Cobalt intoxication can occur after its release from metal-based prostheses, which is generally clinically severe. Therefore, there is a need for the development of a cobalt chelator since there are currently no approved drugs for cobalt intoxication. As flavonoids are known for their metal chelating properties and safety, the screening of cobalt chelating properties was performed in a total of 23 flavonoids by our recently developed new spectrophotometric assay. Further assessment of positive or negative consequences of cobalt chelation was performed both in vitro and ex vivo. Six and thirteen flavonoids significantly chelated cobalt ions at pH 7.5 and 6.8, respectively. Baicalein demonstrated a significant activity even at pH 5.5; however, none of the flavonoids showed chelation at pH 4.5. In general, baicalein and 3-hydroxyflavone were the most active. They also mildly decreased the cobalt-triggered Fenton reaction, but baicalein toxicity toward red blood cells was strongly increased by the addition of cobalt. Quercetin, tested as an example of flavonoid unable to chelate cobalt ions significantly, stimulated both the cobalt-based Fenton reaction and the lysis of erythrocytes in the presence of cobalt. Therefore, 3-hydroxyflavone can serve as a potential template for the development of novel cobalt chelators.

The Department of Pharmaceutical Chemistry and Pharmaceutical Analysis Faculty of Pharmacy in Hradec Králové Charles University Akademika Heyrovského 1203 50005 Hradec Králové Czech Republic

The Department of Pharmacognosy and Pharmaceutical Botany Faculty of Pharmacy in Hradec Králové Charles University Akademika Heyrovského 1203 50005 Hradec Králové Czech Republic

The Department of Pharmacology and Toxicology Faculty of Pharmacy in Hradec Králové Charles University Akademika Heyrovského 1203 50005 Hradec Králové Czech Republic 420 495 067 295

Zobrazit více v PubMed

Paustenbach D. J. Tvermoes B. E. Unice K. M. Finley B. L. Kerger B. D. Crit. Rev. Toxicol. 2013;43:316–362. PubMed

Leyssens L. Vinck B. Van Der Straeten C. Wuyts F. Maes L. Toxicology. 2017;387:43–56. PubMed

Fox K. A. Phillips T. M. Yanta J. H. Abesamis M. G. Clin. Toxicol. (Phila) 2016;54:874–877. PubMed

Kovochich M. Monnot A. Kougias D. G. More S. L. Wilsey J. T. Qiu Q. Q. Perkins L. E. L. Hasgall P. Taneja M. Reverdy E. E. Sague J. Marcello S. Connor K. Scutti J. Christian W. V. Coplan P. Katz L. B. Vreeke M. Calistri-Yeh M. Faiola B. Unice K. Eichenbaum G. Regul. Toxicol. Pharmacol. 2021;122:104910. PubMed

Packer M. Circ.: Heart Failure. 2016;9:e003604. PubMed

Pelclova D. Sklensky M. Janicek P. Lach K. Clin. Toxicol. (Phila) 2012;50:262–265. PubMed

Devlin J. J. Pomerleau A. C. Brent J. Morgan B. W. Deitchman S. Schwartz M. J. Med. Toxicol. 2013;9:405–415. PubMed PMC

Monnot A. D. Kovochich M. Bandara S. B. Wilsey J. T. Christian W. V. Eichenbaum G. Perkins L. E. Hasgall P. Taneja M. Connor K. Regul. Toxicol. Pharmacol. 2021;123:104932. PubMed

Sánchez-Dalmau B. Spencer F. Sánchez-Vela L. Camós-Carreras A. Xarau S. N. Fernández-Valencia J. Arch. Soc. Esp. Oftalmol. (Engl. Ed.) 2021;96:316–320. PubMed

Sanz Pérez M. I. Rico Villoras A. M. Moreno Velasco A. Bartolomé García S. Campo Loarte J. Hip Int. 2019;29:NP1–NP5. PubMed

Umar M. Jahangir N. Khan M. F. Saeed Z. Sultan F. Sultan A. J. Orthop. Surg. (Hong Kong) 2020;28 PubMed

Zheng F. Li Y. Zhang F. Sun Y. Zheng C. Luo Z. Wang Y.-L. Aschner M. Zheng H. Lin L. J. Hazard. Mater. 2021;419 PubMed

Green S. E. Luczak M. W. Morse J. L. DeLoughery Z. Zhitkovich A. Toxicol. Sci. 2013;136:467–477. PubMed PMC

Kasprzak K. S. Free Radical Biol. Med. 2002;32:958–967. PubMed

Biglia A. Morandi V. Monti S. Delvino P. Cavagna L. Montecucco C. Jt., Bone, Spine. 2020;87:652–654. PubMed

Du X. Liu J. Wang Y. Jin M. Ye Q. Toxicol. Ind. Health. 2021;37:280–288. PubMed

Tvermoes B. E. Finley B. L. Unice K. M. Otani J. M. Paustenbach D. J. Galbraith D. A. Food Chem. Toxicol. 2013;53:432–439. PubMed

Choi H. I. Hong J. A. Kim M. S. Lee S. E. Jung S. H. Yoon P. W. Song J. S. Kim J. J. Cardiovasc. Toxicol. 2019;19:82–89. PubMed

Pazzaglia U. E. Apostoli P. Congiu T. Catalani S. Marchese M. Zarattini G. Arch. Orthop. Trauma Surg. 2011;131:1299–1308. PubMed

Kasprzak M. M. Erxleben A. Ochocki J. RSC Adv. 2015;5:45853–45877.

Ross J. A. Kasum C. M. Annu. Rev. Nutr. 2002;22:19–34. PubMed

Fusi F. Trezza A. Tramaglino M. Sgaragli G. Saponara S. Spiga O. Pharmacol. Res. 2020;152:104625. PubMed

Knekt P. Kumpulainen J. Järvinen R. Rissanen H. Heliövaara M. Reunanen A. Hakulinen T. Aromaa A. Am. J. Clin. Nutr. 2002;76:560–568. PubMed

Olszowy M. Plant Biochem. J. 2019;144:135–143. PubMed

Procházková D. Boušová I. Wilhelmová N. Fitoterapia. 2011;82:513–523. PubMed

Wen L. Zhao Y. Jiang Y. Yu L. Zeng X. Yang J. Tian M. Liu H. Yang B. Free Radical Biol. Med. 2017;110:92–101. PubMed

Escandar G. M. Sala L. F. Can. J. Chem. 1991;69:1994–2001.

Liu Y. Guo M. Molecules. 2015;20:8583–8594. PubMed PMC

Vergara V. B. Kalinich J. F. Nutrients. 2021;13:2545. PubMed PMC

Jung J. Y. Mo H. C. Yang K. H. Jeong Y. J. Yoo H. G. Choi N. K. Oh W. M. Oh H. K. Kim S. H. Lee J. H. Kim H. J. Kim W. J. Life Sci. 2007;80:1355–1363. PubMed

Li S. Jiang J. Fang J. Li X. Huang C. Liang W. Wu K. Int. J. Mol. Med. 2021;47:1–11. PubMed

Shi Y. N. Zhang X. Q. Hu Z. Y. Zhang C. J. Liao D. F. Huang H. L. Qin L. Pharmacology. 2019;103:282–290. PubMed

Chen P. Y. Ho Y. R. Wu M. J. Huang S. P. Chen P. K. Tai M. H. Ho C. T. Yen J. H. Food Funct. 2015;6:287–296. PubMed

Ajibade T. O. Oyagbemi A. A. Omobowale T. O. Asenuga E. R. Adigun K. O. Biol. Trace Elem. Res. 2017;175:347–359. PubMed

Akinrinde A. S. Adebiyi O. E. Neurotoxicology. 2019;74:252–263. PubMed

Oyagbemi A. A. Akinrinde A. S. Adebiyi O. E. Jarikre T. A. Omobowale T. O. Ola-Davies O. E. Saba A. B. Emikpe B. O. Adedapo A. A. Environ. Toxicol. Pharmacol. 2020;80:103488. PubMed

Salami A. T. Oyagbemi A. A. Alabi M. V. Olaleye S. B. Biomarkers. 2022:1–13. doi: 10.1080/1354750x.2022.2137235. PubMed DOI

Tanoğlu C. Ersoy A. Çoban T. A. Yazıcı G. N. Mammadov R. Süleyman B. Acta Neurobiol. Exp. (Wars) 2022;82:254–262. PubMed

Kozsup M. Zhou X. Farkas E. Bényei A. C. Bonnet S. Patonay T. Kónya K. Buglyó P. J. Inorg. Biochem. 2021;217:111382. PubMed

Crozier A. Del Rio D. Clifford M. N. Mol. Aspects Med. 2010;31:446–467. PubMed

Lomozová Z. Hrubša M. Conte P. F. Papastefanaki E. Moravcova M. Catapano M. C. Silvestri I. P. Karlíčková J. Kučera R. Macáková K. Food Chem. 2022;394:133461. PubMed

Macáková K. Mladěnka P. Filipský T. Říha M. Jahodář L. Trejtnar F. Bovicelli P. Proietti Silvestri I. Hrdina R. Saso L. Food Chem. 2012;135:2584–2592. PubMed

Parejo I. Codina C. Petrakis C. Kefalas P. J. Pharmacol. Toxicol. Methods. 2000;44:507–512. PubMed

Moravcová M. Hrubša M. Lomozová Z. Catapano M. C. Argento R. Jirkovský E. Kučera R. Mercolini L. Mladěnka P. Med. Chem. 2023;19:495–507. PubMed

Li H. Lu Z. Cheng G. Rong K. Chen F. Chen R. RSC Adv. 2015;5:5059–5067.

Lomozová Z. Catapano M. C. Hrubša M. Karlíčková J. Macáková K. Kučera R. Mladěnka P. J. Agric. Food Chem. 2021;69:5926–5937. PubMed

Mladenka P. Karlickova J. Hrubsa M. Veljovic E. Muratovic S. Carazo A. Mali A. S. Spirtovic-Halilovic S. Saso L. Pour M. Duric K. Appl. Sci. 2020;10:4846.

Sundaram R. L. Sali V. K. Vasanthi H. R. Phytomedicine. 2018;51:196–204. PubMed

Seo S. Seo K. Ki S. H. Shin S. M. Biol. Pharm. Bull. 2016;39:1830–1838. PubMed

Wang B. Zou Y. Yuan Z. L. Xiao J. G. J. Ocul. Pharmacol. Ther. 2003;19:457–464. PubMed

Osada M. Imaoka S. Funae Y. FEBS Lett. 2004;575:59–63. PubMed

Crispo J. A. Ansell D. R. Piche M. Eibl J. K. Khaper N. Ross G. M. Tai T. C. Can. J. Physiol. Pharmacol. 2010;88:429–438. PubMed

Babich H. Gold T. Gold R. Toxicol. Lett. 2005;155:195–205. PubMed

Mladěnka P. Macáková K. Filipský T. Zatloukalová L. Jahodář L. Bovicelli P. Silvestri I. P. Hrdina R. Saso L. J. Inorg. Biochem. 2011;105:693–701. PubMed

Říha M. Karlíčková J. Filipský T. Macáková K. Rocha L. Bovicelli P. Silvestri I. P. Saso L. Jahodář L. Hrdina R. RSC Adv. 2014;4:32628–32638.

Chirug L. Eran Nagar E. Okun Z. Shpigelman A. Food Hydrocolloids. 2021;116:106654.

da Silva W. M. B. de Oliveira Pinheiro S. Alves D. R. de Menezes J. E. S. A. Magalhães F. E. A. Silva F. C. O. Silva J. Marinho E. S. de Morais S. M. Neurotoxic. Res. 2020;37:893–903. PubMed

Hrubša M. Tvrdý V. Kutý M. Valentová K. Křen V. Mladěnka P. J. Agric. Food Chem. 2022;70:6134–6144. PubMed