Izvorni znanstveni članak
https://doi.org/10.2478/aiht-2026-77-4146
Synergistic effects of combined exposure to hydroquinone and nitrofurantoin in T24 bladder cells: an in vitro toxicology study with implications for risk assessment
Ana Huđek Turković
; University of Zagreb Faculty of Food Technology and Biotechnology, Zagreb, Croatia
Željka Stanečić
; BICRO BIOCentre Ltd., Central Laboratory, Zagreb, Croatia
Ana Butorac
; BICRO BIOCentre Ltd., Central Laboratory, Zagreb, Selvita Ltd., Zagreb, Croatia
Vilena Kašuba
; Institute for Medical Research and Occupational Health, Zagreb, Croatia
Marijana Ćurčić
; University of Belgrade Faculty of Pharmacy, Department of Toxicology “Akademik Danilo Soldatović”, Belgrade, Serbia
Antonio Gagić
; University of Zagreb Faculty of Food Technology and Biotechnology, Zagreb, Croatia
Ivana Šola
; University of Zagreb Faculty of Science, Department of Biology, Zagreb, Croatia
Marija Lovrić
; BICRO BIOCentre Ltd., Central Laboratory, Zagreb, Croatia
Gordana Rusak
; University of Zagreb Faculty of Science, Department of Biology, Zagreb, Croatia
Ksenija Durgo
; University of Zagreb Faculty of Food Technology and Biotechnology, Zagreb, Croatia
Sažetak
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.
Ključne riječi
apoptosis; CBMN cytome assay; cytotoxicity; DNA damage; genotoxicity; oxidative stress; proteomics; tandem mass tag labelling
Hrčak ID:
351079
URI
Datum izdavanja:
15.9.2026.
Posjeta: 0 *