Copper pyrithione and zinc pyrithione induce cytotoxicity and neurotoxicity in neuronal/astrocytic co-cultured cells via oxidative stress

Abstract Previous studies on copper pyrithione (CPT) and zinc pyrithione (ZPT) as antifouling agents have mainly focused on marine organisms. Even though CPT and ZPT pose a risk of human exposure, their neurotoxic effects remain to be elucidated. Therefore, in this study, the cytotoxicity and neurot...

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Main Authors: Ha-Na Oh, Woo-Keun Kim
Format: Article
Language:English
Published: Nature Portfolio 2023-12-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-023-49740-8
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author Ha-Na Oh
Woo-Keun Kim
author_facet Ha-Na Oh
Woo-Keun Kim
author_sort Ha-Na Oh
collection DOAJ
description Abstract Previous studies on copper pyrithione (CPT) and zinc pyrithione (ZPT) as antifouling agents have mainly focused on marine organisms. Even though CPT and ZPT pose a risk of human exposure, their neurotoxic effects remain to be elucidated. Therefore, in this study, the cytotoxicity and neurotoxicity of CPT and ZPT were evaluated after the exposure of human SH-SY5Y/astrocytic co-cultured cells to them. The results showed that, in a co-culture model, CPT and ZPT induced cytotoxicity in a dose-dependent manner (~ 400 nM). Exposure to CPT and ZPT suppressed all parameters in the neurite outgrowth assays, including neurite length. In particular, exposure led to neurotoxicity at concentrations with low or no cytotoxicity (~ 200 nM). It also downregulated the expression of genes involved in neurodevelopment and maturation and upregulated astrocyte markers. Moreover, CPT and ZPT induced mitochondrial dysfunction and promoted the generation of reactive oxygen species. Notably, N-acetylcysteine treatment showed neuroprotective effects against CPT- and ZPT-mediated toxicity. We concluded that oxidative stress was the major mechanism underlying CPT- and ZPT-induced toxicity in the co-cultured cells.
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spelling doaj.art-c5743a26bfdf4670a40e2503a65045ad2023-12-31T12:10:00ZengNature PortfolioScientific Reports2045-23222023-12-0113111310.1038/s41598-023-49740-8Copper pyrithione and zinc pyrithione induce cytotoxicity and neurotoxicity in neuronal/astrocytic co-cultured cells via oxidative stressHa-Na Oh0Woo-Keun Kim1Department of Predictive Toxicology, Korea Institute of ToxicologyDepartment of Predictive Toxicology, Korea Institute of ToxicologyAbstract Previous studies on copper pyrithione (CPT) and zinc pyrithione (ZPT) as antifouling agents have mainly focused on marine organisms. Even though CPT and ZPT pose a risk of human exposure, their neurotoxic effects remain to be elucidated. Therefore, in this study, the cytotoxicity and neurotoxicity of CPT and ZPT were evaluated after the exposure of human SH-SY5Y/astrocytic co-cultured cells to them. The results showed that, in a co-culture model, CPT and ZPT induced cytotoxicity in a dose-dependent manner (~ 400 nM). Exposure to CPT and ZPT suppressed all parameters in the neurite outgrowth assays, including neurite length. In particular, exposure led to neurotoxicity at concentrations with low or no cytotoxicity (~ 200 nM). It also downregulated the expression of genes involved in neurodevelopment and maturation and upregulated astrocyte markers. Moreover, CPT and ZPT induced mitochondrial dysfunction and promoted the generation of reactive oxygen species. Notably, N-acetylcysteine treatment showed neuroprotective effects against CPT- and ZPT-mediated toxicity. We concluded that oxidative stress was the major mechanism underlying CPT- and ZPT-induced toxicity in the co-cultured cells.https://doi.org/10.1038/s41598-023-49740-8
spellingShingle Ha-Na Oh
Woo-Keun Kim
Copper pyrithione and zinc pyrithione induce cytotoxicity and neurotoxicity in neuronal/astrocytic co-cultured cells via oxidative stress
Scientific Reports
title Copper pyrithione and zinc pyrithione induce cytotoxicity and neurotoxicity in neuronal/astrocytic co-cultured cells via oxidative stress
title_full Copper pyrithione and zinc pyrithione induce cytotoxicity and neurotoxicity in neuronal/astrocytic co-cultured cells via oxidative stress
title_fullStr Copper pyrithione and zinc pyrithione induce cytotoxicity and neurotoxicity in neuronal/astrocytic co-cultured cells via oxidative stress
title_full_unstemmed Copper pyrithione and zinc pyrithione induce cytotoxicity and neurotoxicity in neuronal/astrocytic co-cultured cells via oxidative stress
title_short Copper pyrithione and zinc pyrithione induce cytotoxicity and neurotoxicity in neuronal/astrocytic co-cultured cells via oxidative stress
title_sort copper pyrithione and zinc pyrithione induce cytotoxicity and neurotoxicity in neuronal astrocytic co cultured cells via oxidative stress
url https://doi.org/10.1038/s41598-023-49740-8
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AT wookeunkim copperpyrithioneandzincpyrithioneinducecytotoxicityandneurotoxicityinneuronalastrocyticcoculturedcellsviaoxidativestress