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

Pentadecapeptide BPC 157 Counteracts Hypertension and Compromised Optic Disc Circulation and Following Atrophy in Rats Subjected to High Fructose Diet

INTRODUCTION We sought to determine whether stable gastric pentadecapeptide BPC 157 in rats subjected to a high fructose diet counteracts hypertension and compromised optic disc circulation and following atrophy. METHODS: Rats were put on a high fructose (80%) diet during a 1 month period. The treated group received BPC 157 in drinking water (10 ng/kg/rat/day). Their blood pressure was regularly measured, and they were subjected to ocular fundus examination. RESULTS At the end of the 1 month period, in control rats, with a mean blood pressure of 146 mmHg, we observed a pale optic disc with well-defined outer borders. In addition, the excavation noticed suggests compromised optic disc circulation and atrophy. Very thin arteries and thick hyperemic veins appeared, resulting in an arterial/vein diameter ratio of about 1/4. An abnormal red reflex and reduced brightness from the choroid suggests a decreased blood flow and choroidal blood filling. Contrarily, in the treated group of rats, who presented with a mean blood pressure of about 132 mmHg, all these changes were significantly attenuated. The optic disc appeared more vivid and healthier with less compromised circulation, and the arterial/vein diameter ratio was about 3/4. The choroid in rats drinking BPC 157 was brighter and with a more pronounced shade of red. CONCLUSION BPC 157 may be considered for treating hypertension, particularly when vascular obstruction is present

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

Stable Gastric Pentadecapeptide BPC 157 Antagonized Local Anesthetic Effect of Lidocaine

Pentadecapeptide BPC 157 was previously shown as a cardioprotective compound in a model of arrhythmia induced by bupivacaine toxicity where it counteracts arrhythmias and prevents lethal outcome much like in other cardiotoxicity mainly related to potassium disturbances, both hyperkalemia and hypokalemia, in vivo and in vitro. We wanted to explore does BPC 157 antagonize effect of lidocai We used Wistar Albino male rats, underwent regional blocks with lidocaine (spinal intrathecal block (lidocaine 6 mg/kg, 0.1 ml/rat, 550 gb.w.) or axillary block (lidocaine 15 mg/kg, 0.3 ml/rat, 220 g b.w.). Rats received BPC 157 (10 μg, 10 ng, 10 pg/kg intraperitoneally or intragastrically) or an equivolume of saline (5 ml/kg), either immediately or at 10 min when local anesthesia was fully established. While lidocaine application produced a prolong function failure, all BPC 157 regimens significantly shortened time to full function recovery in the conditions of full local anesthesia. In other experiments, using a hot plate (55o C for 3 minutes) when rat hind paws were infiltrated with 2% lidocaine (0.1 ml/paw), a subsequent infiltration with BPC 157 (10 μg, 10 ng, 10 pg/kg) results in the faster feet lifting and much less edema. ECG recording documented that the regimens of BPC 157 counteracted the lidocaine-induced arrhythmias. Therefore, it may be possible that BPC 157 acts as the missing antidote to local anesthethics, and potentially deleterious and even life threatening adverse effects of toxic doses of local anesthethics would be markedly attenuated or even abolished

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