups was significantly higher then in BPC 157 threated group (CON day 0. = 158 mmHg, BPC day 0. = 155 mmHg; CON day 25. = 205 mmHg, BPC day 25. = 165 mmHg) .Drop of blood pressure in first few days can be attributed to adapting on the new food that was given to rats. Feeding rats with a high-fat diet is known to produce changes of which one of the consequence is increased blood pressure or hypertension. We proved that pentadecapeptide BPC 157 decreases systolic blood pressure induced by fat diet

Complications of portal triad obstruction and reperfusion in rats. pentadecapeptide BPC 157 counteracts venous and arterial thrombosis and arrhythmias

We wanted to explore effect of pentadecapeptide BPC 157 therapy in temporary portal triad obstruction (PTO) (hepatic artery (HA), portal vein (PV), bile duct occlusion for 30 min in rats), and in reperfusion period in post-PTO-period on the counteraction of the Pringle maneuver complications (cloth formation in the PV, superior mesenteric vein (SMV), lienal vein (LV), inferior caval vein (ICV) HA, peaked P wave and tachycardia). Medication (BPC 157 (10 μg/kg, 10 ng/kg), or saline (5 ml/kg) (controls)) was applied as a bath at the clamped area after portal triad clamping in rats with PTO or at the area that used to be clamped at 1 min or at 24 h reperfusion time. A period of 30 min of PTO produced thrombosis in the ICV, PV, SMV, LV and HA. In BPC 157 treated rats, the weights of the formed clots were smaller. PTO rats exhibited peaked P wave values and tachycardia which were absent in BPC 157-treated rats. Rats in post-PTO-period, during reperfusion exhibited peaked P wave values and tachycardia. Applications of BPC 157 (given at 1 min or at 24 h reperfusion time) resulted in the absence of the peaked P waves. Tachycardia was also affected; sinus rhythm appeared in a normal range of heart frequency. Confronted with Pringle maneuver and its consequences, BPC 157 therapy distinctively mitigates the whole syndrome, involving the counteraction of the course of the thrombosis in both veins and arteries, and ECG acute right ventricular overload