Single- and repeated-dose toxicity study of bevacizumab, ranibizumab, and aflibercept in ARPE-19 cells under normal and oxidative stress conditions

Biochemical Pharmacology
Manuel Saenz-de-ViteriAlfredo García-Layana

Abstract

We assessed the effect of single and repeated doses of bevacizumab, ranibizumab, and aflibercept on cell viability, proliferation, permeability, and apoptosis of ARPE-19 cells. MTT and BrdU assays were used to determine viability and proliferation after single or repeated doses of anti-VEGF drugs under normal and oxidative stress conditions. Caspase-3 expression after single and repeated doses of the 3 drugs was assessed using immunofluorescence. Transepithelial-electrical-resistance (TER) was measured to study the effect of anti-VEGFs on retinal pigment epithelium (RPE) permeability under normal and oxidative stress conditions. Flow cytometry was used to detect intracellular accumulation of the drugs. Finally, a wound healing assay was performed to investigate the effect of the drugs on RPE cell migration. Single and multiple doses of anti-VEGF drugs had no effect on cell viability and proliferation. The oxidative effect of H2O2 decreased cell viability and proliferation; however, no difference was observed between anti-VEGF treatments. Immunofluorescence performed after single and repeated doses of the drugs revealed some caspase-3 expression. Interestingly, anti-VEGFs restored the increased permeability induced by H2O2. The ...Continue Reading

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Oct 11, 2017·Irish Journal of Medical Science·A ŞahinH Yüksel
Mar 6, 2019·The Journal of Dermatological Treatment·Hanan H SabryEssam M Akl
Jun 3, 2018·International Journal of Molecular Sciences·Marina PalmhofStephanie C Joachim
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Mar 10, 2018·Experimental Eye Research·Johann SchottlerAlexa Klettner
May 18, 2021·Current Eye Research·Anna BrinkmannAlexa Klettner

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