Protective effects of resveratrol, quercetin, and their glucuronide derivatives in an in vitro model of Mn- and Al-induced cytotoxicity in SH-SY5Y human neuroblastoma cells

Abstract Manganese and aluminium toxicity has been associated with the pathogenesis of neurodegenerative diseases. Simultaneously, resveratrol and quercetin have been suggested as potentially useful substances in the context of these conditions. Accordingly, we examined whether trans-resveratrol, qu...

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Main Authors: Katarzyna Chamera, Beata Starek-Świechowicz, Bogusława Budziszewska, Maciej Gawlik
Format: Article
Language:English
Published: Springer Nature 2025-07-01
Series:Discover Toxicology
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Online Access:https://doi.org/10.1007/s44339-025-00029-7
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author Katarzyna Chamera
Beata Starek-Świechowicz
Bogusława Budziszewska
Maciej Gawlik
author_facet Katarzyna Chamera
Beata Starek-Świechowicz
Bogusława Budziszewska
Maciej Gawlik
author_sort Katarzyna Chamera
collection DOAJ
description Abstract Manganese and aluminium toxicity has been associated with the pathogenesis of neurodegenerative diseases. Simultaneously, resveratrol and quercetin have been suggested as potentially useful substances in the context of these conditions. Accordingly, we examined whether trans-resveratrol, quercetin, and their glucuronidated metabolites display protective effects against manganese- and aluminium-induced neurotoxicity in an in vitro model, employing the SH-SY5Y cell line. The results demonstrated that both metals harmfully influenced cell viability as they elevated lactate dehydrogenase release and decreased thiazolyl blue tetrazolium bromide reduction. Manganese and aluminium differentially affected apoptotic processes, changing the caspase-3 activity of SH-SY5Y cells. We observed that trans-resveratrol and quercetin displayed protective action against toxicity produced by metals. However, the impact varied and depended on the form/concentration of polyphenols. Regarding manganese, quercetin (5, 10 μM), trans-resveratrol 3-O-β-D-glucuronide, and quercetin 3-O-β-D-glucuronide (both at 20 and 30 μM) were effective against metal-induced alterations of lactate dehydrogenase secretion, whereas trans-resveratrol (5 μM) and quercetin (5, 10, 20 μM) normalized caspase-3 activity. When SH-SY5Y cells were treated with aluminium, trans-resveratrol, quercetin (both at 5 and 10 μM), and trans-resveratrol 3-O-β-D-glucuronide (30 μM) diminished the negative influence of metal on lactate dehydrogenase efflux, while 5 μM quercetin 3-O-β-D-glucuronide improved thiazolyl blue tetrazolium bromide reduction. None of the used polyphenols recovered aluminium-evoked disturbances of caspase-3 activity. Our results confirmed the promising neuroprotective potential of trans-resveratrol, quercetin, and their derivatives against manganese and aluminium toxicity, and may have significant applications for further research related to the harmful impact of the metals on the central nervous system.
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spelling doaj-art-dee5a533b4c54da6aca49568f5ad463c2025-08-20T04:01:46ZengSpringer NatureDiscover Toxicology3004-88932025-07-012111410.1007/s44339-025-00029-7Protective effects of resveratrol, quercetin, and their glucuronide derivatives in an in vitro model of Mn- and Al-induced cytotoxicity in SH-SY5Y human neuroblastoma cellsKatarzyna Chamera0Beata Starek-Świechowicz1Bogusława Budziszewska2Maciej Gawlik3Department of Toxicology, Faculty of Pharmacy, Jagiellonian University Medical CollegeDepartment of Toxicology, Faculty of Pharmacy, Jagiellonian University Medical CollegeDepartment of Toxicology, Faculty of Pharmacy, Jagiellonian University Medical CollegeDepartment of Toxicology, Faculty of Pharmacy, Jagiellonian University Medical CollegeAbstract Manganese and aluminium toxicity has been associated with the pathogenesis of neurodegenerative diseases. Simultaneously, resveratrol and quercetin have been suggested as potentially useful substances in the context of these conditions. Accordingly, we examined whether trans-resveratrol, quercetin, and their glucuronidated metabolites display protective effects against manganese- and aluminium-induced neurotoxicity in an in vitro model, employing the SH-SY5Y cell line. The results demonstrated that both metals harmfully influenced cell viability as they elevated lactate dehydrogenase release and decreased thiazolyl blue tetrazolium bromide reduction. Manganese and aluminium differentially affected apoptotic processes, changing the caspase-3 activity of SH-SY5Y cells. We observed that trans-resveratrol and quercetin displayed protective action against toxicity produced by metals. However, the impact varied and depended on the form/concentration of polyphenols. Regarding manganese, quercetin (5, 10 μM), trans-resveratrol 3-O-β-D-glucuronide, and quercetin 3-O-β-D-glucuronide (both at 20 and 30 μM) were effective against metal-induced alterations of lactate dehydrogenase secretion, whereas trans-resveratrol (5 μM) and quercetin (5, 10, 20 μM) normalized caspase-3 activity. When SH-SY5Y cells were treated with aluminium, trans-resveratrol, quercetin (both at 5 and 10 μM), and trans-resveratrol 3-O-β-D-glucuronide (30 μM) diminished the negative influence of metal on lactate dehydrogenase efflux, while 5 μM quercetin 3-O-β-D-glucuronide improved thiazolyl blue tetrazolium bromide reduction. None of the used polyphenols recovered aluminium-evoked disturbances of caspase-3 activity. Our results confirmed the promising neuroprotective potential of trans-resveratrol, quercetin, and their derivatives against manganese and aluminium toxicity, and may have significant applications for further research related to the harmful impact of the metals on the central nervous system.https://doi.org/10.1007/s44339-025-00029-7ManganeseAluminiumTrans-resveratrolQuercetinNeurotoxicityNeuroprotection
spellingShingle Katarzyna Chamera
Beata Starek-Świechowicz
Bogusława Budziszewska
Maciej Gawlik
Protective effects of resveratrol, quercetin, and their glucuronide derivatives in an in vitro model of Mn- and Al-induced cytotoxicity in SH-SY5Y human neuroblastoma cells
Discover Toxicology
Manganese
Aluminium
Trans-resveratrol
Quercetin
Neurotoxicity
Neuroprotection
title Protective effects of resveratrol, quercetin, and their glucuronide derivatives in an in vitro model of Mn- and Al-induced cytotoxicity in SH-SY5Y human neuroblastoma cells
title_full Protective effects of resveratrol, quercetin, and their glucuronide derivatives in an in vitro model of Mn- and Al-induced cytotoxicity in SH-SY5Y human neuroblastoma cells
title_fullStr Protective effects of resveratrol, quercetin, and their glucuronide derivatives in an in vitro model of Mn- and Al-induced cytotoxicity in SH-SY5Y human neuroblastoma cells
title_full_unstemmed Protective effects of resveratrol, quercetin, and their glucuronide derivatives in an in vitro model of Mn- and Al-induced cytotoxicity in SH-SY5Y human neuroblastoma cells
title_short Protective effects of resveratrol, quercetin, and their glucuronide derivatives in an in vitro model of Mn- and Al-induced cytotoxicity in SH-SY5Y human neuroblastoma cells
title_sort protective effects of resveratrol quercetin and their glucuronide derivatives in an in vitro model of mn and al induced cytotoxicity in sh sy5y human neuroblastoma cells
topic Manganese
Aluminium
Trans-resveratrol
Quercetin
Neurotoxicity
Neuroprotection
url https://doi.org/10.1007/s44339-025-00029-7
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