In Vivo, in Vitro Toxicity and in Vitro Angiogenic Inhibition of Sunitinib Malate

In Vivo, in Vitro Toxicity and in Vitro Angiogenic Inhibition of Sunitinib Malate

Author Dib, Eduardo Autor UNIFESP Google Scholar
Maia, Mauricio Autor UNIFESP Google Scholar
Lima, Acacio de Souza Google Scholar
Fiod Costa, Elaine de Paula Autor UNIFESP Google Scholar
Moraes-Filho, Milton Nunes de Autor UNIFESP Google Scholar
Rodrigues, Eduardo Buechele Autor UNIFESP Google Scholar
Penha, Fernando Marcondes Autor UNIFESP Google Scholar
Coppini, Larissa Pereira Autor UNIFESP Google Scholar
Tenorio de Barros, Nilana Meza Autor UNIFESP Google Scholar
Sinigaglia Galli Coimbra, Rita de Cassia Autor UNIFESP Google Scholar
Magalhaes Junior, Octaviano Autor UNIFESP Google Scholar
Guerra, Tarcisio Autor UNIFESP Google Scholar
Furlani, Bruno de Albuquerque Autor UNIFESP Google Scholar
Freymuller, Edna Autor UNIFESP Google Scholar
Farah, Michel Eid Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Vis Inst IPEPO
Abstract Purpose: To evaluate the in vivo and in vitro toxicity of sunitinib malate, a multikinase inhibitor molecule.Design: Experimental, Prospective, Controlled.Methods: Human retinal pigment epithelial (ARPE-19) and human umbilical vein endothelialcells (HUVECS) were used in a culture toxicity test and exposed to different concentrations of sunitinib malate for 18 hours. the HUVECs also were cultured to evaluate the angiogenesis inhibitory effect of sunitinib malate. Fundus photography and angiographic, electrophysiologic, and histopathologic evaluations with light and electron microscopy were performed in two groups of five rabbits each that received different intravitreal concentrations of the drug. Each rabbit received 0.1 ml of sunitinib malate in the right eye (one group with 12.5 mg/ml, the other group with 25 mg/ml); all animals received 0.1 ml of physiologic saline solution in the left eye. After sacrifice, the eyes were enucleated and fixed with modified Karnovsky solution.Results: No toxicity related to sunitinib malate was observed using an in vitro model with the 12.5 and 25 mg/ml solutions in HUVEC and ARPE cell cultures. No toxicity was observed in the in vivo model with 12.5 mg/ml, but light microscopy showed that the 25 mg/ml solution damaged the photoreceptors layer. No functional changes in the electroretinogram were observed in any group.Conclusions: Sunitinib malate 12.5 mg/ml caused no toxicity in in vivo and in vitro models, but the 25 mg/ml concentration caused retinal changes suggesting toxicity in the in vivo model. Further research with the drug is needed in models of ocular neovascularization.
Keywords Angiogenesis
Choroidal neovascularization
Intravitreal injection
Drug toxicity
Tyrosine kinase inhibitor
Language English
Date 2012-07-01
Published in Current Eye Research. London: Informa Healthcare, v. 37, n. 7, p. 567-574, 2012.
ISSN 0271-3683 (Sherpa/Romeo, impact factor)
Publisher Informa Healthcare
Extent 567-574
Access rights Closed access
Type Article
Web of Science ID WOS:000305010400003

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