Anti–Angiogenic Efficacy of OT–674 in Inhibiting Oxidative Stress and Pro–Angiogenic Growth Factor–Mediated Angiogenesis

Abstract

 

Purpose:

 

To determine the potential effect of the antioxidant OT–674 on inhibition of angiogenesis induced by growth factors and hydrogen peroxide.

 

Methods:

 

The efficacy of OT–674 in inhibiting angiogenesis induced by various stimuli, including oxidative stress (H₂O₂), basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF), was determined using the chick chorioallantoic membrane (CAM) model.

 

Results:

 

Investigation by our and other laboratories has demonstrated that the pro–angiogenic effects of bFGF are blocked by monoclonal antibodies directed toward bFGF or the integrin αvß3 antagonists and that the pro–angiogenic effects of VEGF are blocked by specific VEGF antibodies, or other anti–VEGF strategies, in the CAM model. In this current investigation, the potential anti–angiogenic effect of OT–674 was evaluated in the CAM model, at doses ranging from 100–800 µg. Generation of new blood vessels from existing vessels was promoted two– to three–fold by H₂O₂, bFGF or VEGF. The pro–angiogenic effect of these different mediators was significantly inhibited (P <0.01) by OT–674.

 

Conclusions:

 

These data indicate the broad potential efficacy of OT–674 against the various stimuli used and its potential benefit, either alone or in combination with other single–mechanism–based anti–angiogenic agents, in the prevention and treatment of angiogenesis associated with diabetic retinopathy, macular degeneration, and other ocular disorders.  

 

Keywords: antioxidants • oxidation/oxidative or free radical damage • growth factors/growth factor receptors