Intravitreal bevacizumab effects on VEGF levels in distant organs: an experimental study

Cutan Ocul Toxicol. 2014 Dec;33(4):275-82. doi: 10.3109/15569527.2013.855227. Epub 2013 Nov 14.

Abstract

Purpose: The aim of this study was to determine the effects of single-dose intravitreal bevacizumab on the levels of vascular endothelial growth factor (VEGF) in serum and distant organs.

Methods: Adult New Zealand albino rabbits (n = 40) were divided into experimental and control groups. Experimental rabbits received a single 0.05 ml intravitreal injection of 1.25 mg bevacizumab (Avastin) into the right eye, and control rabbits (n = 8) received no injection. Following injection, group 1 rabbits (n = 8) were sacrificed on day 1, group 2 rabbits (n = 8) on day 7, group 3 rabbits (n = 8) on day 14, and group 4 rabbits (n = 8) on day 28; control rabbits were sacrificed on day 28. After sacrifice, samples of brain, heart, liver, kidney and blood were collected. Levels of VEGF in serum and tissue were measured using enzyme-linked immunosorbent assay. The presence of bevacizumab was evaluated by immunofluorescence staining in tissues.

Results: Positive bevacizumab immunoreactivity was observed in brain, heart and kidney. Serum VEGF levels significantly decreased in groups 3 and 4 compared with controls (p < 0.05). Liver VEGF levels significantly decreased in group 3 compared with controls (p < 0.05).

Conclusions: Intravitreal bevacizumab not only may escape from the blood-retinal barrier and enter the general circulation, but also may be disseminated to distant organs. Our study demonstrates that a single dose of intravitreally injected bevacizumab decreases VEGF levels in serum and liver.

Keywords: Anti-VEGF; brain; heart; intravitreal bevacizumab; kidney; liver; serum; vascular endothelial growth factor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / administration & dosage
  • Angiogenesis Inhibitors / pharmacokinetics
  • Angiogenesis Inhibitors / therapeutic use*
  • Animals
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antibodies, Monoclonal, Humanized / pharmacokinetics
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Bevacizumab
  • Intravitreal Injections
  • Liver / drug effects
  • Liver / metabolism
  • Rabbits
  • Tissue Distribution
  • Vascular Endothelial Growth Factor A / blood
  • Vascular Endothelial Growth Factor A / metabolism*

Substances

  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal, Humanized
  • Vascular Endothelial Growth Factor A
  • Bevacizumab