bpc-157 and Venous-Thrombosis

Rat inferior caval vein (ICV) ligation (up to the right ovarian vein (ROV)) commonly represents a recapitulation of Virchow: with ligation leading to vessel injury, stasis, thrombosis and hemodynamic changes. We revealed that BPC 157's therapy collectively attenuated or counteracted all these events and the full syndrome.. We applied BPC 157 (10 μg, 10 ng/kg) as an early regimen or as a delayed therapy. Assessment includes gross assessment by microcamera; microscopy, venography, bleeding, blood pressure, ECG, thermography, MDA and NO-level in plasma and ICV, and gene expression.. Direct vein injury, thrombosis, thrombocytopenia, prolonged bleeding were all counteracted. Also, rapid presentation of collaterals and redistribution of otherwise trapped blood volume (bypassing through the left ovarian vein (LOV) and other veins), with venous hypertension, arterial hypotension and tachycardia counteraction were shown. BPC 157-rats presented raised plasma NO-values, but normal MDA-values; in ICV tissue reverted low NO-values and counteracted increased MDA-levels. Altered expression of EGR, NOS, SRF, VEGFR and KRAS in ICV, ROV and LOV revealed increased or decreased levels, while some genes continuously remained unchanged.. As a new insight, BPC 157 application largely attenuated or even completely eliminated all consequences of ICV ligation in rats.

Topics: Animals; Biomarkers; Collateral Circulation; Disease Models, Animal; Electrocardiography; Female; Fibrinolytic Agents; Gene Expression Regulation; Hemodynamics; Hemorrhage; Ligation; Male; Malondialdehyde; Nitric Oxide; Peptide Fragments; Phlebography; Proteins; Rats, Wistar; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; Thermography; Thrombocytopenia; Time Factors; Vena Cava, Inferior; Venous Thrombosis

To investigate whether duodenal lesions induced by major venous occlusions can be attenuated by BPC 157 regardless nitric oxide (NO) system involvement.. Male Wistar rats underwent superior anterior pancreaticoduodenal vein (SAPDV)-ligation and were treated with a bath at the ligated SAPDV site (BPC 157 10 μg, 10 ng/kg per 1 mL bath/rat; L-NAME 5 mg/kg per 1 mL bath/rat; L-arginine 100 mg/kg per 1 mL bath/rat, alone and/or together; or BPC 157 10 μg/kg instilled into the rat stomach, at 1 min ligation-time). We recorded the vessel presentation (filled/appearance or emptied/disappearance) between the 5 arcade vessels arising from the SAPDV on the ventral duodenum side, the inferior anterior pancreaticoduodenal vein (IAPDV) and superior mesenteric vein (SMV) as bypassing vascular pathway to document the duodenal lesions presentation; increased NO- and oxidative stress [malondialdehyde (MDA)]-levels in duodenum.. Unlike the severe course in the SAPDV-ligated controls, after BPC 157 application, the rats exhibited strong attenuation of the mucosal lesions and serosal congestion, improved vessel presentation, increased interconnections, increased branching by more than 60% from the initial value, the IAPDV and SMV were not congested. Interestingly, after 5 min and 30 min of L-NAME and L-arginine treatment alone, decreased mucosal and serosal duodenal lesions were observed; their effect was worsened at 24 h, and no effect on the collateral vessels and branching was seen. Together, L-NAME+L-arginine antagonized each other's response, and thus, there was an NO-related effect. With BPC 157, all SAPDV-ligated rats receiving L-NAME and/or L-arginine appeared similar to the rats treated with BPC 157 alone. Also, BPC 157 in SAPDV-ligated rats normalized levels of NO and MDA, two oxidative stress markers, in duodenal tissues.. BPC 157, rapidly bypassing occlusion, rescued the original duodenal flow through IAPDV to SMV flow, an effect related to the NO system and reduction of free radical formation.

Topics: Animals; Arginine; Colitis, Ischemic; Collateral Circulation; Disease Models, Animal; Duodenum; Humans; Male; NG-Nitroarginine Methyl Ester; Nitric Oxide; Oxidative Stress; Peptide Fragments; Protective Agents; Proteins; Random Allocation; Rats; Rats, Wistar; Treatment Outcome; Veins; Venous Thrombosis