Effect of sorafenib on experimental choroidal neovascularization in the rat

Abstract

Purpose: This study was designed to evaluate the effect of sorafenib administration on laser-induced experimental choroidal neovascularization (CNV) in rats.Methods: A total of 36 rats were divided into three groups. Sorafenib, an oral, multitargeted receptor tyrosine kinase inhibitor, was administered at a dose of 10 mg/kg per day (n = 12) or 30 mg/kg per day (n = 12) for 1 day before the laser induction of CNV. Rats continued to receive the drug for 14 days. Fluorescein angiograms were analysed for CNV dye leakage and the thickness of CNV was assessed by histology. The levels of vascular endothelial growth factor, platelet-derived growth factor, monocyte chemoattractant protein-1 and intercellular adhesion molecule-1 mRNA were measured by the use of real-time quantitative reverse-transcription polymerase chain reaction.Results: Sorafenib-treated rats had significantly less fluorescence leakage as compared with vehicletreated rats (P < 0.05), The CNV thickness in sorafenib-treated rats was significantly reduced as compared with vehicle-treated rats in a dosedependent manner (P = 0.00163 for 10 mg/kg and P < 0.00001 for 30 mg/kg). After sorafenib (30 mg/ kg) administration, expression of the vascular endothelial growth factor and intercellular adhesion molecule-1 genes was significantly decreased (P < 0.05 and P = 0.00802). Conclusion:These results suggest that sorafenib may be potentially beneficial for the treatment of CNV in human; further studies on this subject are warranted.

Safe dose of intravitreal imatinib and its effect on laser-induced choroidal neovascularization: a rat-model experiment

“…Some investigators studied the effects of other receptor tyrosine kinase inhibitors on laser-induced CNV in rats or mice. Park et al investigated the effect of sorafenib, an orally administered, multi-targeted receptor tyrosine kinase inhibitor, on CNV progression in a rat CNV model, and showed that the drug inhibited laser-induced CNV [27]. Kang and co-workers evaluated the anti-angiogenic effects of the VEGF receptor tyrosine kinase inhibitor, cediranib, in an experimental laser-induced CNV model [28].…”

Captopril attenuates hypertension and renal injury induced by the vascular endothelial growth factor inhibitor sorafenib

“…The doses of sorafenib and captopril were chosen based on previous studies in rats. [18][19][20][21] Blood pressure measurements Rats were anaesthetized with isoflurane and radiotelemetry transmitters (PA-C40; Data Science International, St Paul, MN, USA) were implanted. In implanting the radiotransmitter, the fluid-filled catheter of the transmitter was inserted into the right carotid artery and the body of the transmitter was placed subcutaneously at the back.…”

Antiangiogenic Effects of Topically Administered Multiple Kinase Inhibitor, Motesanib (AMG 706), on Experimental Choroidal Neovascularization in Mice

“…Many investigators have reported that orally or intravitreally administered RTK inhibitors have therapeutic potential in CNV treatment by inhibiting RTK-related signaling pathways. 20,21 Motesanib is a multiple receptor TKI that selectively targets and inhibits VEGFR-1 (IC 50 = 2 nM), VEGFR-2 (IC 50 = 3 nM), VEGFR-3 (IC 50 = 6 nM), PDGFR (IC 50 = 84 nM), and c-Kit (IC 50 = 8 nM), thereby inhibiting angiogenesis. Oral administration of motesanib potently inhibited VEGF-induced angiogenesis in the rat corneal model and induced regression of A431 tumor xenografts.…”