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

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

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 bile duct ligated (bdl) rats

Pentadecapeptide BPC 157 demonstrates beneficial healing and anti-inflammatory effects on gastrointestinal and many extra - gastrointestinal tissues. Bile duct ligation causes inflammation and fibrotic changes in the liver. We wanted to explore effect of BPC 157 on bile duct ligation (BDL) in rats. Rats received BPC 157 perorally, in drinking water (0.16μg/ml, 0.16ng/ml,), or 10 μg/kg, 10 ng/kg intraperitoneally, first application at 30 min after surgery, last at 24h before sacrifice. Alternatively, delayed therapy, BPC 157 perorally, in drinking water (0.16μg/ml), started at the end of week 4 . Controls received simultaneously drinking water or an equal volume of saline (5ml/kg) intraperitoneally. At the end of the 2nd week, quantitative measurement of IL-1, IL-6 and TNF-α has been utilized using ELISA kits and NOS-3 Western Blot Analysis was performed. For assessing cell proliferation rate antibodies of monoclonal mouse Ki-67 were used at the 2, 4, 6, 8 week of BDL. Western blot analysis of NOS-3 expression in liver tissue showed that BPC 157 decreased the expression of NOS-3 protein. At 2 weeks, BDL-rat regularly exhibited the increased TNF-α, IL-6 and IL-1β liver levels but these values were counteracted with the administration of BPC 157 in drinking water. Since 2nd week until the 8th week, we noted decreased LI of Ki-67. This research shows that BPC 157 decreases hepatocyte proliferative activity, counteracts increased NOS–3 expresion, as well as increased IL-6, TNF-α, IL-1β in liver tissue

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 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

Stable Gastric Pentadecapeptide BPC 157 in Rats with Episcleral Veins Cauterization, Glaucoma Model, Preserved Retinal and Optic Nerve Integrity

BPC 157 (LD1 not achieved) was implemented as an anti-ulcer peptide in IBD trials and now in a multiple sclerosis trial. BPC 157 maintained corneal transparency, total debridement of corneal epithelium cured with no corneal neovascularization, perforating corneal incisions in rats successfully closed and no new vessels, providing a particular healing and vascular effect. We wanted to explore effect of BPC 157 in rats with glaucoma, induced by episcleral veins cauterization. Randomly assigned operated male Wistar rats, 250g (two dorsal episcleral veins and one temporal episcleral vein isolated from the surrounding tissues; a cautery specifically applied to the selected vein), were further studied. Medication (pentadecapeptide BPC 157 (10μg/kg) (Diagen, Slovenia) intraperitoneally) or an equivolume of 0.9%NaCl (5ml/kg) intraperitoneally (controls)) was applied immediately after surgery, and then once time daily. Histopathological retinal and optic nerve samples were obtained after sacrifice at 24h, 4 and 6-weeks interval. At 24h, 4 and 6 weeks after surgery controls exhibited ganglion cell layer and optic nerve thinning. All BPC 157 rats exhibited only slight or none ganglion cell layer or optic nerve thinning. Pentadecapeptide BPC 157 continuously counteracts the effects of episcleral veins cauterization on morphological changes of ganglion cell layer and optic nerve

Stable Gastric Pentadecapeptide BPC 157 in Rats with Episcleral Veins Cauterization, Glaucoma Model, Preserved Retinal and Optic Nerve Integrity

BPC 157 (LD1 not achieved) was implemented as an anti-ulcer peptide in IBD trials and now in a multiple sclerosis trial. BPC 157 maintained corneal transparency, total debridement of corneal epithelium cured with no corneal neovascularization, perforating corneal incisions in rats successfully closed and no new vessels, providing a particular healing and vascular effect. We wanted to explore effect of BPC 157 in rats with glaucoma, induced by episcleral veins cauterization. Randomly assigned operated male Wistar rats, 250g (two dorsal episcleral veins and one temporal episcleral vein isolated from the surrounding tissues; a cautery specifically applied to the selected vein), were further studied. Medication (pentadecapeptide BPC 157 (10μg/kg) (Diagen, Slovenia) intraperitoneally) or an equivolume of 0.9%NaCl (5ml/kg) intraperitoneally (controls)) was applied immediately after surgery, and then once time daily. Histopathological retinal and optic nerve samples were obtained after sacrifice at 24h, 4 and 6-weeks interval. At 24h, 4 and 6 weeks after surgery controls exhibited ganglion cell layer and optic nerve thinning. All BPC 157 rats exhibited only slight or none ganglion cell layer or optic nerve thinning. Pentadecapeptide BPC 157 continuously counteracts the effects of episcleral veins cauterization on morphological changes of ganglion cell layer and optic nerve

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

Stable Gastric Pentadecapeptide BPC 157 in Rats with Episcleral Veins Cauterization, Glaucoma Model, Preserved Retinal and Optic Nerve Integrity

BPC 157 (LD1 not achieved) was implemented as an anti-ulcer peptide in IBD trials and now in a multiple sclerosis trial. BPC 157 maintained corneal transparency, total debridement of corneal epithelium cured with no corneal neovascularization, perforating corneal incisions in rats successfully closed and no new vessels, providing a particular healing and vascular effect. We wanted to explore effect of BPC 157 in rats with glaucoma, induced by episcleral veins cauterization. Randomly assigned operated male Wistar rats, 250g (two dorsal episcleral veins and one temporal episcleral vein isolated from the surrounding tissues; a cautery specifically applied to the selected vein), were further studied. Medication (pentadecapeptide BPC 157 (10μg/kg) (Diagen, Slovenia) intraperitoneally) or an equivolume of 0.9%NaCl (5ml/kg) intraperitoneally (controls)) was applied immediately after surgery, and then once time daily. Histopathological retinal and optic nerve samples were obtained after sacrifice at 24h, 4 and 6-weeks interval. At 24h, 4 and 6 weeks after surgery controls exhibited ganglion cell layer and optic nerve thinning. All BPC 157 rats exhibited only slight or none ganglion cell layer or optic nerve thinning. Pentadecapeptide BPC 157 continuously counteracts the effects of episcleral veins cauterization on morphological changes of ganglion cell layer and optic nerve