A Time Course of Bevacizumab (Anti-VEGF) Effect on Rat Peritoneum: Relations Between Antiadhesive Action and Fibrin Regulation Enzymes.

Abstract

BACKGROUND:

To investigate the early and late antiadhesive effect and any changes of fibrin matrix regulation enzymes on rat peritoneum, after local administration of bevacizumab.

METHODS:

Rats were subjected to cecal abrasion. Bevacizumab (5 mg/kg) against placebo was given intraperitoneally. On the 2nd, 14th, and 28th postoperative days adhesions were scored, and tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1), matrix metalloproteinase-9 (MMP-9), degree of fibrosis, and angiogenesis were measured in abrased cecum and in intact parietal peritoneum.

RESULTS:

Bevacizumab significantly reduced adhesions up to 15% on the 2nd, 52.5% on the 14th, and 55% on the 28th postoperative day, and significantly increased tPA concentrations in peritoneum. PAI-1 was decreased, and a significantly higher tPA/PAI-1 ratio along with an increase of MMP-9 was measured at all time points. Fibrosis and angiogenesis were significantly lower on the 14th and 28th postoperative days.

CONCLUSIONS:

Local bevacizumab administration has a strong early and late antiadhesive action on rat peritoneum, mediated by changes in the tPA/PAI-1 and MMP balance in favor of fibrinolysis up to 28 days after operations.

• Authors: Aikaterini-Eftychia Micha, Kyriakos Psarras, Odysseas Ouroumidis, Evangelia Siska, Efthymia Vlachaki, Aristotelis Lymperopoulos, Nikolaos Symeonidis, Christina Nikolaidou, Ioannis Venizelos, George Koliakos, Theodoros E Pavlidis
• Journal: Surgical innovation (Surg Innov) Vol. 24 Issue 6 Pg. 543-551 (Dec 2017) ISSN: 1553-3514 [Electronic] United States
• PMID: 28877644 (Publication Type: Journal Article)

Chemical References

• Angiogenesis Inhibitors
• Plasminogen Activator Inhibitor 1
• Bevacizumab
• Tissue Plasminogen Activator
• Matrix Metalloproteinase 9

Topics

• Angiogenesis Inhibitors (pharmacology)
• Animals
• Bevacizumab (pharmacology)
• Cecum (drug effects, pathology)
• Fibrinolysis (drug effects)
• Male
• Matrix Metalloproteinase 9 (metabolism)
• Peritoneum (drug effects, pathology)
• Plasminogen Activator Inhibitor 1 (metabolism)
• Rats
• Rats, Wistar
• Tissue Adhesions (prevention & control)
• Tissue Plasminogen Activator (metabolism)