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P. Rat, M. Dutot, F. Dufernez, J.-M. Warnet; Evaluation of Ocular Cytotoxicity Induced by Chloroquine. Invest. Ophthalmol. Vis. Sci. 2007;48(13):553.
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Chloroquine is a medication used in the treatment or prevention of malaria. It was recently prescribed at higher doses to treat chikungunya virus; but high doses of chloroquine can induce ocular and cardiac toxicity. The aim of our study is to evaluate chloroquine cytotoxicty on retinal cells.
A range of chloroquine concentrations (0.02 to 1000µM) was incubated on ARPE-19 cells (human retinal cell line). Cell viability (necrosis) was evaluated using the neutral red and the MTT tests. Phosphatidylserines translocation, DNA fragmentation (SubG1 peak) and P2X7 cell death receptor activation were evaluated to study apoptosis. All these tests were performed by cytofluorometry adapted to microplate and flow cytometry.
Up to 10µM, chloroquine did not induce necrosis, but a hormesis effect was observed. Necrosis was observed after incubation with 20µM chloroquine (IC50 = 60µM). Early apoptosis was induced with 5µM chloroquine and 25µM induced important apoptosis. P2X7 cell death receptor was activated after incubation with 40µM chloroquine.
Side effects of chloroquine can be more pronounced with higher doses used to treat chikungunya virus since we observed apopto-necrosis on ocular cells. P2X7 receptor inhibitors could decrease chloroquine toxic effects.
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