Antiproliferative and Cytotoxic Activities of Fluorescein—A Diagnostic Angiography Dye

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.

Photochemistry of Common Xanthene Fluorescent Dyes as Efficient Visible-light Activatable CO-Releasing Molecules

“…In this work, we demonstrate that extensive irradiation of common organic dyes, fluorescein, eosin Y, and rose bengal, with green and white visible light leads to the release of carbon monoxide in biologically relevant yields. 64 The release of CO was evidenced and quantified by independent analytical methods, such as optical spectroscopy, chromatography and mass spectroscopy techniques. In addition, 13 C isotopic labeling was utilized to identify the origin of CO formation.…”

“…Biological aspects of the CO photoproduction from fluorescein are discussed in a currently submitted article. 64…”

Common xanthene fluorescent dyes are visible-light activatable CO-releasing molecules

“…In conclusion, we demonstrate that extensive irradiation of fluorescein, eosin Y, and rose bengal with green and white light leads to the release of CO in amounts that can affect physiological processes in cells. 54 The release of CO was evidenced and quantified by independent optical spectroscopy, chromatography, and MS techniques. Also, 13 C labeling was utilized to identify the origin of CO, suggesting that at least two individual reaction pathways are responsible.…”

“…The related biological aspects of these transformations are discussed in a recently published article. 54…”

Advanced ultrawide-field optical coherence tomography angiography identifies previously undetectable changes in biomechanics-related parameters in nonpathological myopic fundus

“…However, color Doppler does not provide sufficient resolution to view delicate vasculature in the retina and choroid. Fundus fluorescein angiography (FFA) remains the gold standard to examine the structure of retinal vessels and the integrity of the blood–retina barrier, yet its invasive nature and potential cytotoxicity render it unideal for examining non-pathological myopia ( Kornblau and El-Annan, 2019 ; Šranková et al, 2022 ). The emergence of OCTA, a fast and noninvasive technology with high resolution, has greatly improved the convenience, compliance of subject, and accuracy in examining fundus hemodynamics and vasculature ( Hormel et al, 2021 ).…”