Neurotoxic effects of chloroquine in vitro

Bruinink, A.; Zimmermann, Gaby; Riesen, F.

doi:10.1007/bf01977360

Cited by 28 publications

(9 citation statements)

References 26 publications

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“…It is possible that the results of the current study are in part due to atropine's similar anti-cholinergic actions. Indeed, increased GFAP staining induced by the anti-AChE nerve agent soman and the cholinergic agonist carbachol was shown to be greatly reduced or prevented by pre-treatment with atropine both in vivo and in vitro (Zimmer et al 1998;Bruinink et al 1991).…”

Section: Discussionmentioning

confidence: 97%

Single-Cell ELISA and Flow Cytometry as Methods for Highlighting Potential Neuronal and Astrocytic Toxicant Specificity

et al. 2010

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The timeline imposed by recent worldwide chemical legislation is not amenable to conventional in vivo toxicity testing, requiring the development of rapid, economical in vitro screening strategies which have acceptable predictive capacities. When acquiring regulatory neurotoxicity data, distinction on whether a toxic agent affects neurons and/or astrocytes is essential. This study evaluated neurofilament (NF) and glial fibrillary acidic protein (GFAP) directed single-cell (S-C) ELISA and flow cytometry as methods for distinguishing cell-specific cytoskeletal responses, using the established human NT2 neuronal/astrocytic (NT2.N/A) co-culture model and a range of neurotoxic (acrylamide, atropine, caffeine, chloroquine, nicotine) and non-neurotoxic (chloramphenicol, rifampicin, verapamil) test chemicals. NF and GFAP directed flow cytometry was able to identify several of the test chemicals as being specifically neurotoxic (chloroquine, nicotine) or astrocytoxic (atropine, chloramphenicol) via quantification of cell death in the NT2.N/A model at cytotoxic concentrations using the resazurin cytotoxicity assay. Those neurotoxicants with low associated cytotoxicity are the most significant in terms of potential hazard to the human nervous system. The NF and GFAP directed S-C ELISA data predominantly demonstrated the known neurotoxicants only to affect the neuronal and/or astrocytic cytoskeleton in the NT2.N/A cell model at concentrations below those affecting cell viability. This report concluded that NF and GFAP directed S-C ELISA and flow cytometric methods may prove to be valuable additions to an in vitro screening strategy for differentiating cytotoxicity from specific neuronal and/or astrocytic toxicity. Further work using the NT2.N/A model and a broader array of toxicants is appropriate in order to confirm the applicability of these methods.

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Section: Discussionmentioning

confidence: 97%

Single-Cell ELISA and Flow Cytometry as Methods for Highlighting Potential Neuronal and Astrocytic Toxicant Specificity

et al. 2010

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“…Oxidative stress caused by photosensitizing plus lysosomal dysfunction has additional effects. The RPE is more sensitive to chloroquine damage than the retina [19] . An additional reason why RPE cells -as well as ganglion cells [7] -are the most affected cells of the retina, is their normally highly degradative lysosomal activity.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Lysosomal Degradation in Retinal Pigment Epithelium Cells Induces Exocytosis of Phagocytic Residual Material at the Basolateral Plasma Membrane

Peters¹,

Reinthal²,

Blitgen-Heinecke³

et al. 2006

Ophthalmic Res

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Purpose: To analyze chloroquine-induced morphological changes in the retinal pigment epithelium (RPE) and Bruch’s membrane (BM). Methods: Retina-choroid complexes of chloroquine-treated Long-Evans rats were analyzed by electron microscopy. Results: Intercellular spaces between the RPE cells and BM were enlarged. Residual material from phagosomes was released into these enlarged spaces. Debris accumulated within BM and encircled choriocapillaris endothelial cells. Conclusion: There is a release of undegraded phagocytic material (rod outer segments) into the extracellular space between BM and RPE cells, following inhibition of lysosomal degradation. Electron-dense deposits in BM and choriocapillaris may lead to reduced oxygen and nutrition flow.

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“…Tamoxifen, an amphi philic cationic drug, has been reported to cause corneal opacities and changes in the neural reti na and retinal pigment epithelium [4,5]. Chloroquinc treatment causes corneal opacities and retinopathy, which is characterized by a degen eration of ROS [6,7].The aim of this study was to investigate the effects of tamoxifen and chloroquine on the ac tivity of two lysosomal enzymes (cathepsin D and N-acetyl-(3-D-glucosaminidase) in cultur ed RPE cells. As a marker o f cytotoxicity, the leakage of cytosolic lactate dehydrogenase (LDH) was measured.…”

mentioning

confidence: 99%

Retinal Pigment Epithelium Cell Culture as a Model for Evaluation of the Toxicity of Tamoxifen and Chloroquine

1995

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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-β-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.

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Neurotoxic effects of chloroquine in vitro

Cited by 28 publications

References 26 publications

Single-Cell ELISA and Flow Cytometry as Methods for Highlighting Potential Neuronal and Astrocytic Toxicant Specificity

Single-Cell ELISA and Flow Cytometry as Methods for Highlighting Potential Neuronal and Astrocytic Toxicant Specificity

Inhibition of Lysosomal Degradation in Retinal Pigment Epithelium Cells Induces Exocytosis of Phagocytic Residual Material at the Basolateral Plasma Membrane

Retinal Pigment Epithelium Cell Culture as a Model for Evaluation of the Toxicity of Tamoxifen and Chloroquine

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