The potential of nanomaterials use is huge, especially in fields such as medicine or industry. Due to widespread use of nanomaterials, their cytotoxicity and involvement in cellular pathways ought to be evaluated in detail. Nanomaterials can induce the production of a number of substances in cells, including reactive oxygen species (ROS), participating in physiological and pathological cellular processes. These highly reactive substances include: superoxide, singlet oxygen, hydroxyl radical, and hydrogen peroxide. For overall assessment, there are a number of fluorescent probes in particular that are very specific and selective for given ROS. In addition, due to the involvement of ROS in a number of cellular signaling pathways, understanding the principle of ROS production induced by nanomaterials is very important. For defense, the cells have a number of reparative and especially antioxidant mechanisms. One of the most potent antioxidants is a tripeptide glutathione. Thus, the glutathione depletion can be a characteristic manifestation of harmful effects caused by the prooxidative-acting of nanomaterials in cells. For these reasons, here we would like to provide a review on the current knowledge of ROS-mediated cellular nanotoxicity manifesting as glutathione depletion, including an overview of approaches for the detection of ROS levels in cells.

Department of Biological and Biochemical Sciences Faculty of Chemical Technology University of Pardubice Studentska 573 532 10 Pardubice Czech Republic

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Hayyan M., Hashim M.A., AlNashef I.M. Superoxide Ion: Generation and Chemical Implications. Chem. Rev. 2016;116:3029–3085. doi: 10.1021/acs.chemrev.5b00407. PubMed DOI

Lushchak V.I. Free radicals, reactive oxygen species, oxidative stress and its classification. Chem. Biol. Interact. 2014;224:164–175. doi: 10.1016/j.cbi.2014.10.016. PubMed DOI

Juan C.A., Perez de la Lastra J.M., Plou F.J., Perez-Lebena E. The Chemistry of Reactive Oxygen Species (ROS) Revisited: Outlining Their Role in Biological Macromolecules (DNA, Lipids and Proteins) and Induced Pathologies. Int. J. Mol. Sci. 2021;22:4642. doi: 10.3390/ijms22094642. PubMed DOI PMC

Simon H.U., Haj-Yehia A., Levi-Schaffer F. Role of reactive oxygen species (ROS) in apoptosis induction. Apoptosis. 2000;5:415–418. doi: 10.1023/A:1009616228304. PubMed DOI

Wagner H., Cheng J.W., Ko E.Y. Role of reactive oxygen species in male infertility: An updated review of literature. Arab. J. Urol. 2018;16:35–43. doi: 10.1016/j.aju.2017.11.001. PubMed DOI PMC

Ott M., Gogvadze V., Orrenius S., Zhivotovsky B. Mitochondria, oxidative stress and cell death. Apoptosis. 2007;12:913–922. doi: 10.1007/s10495-007-0756-2. PubMed DOI

Zhao R.Z., Jiang S., Zhang L., Yu Z.B. Mitochondrial electron transport chain, ROS generation and uncoupling (Review) Int. J. Mol. Med. 2019;44:3–15. doi: 10.3892/ijmm.2019.4188. PubMed DOI PMC

Suski J., Lebiedzinska M., Bonora M., Pinton P., Duszynski J., Wieckowski M.R. Relation Between Mitochondrial Membrane Potential and ROS Formation. Methods Mol. Biol. 2018;1782:357–381. PubMed

Mazat J.P., Devin A., Ransac S. Modelling mitochondrial ROS production by the respiratory chain. Cell Mol. Life Sci. 2020;77:455–465. doi: 10.1007/s00018-019-03381-1. PubMed DOI PMC

Parey K., Wirth C., Vonck J., Zickermann V. Respiratory complex I—structure, mechanism and evolution. Curr. Opin. Struct. Biol. 2020;63:1–9. doi: 10.1016/j.sbi.2020.01.004. PubMed DOI

Husen P., Nielsen C., Martino C.F., Solov’yov I.A. Molecular Oxygen Binding in the Mitochondrial Electron Transfer Flavoprotein. J. Chem. Inf. Model. 2019;59:4868–4879. doi: 10.1021/acs.jcim.9b00702. PubMed DOI

Mailloux R.J. An Update on Mitochondrial Reactive Oxygen Species Production. Antioxidants. 2020;9:472. doi: 10.3390/antiox9060472. PubMed DOI PMC

Papa S., Skulachev V.P. Reactive oxygen species, mitochondria, apoptosis and aging. Mol. Cell BioChem. 1997;174:305–319. doi: 10.1023/A:1006873518427. PubMed DOI

Ventura J.J., Cogswell P., Flavell R.A., Baldwin A.S., Jr., Davis R.J. JNK potentiates TNF-stimulated necrosis by increasing the production of cytotoxic reactive oxygen species. Genes Dev. 2004;18:2905–2915. doi: 10.1101/gad.1223004. PubMed DOI PMC

Zhang M., Harashima N., Moritani T., Huang W., Harada M. The Roles of ROS and Caspases in TRAIL-Induced Apoptosis and Necroptosis in Human Pancreatic Cancer Cells. PLoS ONE. 2015;10:e0127386. doi: 10.1371/journal.pone.0127386. PubMed DOI PMC

Yang J., Zhao X., Tang M., Li L., Lei Y., Cheng P., Guo W., Zheng Y., Wang W., Luo N., et al. The role of ROS and subsequent DNA-damage response in PUMA-induced apoptosis of ovarian cancer cells. Oncotarget. 2017;8:23492–23506. doi: 10.18632/oncotarget.15626. PubMed DOI PMC

Liou G.Y., Storz P. Reactive oxygen species in cancer. Free Radic. Res. 2010;44:479–496. doi: 10.3109/10715761003667554. PubMed DOI PMC

Storz P. Reactive oxygen species in tumor progression. Front. BioSci. 2005;10:1881–1896. doi: 10.2741/1667. PubMed DOI

Zhou B., Guo X., Yang N., Huang Z., Huang L., Fang Z., Zhang C., Li L., Yu C. Surface engineering strategies of gold nanomaterials and their applications in biomedicine and detection. J. Mater. Chem. B. 2021;9:5583–5598. doi: 10.1039/D1TB00181G. PubMed DOI

Sakr T.M., Korany M., Katti K.V. Selenium nanomaterials in biomedicine—An overview of new opportunities in nanomedicine of selenium. J. Drug Deliv. Sci. Technol. 2018;46:223–233. doi: 10.1016/j.jddst.2018.05.023. DOI

Mehlenbacher R.D., Kolbl R., Lay A., Dionne J.A. Nanomaterials for in vivo imaging of mechanical forces and electrical fields. Nat. Rev. Mater. 2017;3:1–17. doi: 10.1038/natrevmats.2017.80. DOI

Musial J., Krakowiak R., Mlynarczyk D.T., Goslinski T., Stanisz B.J. Titanium Dioxide Nanoparticles in Food and Personal Care Products-What Do We Know about Their Safety? Nanomaterials. 2020;10:1110. doi: 10.3390/nano10061110. PubMed DOI PMC

Holmila R.J., Vance S.A., King S.B., Tsang A.W., Singh R., Furdui C.M. Silver Nanoparticles Induce Mitochondrial Protein Oxidation in Lung Cells Impacting Cell Cycle and Proliferation. Antioxidants. 2019;8:552. doi: 10.3390/antiox8110552. PubMed DOI PMC

Drasler B., Sayre P., Steinhäuser K.G., Petri-Fink A., Rothen-Rutishauser B. In vitro approaches to assess the hazard of nanomaterials. NanoImpact. 2017;8:99–116. doi: 10.1016/j.impact.2017.08.002. DOI

Yin J.J., Liu J., Ehrenshaft M., Roberts J.E., Fu P.P., Mason R.P., Zhao B. Phototoxicity of nano titanium dioxides in HaCaT keratinocytes--generation of reactive oxygen species and cell damage. Toxicol. Appl. Pharmacol. 2012;263:81–88. doi: 10.1016/j.taap.2012.06.001. PubMed DOI PMC

Ray P.C., Yu H.T., Fu P.P. Toxicity and Environmental Risks of Nanomaterials: Challenges and Future Needs. J. Environ. Sci. Health C. 2009;27:1–35. doi: 10.1080/10590500802708267. PubMed DOI PMC

Daimon T., Nosaka Y. Formation and behavior of singlet molecular oxygen in TiO2 photocatalysis studied by detection of near-infrared phosphorescence. J. Phys. Chem. C. 2007;111:4420–4424. doi: 10.1021/jp070028y. DOI

Phaniendra A., Jestadi D.B., Periyasamy L. Free Radicals: Properties, Sources, Targets, and Their Implication in Various Diseases. Indian J. Clin. Biochem. 2015;30:11–26. doi: 10.1007/s12291-014-0446-0. PubMed DOI PMC

Yang H., Liu C., Yang D., Zhang H., Xi Z. Comparative study of cytotoxicity, oxidative stress and genotoxicity induced by four typical nanomaterials: The role of particle size, shape and composition. J. Appl. Toxicol. 2009;29:69–78. doi: 10.1002/jat.1385. PubMed DOI

He X., Sanders S., Aker W.G., Lin Y., Douglas J., Hwang H.M. Assessing the effects of surface-bound humic acid on the phototoxicity of anatase and rutile TiO2 nanoparticles in vitro. J. Environ. Sci. 2016;42:50–60. doi: 10.1016/j.jes.2015.05.028. PubMed DOI

Zhang J., Wang B., Wang H., He H., Wu Q., Qin X., Yang X., Chen L., Xu G., Yuan Z., et al. Disruption of the superoxide anions-mitophagy regulation axis mediates copper oxide nanoparticles-induced vascular endothelial cell death. Free Radic. Biol. Med. 2018;129:268–278. doi: 10.1016/j.freeradbiomed.2018.09.032. PubMed DOI

Onodera A., Nishiumi F., Kakiguchi K., Tanaka A., Tanabe N., Honma A., Yayama K., Yoshioka Y., Nakahira K., Yonemura S., et al. Short-term changes in intracellular ROS localisation after the silver nanoparticles exposure depending on particle size. Toxicol. Rep. 2015;2:574–579. doi: 10.1016/j.toxrep.2015.03.004. PubMed DOI PMC

Ahamed M., Akhtar M.J., Raja M., Ahmad I., Siddiqui M.K., AlSalhi M.S., Alrokayan S.A. ZnO nanorod-induced apoptosis in human alveolar adenocarcinoma cells via p53, survivin and bax/bcl-2 pathways: Role of oxidative stress. Nanomedicine. 2011;7:904–913. doi: 10.1016/j.nano.2011.04.011. PubMed DOI

Jimenez-Relinque E., Castellote M. Hydroxyl radical and free and shallowly trapped electron generation and electron/hole recombination rates in TiO2 photocatalysis using different combinations of anatase and rutile. Appl. Catal. A Gen. 2018;565:20–25. doi: 10.1016/j.apcata.2018.07.045. DOI

Thit A., Selck H., Bjerregaard H.F. Toxic mechanisms of copper oxide nanoparticles in epithelial kidney cells. Toxicol. In Vitro. 2015;29:1053–1059. doi: 10.1016/j.tiv.2015.03.020. PubMed DOI

Thubagere A., Reinhard B.M. Nanoparticle-induced apoptosis propagates through hydrogen-peroxide-mediated bystander killing: Insights from a human intestinal epithelium in vitro model. ACS Nano. 2010;4:3611–3622. doi: 10.1021/nn100389a. PubMed DOI

Gao W., Xu K., Ji L., Tang B. Effect of gold nanoparticles on glutathione depletion-induced hydrogen peroxide generation and apoptosis in HL7702 cells. Toxicol. Lett. 2011;205:86–95. doi: 10.1016/j.toxlet.2011.05.1018. PubMed DOI

Wang J.X., Fan Y.B., Gao Y., Hu Q.H., Wang T.C. TiO2 nanoparticles translocation and potential toxicological effect in rats after intraarticular injection. Biomaterials. 2009;30:4590–4600. doi: 10.1016/j.biomaterials.2009.05.008. PubMed DOI

Guo D., Bi H., Liu B., Wu Q., Wang D., Cui Y. Reactive oxygen species-induced cytotoxic effects of zinc oxide nanoparticles in rat retinal ganglion cells. Toxicol. In Vitro. 2013;27:731–738. doi: 10.1016/j.tiv.2012.12.001. PubMed DOI

Yang E.J., Kim S., Kim J.S., Choi I.H. Inflammasome formation and IL-1beta release by human blood monocytes in response to silver nanoparticles. Biomaterials. 2012;33:6858–6867. doi: 10.1016/j.biomaterials.2012.06.016. PubMed DOI

Hirakawa K., Hirano T. Singlet oxygen generation photocatalyzed by TiO2 particles and its contribution to biomolecule damage. Chem. Lett. 2006;35:832–833. doi: 10.1246/cl.2006.832. DOI

Lee S.H., Jun B.H. Silver Nanoparticles: Synthesis and Application for Nanomedicine. Int. J. Mol. Sci. 2019;20:865. doi: 10.3390/ijms20040865. PubMed DOI PMC

Zhou Z., Song J., Tian R., Yang Z., Yu G., Lin L., Zhang G., Fan W., Zhang F., Niu G., et al. Activatable Singlet Oxygen Generation from Lipid Hydroperoxide Nanoparticles for Cancer Therapy. Angew. Chem. Int. Ed. Engl. 2017;56:6492–6496. doi: 10.1002/anie.201701181. PubMed DOI PMC

Abdal Dayem A., Hossain M.K., Lee S.B., Kim K., Saha S.K., Yang G.M., Choi H.Y., Cho S.G. The Role of Reactive Oxygen Species (ROS) in the Biological Activities of Metallic Nanoparticles. Int. J. Mol. Sci. 2017;18:120. doi: 10.3390/ijms18010120. PubMed DOI PMC

Kermanizadeh A., Jantzen K., Ward M.B., Durhuus J.A., Juel Rasmussen L., Loft S., Moller P. Nanomaterial-induced cell death in pulmonary and hepatic cells following exposure to three different metallic materials: The role of autophagy and apoptosis. Nanotoxicology. 2017;11:184–200. doi: 10.1080/17435390.2017.1279359. PubMed DOI

Ge D., Du Q., Ran B., Liu X., Wang X., Ma X., Cheng F., Sun B. The neurotoxicity induced by engineered nanomaterials. Int. J. Nanomed. 2019;14:4167–4186. doi: 10.2147/IJN.S203352. PubMed DOI PMC

Fridovich I. Biological effects of the superoxide radical. Arch. BioChem. Biophys. 1986;247:1–11. doi: 10.1016/0003-9861(86)90526-6. PubMed DOI

Apel K., Hirt H. Reactive oxygen species: Metabolism, oxidative stress, and signal transduction. Annu. Rev. Plant. Biol. 2004;55:373–399. doi: 10.1146/annurev.arplant.55.031903.141701. PubMed DOI

McIntyre M., Bohr D.F., Dominiczak A.F. Endothelial function in hypertension: The role of superoxide anion. Hypertension. 1999;34:539–545. doi: 10.1161/01.HYP.34.4.539. PubMed DOI

Bielski B.H.J., Cabelli D.E. Superoxide and Hydroxyl Radical Chemistry in Aqueous Solution. Act. Oxyg. Chem. 1995;2:66–104.

Ahsan H., Ali A., Ali R. Oxygen free radicals and systemic autoimmunity. Clin. Exp. Immunol. 2003;131:398–404. doi: 10.1046/j.1365-2249.2003.02104.x. PubMed DOI PMC

Perry J.J.P., Shin D.S., Getzoff E.D., Tainer J.A. The structural biochemistry of the superoxide dismutases. Bba-Proteins Proteom. 2010;1804:245–262. doi: 10.1016/j.bbapap.2009.11.004. PubMed DOI PMC

Borgstahl G.E.O., Oberley-Deegan R.E. Superoxide Dismutases (SODs) and SOD Mimetics. Antioxidants. 2018;7:156. doi: 10.3390/antiox7110156. PubMed DOI PMC

Landis G.N., Tower J. Superoxide dismutase evolution and life span regulation. Mech. Ageing Dev. 2005;126:365–379. doi: 10.1016/j.mad.2004.08.012. PubMed DOI

Loschen G., Flohe L., Chance B. Respiratory Chain Linked H2o2 Production in Pigeon Heart Mitochondria. FEBS Lett. 1971;18:261–264. doi: 10.1016/0014-5793(71)80459-3. PubMed DOI

Loschen G., Azzi A., Richter C., Flohe L. Superoxide Radicals as Precursors of Mitochondrial Hydrogen-Peroxide. FEBS Lett. 1974;42:68–72. doi: 10.1016/0014-5793(74)80281-4. PubMed DOI

Wilson D.F., Erecinska M., Dutton P.L. Thermodynamic Relationships in Mitochondrial Oxidative-Phosphorylation. Annu. Rev. Biophys. Bio. 1974;3:203–230. doi: 10.1146/annurev.bb.03.060174.001223. PubMed DOI

Ballard J.W., Youngson N.A. Review: Can diet influence the selective advantage of mitochondrial DNA haplotypes? Biosci. Rep. 2015;35 doi: 10.1042/BSR20150232. PubMed DOI PMC

Liu Y.B., Fiskum G., Schubert D. Generation of reactive oxygen species by the mitochondrial electron transport chain. J. NeuroChem. 2002;80:780–787. doi: 10.1046/j.0022-3042.2002.00744.x. PubMed DOI

Kushnareva Y., Murphy A.N., Andreyev A. Complex I-mediated reactive oxygen species generation: Modulation by cytochrome c and NAD(P)+ oxidation-reduction state. Biochem. J. 2002;368:545–553. doi: 10.1042/bj20021121. PubMed DOI PMC

Murphy M.P. How mitochondria produce reactive oxygen species. Biochem. J. 2009;417:1–13. doi: 10.1042/BJ20081386. PubMed DOI PMC

Wikstrom M.K., Berden J.A. Oxidoreduction of cytochrome b in the presence of antimycin. Biochim. Biophys. Acta. 1972;283:403–420. doi: 10.1016/0005-2728(72)90258-7. PubMed DOI

Muller F., Crofts A.R., Kramer D.M. Multiple Q-cycle bypass reactions at the Qo site of the cytochiome bc1 complex. Biochemistry. 2002;41:7866–7874. doi: 10.1021/bi025581e. PubMed DOI

Bleier L., Drose S. Superoxide generation by complex III: From mechanistic rationales to functional consequences. Biochim. Biophys. Acta. 2013;1827:1320–1331. doi: 10.1016/j.bbabio.2012.12.002. PubMed DOI

Grzelak A., Wojewodzka M., Meczynska-Wielgosz S., Zuberek M., Wojciechowska D., Kruszewski M. Crucial role of chelatable iron in silver nanoparticles induced DNA damage and cytotoxicity. Redox Biol. 2018;15:435–440. doi: 10.1016/j.redox.2018.01.006. PubMed DOI PMC

Jayaram D.T., Payne C.K. Intracellular Generation of Superoxide by TiO2 Nanoparticles Decreases Histone Deacetylase 9 (HDAC9), an Epigenetic Modifier. Bioconjug. Chem. 2020;31:1354–1361. doi: 10.1021/acs.bioconjchem.0c00091. PubMed DOI

Masoud R., Bizouarn T., Trepout S., Wien F., Baciou L., Marco S., Houee Levin C. Titanium Dioxide Nanoparticles Increase Superoxide Anion Production by Acting on NADPH Oxidase. PLoS ONE. 2015;10:e0144829. doi: 10.1371/journal.pone.0144829. PubMed DOI PMC

Akhtar M.J., Kumar S., Alhadlaq H.A., Alrokayan S.A., Abu-Salah K.M., Ahamed M. Dose-dependent genotoxicity of copper oxide nanoparticles stimulated by reactive oxygen species in human lung epithelial cells. Toxicol. Ind. Health. 2016;32:809–821. doi: 10.1177/0748233713511512. PubMed DOI

Piret J.P., Jacques D., Audinot J.N., Mejia J., Boilan E., Noel F., Fransolet M., Demazy C., Lucas S., Saout C., et al. Copper (II) oxide nanoparticles penetrate into HepG2 cells, exert cytotoxicity via oxidative stress and induce pro-inflammatory response. Nanoscale. 2012;4:7168–7184. doi: 10.1039/c2nr31785k. PubMed DOI

Piao M.J., Kang K.A., Lee I.K., Kim H.S., Kim S., Choi J.Y., Choi J., Hyun J.W. Silver nanoparticles induce oxidative cell damage in human liver cells through inhibition of reduced glutathione and induction of mitochondria-involved apoptosis. Toxicol. Lett. 2011;201:92–100. doi: 10.1016/j.toxlet.2010.12.010. PubMed DOI

Zielonka J., Srinivasan S., Hardy M., Ouari O., Lopez M., Vasquez-Vivar J., Avadhani N.G., Kalyanaraman B. Cytochrome c-mediated oxidation of hydroethidine and mito-hydroethidine in mitochondria: Identification of homo- and heterodimers. Free Radic. Biol. Med. 2008;44:835–846. doi: 10.1016/j.freeradbiomed.2007.11.013. PubMed DOI PMC

Ross M.F., Kelso G.F., Blaikie F.H., James A.M., Cocheme H.M., Filipovska A., Da Ros T., Hurd T.R., Smith R.A.J., Murphy M.P. Lipophilic triphenylphosphonium cations as tools in mitochondrial bioenergetics and free radical biology. Biochemistry. 2005;70:222–230. doi: 10.1007/s10541-005-0104-5. PubMed DOI

Robinson K.M., Janes M.S., Pehar M., Monette J.S., Ross M.F., Hagen T.M., Murphy M.P., Beckman J.S. Selective fluorescent imaging of superoxide in vivo using ethidium-based probes. Proc. Natl. Acad. Sci. USA. 2006;103:15038–15043. doi: 10.1073/pnas.0601945103. PubMed DOI PMC

Kauffman M.E., Kauffman M.K., Traore K., Zhu H., Trush M.A., Jia Z., Li Y.R. MitoSOX-Based Flow Cytometry for Detecting Mitochondrial ROS. React. Oxyg. Species. 2016;2:361–370. doi: 10.20455/ros.2016.865. PubMed DOI PMC

Mukhopadhyay P., Rajesh M., Yoshihiro K., Hasko G., Pacher P. Simple quantitative detection of mitochondrial superoxide production in live cells. BioChem. Biophys. Res. Commun. 2007;358:203–208. doi: 10.1016/j.bbrc.2007.04.106. PubMed DOI PMC

Roelofs B.A., Ge S.X., Studlack P.E., Polster B.M. Low micromolar concentrations of the superoxide probe MitoSOX uncouple neural mitochondria and inhibit complex IV. Free Radic. Biol. Med. 2015;86:250–258. doi: 10.1016/j.freeradbiomed.2015.05.032. PubMed DOI PMC

Ohyashiki T., Nunomura M., Katoh T. Detection of superoxide anion radical in phospholipid liposomal membrane by fluorescence quenching method using 1,3-diphenylisobenzofuran. Bba-Biomembranes. 1999;1421:131–139. doi: 10.1016/S0005-2736(99)00119-4. PubMed DOI

Krieg M. Determination of singlet oxygen quantum yields with 1,3-diphenylisobenzofuran in model membrane systems. J. BioChem. Biophys. Methods. 1993;27:143–149. doi: 10.1016/0165-022X(93)90058-V. PubMed DOI

Zamojc K., Zdrowowicz M., Rudnicki-Velasquez P.B., Krzyminski K., Zaborowski B., Niedzialkowski P., Jacewicz D., Chmurzynski L. The development of 1,3-diphenylisobenzofuran as a highly selective probe for the detection and quantitative determination of hydrogen peroxide. Free Radic. Res. 2017;51:38–46. doi: 10.1080/10715762.2016.1262541. PubMed DOI

Andresen M., Regueira T., Bruhn A., Perez D., Strobel P., Dougnac A., Marshall G., Leighton F. Lipoperoxidation and protein oxidative damage exhibit different kinetics during septic shock. Mediat. Inflamm. 2008 doi: 10.1155/2008/168652. PubMed DOI PMC

Wu D.F., Cederbaum A.I. Alcohol, oxidative stress, and free radical damage. Alcohol. Res. Health. 2003;27:277–284. PubMed PMC

Halliwell B., Chirico S. Lipid-Peroxidation ― Its Mechanism, Measurement, and Significance. Am. J. Clin. Nutr. 1993;57:715–725. doi: 10.1093/ajcn/57.5.715S. PubMed DOI

Wang X., Zhang L. Kinetic study of hydroxyl radical formation in a continuous hydroxyl generation system. RSC Adv. 2018;8:40632–40638. doi: 10.1039/C8RA08511K. PubMed DOI PMC

Kehrer J.P. The Haber-Weiss reaction and mechanisms of toxicity. Toxicology. 2000;149:43–50. doi: 10.1016/S0300-483X(00)00231-6. PubMed DOI

Weinstein J., Bielski B.H.J. Kinetics of the Interaction of Ho2 and O2-Radicals with Hydrogen-Peroxide—Haber-Weiss Reaction. J. Am. Chem. Soc. 1979;101:58–62. doi: 10.1021/ja00495a010. DOI

Koppenol W.H. The Haber-Weiss cycle—70 years later. Redox Rep. 2001;6:229–234. doi: 10.1179/135100001101536373. PubMed DOI

Fischbacher A., von Sonntag C., Schmidt T.C. Hydroxyl radical yields in the Fenton process under various pH, ligand concentrations and hydrogen peroxide/Fe (II) ratios. Chemosphere. 2017;182:738–744. doi: 10.1016/j.chemosphere.2017.05.039. PubMed DOI

Wang T., Zhang H., Liu H., Yuan Q., Ren F., Han Y., Sun Q., Li Z., Gao M. Boosting H2O2-Guided Chemodynamic Therapy of Cancer by Enhancing Reaction Kinetics through Versatile Biomimetic Fenton Nanocatalysts and the Second Near-Infrared Light Irradiation. Adv. Funct. Mater. 2019;30 doi: 10.1002/adfm.201906128. DOI

Li X., Hao S.J., Han A.L., Yang Y.Y., Fang G.Z., Liu J.F., Wang S. Intracellular Fenton reaction based on mitochondria-targeted copper (II)-peptide complex for induced apoptosis. J. Mater. Chem. B. 2019;7:4008–4016. doi: 10.1039/C9TB00569B. DOI

Hackenberg S., Scherzed A., Technau A., Kessler M., Froelich K., Ginzkey C., Koehler C., Burghartz M., Hagen R., Kleinsasser N. Cytotoxic, genotoxic and pro-inflammatory effects of zinc oxide nanoparticles in human nasal mucosa cells in vitro. Toxicol. In Vitro. 2011;25:657–663. doi: 10.1016/j.tiv.2011.01.003. PubMed DOI

Ekici S., Turkarslan S., Pawlik G., Dancis A., Baliga N.S., Koch H.G., Daldal F. Intracytoplasmic copper homeostasis controls cytochrome c oxidase production. mBio. 2014;5 doi: 10.1128/mBio.01055-13. PubMed DOI PMC

Huang G., Chen H., Dong Y., Luo X., Yu H., Moore Z., Bey E.A., Boothman D.A., Gao J. Superparamagnetic iron oxide nanoparticles: Amplifying ROS stress to improve anticancer drug efficacy. Theranostics. 2013;3:116–126. doi: 10.7150/thno.5411. PubMed DOI PMC

Lehman S.E., Morris A.S., Mueller P.S., Salem A.K., Grassian V.H., Larsen S.C. Silica nanoparticle-generated ROS as a predictor of cellular toxicity: Mechanistic insights and safety by design. Environ. Sci-Nano. 2016;3:56–66. doi: 10.1039/C5EN00179J. PubMed DOI PMC

Chairuangkitti P., Lawanprasert S., Roytrakul S., Aueviriyavit S., Phummiratch D., Kulthong K., Chanvorachote P., Maniratanachote R. Silver nanoparticles induce toxicity in A549 cells via ROS-dependent and ROS-independent pathways. Toxicol. In Vitro. 2013;27:330–338. doi: 10.1016/j.tiv.2012.08.021. PubMed DOI

Fang X.W., Mark G., von Sonntag C. OH radical formation by ultrasound in aqueous solutions Part І: The chemistry underlying the terephthalate dosimeter. Ultrason. SonoChem. 1996;3:57–63. doi: 10.1016/1350-4177(95)00032-1. DOI

Yan E.B., Unthank J.K., Castillo-Melendez M., Miller S.L., Langford S.J., Walker D.W. Novel method for in vivo hydroxyl radical measurement by microdialysis in fetal sheep brain in utero. J. Appl. Physiol. 2005;98:2304–2310. doi: 10.1152/japplphysiol.00617.2004. PubMed DOI

Yapici N.B., Jockusch S., Moscatelli A., Mandalapu S.R., Itagaki Y., Bates D.K., Wiseman S., Gibson K.M., Turro N.J., Bi L.R. New Rhodamine Nitroxide Based Fluorescent Probes for Intracellular Hydroxyl Radical Identification in Living Cells. Org. Lett. 2012;14:50–53. doi: 10.1021/ol202816m. PubMed DOI

Bai X.Y., Huang Y.Y., Lu M.Y., Yang D. HKOH-1: A Highly Sensitive and Selective Fluorescent Probe for Detecting Endogenous Hydroxyl Radicals in Living Cells. Angew. Chem. Int. Ed. 2017;56:12873–12877. doi: 10.1002/anie.201705873. PubMed DOI

Cheng X., Guo H., Zhang Y., Wu X., Liu Y. Non-photochemical production of singlet oxygen via activation of persulfate by carbon nanotubes. Water Res. 2017;113:80–88. doi: 10.1016/j.watres.2017.02.016. PubMed DOI

Cadenas E. Biochemistry of Oxygen-Toxicity. Annu. Rev. BioChem. 1989;58:79–110. doi: 10.1146/annurev.bi.58.070189.000455. PubMed DOI

Agnez-Lima L.F., Melo J.T.A., Silva A.E., Oliveira A.H.S., Timoteo A.R.S., Lima-Bessa K.M., Martinez G.R., Medeiros M.H.G., Di Mascio P., Galhardo R.S., et al. DNA damage by singlet oxygen and cellular protective mechanisms. Mutat. Res. Rev. Mutat. 2012;751:15–28. doi: 10.1016/j.mrrev.2011.12.005. PubMed DOI

Hampton M.B., Kettle A.J., Winterbourn C.C. Inside the neutrophil phagosome: Oxidants, myeloperoxidase, and bacterial killing. Blood. 1998;92:3007–3017. doi: 10.1182/blood.V92.9.3007. PubMed DOI

Bigot E., Bataille R., Patrice T. Increased singlet oxygen-induced secondary ROS production in the serum of cancer patients. J. PhotoChem. PhotoBiol. B. 2012;107:14–19. doi: 10.1016/j.jphotobiol.2011.11.003. PubMed DOI

Sies H., Menck C.F.M. Singlet Oxygen Induced DNA Damage. Mutat Res. 1992;275:367–375. doi: 10.1016/0921-8734(92)90039-R. PubMed DOI

Kanofsky J.R. Singlet Oxygen Production by Biological-Systems. Chem. Biol. Interact. 1989;70:1–28. doi: 10.1016/0009-2797(89)90059-8. PubMed DOI

Dumont E., Gruber R., Bignon E., Morell C., Moreau Y., Monari A., Ravanat J.L. Probing the reactivity of singlet oxygen with purines. Nucleic Acids Res. 2016;44:56–62. doi: 10.1093/nar/gkv1364. PubMed DOI PMC

Davies M.J. Singlet oxygen-mediated damage to proteins and its consequences. BioChem. Biophys. Res. Commun. 2003;305:761–770. doi: 10.1016/S0006-291X(03)00817-9. PubMed DOI

Gracanin M., Hawkins C.L., Pattison D.I., Davies M.J. Singlet-oxygen-mediated amino acid and protein oxidation: Formation of tryptophan peroxides and decomposition products. Free Radic. Bio Med. 2009;47:92–102. doi: 10.1016/j.freeradbiomed.2009.04.015. PubMed DOI

Hirakawa T., Nosaka Y. Properties of O2.− and OH center dot formed in TiO2 aqueous suspensions by photocatalytic reaction and the influence of H2O2 and some ions. Langmuir. 2002;18:3247–3254. doi: 10.1021/la015685a. DOI

Kim S.Y., Lee S.M., Park J.W. Antioxidant enzyme inhibitors enhance singlet oxygen-induced cell death in HL-60 cells. Free Radic. Res. 2006;40:1190–1197. doi: 10.1080/10715760600887768. PubMed DOI

Deng J., Liu F., Wang L., An Y., Gao M., Wang Z., Zhao Y. Hypoxia- and singlet oxygen-responsive chemo-photodynamic Micelles featured with glutathione depletion and aldehyde production. Biomater. Sci. 2018;7:429–441. doi: 10.1039/C8BM01042K. PubMed DOI

Kim S.Y., Lee S.M., Tak J.K., Choi K.S., Kwon T.K., Park J.W. Regulation of singlet oxygen-induced apoptosis by cytosolic NADP+-dependent isocitrate dehydrogenase. Mol. Cell Biochem. 2007;302:27–34. doi: 10.1007/s11010-007-9421-x. PubMed DOI

Umezawa N., Tanaka K., Urano Y., Kikuchi K., Higuchi T., Nagano T. Novel Fluorescent Probes for Singlet Oxygen. Angew. Chem. Int. Ed. Engl. 1999;38:2899–2901. doi: 10.1002/(SICI)1521-3773(19991004)38:19<2899::AID-ANIE2899>3.0.CO;2-M. PubMed DOI

Brega V., Yan Y., Thomas S.W., 3rd Acenes beyond organic electronics: Sensing of singlet oxygen and stimuli-responsive materials. Org. Biomol. Chem. 2020;18:9191–9209. doi: 10.1039/D0OB01744B. PubMed DOI

Ruiz-Gonzalez R., Bresoli-Obach R., Gulias O., Agut M., Savoie H., Boyle R.W., Nonell S., Giuntini F. NanoSOSG: A Nanostructured Fluorescent Probe for the Detection of Intracellular Singlet Oxygen. Angew. Chem. Int. Ed. Engl. 2017;56:2885–2888. doi: 10.1002/anie.201609050. PubMed DOI

Lennicke C., Rahn J., Lichtenfels R., Wessjohann L.A., Seliger B. Hydrogen peroxide—Production, fate and role in redox signaling of tumor cells. Cell Commun. Signal. 2015;13:39. doi: 10.1186/s12964-015-0118-6. PubMed DOI PMC

Hossain M.A., Bhattacharjee S., Armin S.M., Qian P., Xin W., Li H.Y., Burritt D.J., Fujita M., Tran L.S. Hydrogen peroxide priming modulates abiotic oxidative stress tolerance: Insights from ROS detoxification and scavenging. Front. Plant. Sci. 2015;6:420. doi: 10.3389/fpls.2015.00420. PubMed DOI PMC

Halliwell B., Clement M.V., Long L.H. Hydrogen peroxide in the human body. FEBS Lett. 2000;486:10–13. doi: 10.1016/S0014-5793(00)02197-9. PubMed DOI

Mates J.M., Perez-Gomez C., De Castro I.N. Antioxidant enzymes and human diseases. Clin. Biochem. 1999;32:595–603. doi: 10.1016/S0009-9120(99)00075-2. PubMed DOI

Angermuller S., Islinger M., Volkl A. Peroxisomes and reactive oxygen species, a lasting challenge. HistoChem. Cell Biol. 2009;131:459–463. doi: 10.1007/s00418-009-0563-7. PubMed DOI

Topo E., Fisher G., Sorricelli A., Errico F., Usiello A., D’Aniello A. Thyroid hormones and D-aspartic acid, D-aspartate oxidase, D-aspartate racemase, H2O2, and ROS in rats and mice. Chem. Biodivers. 2010;7:1467–1478. doi: 10.1002/cbdv.200900360. PubMed DOI

Royall J.A., Ischiropoulos H. Evaluation of 2’,7’-Dichlorofluorescin and Dihydrorhodamine 123 as Fluorescent-Probes for Intracellular H2o2 in Cultured Endothelial-Cells. Arch. Biochem. Biophys. 1993;302:348–355. doi: 10.1006/abbi.1993.1222. PubMed DOI

Rastogi R.P., Singh S.P., Hader D.P., Sinha R.P. Detection of reactive oxygen species (ROS) by the oxidant-sensing probe 2’,7’-dichlorodihydrofluorescein diacetate in the cyanobacterium Anabaena variabilis PCC 7937. Biochem. Biophys. Res. Commun. 2010;397:603–607. doi: 10.1016/j.bbrc.2010.06.006. PubMed DOI

Gomes A., Fernandes E., Lima J.L.F.C. Fluorescence probes used for detection of reactive oxygen species. J. Biochem. Bioph Meth. 2005;65:45–80. doi: 10.1016/j.jbbm.2005.10.003. PubMed DOI

Crow J.P. Dichlorodihydrofluorescein and dihydrorhodamine 123 are sensitive indicators of peroxynitrite in vitro: Implications for intracellular measurement of reactive nitrogen and oxygen species. Nitric Oxide. 1997;1:145–157. doi: 10.1006/niox.1996.0113. PubMed DOI

Chignell C.F., Sik R.H. A photochemical study of cells loaded with 2’,7’-dichlorofluorescin: Implications for the detection of reactive oxygen species generated during UVA irradiation. Free Radic. Biol. Med. 2003;34:1029–1034. PubMed

Zhu H., Bannenberg G.L., Moldeus P., Shertzer H.G. Oxidation pathways for the intracellular probe 2’,7’-dichlorofluorescein. Arch. Toxicol. 1994;68:582–587. doi: 10.1007/s002040050118. PubMed DOI

Lebel C.P., Ischiropoulos H., Bondy S.C. Evaluation of the Probe 2’,7’-Dichlorofluorescin as an Indicator of Reactive Oxygen Species Formation and Oxidative Stress. Chem. Res. Toxicol. 1992;5:227–231. doi: 10.1021/tx00026a012. PubMed DOI

Hsiao I.L., Huang Y.J. Titanium Oxide Shell Coatings Decrease the Cytotoxicity of ZnO Nanoparticles. Chem. Res. Toxicol. 2011;24:303–313. doi: 10.1021/tx1001892. PubMed DOI

Akhtar M.J., Ahamed M., Kumar S., Khan M.M., Ahmad J., Alrokayan S.A. Zinc oxide nanoparticles selectively induce apoptosis in human cancer cells through reactive oxygen species. Int. J. Nanomed. 2012;7:845–857. PubMed PMC

Sharma V., Anderson D., Dhawan A. Zinc oxide nanoparticles induce oxidative DNA damage and ROS-triggered mitochondria mediated apoptosis in human liver cells (HepG2) Apoptosis. 2012;17:852–870. doi: 10.1007/s10495-012-0705-6. PubMed DOI

Setyawati M.I., Tay C.Y., Leong D.T. Effect of zinc oxide nanomaterials-induced oxidative stress on the p53 pathway. Biomaterials. 2013;34:10133–10142. doi: 10.1016/j.biomaterials.2013.09.024. PubMed DOI

Aliakbari F., Haji Hosseinali S., Khalili Sarokhalil Z., Shahpasand K., Akbar Saboury A., Akhtari K., Falahati M. Reactive oxygen species generated by titanium oxide nanoparticles stimulate the hemoglobin denaturation and cytotoxicity against human lymphocyte cell. J. Biomol. Struct. Dyn. 2019;37:4875–4881. doi: 10.1080/07391102.2019.1568305. PubMed DOI

Bhattacharya K., Davoren M., Boertz J., Schins R.P., Hoffmann E., Dopp E. Titanium dioxide nanoparticles induce oxidative stress and DNA-adduct formation but not DNA-breakage in human lung cells. Part. Fibre Toxicol. 2009;6:17. doi: 10.1186/1743-8977-6-17. PubMed DOI PMC

Liu S., Xu L., Zhang T., Ren G., Yang Z. Oxidative stress and apoptosis induced by nanosized titanium dioxide in PC12 cells. Toxicology. 2010;267:172–177. doi: 10.1016/j.tox.2009.11.012. PubMed DOI

Park E.J., Yi J., Chung K.H., Ryu D.Y., Choi J., Park K. Oxidative stress and apoptosis induced by titanium dioxide nanoparticles in cultured BEAS-2B cells. Toxicol. Lett. 2008;180:222–229. doi: 10.1016/j.toxlet.2008.06.869. PubMed DOI

Miwa S., Treumann A., Bell A., Vistoli G., Nelson G., Hay S., von Zglinicki T. Carboxylesterase converts Amplex red to resorufin: Implications for mitochondrial H2O2 release assays. Free Radic. Biol. Med. 2016;90:173–183. doi: 10.1016/j.freeradbiomed.2015.11.011. PubMed DOI PMC

Zhu A., Romero R., Petty H.R. A sensitive fluorimetric assay for pyruvate. Anal. BioChem. 2010;396:146–151. doi: 10.1016/j.ab.2009.09.017. PubMed DOI PMC

Towne V., Will M., Oswald B., Zhao Q.J. Complexities in horseradish peroxidase-catalyzed oxidation of dihydroxyphenoxazine derivatives: Appropriate ranges for pH values and hydrogen peroxide concentrations in quantitative analysis. Anal. Biochem. 2004;334:290–296. doi: 10.1016/j.ab.2004.07.037. PubMed DOI

Debski D., Smulik R., Zielonka J., Michalowski B., Jakubowska M., Debowska K., Adamus J., Marcinek A., Kalyanaraman B., Sikora A. Mechanism of oxidative conversion of Amplex (R) Red to resorufin: Pulse radiolysis and enzymatic studies. Free Radic. Bio Med. 2016;95:323–332. doi: 10.1016/j.freeradbiomed.2016.03.027. PubMed DOI PMC

Niethammer P., Grabher C., Look A.T., Mitchison T.J. A tissue-scale gradient of hydrogen peroxide mediates rapid wound detection in zebrafish. Nature. 2009;459:996–999. doi: 10.1038/nature08119. PubMed DOI PMC

Maeda H., Fukuyasu Y., Yoshida S., Fukuda M., Saeki K., Matsuno H., Yamauchi Y., Yoshida K., Hirata K., Miyamoto K. Fluorescent probes for hydrogen peroxide based on a non-oxidative mechanism. Angew. Chem. Int. Ed. Engl. 2004;43:2389–2391. doi: 10.1002/anie.200452381. PubMed DOI

Wolfbeis O.S., Durkop A., Wu M., Lin Z.H. A europium-ion-based luminescent sensing probe for hydrogen peroxide. Angew. Chem. Int. Ed. 2002;41:4495–4498. doi: 10.1002/1521-3773(20021202)41:23<4495::AID-ANIE4495>3.0.CO;2-I. PubMed DOI

Staniek K., Nohl H. H2O2 detection from intact mitochondria as a measure for one-electron reduction of dioxygen requires a non-invasive assay system. Bba-Bioenergetics. 1999;1413:70–80. doi: 10.1016/S0005-2728(99)00083-3. PubMed DOI

Bartosz G. Use of spectroscopic probes for detection of reactive oxygen species. Clin. Chim. Acta. 2006;368:53–76. doi: 10.1016/j.cca.2005.12.039. PubMed DOI

Mohammadinejad R., Moosavi M.A., Tavakol S., Vardar D.O., Hosseini A., Rahmati M., Dini L., Hussain S., Mandegary A., Klionsky D.J. Necrotic, apoptotic and autophagic cell fates triggered by nanoparticles. Autophagy. 2019;15:4–33. doi: 10.1080/15548627.2018.1509171. PubMed DOI PMC

Mittler R., Vanderauwera S., Suzuki N., Miller G., Tognetti V.B., Vandepoele K., Gollery M., Shulaev V., Van Breusegem F. ROS signaling: The new wave? Trends Plant. Sci. 2011;16:300–309. doi: 10.1016/j.tplants.2011.03.007. PubMed DOI

Zhang J., Wang X., Vikash V., Ye Q., Wu D., Liu Y., Dong W. ROS and ROS-Mediated Cellular Signaling. Oxid Med. Cell Longev. 2016 doi: 10.1155/2016/4350965. PubMed DOI PMC

Bae Y.S., Oh H., Rhee S.G., Yoo Y.D. Regulation of reactive oxygen species generation in cell signaling. Mol. Cells. 2011;32:491–509. doi: 10.1007/s10059-011-0276-3. PubMed DOI PMC

Bonizzi G., Karin M. The two NF-kappaB activation pathways and their role in innate and adaptive immunity. Trends Immunol. 2004;25:280–288. doi: 10.1016/j.it.2004.03.008. PubMed DOI

Kaul N., Gopalakrishna R., Gundimeda U., Choi J., Forman H.J. Role of protein kinase C in basal and hydrogen peroxide-stimulated NF-kappa B activation in the murine macrophage J774A.1 cell line. Arch. Biochem. Biophys. 1998;350:79–86. doi: 10.1006/abbi.1997.0487. PubMed DOI

Schmidt K.N., Amstad P., Cerutti P., Baeuerle P.A. The roles of hydrogen peroxide and superoxide as messengers in the activation of transcription factor NF-kappa B. Chem. Biol. 1995;2:13–22. doi: 10.1016/1074-5521(95)90076-4. PubMed DOI

Schoonbroodt S., Ferreira V., Best-Belpomme M., Boelaert J.R., Legrand-Poels S., Korner M., Piette J. Crucial role of the amino-terminal tyrosine residue 42 and the carboxyl-terminal PEST domain of I kappa B alpha in NF-kappa B activation by an oxidative stress. J. Immunol. 2000;164:4292–4300. doi: 10.4049/jimmunol.164.8.4292. PubMed DOI

Takada Y., Mukhopadhyay A., Kundu G.C., Mahabeleshwar G.H., Singh S., Aggarwal B.B. Hydrogen peroxide activates NF-kappa B through tyrosine phosphorylation of I kappa B alpha and serine phosphorylation of p65: Evidence for the involvement of I kappa B alpha kinase and Syk protein-tyrosine kinase. J. Biol. Chem. 2003;278:24233–24241. doi: 10.1074/jbc.M212389200. PubMed DOI

Liu X., Lu B., Fu J., Zhu X., Song E., Song Y. Amorphous silica nanoparticles induce inflammation via activation of NLRP3 inflammasome and HMGB1/TLR4/MYD88/NF-kb signaling pathway in HUVEC cells. J. Hazard. Mater. 2021;404:124050. doi: 10.1016/j.jhazmat.2020.124050. PubMed DOI

Kyriakis J.M., Avruch J. Sounding the alarm: Protein kinase cascades activated by stress and inflammation. J. Biol. Chem. 1996;271:24313–24316. doi: 10.1074/jbc.271.40.24313. PubMed DOI

Nakano H., Nakajima A., Sakon-Komazawa S., Piao J.H., Xue X., Okumura K. Reactive oxygen species mediate crosstalk between NF-kappaB and JNK. Cell Death Differ. 2006;13:730–737. doi: 10.1038/sj.cdd.4401830. PubMed DOI

Torres M., Forman H.J. Redox signaling and the MAP kinase pathways. Biofactors. 2003;17:287–296. doi: 10.1002/biof.5520170128. PubMed DOI

Dabrowski A., Boguslowicz C., Dabrowska M., Tribillo I., Gabryelewicz A. Reactive oxygen species activate mitogen-activated protein kinases in pancreatic acinar cells. Pancreas. 2000;21:376–384. doi: 10.1097/00006676-200011000-00008. PubMed DOI

Guyton K.Z., Liu Y., Gorospe M., Xu Q., Holbrook N.J. Activation of mitogen-activated protein kinase by H2O2. Role in cell survival following oxidant injury. J. Biol. Chem. 1996;271:4138–4142. doi: 10.1074/jbc.271.8.4138. PubMed DOI

Hou N., Torii S., Saito N., Hosaka M., Takeuchi T. Reactive oxygen species-mediated pancreatic beta-cell death is regulated by interactions between stress-activated protein kinases, p38 and c-Jun N-terminal kinase, and mitogen-activated protein kinase phosphatases. Endocrinology. 2008;149:1654–1665. doi: 10.1210/en.2007-0988. PubMed DOI

Choi B.H., Hur E.M., Lee J.H., Jun D.J., Kim K.T. Protein kinase Cdelta-mediated proteasomal degradation of MAP kinase phosphatase-1 contributes to glutamate-induced neuronal cell death. J. Cell Sci. 2006;119:1329–1340. doi: 10.1242/jcs.02837. PubMed DOI

Matsuzawa A., Saegusa K., Noguchi T., Sadamitsu C., Nishitoh H., Nagai S., Koyasu S., Matsumoto K., Takeda K., Ichijo H. ROS-dependent activation of the TRAF6-ASK1-p38 pathway is selectively required for TLR4-mediated innate immunity. Nat. Immunol. 2005;6:587–592. doi: 10.1038/ni1200. PubMed DOI

Pitzschke A., Djamei A., Bitton F., Hirt H. A Major Role of the MEKK1-MKK1/2-MPK4 Pathway in ROS Signalling. Mol. Plant. 2009;2:120–137. doi: 10.1093/mp/ssn079. PubMed DOI PMC

Lluis J.M., Buricchi F., Chiarugi P., Morales A., Fernandez-Checa J.C. Dual role of mitochondrial reactive oxygen species in hypoxia signaling: Activation of nuclear factor-kB via c-SRC and oxidant-dependent cell death. Cancer Res. 2007;67:7368–7377. doi: 10.1158/0008-5472.CAN-07-0515. PubMed DOI

Dong J., Ramachandiran S., Tikoo K., Jia Z., Lau S.S., Monks T.J. EGFR-independent activation of p38 MAPK and EGFR-dependent activation of ERK1/2 are required for ROS-induced renal cell death. Am. J. Physiol. Renal Physiol. 2004;287:1049–1058. doi: 10.1152/ajprenal.00132.2004. PubMed DOI

Forman H.J., Torres M. Reactive oxygen species and cell signaling: Respiratory burst in macrophage signaling. Am. J. Respir. Crit. Care Med. 2002;166 doi: 10.1164/rccm.2206007. PubMed DOI

Cheng G., Guo W., Han L., Chen E., Kong L., Wang L., Ai W., Song N., Li H., Chen H. Cerium oxide nanoparticles induce cytotoxicity in human hepatoma SMMC-7721 cells via oxidative stress and the activation of MAPK signaling pathways. Toxicol. In Vitro. 2013;27:1082–1088. doi: 10.1016/j.tiv.2013.02.005. PubMed DOI

Guo C., Xia Y., Niu P., Jiang L., Duan J., Yu Y., Zhou X., Li Y., Sun Z. Silica nanoparticles induce oxidative stress, inflammation, and endothelial dysfunction in vitro via activation of the MAPK/Nrf2 pathway and nuclear factor-kappaB signaling. Int. J. Nanomed. 2015;10:1463–1477. doi: 10.2147/IJN.S76114. PubMed DOI PMC

You R., Ho Y.S., Hung C.H., Liu Y., Huang C.X., Chan H.N., Ho S.L., Lui S.Y., Li H.W., Chang R.C. Silica nanoparticles induce neurodegeneration-like changes in behavior, neuropathology, and affect synapse through MAPK activation. Part. Fibre Toxicol. 2018;15:28. doi: 10.1186/s12989-018-0263-3. PubMed DOI PMC

Hu Q., Wang H., He C., Jin Y., Fu Z. Polystyrene nanoparticles trigger the activation of p38 MAPK and apoptosis via inducing oxidative stress in zebrafish and macrophage cells. Environ. Pollut. 2021;269:116075. doi: 10.1016/j.envpol.2020.116075. PubMed DOI

Zhou Y., Ji J., Ji L., Wang L., Hong F. Respiratory exposure to nano-TiO2 induces pulmonary toxicity in mice involving reactive free radical-activated TGF-beta/Smad/p38MAPK/Wnt pathways. J. Biomed. Mater. Res. A. 2019;107:2567–2575. doi: 10.1002/jbm.a.36762. PubMed DOI

Yi C., Liu D., Fong C.C., Zhang J., Yang M. Gold nanoparticles promote osteogenic differentiation of mesenchymal stem cells through p38 MAPK pathway. ACS Nano. 2010;4:6439–6448. doi: 10.1021/nn101373r. PubMed DOI

Wang Q., Chen B., Cao M., Sun J., Wu H., Zhao P., Xing J., Yang Y., Zhang X., Ji M., et al. Response of MAPK pathway to iron oxide nanoparticles in vitro treatment promotes osteogenic differentiation of hBMSCs. Biomaterials. 2016;86:11–20. doi: 10.1016/j.biomaterials.2016.02.004. PubMed DOI

Vousden K.H., Lu X. Live or let die: The cell’s response to p53. Nat. Rev. Cancer. 2002;2:594–604. doi: 10.1038/nrc864. PubMed DOI

Liu B., Chen Y., St Clair D.K. ROS and p53: A versatile partnership. Free Radic. Biol. Med. 2008;44:1529–1535. doi: 10.1016/j.freeradbiomed.2008.01.011. PubMed DOI PMC

Song Y.X., Li X.W., Li Y., Li N., Shi X.X., Ding H.Y., Zhang Y.H., Li X.B., Liu G.W., Wang Z. Non-esterified fatty acids activate the ROS-p38-p53/Nrf2 signaling pathway to induce bovine hepatocyte apoptosis in vitro. Apoptosis. 2014;19:984–997. doi: 10.1007/s10495-014-0982-3. PubMed DOI

Nakano K., Vousden K.H. PUMA, a novel proapoptotic gene, is induced by p53. Mol. Cell. 2001;7:683–694. doi: 10.1016/S1097-2765(01)00214-3. PubMed DOI

Liu B.R., Yuan B., Zhang L., Mu W.M., Wang C.M. ROS/p38/p53/Puma signaling pathway is involved in emodin-induced apoptosis of human colorectal cancer cells. Int. J. Clin. Exp. Med. 2015;8:15413–15422. PubMed PMC

Yu J., Zhang L. PUMA, a potent killer with or without p53. Oncogene. 2008;27:71–83. doi: 10.1038/onc.2009.45. PubMed DOI PMC

Samuelsen J.T., Dahl J.E., Karlsson S., Morisbak E., Becher R. Apoptosis induced by the monomers HEMA and TEGDMA involves formation of ROS and differential activation of the MAP-kinases p38, JNK and ERK. Dent. Mater. 2007;23:34–39. doi: 10.1016/j.dental.2005.11.037. PubMed DOI

Sakon S., Xue X., Takekawa M., Sasazuki T., Okazaki T., Kojima Y., Piao J.H., Yagita H., Okumura K., Doi T., et al. NF-kappaB inhibits TNF-induced accumulation of ROS that mediate prolonged MAPK activation and necrotic cell death. Embo J. 2003;22:3898–3909. doi: 10.1093/emboj/cdg379. PubMed DOI PMC

Kamata H., Honda S., Maeda S., Chang L., Hirata H., Karin M. Reactive oxygen species promote TNFalpha-induced death and sustained JNK activation by inhibiting MAP kinase phosphatases. Cell. 2005;120:649–661. doi: 10.1016/j.cell.2004.12.041. PubMed DOI

Akcan R., Aydogan H.C., Yildirim M.S., Tastekin B., Saglam N. Nanotoxicity: A challenge for future medicine. Turk. J. Med. Sci. 2020;50:1180–1196. doi: 10.3906/sag-1912-209. PubMed DOI PMC

Graham U.M., Dozier A.K., Oberdorster G., Yokel R.A., Molina R., Brain J.D., Pinto J.M., Weuve J., Bennett D.A. Tissue Specific Fate of Nanomaterials by Advanced Analytical Imaging Techniques—A Review. Chem. Res. Toxicol. 2020;33:1145–1162. doi: 10.1021/acs.chemrestox.0c00072. PubMed DOI PMC

Pu S., Gong C., Robertson A.W. Liquid cell transmission electron microscopy and its applications. R. Soc. Open Sci. 2020;7:191204. doi: 10.1098/rsos.191204. PubMed DOI PMC

Kiio T.M., Park S. Nano-scientific Application of Atomic Force Microscopy in Pathology: From Molecules to Tissues. Int. J. Med. Sci. 2020;17:844–858. doi: 10.7150/ijms.41805. PubMed DOI PMC

Erofeev A., Gorelkin P., Garanina A., Alova A., Efremova M., Vorobyeva N., Edwards C., Korchev Y., Majouga A. Novel method for rapid toxicity screening of magnetic nanoparticles. Sci. Rep. 2018;8:7462. doi: 10.1038/s41598-018-25852-4. PubMed DOI PMC

Rahman L., Williams A., Gelda K., Nikota J., Wu D., Vogel U., Halappanavar S. 21st Century Tools for Nanotoxicology: Transcriptomic Biomarker Panel and Precision-Cut Lung Slice Organ Mimic System for the Assessment of Nanomaterial-Induced Lung Fibrosis. Small. 2020;16 doi: 10.1002/smll.202000272. PubMed DOI

Kohl Y., Runden-Pran E., Mariussen E., Hesler M., El Yamani N., Longhin E.M., Dusinska M. Genotoxicity of Nanomaterials: Advanced In Vitro Models and High Throughput Methods for Human Hazard Assessment-A Review. Nanomaterials (Basel) 2020;10:1911. doi: 10.3390/nano10101911. PubMed DOI PMC

Zhang M., Xu C., Jiang L., Qin J. A 3D human lung-on-a-chip model for nanotoxicity testing. Toxicol. Res. 2018;7:1048–1060. doi: 10.1039/C8TX00156A. PubMed DOI PMC

Yin F., Zhu Y., Zhang M., Yu H., Chen W., Qin J. A 3D human placenta-on-a-chip model to probe nanoparticle exposure at the placental barrier. Toxicol. In Vitro. 2019;54:105–113. doi: 10.1016/j.tiv.2018.08.014. PubMed DOI

van Duinen V., Trietsch S.J., Joore J., Vulto P., Hankemeier T. Microfluidic 3D cell culture: From tools to tissue models. Curr. Opin. Biotechnol. 2015;35:118–126. doi: 10.1016/j.copbio.2015.05.002. PubMed DOI

Structure-Guided Design of N-Methylpropargylamino-Quinazoline Derivatives as Multipotent Agents for the Treatment of Alzheimer's Disease