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In rats with occluded renal artery, BPC 157 therapy counteracts oxidative stress, portal and caval hypertension, and aortal hypertension, gastric and small intestine, heart, lung and liver lesions

AIM. Pentadecapeptide BPC 157 attenuates ischemic and ischemia-reperfusion injury through collateral vascular pathways recruitment (Curr Pharm Des 2018 ; 24:1990–2001). Recently, BPC 157 administration, rapidly reversed major venous occlusion syndromes, inferior caval vein syndrome, Pringle maneuver, ischemia, reperfusion and Budd-Chiari syndrome (Vascul Pharmacol. 2018, World J Hepatol, 2020, World J Gastrointest Pathophysiol. 2020). Here, we investigated BPC 157 effects on acute unilateral renal ischemia injuryinduced hypertension in portal vein (PV), inferior vena cava (IVC), and abdominal aorta (AA) hypotension, venous thrombosis and distant organ dysfunctions and lesions, including the heart, lungs, liver, stomach and intestine. METHODS. Medication (/kg) (BPC 157 (10 μg or ng) or saline (5 ml)) was applied in rats as an abdominal bath immediately after the right renal artery was ligated. 10min, 1h, and 24h after ligation ECG, USB microcamera recording, intravascular cannulation, thrombi extraction, and histopathological analysis was performed. Oxidative stress was assessed in the collected ischemic renal tissue by quantifying thiobarbituric acid-reactive species as malondialdehyde (MDA) equivalents and NO levels were determined using the Griess reaction at 24h. Gastric mucosal lesions were measured using ImageJ software area (A) measurement option and areas were compared via ratios (A(con)/A(BPC)). RESULTS. 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 and complete renal infarction (24h), whereas the treated rats exhibited only partial renal infarction (24h) (Fig.1). Treated rats showed significantly smaller gastric lesions compared to control rats (A(con)/A(BPC)= 12.26±0.93) (Fig.1). Histopathological findings confirmed complete acute tubular necrosis (ATN), liver congestion, subendocardial necrosis, lung congestion, and intestinal villous necrosis in control rats, whereas treated rats showed only partial ATN (Fig.2). MDA concentration in the affected kidney samples was significantly lower and NO levels remained normal in the treated group (Fig.2). CONCLUSION. In rats with occluded renal artery, BPC 157 therapy counteracts oxidative stress, portal and caval hypertension, and aortal hypertension, gastric and small intestine, heart, lung and liver lesions.

BPC 157 ; renal artery occlusion

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