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Pentadecapeptide BPC 157 therapy in bile duct ligated (BDL) rats. In rats with cirrhosis and portal hypertension, BPC 157 may be useful also in the conditions of the increased intracranial pressure and vessels obstruction

Aim. We hypothesized that BPC 157 therapy in bile duct ligated (BDL) cirrhosis rats counteracts increased pressure in the superior sagittal sinus and thrombosis formation. Previously (Eur J Pharmacol 2019 ; 847:130-142), BPC 157 therapy cured rats with BDLcirrhosis, subsequent gross (i.e., jaundice, weight loss, liver enlargement), microscopy and biochemistry presentation. BPC 157 counteracts the piecemeal necrosis, focal lytic necrosis, apoptosis and focal inflammation, disturbed cell proliferation (Ki-67-staining), cytoskeletal structure in the hepatic stellate cell (α-SMA staining), collagen presentation (Mallory staining). BPC 157 was given per-orally, continuously in drinking water, or intraperitoneally, first application at 30 min after surgery, last at 24h before sacrifice. Delayed therapy, BPC 157 per-orally, started at the end of the week 4. In BDL-liver, BPC 157 counteracts the increased NOS3 expression, IL-6, TNF-α, IL-1β levels, and normalizes MDA and NO-levels. Portal hypertension in BDL-rats is either not even developed or rapidly abated, depending on the given BPC 157's regimen. In rats with inferior caval vein occlusion, BPC 157 counteracted venous hypertension and aortal hypotension, and thrombosis formation (Vascul Pharmacol 2018 ; 106:54-66). Methods. In anesthetized 8 week BDL rats, we made a single burr hole in the rostral part of the sagittal suture, above the superior sagittal sinus, cannulated the anterior part of the sinus by Braun intravenous cannules, and measured intravascular pressure, before and after medication (BPC 157 10µg, 10ng/kg, or saline, 1 ml/rat given intragastrically)- .Portal and caval hypertension and aortal hypotension and thrombosis were assessed as described (Vascul Pharmacol 2018 ; 106:54-66). Results. Healthy rats exhibit the following pressure values: superior sagittal sinus between -26 and -28 mmHg ; portal pressure between 3 and 5 mm Hg or like the pressure in the inferior caval vein (providing at least 1 mm Hg higher values in the portal vein) ; abdominal aorta blood pressure values between 100 and120 mm Hg at the level of bifurcation. BPC 157 counteracted considerably increased pressure values in the superior sagittal sinus (33±2 mmHg (controls) vs. -24±2 (µg), -26±2 (ng)). There were also counteracted portal hypertension (40±5 mmHg (controls) vs. 7±2 (µg), 8±2 (ng)), caval hypertension (30±2 mmHg(controls) vs. 5±2 (µg), 7±2 (ng)) and aortal hypotension (83±3 mmHg(controls) vs. 121±2 (µg) , 119±2 (ng)). Accordingly, thrombosis was markedly attenuated (superior mesenteric vein 0.0182±0.0006 g (controls) vs. 0.0072±0.0010 (µg), 0.0089±0.0008 (ng)) and artery 0.0073±0.0006 g (controls) vs. 0.0025±0.0007 (µg), 0.0032±0.0008 (ng)). Conclusion. In rats with cirrhosis and portal hypertension, BPC 157 may be useful also in the conditions of the increased incranial pressure and vessels obstruction.

bile duct ligation ; hepatic cirrhosis ; BPC 157

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