Retinal pigment epithelium cell culture as a model for evaluation of the toxicity of tamoxifen and chloroquine.
The retinal pigment epithelium (RPE) removes the outer segments of photoreceptor cells by phagocytosis. We studied the effects of tamoxifen and chloroquine on the activity of the lysosomal enzymes N-acetyl-beta-glucosaminidase and cathepsin D in RPE in vitro to evaluate the possible eye toxicity caused by these drugs. The results show decreases in the activities of lysosomal enzymes after drug exposure. The enzymes tested seemed to be more sensitive to tamoxifen than to chloroquine. A profound decrease in the activities of the lysosomal enzymes only started at concentrations above therapeutic dose levels.
Toimela
T
T
Medical School, University of Tampere, Finland.
Tähti
H
H
Salminen
L
L
D000118:Acetylglucosaminidase / Q000378:metabolism; D000818:Animals; D000962:Antimalarials / Q000633:toxicity*; D002402:Cathepsin D / Q000378:metabolism; D002478:Cells, Cultured; D002738:Chloroquine / Q000633:toxicity*; D004341:Drug Evaluation; D004965:Estrogen Antagonists / Q000633:toxicity*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008247:Lysosomes / Q000201:enzymology; D010857:Pigment Epithelium of Eye / Q000187:drug effects* / Q000201:enzymology; D013552:Swine; D013629:Tamoxifen / Q000633:toxicity*
D000962:Antimalarials; D004965:Estrogen Antagonists; D013629:Tamoxifen; D002738:Chloroquine; D007770:L-Lactate Dehydrogenase; D000118:Acetylglucosaminidase; D002402:Cathepsin D