In vitro and in vivo Toxicity of Sunitinib Maleate

Abstract

Purpose: : To evaluate in vivo and in vitro toxicity of Sunitinib Maleate.

Methods: : 1) Use of Retinal pigment epithelium (RPE) cells in a culture toxicity test, exposed with different concentrations of sunitinib Maleate in 24 hours; 2) fundus photograph, angiographic, electrofisiological and histopathological evaluation with light and electronic microscopy were performed in ten rabbits divided in 2 groups of five animals, each with different intravitreal concentrations injected. Each rabbit received 0,1mL of sunitinib maleate in the right eye (one group with 12,5mg/mL and other with 25mg/mL) and all of them received 0,1mL of physiologic saline solution in the left eye. All animals were killed by intravenous pentobarbital injection and the eyes were enucleated and fixed with modified Karnovsky solution.

Results: : No toxicity was observed in in vitro model with 12.5mg/mL and 25mg/mL solutions using RPE culture. No toxicity was observed in in vivo model with 12.5mg/mL, but damage to the photoreceptors layer was seen in 25mg/mL with light microscopy. No functional changes in the electroretinogram were observed in any group.

Conclusions: : Sunitinib Maleate in vivo and in vitro models caused no toxicity with 12.5mg/mL but caused retinal alterations suggesting toxicity with in vivo model using 25mg/mL. Further research using this drug in models of ocular neovascularization are needed.

Keywords: retina • drug toxicity/drug effects • neovascularization