Biological Effects of Fluorescein Photochemistry: Comparison
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Fluorescein is a fluorescent organic dye used as tracer, contrasting agent or a diagnostic tool in various fields of medicine and natural sciences in general. Although fluorescein is a compound with relatively low toxicity, after photoactivation, it releases potentially toxic molecules, such as singlet oxygen and, as have been recently demonstrated, also carbon monoxide. Since both of these molecules are biologically active, it is essential to explore potential biological effects of fluorescein photochemistry.

  • fluorescein
  • irradiation
  • singlet oxygen
  • carbon monoxide
  • cytotoxicity
  • metabolism
  • proliferation

1.  Introduction

Fluorescein is a fluorescent small-molecule organic dye that exhibits strong fluorescence at neutral and alkalic pH in aqueous media. In these conditions, its main absorption peak is at 490 nm (ε490 = 76 900 M−1 cm−1) and is commonly employed in cellular biology as a the qurantum yield of the subsequent fluorescence is 0.93[1].cer. Its is a dark orange powder soluble in water and when dissolvsodium salt is widely used in proper conditions, emitting bright green fluorescence (with maximum emission at 515 nm[2]). It bclinical medicinelongs, to a group of xanthene dyes that includes substances like eosin Y or rhodamine B. It was first synthesized by Adolf von Baeyer around 1871 by condensation of resorcinol and particularly as a diagnostic tool in ophthalic anhydride catalmologyzed with zinc chloride[31][4].

2.  Application

Fluorescein isIt a broadly applied substance in various fields. For instance, it is commonly employed as a tracer. Some examples of this fluoresceinhas also been studied for new therapeutic application are utilization as a ground-water tracer[5], and use for ins in vestigating molecular movement in the bone lacunar-canalicular system[6]rious or for examining extravasation to study blood-spinal cord barrier permeability on animal modelields, such as[7][8]. Fluorescein can be also applied as a topical fluorescent contrast agent for microendoscoprology of gastrointestinal[2][93] or urinary tract[104] and as a pH sensitive corrosion indicatoneurosur[11][12].

Morgeover, it is extensively employed in ophthalmology as a diagnostic tool[135][146][15][16]. 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[177]. An example of a well-established and frequently used fluorescein diagnostic technique is fluorescein angiography[13][18][19]. During diagnostic procedures, it can be administered locally[208], orally[219], or intravenously[2210] with subsequent irradiation of the area of interest using blue light[131][233][244] (≈490 nm[2511][2612]). T

Althere are also studies that points to ugh fluorescein’s utilization in the labeling of brain tumor tissue (high-grade gliomas) to obtain better results of its resection[27][28][29] is considered to be generally safe, it is a photoactive compound whose biological effects associated with this activity have been neglected to date. For example, . Ffluorescein is capable of accumulating in cerebral areas with damaged blood-brain barrierknown to photosensitize oxygen to form singlet oxygen (1O2)[13][3014]. and therefore ensure better resection due to contrast-enhanced borderline of malignant and healthy tissue[28].Furthermore, it has been recently demonstrated that a fluorescein analog, xanthene-9-carboxylic In addition, there exist studies supporting use in urology, specifically, in bladder[31][23]cid, releases carbon monoxide (CO) upon photoactivation by and penile[24] cancer surgery.

3.  New discoveries

Fluorescein Irradiation Produces Biologically Active Compounds

Fluorescein in lightself[15] vis a relatively nontoxic substance (LD50 = 6.7 g/kg for rats[32], whia decarbonylation of the ch is almost 20x greater than LD50 rboxyl group. Although fluor caffeine[33]escein oris 2x more than this value for NaCstructurall[34]).y Howdiffever, it is a photoactive compound whose biological effects associated with this activity have been neglected to date. For example, fluorescein is known to photosensitize oxygen to form singlet oxygen (1O2)[35][36]. Addirent, it was hypothesized that it may also undergo the photodecarbonylation reaction. This hypothesis has been recentionally, Martinek et al.[37]y confirmed, as and Srankova et al.[3816] had shown that carbon monoxide (CO) is produced through photochemical degradation of fluorescein in a relatively high chemical yield of 40%.

Both 1O2 and CO are biologically active molecules that affect physiological processes in the human body[3917][4018][4119]. Over the past three decades, they have also been thoroughly studied for their use in the treatment of various diseases. 1O2 is a very reactive molecule, the cytotoxic properties of which are utilized in medicine, e.g., in photodynamic therapy[4220]. CO, in low concentration, acts in the body as a s an important gasotransmitter mediatingwith anti-inflammatory[4321], antiapoptotic[4422], and antiproliferative properties[23]. Its anticancer action was also studied in the researcher's laboratory, showing a positive effect on the survival rate of mice xenotransplanted with pancreatic cancer[4524]. Although  1O2  and CO are being investigated for their potential therapeutic use in the treatment of various diseases, they applications, both exert cytotoxicity at higher concentrations, particularly when their transport to target sites is not strictly controlled. While  1O2 causes oxidative damage and cell death[4625][4726][4827][4928], the toxicity of CO is related to its high binding affinity to blood hemoglobin[5029][5130][5231][5332] or the heme moiety of extravascular hemoproteins[5433][5534] such as cytochrome c oxidase[5635], affecting their oxygen carrier properties or enzymatic activities, respectively. In addition, CO can trigger oxidative stress[5736] and lipoperoxidation[5837].

Flu

2.  Impact of Fluorescein Irradiation on Biological Systems

Cytorescein Irradiation Impacts Physiological Processes of HepG2 cellsoxicity of fluorescein

Cytotoxicity of fluorescein irradiation

AFluorescein is has been relatively nontoxic compound (LD50 = 6.7 g/kg for rats[38]), and it is widelry useady mentioned in this entry,d in medicine for diagnostic purposes, as it exhibits strong fluorescein posnce in aqueous media[1][2][4][6]. This dyeses relatively is also used as a fluorescent label in target tissues[1][5]. lLow toxicity. Intracellular was also observed for its stable photoproducts, created by exhaustive fluorescein (administrated in the formdiacetate (FDA) irradiation (FDA is used to study intracellular effects of fluorescein diacetate (FDA) which, as, unlike fluorescein, it is able to penetrate the cellular membrane where it is hydrolyzed to fluorescein [5939]) also showed minimal toxicity (Figure 1, graphs A and B). Low toxicity was also observed for its stable photoproducts (Figure 1, graphs C and D). However, simultaneous irradiation of cells treated with fluorescein led to a significant and time-dependent decrease in cell viability (Figure 1, graphs E and F), suggesting that one or more photoproducts formed during irradiation, which were not present in the solutions upon exhaustive irradiation (= stable photoproducts), were responsible for the observed cytotoxicity. This means that these species must be either volatile or short-lived (although reactive), pointing to CO and 1O2[3816].

Figure 1. Viability of HepG2 cells treated with solutions of non-irradiated FDA solution (A, B), solution of fluorescein photoproducts (C, D; tir = 24 h, I = 160 mW/cm2 prior to the treatment, FDA concentration = initial concentration of FDA prior irradiation), or simultaneously irradiated solutions of FDA (E, F; irradiation throughout the entire incubation time 2 or 24 h, I = 160 mW/cm2, FDA concentration = FDA initial concentration prior irradiation); *p ≤ 0.05 vs. untreated control.

Effect on Krebs Cycle

ExThis data was, however, obtained upon losure of ng irradiation times. Therefore, to obtain more clinically relevant data, as diagnostic fluorescein angiography lasts only a few minutes, HepG2 cells to irradiation of intracellreated with FDA or fluorescein were irradiated for 30 min, and analyzed immediately, or after further incubation for 2 or 24 h in the dark. Irradiation of cells treated with FDA showed a significant decrease in cell viability (≤ 80%) in the majority of the analyzed concentrations (19-300 μmol/l) for 2 and 24 h incubation intervalar s; whereas this effect was much weaker when cells were treated with fluorescein[16].

Effect on Krebs Cycle

To elucidate the effects of fluorescein irradiation on cellular metabolism, the concentrations ofurthermore, Krebs cycle intermediates and its anaplerotic pathways were analyzed in HepG2 cells. HepG2 cells treated with FDA were irradiated directly to find the immediate impact of the photochemical transformation of fluorescein to photoproducts, including 1O2 and CO. This resulted in a significant decrease in the majority of metabolites, with the most significant changes in the concentrations of lactate, 2-hydroxyglutarateHG, 2-oxoglutarateOG, and citrate (<30% those of control)[3816]. This indicates that the above-mentioned biologically active by-products of fluorescein photoexcitation might affect the overall cellular energetic metabolism.

To test the hypothesis that the produced CO is responsible for decreased cell metabolism, HepG2 cells were incubated in an atmosphere containing 100 ppm of CO. A significant decrease in the concentrations of the Krebs cycle intermediates (2-hydroxyglutarateHG, glutamate, 2-oxoglutarateOG, and citrate) was also oobserved following CO treatment (enriched CO atmospfor 2 here, 100 ppm)[3816], confirming the key role of this molecule in theis observed attenuation of cell metabolism caused by fluorescein irradiationprocess. These results correspond to those observed upon CO exposure that demonstrated the inhibition of respiration and glycolysis and a decrease in some Krebs cycle metabolites[6040]. On the other hand, some published data have proved that CO can promote oxidative phosphorylation[6141][6242], mitochondrial biogenesis[6343], and even an increase in cytochrome c oxidase activity[6444], suggesting that the effect of CO is concentration- and tissue-dependent and reflects the overall cell/tissue status or oxygen level. In case, significant inhibition of the Krebs cycle was observed, which coincided with a relatively high FDA concentration and a long exposure to generated and simultaneously irradiated fluorescein.

Effect on Cell Cycle

Irradiation of FDA-treated cells also resulted in a significant increase in the G0 phase and a simultaneous decrease in G2/M phase (18% decrease when compared to control) of cell cycle, indicating reduced proliferation and thus the antiproliferative and anticancer potential of fluorescein. No significant effectTo assess the function of CO (enriched , an analogous experiment was performed under a CO atmosphere, 100 ppm). No significant effect of CO was observed on cell cycle progression, indicating no involvement of the CO released during the photoreaction in this process[3816]. However, CO has been suggested to affect the cell cycle[6545][6646], showing that this effect might be both dose- and cell-dependent.

Comparison of Different Fluorescein Administration Modes

TCompareatment of cells with freeing the effects of the two modes of fluorescein compared to treatment with FDA gave different results. Comparing the effects of these two modes of (free fluorescein and cell-targeted fluorescein treatmentin in the form of FDA) helped to assess the biological effects of  1O2 and CO when produced both intra- and extracellularly. Comparisons of the cell viability indicated that when administered as a free acid, fluorescein’s negative impact on viability is significantly smaller[3816]. In this case, the 1O2 molecules released during the photoreaction do not necessarily reach the intracellular compartment because of the short half-life of 1O2 (τ1/2 = 3–4 μs[6747]). On the other hand, the long-lived CO (τ1/2 = 3–4 h) can freely pass through the plasma membrane and affect cellular processes when generated extracellularly, as shown by Lazarus et al.[6848], who studied the intra- vs. extracellular delivery of CO using two types of CO-releasing molecules (CORMs) differing in their cellular localization. They showed that extracellular CO production exhibited a lower toxic effect on cells, whereas anti-inflammatory cell signaling processes were similar to those of intracellular delivery.

Impact of O

2

Concentration on Cytotoxicity of Fluorescein Irradiation

Fluorescein irradiation cytotoExicity experiments performed in a hypoxic chamber (a 9% O2 level was set according to the measured O2 level in rat livers[49]) showed that hypoxia was associated with a significantly lower drop in the viability of cells treated when ith either fluorescein or FDA when compared to thatwith cells under normoxic conditions. Three different ways of how the O2 level may influence this parameter were proposed. A lower O2 level can result in: a lower yield of 1O2 (fewer O2 molecules available for sensitization); reduced efficiency of the fluorescein photoreaction (if 1O2 is responsible for its degradation) and thus less efficient CO release; or a different cellular metabolic status, any of which ultimately affects the cell’s survival[3816].

43.  Conclusion and Outlook

FluoIrescein is a widely used fluorescent dye that has found its applicradiation in many fields of natural sciences. Medicine is no exception, where of fluorescein plays the role of a tracer, contrast compound or diagnostic agent, etc. For many of these applications is fluorescein irradiated to yield fluorescence. It was found that this irradiation results in the results in the production of the biologically active molecules 1O2  and CO. Experiments on HepG2 cells also showed cyThese molecules might be responsible for the phototoxicity, attenuation of metabolism and de of fluorescein, which increased proliferation as a result of fluorescein is with increasing dosage, times of irradiation. This may indicate that volatile and reactive molecules produced during, and tissue oxygenation levels. Moreover, the fluorescein photochemical reaction, from which products 1O2 andffect CO were identified, are responsible for some adverse effects observed with fluorescein administcell metabolism and proliferation to patients. On the other hand, as fluorescein. As it releases CO in substantial amounts, it might even be used therapeutically as a photoCORM to release CO into target tissues. Another possibility of application is to employ both bioactive molecules, 1O2 and CO, for t irradiated withe therapeutic action, for example, in the treatment of cancerlight.

References

  1. Robert Sjöback; Jan Nygren; Mikael Kubista; Absorption and fluorescence properties of fluorescein. Rosario Brancato; Francesco Bandello; Rosangela Lattanzio; Iris fluorescein angiography in clinical practice. Spurvectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy of Ophthalmology 1995, 51, L7-L21, 10.1016/0584-8539(95)01421-p.7, 42, 41-70, 10.1016/s0039-6257(97)84042-8.
  2. Monique M. Martin; Lars Lindqvist; The pH dependence of fluorescein fluorescence. Philippe E. Zimmern; David Laub; Gary E. Leach; Fluorescein Angiography of the Bladder: Technique and Relevance to Bladder Cancer and Interstitial Cystitis Patients. Journal of Luminescence Urology 19975, 10, 381-390, 10.1016/0022-2313(75)90003-4.54, 62-65, 10.1016/s0022-5347(01)67225-2.
  3. Wei-Chuan Sun; Kyle R. Gee; And Dieter H. Klaubert; Richard P. Haugland; Synthesis of Fluorinated Fluoresceins. The Geoffrey A. Sonn; Sha-Nita E. Jones; Tatum V. Tarin; Christine B. Du; Kathleen E. Mach; Kristin C. Jensen; Joseph C. Liao; Optical Biopsy of Human Bladder Neoplasia With In Vivo Confocal Laser Endomicroscopy. Journal of OUrganic Chemistrology 1 200997, 6, 182, 6469-6475, 10.1021/jo9706178., 1299-1305, 10.1016/j.juro.2009.06.039.
  4. von Baeyer, A.; Ueber ein neue Klasse von Farbstoffen. BeEugene Shkolyar; Mark A. Laurie; Kathleen E. Mach; Dharati R. Trivedi; Dimitar V. Zlatev; Timothy C. Chang; Thomas J. Metzner; John T. Leppert; Chia-Sui Kao; Joseph C. Liao; et al. Optical biopsy of penile cancer with in vivo confocal laser endomicroscopy. Urologichte der Deutschen Chemischen Gesellschaf Oncology: Seminars and Original Investigat ions 201871, 4, 555-558.9, 37, 809.e1-809.e8, 10.1016/j.urolonc.2019.08.018.
  5. David A. Sabatini; T. Ai Austin; Characteristics of Rhodamine WT and Fluorescein as Adsorbing Ground-Water Tracers. GFrancesco Acerbi; Morgan Broggi; Marica Eoli; Elena Anghileri; Claudio Cavallo; Carlo Boffano; Roberto Cordella; Lucia Cuppini; Bianca Pollo; Marco Schiariti; et al.Sergio VisintiniChiara OrsiEmanuele La CorteGiovanni BroggiPaolo Ferroli Is fluorescein-guided technique able to help in resection of high-grade gliomas?. Neurosundwater rgical Focus 201991, 29, 341-349, 10.1111/j.1745-6584.1991.tb00524.x.4, 36, E5, 10.3171/2013.11.focus13487.
  6. Liyun Wang; Yilin Wang; Yuefeng Han; Scott C. Henderson; Robert J. Majeska; Sheldon Weinbaum; Mitchell B. Schaffler; In situ measurement of solute transport in the bone lacunar-canalicular system. PLinda M. Wang; Matei A. Banu; Peter Canoll; Jeffrey N. Bruce; Rationale and Clinical Implications of Fluorescein-Guided Supramarginal Resection in Newly Diagnosed High-Grade Glioma. Froceedings of the National Academtiers in Oncology of Sciences 2005, 21, 1102, 11911-11916, 10.1073/pnas.0505193102., -, 10.3389/fonc.2021.666734.
  7. Dimitris N Xanthos; Isabella Püngel; Gabriele Wunderbaldinger; Jürgen Sandkühler; Effects of Peripheral Inflammation on the Blood-Spinal Cord Barrier. Molecular Pain 2012, 8, 44-44, 10.1186/1744-8069-8-44.22nd Model List of Essential Medicines . World Health Organization. Retrieved 2022-4-21
  8. Nick Cochran; Travis Rush; Susan C. Buckingham; Erik D. Roberson; The Alzheimer's disease risk factor CD2AP maintains blood–brain barrier integrity. Human Molecular Genetics 2015, 24, 6667-6674, 10.1093/hmg/ddv371.British National Formulary 81 . Web of Pharma. Retrieved 2022-4-21
  9. Sandra P. Prieto; Keith K. Lai; Jonathan A. Laryea; Jason Mizell; William C. Mustain; Timothy J. Muldoon; Fluorescein as a topical fluorescent contrast agent for quantitative microendoscopic inspection of colorectal epithelium. BioTsutomu Hara; Mikino Inami; Takako Hara; Efficacy and safety of fluorescein angiography with orally administered sodium fluorescein. Amedrical Optics Express 20n Journal of Ophthalmology 17, 8, 2324-2338, 10.1364/boe.8.002324.998, 126, 560-564, 10.1016/s0002-9394(98)00112-3.
  10. Timothy C. Chang; Jen-Jane Liu; Joseph C. Liao; Probe-based confocal laser endomicroscopy of the urinary tract: the technique.. JoHarold R. Novotny; David L. Alvis; A Method of Photographing Fluorescence in Circulating Blood in the Human Retina. Circurnal of Visualized Experimeationts 20 19613, -, e4409, 10.3791/4409., 24, 82-86, 10.1161/01.cir.24.1.82.
  11. Maher A. Alodan; William H. Smyrl; Detection of Localized Corrosion Using Fluorescence Microscopy. Journal of The Oliver R. Marmoy; Robert H. Henderson; Kuan Ooi; Recommended protocol for performing oral fundus fluorescein angiography (FFA) in children. Elyectrochemical Society 1997, 144, L282-L284, 10.1149/1.1838010. 2020, 36, 234-236, 10.1038/s41433-020-01328-6.
  12. L.M. Calle; W. Li; Microencapsulated indicators and inhibitors for corrosion detection and control. HDaniel X. Hammer; R. Daniel Ferguson; Ankit H. Patel; Vanessa Vazquez; Deeba Husain; Angiography with a multifunctional line scanning ophthalmoscope. Journandbookl of Smart Coatings for Materials Protection Biomedical Optics 2014, -, 370-422, 10.1533/9780857096883.2.370.2, 17, 0260081-02600811, 10.1117/1.jbo.17.2.026008.
  13. Rosario Brancato; Francesco Bandello; Rosangela Lattanzio; Iris fluorescein angiography in clinical practice. SuYoshiharu Usui; DETERMINATION OF QUANTUM YIELD OF SINGLET OXYGEN FORMATION BY PHOTOSENSITIZATION. Chemistrvey of Ophthalmology Letters 1997, 43, 2, 41-70, 10.1016/s0039-6257(97)84042-8., 743-744, 10.1246/cl.1973.743.
  14. FRCS Caroline J MacEwan; Frcs James D H Young; The Fluorescein Disappearance Test (FDT): An Evaluation of Its Use in Infants. JE. Gandin; Y. Lion; A. Van de Vorst; QUANTUM YIELD OF SINGLET OXYGEN PRODUCTION BY XANTHENE DERIVATIVES. Phournal tof Pediatric Ophthalmchemistry and Photobiology & Strabismus 1991, 28, 302-305, 10.3928/0191-3913-19911101-04.83, 37, 271-278, 10.1111/j.1751-1097.1983.tb04472.x.
  15. Revelle Littlewood; Susan P Mollan; Irene M Pepper; Simon J Hickman; The Utility of Fundus Fluorescein Angiography in Neuro-Ophthalmology. NLovely Angel Panamparambil Antony; Tomáš Slanina; Peter Šebej; Tomáš Šolomek; Petr Klán; Fluorescein Analogue Xanthene-9-Carboxylic Acid: A Transition-Metal-Free CO Releasing Molecule Activated by Green Light. Organic Letteuro-Ophthalmology s 2019, 43, 217-234, 10.1080/01658107.2019.1604764.3, 15, 4552-4555, 10.1021/ol4021089.
  16. Daniel Sibley; Daniel F. P. Larkin; Update on Herpes simplex keratitis management. EyMária Šranková; Aleš Dvořák; Marek Martínek; Peter Šebej; Petr Klán; Libor Vítek; Lucie Muchová; Antiproliferative and Cytotoxic Activities of Fluorescein—A Diagnostic Angiography Dye. International Journal of Molecular Science s 20220, , 234, 2219-2226, 10.1038/s41433-020-01153-x., 1504, 10.3390/ijms23031504.
  17. 22nd Model List of Essential Medicines . World Health Organization. Retrieved 2022-4-21Stefan W. Ryter; Leo E. Otterbein; Carbon monoxide in biology and medicine. BioEssays 2004, 26, 270-280, 10.1002/bies.20005.
  18. Maurice F. Rabb; Thomas C. Burton; Howard Schatz; Lawrence A. Yannuzzi; Fluorescein angiography of the fundus: A schematic approach to interpretation. Survey Briviba, K.; Klotz, L.-O.; Sies, H.; Toxic and signaling effects of photochemically or chemically generated singlet oxygen in biological systems. Biofl. Ophthalmology Chem. 19978, 22, 387-403, 10.1016/0039-6257(78)90134-0., 378,, 1259–1265.
  19. Alberto La Mantia; Rengin A. Kurt; Samantha Mejor; Catherine Egan; Adnan Tufail; Pearse A. Keane; Dawn A. Sim; COMPARING FUNDUS FLUORESCEIN ANGIOGRAPHY AND SWEPT-SOURCE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY IN THE EVALUATION OF DIABETIC MACULAR PERFUSION. RetDevasagayam, T.; Kamat, J.P.; Biological significance of singlet oxygen. Indiana J. Exp. Biol. 20019, 39, 926-937, 10.1097/iae.0000000000002045.2, 40, 680–692.
  20. British National Formulary 81 . Web of Pharma. Retrieved 2022-4-21Patrizia Agostinis; Kristian Berg; Keith A. Cengel Md; Thomas H. Foster; Albert W. Girotti; Sandra O. Gollnick; Stephen M. Hahn Md; Michael R. Hamblin; Asta Juzeniene; David Kessel; et al.Mladen KorbelikJohan MoanPawel MrozDominika Nowis MdJacques PietteBrian C. WilsonJakub Golab Photodynamic therapy of cancer: An update. CA: A Cancer Journal for Clinicians 2011, 61, 250-281, 10.3322/caac.20114.
  21. Tsutomu Hara; Mikino Inami; Takako Hara; Efficacy and safety of fluorescein angiography with orally administered sodium fluorescein. AmLeo E. Otterbein; Fritz H. Bach; Jawed Alam; Miguel Soares; Hong Tao Lu; Mark Allen Wysk; Roger J. Davis; Richard A. Flavell; Augustine M. K. Choi; Carbon monoxide has anti-inflammatory effects involving the mitogen-activated protein kinase pathway. Nature Merdican Journal of Ophthalmology 1998, 12ine 2000, 6, 560-564, 10.1016/s0002-9394(98)00112-3., 422-428, 10.1038/74680.
  22. Harold R. Novotny; David L. Alvis; A Method of Photographing Fluorescence in Circulating Blood in the Human Retina. CiSophie Brouard; Leo E. Otterbein; Josef Anrather; Edda Tobiasch; Fritz H. Bach; Augustine M.K. Choi; Miguel Soares; Carbon Monoxide Generated by Heme Oxygenase 1 Suppresses Endothelial Cell Apoptosis. Jourcunalatio of Experimental Medicin 1961, e 2000, 1924, 82-86, 10.1161/01.cir.24.1.82., 1015-1026, 10.1084/jem.192.7.1015.
  23. Geoffrey A. Sonn; Sha-Nita E. Jones; Tatum V. Tarin; Christine B. Du; Kathleen E. Mach; Kristin C. Jensen; Joseph C. Liao; Optical Biopsy of Human Bladder Neoplasia With In Vivo Confocal Laser Endomicroscopy. Toshisuke Morita; S. Alex Mitsialis; Hideo Koike; Yuxiang Liu; Stella Kourembanas; Carbon Monoxide Controls the Proliferation of Hypoxic Vascular Smooth Muscle Cells. Journal of UrBiological Chemistry 200 199, 187, 272, 1299-1305, 10.1016/j.juro.2009.06.039., 32804-32809, 10.1074/jbc.272.52.32804.
  24. Eugene Shkolyar; Mark A. Laurie; Kathleen E. Mach; Dharati R. Trivedi; Dimitar V. Zlatev; Timothy C. Chang; Thomas J. Metzner; John T. Leppert; Chia-Sui Kao; Joseph C. Liao; et al. Optical biopsy of penile cancer with in vivo confocal laser endomicroscopy. UrologLibor Vítek; Helena Gbelcová; Lucie Muchová; Kateřina Váňová; Jaroslav Zelenka; Renata Koníčková; Jakub Šuk; Marie Zadinova; Zdeněk Knejzlík; Shakil Ahmad; et al.Takeshi FujisawaAsif AhmedTomáš Ruml Antiproliferative effects of carbon monoxide on pancreatic cancer. Dic Oncology: Seminars and Original Investigationestive and Liver Diseas e 2019, 37, 809.e1-809.e8, 10.1016/j.urolonc.2019.08.018.4, 46, 369-375, 10.1016/j.dld.2013.12.007.
  25. Oliver R. Marmoy; Robert H. Henderson; Kuan Ooi; Recommended protocol for performing oral fundus fluorescein angiography (FFA) in children. EyM L Agarwal; M E Clay; E J Harvey; H H Evans; A R Antunez; N L Oleinick; Photodynamic therapy induces rapid cell death by apoptosis in L5178Y mouse lymphoma cells.. Cancer Rese 2020, 36, 234-236, 10.1038/s41433-020-01328-6.arch 1991, 51, 5993-6.
  26. Daniel X. Hammer; R. Daniel Ferguson; Ankit H. Patel; Vanessa Vazquez; Deeba Husain; Angiography with a multifunctional line scanning ophthalmoscope. JouW M Star; H P Marijnissen; A E Van Den Berg-Blok; J A Versteeg; K A Franken; H S Reinhold; Destruction of rat mammary tumor and normal tissue microcirculation by hematoporphyrin derivative photoradiation observed in vivo in sandwich observation chambers.. Cancernal of Biomedical Optics 20Research 12, 17, 0260081-02600811, 10.1117/1.jbo.17.2.026008.986, 46, -.
  27. Linda M. Wang; Matei A. Banu; Peter Canoll; Jeffrey N. Bruce; Rationale and Clinical Implications of Fluorescein-Guided Supramarginal Resection in Newly Diagnosed High-Grade Glioma. FNorman I. Krinsky; Singlet oxygen in biological systems. Troentiers in Oncology 202ds in Biochemical Sciences 1, 11, -, 10.3389/fonc.2021.666734.977, 2, 35-38, 10.1016/0968-0004(77)90253-5.
  28. Francesco Acerbi; Morgan Broggi; Marica Eoli; Elena Anghileri; Claudio Cavallo; Carlo Boffano; Roberto Cordella; Lucia Cuppini; Bianca Pollo; Marco Schiariti; et al.Sergio VisintiniChiara OrsiEmanuele La CorteGiovanni BroggiPaolo Ferroli Is fluorescein-guided technique able to help in resection of high-grade gliomas?. NMichael J. Davies; Singlet oxygen-mediated damage to proteins and its consequences. Biocheurmical and Biosurgical Focuphysical Research Communications 20014, 3, 36, E5, 10.3171/2013.11.focus13487.05, 761-770, 10.1016/s0006-291x(03)00817-9.
  29. Francesco Acerbi; Claudio Cavallo; Morgan Broggi; Roberto Cordella; Elena Anghileri; Marica Eoli; Marco Schiariti; Giovanni Broggi; Paolo Ferroli; Fluorescein-guided surgery for malignant gliomas: a review. NeurIvan Blumenthal; Carbon Monoxide Poisoning. Josurgical Revinal of the Royal Society of Medicinew 20014, 37, 547-557, 10.1007/s10143-014-0546-6., 94, 270-272, 10.1177/014107680109400604.
  30. Oskar Steinwall; Igor Klatzo; Selective Vulnerability of the Blood-Brain Barrier in Chemically Induced Lesions*. C. G. Douglas; J. S. Haldane; The laws of combination of haemoglobin with carbon monoxide and oxygen. The Journal of NeuropatPhology & Experimental Neurysiology 1966, 25, 542-559, 10.1097/00005072-196610000-00004.12, 44, 275-304, 10.1113/jphysiol.1912.sp001517.
  31. Philippe E. Zimmern; David Laub; Gary E. Leach; Fluorescein Angiography of the Bladder: Technique and Relevance to Bladder Cancer and Interstitial Cystitis Patients. Journal of Urology 1995, 154, 62-65, 10.1016/s0022-5347(01)67225-2.Bernard, C. . Leçons sur Les Effets des Substances Toxiques et Médicamenteuses; Librairie, J.B., Ed.; Baillière et Fils: Leon, France, 1857; pp. -.
  32. Samuel L. Yankell; Joseph J. Loux; Acute Toxicity Testing of Erythrosine and Sodium Fluorescein in Mice and Rats. John Haldane; J. Lorrain Smith; The Absorption of Oxygen by the Lungs. The Journal of Perhysiodontology 18977, 48, 228-231, 10.1902/jop.1977.48.4.228., 22, 231-258, 10.1113/jphysiol.1897.sp000689.
  33. Richard H. Adamson; The acute lethal dose 50 (LD50) of caffeine in albino rats. RegNorman Nomof; James Hopper; Ellen Brown; Kenneth Scott; Reidar Wennesland; Simultaneous Determinations of the Total Volume of Red Blood Cells by Use of Carbon Monoxide and Chromium51 IN HEALTHY AND DISEASED HUMAN SUBJECTS1. Journalatory Toxicology and Pharmacology 20 of Clinical Investigation 16, 80, 274-276, 10.1016/j.yrtph.2016.07.011.954, 33, 1382-1387, 10.1172/jci103015.
  34. E Walum; Acute oral toxicity.. ERonald F. Coburn; THE CARBON MONOXIDE BODY STORES. Anvironmental Health Perspectivals of the New York Academy of Sciences 1998, 70, 106, 497-503, 10.1289/ehp.98106497.74, 11-22, 10.1111/j.1749-6632.1970.tb49768.x.
  35. Yoshiharu Usui; DETERMINATION OF QUANTUM YIELD OF SINGLET OXYGEN FORMATION BY PHOTOSENSITIZATION. CÒscar Miró; Jordi Casademont; Antoni Barrientos; Álvaro Urbano-Márquez; Francesc Cardellach; Mitochondrial Cytochrome c Oxidase Inhibition during Acute Carbon Monoxide Poisoning. Phearmistracology & Toxicology Letters 19973, 8, 82, 743-744, 10.1246/cl.1973.743., 199-202, 10.1111/j.1600-0773.1998.tb01425.x.
  36. E. Gandin; Y. Lion; A. Van de Vorst; QUANTUM YIELD OF SINGLET OXYGEN PRODUCTION BY XANTHENE DERIVATIVES. PhJ Zhang; C A Piantadosi; Mitochondrial oxidative stress after carbon monoxide hypoxia in the rat brain.. Joturnal ochemistry and Photobiology f Clinical Investigation 19983, 37, 271-278, 10.1111/j.1751-1097.1983.tb04472.x.2, 90, 1193-1199, 10.1172/jci115980.
  37. Marek Martínek; Lucie Ludvíková; Mária Šranková; Rafael Navrátil; Lucie Muchová; Jiří Huzlík; Libor Vítek; Petr Klán; Peter Šebej; Photochemistry of Common Xanthene Fluorescent Dyes as Efficient Visible-light Activatable CO-Releasing Molecules. S. R. Thom; Carbon monoxide-mediated brain lipid peroxidation in the rat. Journual of Applied Physiol 2ogy 199022, -, -, 10.26434/chemrxiv-2022-pn3x0., 68, 997-1003, 10.1152/jappl.1990.68.3.997.
  38. Mária Šranková; Aleš Dvořák; Marek Martínek; Peter Šebej; Petr Klán; Libor Vítek; Lucie Muchová; Antiproliferative and Cytotoxic Activities of Fluorescein—A Diagnostic Angiography Dye. International Samuel L. Yankell; Joseph J. Loux; Acute Toxicity Testing of Erythrosine and Sodium Fluorescein in Mice and Rats. Journal of MolPecular Sciences 2022, 23, 1504, 10.3390/ijms23031504.riodontology 1977, 48, 228-231, 10.1902/jop.1977.48.4.228.
  39. Stefan W. Ryter; Leo E. Otterbein; Carbon monoxide in biology and medicine. BioEssays 2004, 26, 270-280, 10.1002/bies.20005.Rotman, B.; Papermaster, B.W. Membrane properties of living mammalian cells as studied by enzymatic hydrolysis of fluorogenic esters. Proc. Natl. Acad. Sci. USA 1966, 55, 134.
  40. Briviba, K.; Klotz, L.-O.; Sies, H.; Toxic and signaling effects of photochemically or chemically generated singlet oxygen in biological systems. BPatrycja Kaczara; Barbara Sitek; Kamil Przyborowski; Anna Kurpinska; Kamil Kus; Marta Stojak; Stefan Chlopicki; Antiplatelet Effect of Carbon Monoxide Is Mediated by NAD + and ATP Depletion. Arterioscl. Chem.erosis, Thrombosis, and Vascular 1997, 378,, 1259–1265.Biology 2020, 40, 2376-2390, 10.1161/atvbaha.120.314284.
  41. Devasagayam, T.; Kamat, J.P.; Biological significance of singlet oxygen. IndianMarialuisa Lavitrano; Ryszard T. Smolenski; Antonino Musumeci; Massimo Maccherini; Ewa Slominska; Ernesto Florio; Adele Bracco; Antonio Mancini; Giorgio Stassi; Mariella Patti; et al.Roberto GiovannoniAlberto FroioFelicetta SimeoneMonica ForniMaria Laura BacciGiuseppe D'AliseEmanuele CozziLeo E. OtterbeinMagdi H. YacoubFritz H. BachFulvio Calise Carbon monoxide improves cardiac energetics and safeguards the heart during reperfusion after cardiopulmonary bypass in pigs. The J. FASExp. BioB Journal. 2002, 40, 680–692.4, 18, 1093-1095, 10.1096/fj.03-0996fje.
  42. Patrizia Agostinis; Kristian Berg; Keith A. Cengel Md; Thomas H. Foster; Albert W. Girotti; Sandra O. Gollnick; Stephen M. Hahn Md; Michael R. Hamblin; Asta Juzeniene; David Kessel; et al.Mladen KorbelikJohan MoanPawel MrozDominika Nowis MdJacques PietteBrian C. WilsonJakub Golab Photodynamic therapy of cancer: An update. CA: ATung-Yu Tsui; Yeung-Tung Siu; Hans J. Schlitt; Sheung-Tat Fan; Heme oxygenase-1-derived carbon monoxide stimulates adenosine triphosphate generation in human hepatocyte. Biochemical Cancer Journal for Cliniciad Biophysical Research Communications 20011, 5, 3361, 250-281, 10.3322/caac.20114., 898-902, 10.1016/j.bbrc.2005.08.187.
  43. Leo E. Otterbein; Fritz H. Bach; Jawed Alam; Miguel Soares; Hong Tao Lu; Mark Allen Wysk; Roger J. Davis; Richard A. Flavell; Augustine M. K. Choi; Carbon monoxide has anti-inflammatory effects involving the mitogen-activated protein kinase pathway. NatHagit B. Suliman; Martha S. Carraway; Lynn G. Tatro; Claude A. Piantadosi; A new activating role for CO in cardiac mitochondrial biogenesis. Journal of Ce Medicinll Science 2000, 6, 422-428, 10.1038/74680.7, 120, 299-308, 10.1242/jcs.03318.
  44. Sophie Brouard; Leo E. Otterbein; Josef Anrather; Edda Tobiasch; Fritz H. Bach; Augustine M.K. Choi; Miguel Soares; Carbon Monoxide Generated by Heme Oxygenase 1 Suppresses Endothelial Cell Apoptosis. JournalCláudia Sf Queiroga; Ana S Almeida; Paula M Alves; Catherine Brenner; Helena LA Vieira; Carbon monoxide prevents hepatic mitochondrial membrane permeabilization. BMC of ExpCerimental Medicine ll Biology 2000, 11, 192, 1015-1026, 10.1084/jem.192.7.1015., 10-10, 10.1186/1471-2121-12-10.
  45. Toshisuke Morita; S. Alex Mitsialis; Hideo Koike; Yuxiang Liu; Stella Kourembanas; Carbon Monoxide Controls the Proliferation of Hypoxic Vascular Smooth Muscle Cells. Ruiping Song; Raja S. Mahidhara; Fang Liu; Wen Ning; Leo E. Otterbein; Augustine M. K. Choi; Carbon Monoxide Inhibits Human Airway Smooth Muscle Cell Proliferation via Mitogen-Activated Protein Kinase Pathway. American Journal of BRespiological Chemistrratory Cell and Molecular Biology 1997, 2002, 272, 32804-32809, 10.1074/jbc.272.52.32804., 603-610, 10.1165/rcmb.4851.
  46. M L Agarwal; M E Clay; E J Harvey; H H Evans; A R Antunez; N L Oleinick; Photodynamic therapy induces rapid cell death by apoptosis in L5178Y mouse lymphoma cells.. CancHyun-Ock Pae; Gi-Su Oh; Byung-Min Choi; Soo-Cheon Chae; Young-Myeong Kim; Khee-Rhin Chung; Hun-Taeg Chung; Carbon Monoxide Produced by Heme Oxygenase-1 Suppresses T Cell Proliferation via Inhibition of IL-2 Production. The Jour Research 1991, 5nal of Immunology 2004, 1, 5993-6.72, 4744-4751, 10.4049/jimmunol.172.8.4744.
  47. W M Star; H P Marijnissen; A E Van Den Berg-Blok; J A Versteeg; K A Franken; H S Reinhold; Destruction of rat mammary tumor and normal tissue microcirculation by hematoporphyrin derivative photoradiation observed in vivo in sandwich observation chambers.. CFrancis Wilkinson; W. Phillip Helman; Alberta B. Ross; Rate Constants for the Decay and Reactions of the Lowest Electronically Excited Singlet State of Molecular Oxygen in Solution. An Expanded and Revised Compilation. Journal of Physical and Chemicer Research al Reference Data 19986, 5, 246, -., 663-677, 10.1063/1.555965.
  48. Norman I. Krinsky; Singlet oxygen in biological systems. TLivia S. Lazarus; Casey Simons; Ashley Arcidiacono; Abby Benninghoff; Lisa M. Berreau; Extracellular vs Intracellular Delivery of CO: Does It Matter for a Stable, Diffusible Gasotransmitter?. Jourends in Biochemical Scienceal of Medicinal Chemis try 201977, , 62, 35-38, 10.1016/0968-0004(77)90253-5., 9990-9995, 10.1021/acs.jmedchem.9b01254.
  49. Michael J. Davies; Singlet oxygen-mediated damage to proteins and its consequences. Biochemical and Biophysical Research Communications 2003, 305, 761-770, 10.1016/s0006-291x(03)00817-9.
  50. Ivan Blumenthal; Carbon Monoxide Poisoning. Journal of the Royal Society of Medicine 2001, 94, 270-272, 10.1177/014107680109400604.
  51. C. G. Douglas; J. S. Haldane; The laws of combination of haemoglobin with carbon monoxide and oxygen. The Journal of Physiology 1912, 44, 275-304, 10.1113/jphysiol.1912.sp001517.
  52. Bernard, C. . Leçons sur Les Effets des Substances Toxiques et Médicamenteuses; Librairie, J.B., Ed.; Baillière et Fils: Leon, France, 1857; pp. -.
  53. John Haldane; J. Lorrain Smith; The Absorption of Oxygen by the Lungs. The Journal of Physiology 1897, 22, 231-258, 10.1113/jphysiol.1897.sp000689.
  54. Norman Nomof; James Hopper; Ellen Brown; Kenneth Scott; Reidar Wennesland; Simultaneous Determinations of the Total Volume of Red Blood Cells by Use of Carbon Monoxide and Chromium51 IN HEALTHY AND DISEASED HUMAN SUBJECTS1. Journal of Clinical Investigation 1954, 33, 1382-1387, 10.1172/jci103015.
  55. Ronald F. Coburn; THE CARBON MONOXIDE BODY STORES. Annals of the New York Academy of Sciences 1970, 174, 11-22, 10.1111/j.1749-6632.1970.tb49768.x.
  56. Òscar Miró; Jordi Casademont; Antoni Barrientos; Álvaro Urbano-Márquez; Francesc Cardellach; Mitochondrial Cytochrome c Oxidase Inhibition during Acute Carbon Monoxide Poisoning. Pharmacology & Toxicology 1998, 82, 199-202, 10.1111/j.1600-0773.1998.tb01425.x.
  57. J Zhang; C A Piantadosi; Mitochondrial oxidative stress after carbon monoxide hypoxia in the rat brain.. Journal of Clinical Investigation 1992, 90, 1193-1199, 10.1172/jci115980.
  58. S. R. Thom; Carbon monoxide-mediated brain lipid peroxidation in the rat. Journal of Applied Physiology 1990, 68, 997-1003, 10.1152/jappl.1990.68.3.997.
  59. B Rotman; B W Papermaster; Membrane properties of living mammalian cells as studied by enzymatic hydrolysis of fluorogenic esters.. Proceedings of the National Academy of Sciences 1966, 55, 134-141, 10.1073/pnas.55.1.134.
  60. Patrycja Kaczara; Barbara Sitek; Kamil Przyborowski; Anna Kurpinska; Kamil Kus; Marta Stojak; Stefan Chlopicki; Antiplatelet Effect of Carbon Monoxide Is Mediated by NAD + and ATP Depletion. Arteriosclerosis, Thrombosis, and Vascular Biology 2020, 40, 2376-2390, 10.1161/atvbaha.120.314284.
  61. Marialuisa Lavitrano; Ryszard T. Smolenski; Antonino Musumeci; Massimo Maccherini; Ewa Slominska; Ernesto Florio; Adele Bracco; Antonio Mancini; Giorgio Stassi; Mariella Patti; et al.Roberto GiovannoniAlberto FroioFelicetta SimeoneMonica ForniMaria Laura BacciGiuseppe D'AliseEmanuele CozziLeo E. OtterbeinMagdi H. YacoubFritz H. BachFulvio Calise Carbon monoxide improves cardiac energetics and safeguards the heart during reperfusion after cardiopulmonary bypass in pigs. The FASEB Journal 2004, 18, 1093-1095, 10.1096/fj.03-0996fje.
  62. Tung-Yu Tsui; Yeung-Tung Siu; Hans J. Schlitt; Sheung-Tat Fan; Heme oxygenase-1-derived carbon monoxide stimulates adenosine triphosphate generation in human hepatocyte. Biochemical and Biophysical Research Communications 2005, 336, 898-902, 10.1016/j.bbrc.2005.08.187.
  63. Hagit B. Suliman; Martha S. Carraway; Lynn G. Tatro; Claude A. Piantadosi; A new activating role for CO in cardiac mitochondrial biogenesis. Journal of Cell Science 2007, 120, 299-308, 10.1242/jcs.03318.
  64. Cláudia Sf Queiroga; Ana S Almeida; Paula M Alves; Catherine Brenner; Helena LA Vieira; Carbon monoxide prevents hepatic mitochondrial membrane permeabilization. BMC Cell Biology 2011, 12, 10-10, 10.1186/1471-2121-12-10.
  65. Ruiping Song; Raja S. Mahidhara; Fang Liu; Wen Ning; Leo E. Otterbein; Augustine M. K. Choi; Carbon Monoxide Inhibits Human Airway Smooth Muscle Cell Proliferation via Mitogen-Activated Protein Kinase Pathway. American Journal of Respiratory Cell and Molecular Biology 2002, 27, 603-610, 10.1165/rcmb.4851.
  66. Hyun-Ock Pae; Gi-Su Oh; Byung-Min Choi; Soo-Cheon Chae; Young-Myeong Kim; Khee-Rhin Chung; Hun-Taeg Chung; Carbon Monoxide Produced by Heme Oxygenase-1 Suppresses T Cell Proliferation via Inhibition of IL-2 Production. The Journal of Immunology 2004, 172, 4744-4751, 10.4049/jimmunol.172.8.4744.
  67. Francis Wilkinson; W. Phillip Helman; Alberta B. Ross; Rate Constants for the Decay and Reactions of the Lowest Electronically Excited Singlet State of Molecular Oxygen in Solution. An Expanded and Revised Compilation. Journal of Physical and Chemical Reference Data 1995, 24, 663-677, 10.1063/1.555965.
  68. Livia S. Lazarus; Casey Simons; Ashley Arcidiacono; Abby Benninghoff; Lisa M. Berreau; Extracellular vs Intracellular Delivery of CO: Does It Matter for a Stable, Diffusible Gasotransmitter?. Journal of Medicinal Chemistry 2019, 62, 9990-9995, 10.1021/acs.jmedchem.9b01254.
  69. Oskar Steinwall; Igor Klatzo; Selective Vulnerability of the Blood-Brain Barrier in Chemically Induced Lesions*. Journal of Neuropathology & Experimental Neurology 1966, 25, 542-559, 10.1097/00005072-196610000-00004.
  70. Richard H. Adamson; The acute lethal dose 50 (LD50) of caffeine in albino rats. Regulatory Toxicology and Pharmacology 2016, 80, 274-276, 10.1016/j.yrtph.2016.07.011.
  71. E Walum; Acute oral toxicity.. Environmental Health Perspectives 1998, 106, 497-503, 10.1289/ehp.98106497.
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