Antiproliferative and Cytotoxic Activities of Fluorescein-A Diagnostic Angiography Dye.

Mária Šranková,Marek Martínek,Libor Vítek,Aleš Dvořák,Lucie Muchová,Peter Šebej,Petr Klán

doi:10.3390/ijms23031504

Abstract

Fluorescein is a fluorescent dye used as a diagnostic tool in various fields of medicine. Although fluorescein itself possesses low toxicity, after photoactivation, it releases potentially toxic molecules, such as singlet oxygen (1O2) and, as we demonstrate in this work, also carbon monoxide (CO). As both of these molecules can affect physiological processes, the main aim of this study was to explore the potential biological impacts of fluorescein photochemistry. In our in vitro study in a human hepatoblastoma HepG2 cell line, we explored the possible effects on cell viability, cellular energy metabolism, and the cell cycle. We observed markedly lowered cell viability (≈30%, 75–2400 μM) upon irradiation of intracellular fluorescein and proved that this decrease in viability was dependent on the cellular oxygen concentration. We also detected a significantly decreased concentration of Krebs cycle metabolites (lactate and citrate < 30%; 2-hydroxyglutarate and 2-oxoglutarate < 10%) as well as cell cycle arrest (decrease in the G2 phase of 18%). These observations suggest that this photochemical reaction could have important biological consequences and may account for some adverse reactions observed in fluorescein-treated patients. Additionally, the biological activities of both 1O2 and CO might have considerable therapeutic potential, particularly in the treatment of cancer.

Highlights

Fluorescein is a fluorescent small-molecule organic dye that is commonly employed in cellular biology as a tracer
To test the hypothesis that both carbon monoxide (CO) and 1 O2 are released upon fluorescein photoexcitation, fluorescein solution was irradiated with white light, and the amounts of both gaseous molecules produced were quantified
Fluorescein is a relatively nontoxic compound (LD50 = 6.7 g/kg for rats [39]), and it Fluorescein is a relatively nontoxic compound (LD50 = 6.7 g/kg for rats [39]), an is widely used in medicine for diagnostic purposes, as it exhibits strong fluorescence in widely used in medicine for diagnostic purposes, as it exhibits strong fluorescen aqueous media [1,2,4,6]

Summary

Introduction

Fluorescein is a fluorescent small-molecule organic dye that is commonly employed in cellular biology as a tracer. Its sodium salt is widely used in clinical medicine, as a diagnostic tool in ophthalmology [1]. It has been studied for new therapeutic applications in various fields, such as urology [2–4] and neurosurgery [5,6]. Having an important role in the diagnostics of ocular diseases, fluorescein has been included on the List of Essential Medicines, published by the World Health Organization [7]. During diagnostic procedures, it can be administered locally [8], orally [9], or intravenously [10]. Some of us have demonstrated that a fluorescein analog, xanthene-9-carboxylic

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