Synergistic effects of combined exposure to hydroquinone and nitrofurantoin in T24 bladder cells: an in vitro toxicology study with implications for risk assessment.
6 affiliations
- 1University of Zagreb Faculty of Food Technology and Biotechnology, Zagreb, Croatia.
- 2BICRO BIOCentre Ltd., Central Laboratory, Zagreb, Croatia.
- 3Selvita Ltd., Zagreb, Croatia.
- 4Institute for Medical Research and Occupational Health, Zagreb, Croatia.
- 5University of Belgrade Faculty of Pharmacy, Department of Toxicology "Akademik Danilo Soldatović", Belgrade, Serbia.
- 6University of Zagreb Faculty of Science, Department of Biology, Zagreb, Croatia.
Abstract
Hydroquinone, the main active component of bearberry [Arctostaphylos uva-ursi (L.) Spreng.], is sometimes used together with the antibiotic nitrofurantoin to treat urinary tract infections. The aim of this in vitro study was to test the hypothesis that co-exposure to hydroquinone and nitrofurantoin would result in greater cytotoxic, oxidative, and genotoxic effects than exposure to either compound alone. To do that, we assessed single and combined toxic effects of two- and eight-hour exposure to both compounds in T24 human bladder carcinoma cells due to their stability and retention of key signalling pathways involved in oxidative stress, DNA repair, and apoptosis. Cytotoxicity and oxidative stress were assessed with the neutral red and 2',7'-dichlorodihydrofluorescein diacetate assays and genotoxicity with the cytokinesis-block micronucleus cytome assay. Proteomic changes were examined using tandem mass tag labelling followed by mass spectrometry. Combined exposure to hydroquinone and nitrofurantoin produced a synergistic increase in cytotoxic and genotoxic effects compared to single-compound treatments, including reduced nuclear division index and activation of pathways related to oxidative stress, DNA damage, and proteotoxic stress. These findings highlight the importance of evaluating interactions between plant-derived hydroquinone and nitrofurantoin in risk assessment of combined exposure during therapy.
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BibTeX
@article{turkovic2026synergistic,
title = {{Synergistic effects of combined exposure to hydroquinone and nitrofurantoin in T24 bladder cells: an in vitro toxicology study with implications for risk assessment.}},
author = {Ana Huđek Turković and Željka Stanečić and Ana Butorac and Vilena Kašuba and Marijana Ćurčić and Antonio Gagić and Ivana Šola and Marija Lovrić and Gordana Rusak and Ksenija Durgo},
journal = {Arhiv za higijenu rada i toksikologiju},
year = {2026},
month = sep,
doi = {10.2478/aiht-2026-77-4146},
url = {https://europepmc.org/article/MED/42859409},
note = {CC BY},
}
RIS
TY - JOUR
TI - Synergistic effects of combined exposure to hydroquinone and nitrofurantoin in T24 bladder cells: an in vitro toxicology study with implications for risk assessment.
AU - Ana Huđek Turković
AU - Željka Stanečić
AU - Ana Butorac
AU - Vilena Kašuba
AU - Marijana Ćurčić
AU - Antonio Gagić
AU - Ivana Šola
AU - Marija Lovrić
AU - Gordana Rusak
AU - Ksenija Durgo
PY - 2026
DA - 2026/09/25
JO - Arhiv za higijenu rada i toksikologiju
DO - 10.2478/aiht-2026-77-4146
UR - https://europepmc.org/article/MED/42859409
AB - Hydroquinone, the main active component of bearberry [Arctostaphylos uva-ursi (L.) Spreng.], is sometimes used together with the antibiotic nitrofurantoin to treat urinary tract infections. The aim of this in vitro study was to test the hypothesis that co-exposure to hydroquinone and nitrofurantoin would result in greater cytotoxic, oxidative, and genotoxic effects than exposure to either compound alone. To do that, we assessed single and combined toxic effects of two- and eight-hour exposure to both compounds in T24 human bladder carcinoma cells due to their stability and retention of key signalling pathways involved in oxidative stress, DNA repair, and apoptosis. Cytotoxicity and oxidative stress were assessed with the neutral red and 2',7'-dichlorodihydrofluorescein diacetate assays and genotoxicity with the cytokinesis-block micronucleus cytome assay. Proteomic changes were examined using tandem mass tag labelling followed by mass spectrometry. Combined exposure to hydroquinone and nitrofurantoin produced a synergistic increase in cytotoxic and genotoxic effects compared to single-compound treatments, including reduced nuclear division index and activation of pathways related to oxidative stress, DNA damage, and proteotoxic stress. These findings highlight the importance of evaluating interactions between plant-derived hydroquinone and nitrofurantoin in risk assessment of combined exposure during therapy.
SN - 0004-1254
SN - 1848-6312
ER -