Abstract
The effects of 29 substances, including known antioxidants, anti-radiation agents, amino acids, and vitamins, on the luminescence intensity of E. coli K12 MG1655 (pSoxS-lux) and MG1655 (pKatG-lux) bacterial cells induced by paraquat and peroxide, respectively, were studied. The luminescence of biosensors occurs as a result of activation of the soxS and katA gene promoters in response to an increase in the concentration of superoxide radicals and H2O2 in the cell. In the case of an antioxidant effect exerted by a substance under study, the intensity of the induced luminescence decreases, and in the case of a prooxidant effect, the luminescence intensity increases. Antioxidant activity was exhibited by 23 of 29 substances (79%) on the pKatG-lux biosensor and 22 of 29 substances (76%) on the pSoxS-lux biosensor. The studied anti-radiation agents (ten substances) showed different degrees of pro- and antioxidant activity. Lithium salt of glutathione disulfide, glutoxim, ginestein, and indraline significantly reduced the level of induced luminescence in both biosensors; magnesium salt of glutathione disulfide, zinc salt of reduced glutathione, and molixane, only in the pSoxS-lux biosensor; and cistamine and 5-AED, only in the pKatG-lux biosensor. Among the anti-radiation agents, a high prooxidant activity on the pKatG-lux biosensor at low concentrations was shown by lithium and magnesium salts of glutathione disulfide, zinc salt of reduced glutathione, molixane, and indralin (B-190); and on the pSoxS-lux biosensor, by genistein, cystamine, and 5-АED. The applicability of lux-biosensors for primary evaluation of the potential antioxidant and radioprotective activity of chemicals is discussed.
Similar content being viewed by others
REFERENCES
Men’shchikova, E.B., Lankin, V.Z., Zenkov, N.K., et al., Okislitel’nyi stress—prooksidanty i antioksidanty (Oxidative Stress—Prooxidants and Antioxidants), Moscow: Slovo, 2006.
Kostyuk, V.A. and Potapovich, A.I., Bioradikaly i bioantioksidanty (Bioradicals and Bioantioxidants), Minsk: Belarus. Gos. Univ., 2004.
Papas, A.M., Lipid-Soluble Antioxidants. Biochemistry and Clinical Application, Basel: Birkhauser Verlag, 1992, рр. 123–149.
Shakhmardanova, S.A., Gulevskaya, O.N., Seletskaya, V.V., et al., Antioxidants: classification, pharmacological properties, and use in medical practice, Zh. Fund. Med. Biol., 2016, no. 3, pp. 3–15.
Zaitsev, V.G., Ostrovskii, O.V., and Zakrevskii, V.I., Relationship between chemical structure and target as a basis of classification of antioxidants of direct action, Eksp. Klin. Farmakol., 2003, vol. 66, no. 4, pp. 66–70.
Khasanov, V.V., Ryzhova, G.L, and Maltseva, E.V., Methods for study of antioxidants, Khim. Rastit. Syr’ya, 2004, no. 3, pp. 63–75.
Vladimirov, Yu.A., Proskurnina, E.V., and Izmajlov, D.Yu., Kinetic chemiluminescence as a method for study of free radical reactions, Biophysics (Moscow), 2011, vol. 56, no. 6, pp. 1055–1062.
Yang, B., Kotani, A., Arai, K., and Kusu, F., Estimation of the antioxidant activities of flavonoids from their oxidation potentials, Anal. Sci., 2001, vol. 17, no. 3, pp. 599–604.
Gupta, D., Methods for determination of antioxidant capacity: a review, Int. J. Pharm. Sci. Res., 2015, vol. 6, no. 2, pp. 546–566.
Lyahovich, V.V., Vavilin, V.A., Zenkov, N.K., and Menshchikova, E.B., Active defense under oxidative stress. The antioxidant responsive element, Biochemistry (Moscow), 2006, vol. 71, no. 9, pp. 962–974.
Kotova, V.Yu., Manukhov, I.V., and Zavilgelskii, G.B., Lux-biosensors for the detection of SOS response, heat shock, and oxidative stress, Biotekhnologiya, 2009, no. 6, pp. 16–25.
Igonina, E.V., Marsova, M.V., and Abilev, S.K., Lux-biosensors: screening biologically active compounds for genotoxicity, Ekol. Genet., 2016, vol. 9, no. 4, pp. 52–62.
Marsova, M., Abilev, S., Poluektova, E., and Danilenko, V., A bioluminescent test system reveals valuable antioxidant properties of lactobacillus strains from human microbiota, J. Microbiol. Biotechnol., 2018, vol. 34, pp. 1–9.
Prazdnova, E.V., Chistyakov, V.A., Churilov, M.N., et al., DNA-protection and antioxidant properties of fermentates from Bacillus amyloliquefaciens B-1895 and Bacillus subtilis KATMIRA 1933, Lett. Appl. Microbiol., 2015, vol. 61, pp. 549–554.
Gitelson, J.I., Rodicheva, Eh.K., Medvedeva, S.E., et al., Svetyashchiesya bakterii (Luminescent Bacteria), Novosibirsk: Nauka, 1984.
Grebenyuk, A.N., Zatsepin, V.V., Nazarov, V.B., and Vlasenko, T.N., Modern opportunities of drug prevention and early treatment of radiation injuries, Voen.-Med. Zh., 2011, vol. 332, no. 2, pp. 13–17.
Grebenyuk, A.N. and Legeza, V.I., Prospects of using radioprotectors to improve the efficiency of medical radiation protection of the Armed Forces, Voen.-Med. Zh., 2013, vol. 334, no. 7, pp. 46–50.
Grebenyuk, A.N., Legeza, V.I., and Tarumov, R.A., Radiomitigators: prospects for use in the medical radiation protection system, Voen.-Med. Zh., 2014, vol. 335, no. 6, pp. 39–43.
Misra, H.P., Generation of superoxide free radical during the autoxidation of thiols, J. Biol. Chem., 1974, vol. 249, pp. 2151–2155.
Munday, R., Toxicity of thiols and disulphides: involvement of free-radical species, Free Radic. Biol. Med., 1989, vol. 7, pp. 659–673.
Long, L.H. and Halliwell, B., Oxidation and generation of hydrogen peroxide by thiol compounds in commonly used cell culture media, Biochem. Biophys. Res. Commun., 2001, vol. 286, pp. 991–994.
Solov’eva, M.E., Solov’ev, V.V., Fashutdinova, A.A., et al., Prooxidant and cytotoxic effects of N-acetylcysteine and glutathione in combination with vitamin B12, Tsitologiia, 2007, vol. 49, no. 1, pp. 70–78.
Kalinina, E.V., Chernov, N.N., and Novichkova, M.D., The role of glutathione, glutathione transferase, and glutaredoxin in regulation of redox-dependent processes, Usp. Biol. Khim., 2014, vol. 54, pp. 299–348.
Tebay, T.E., Robertson, H., Durant, S.T., et al., Mechanisms of activation of the transcription factor Nrf2 by redox stressors, nutrient cues, and energy status and the pathways through which it attenuates degenerative disease, Free Radic. Biol. Med., 2015, vol. 88, pp. 108–146.
Osburn, W.O. and Kensler, T.W., Nrf2 signaling: an adaptive response pathway for protection against environmental toxic insults, Mutat. Res., 2008, vol. 659, pp. 31–39.
Kensler, T.W., Wakabayashi, N., and Biswal, S., Cell survival responses to environmental stresses via the Keap1–Nrf2–ARE pathway, Annu. Rev. Pharmacol. Toxicol., 2007, vol. 47, pp. 89–116.
Taguchi, K., Motohashi, H., and Yamamoto, M., Molecular mechanisms of the Keap1–Nrf2 pathway in stress response and cancer evolution, Genes Cells, 2011, vol. 16, pp. 123–140.
Ma, Q. and He, X., Molecular basis of electrophilic and oxidative defense: promises and perils of Nrf2, Pharmacol. Rev., 2012, vol. 64, pp. 1055–1081.
Tkachev, V.O., Menshchikova, E.B., and Zenkov, N.K., Mechanism of the Nrf2/Keap1/ARE signaling system, Biochemistry (Moscow), 2011, vol. 76, no. 4, pp. 407–422.
Giudice, A. and Arra, C., Review of molecular mechanisms involved in the activation of the Nrf2-ARE signaling pathway by chemopreventive agents, Methods Mol. Biol., 2010, vol. 647, pp. 37–74.
Raghunath, A., Sundarraja, R., Nagarajan, R., et al., Antioxidant response elements: discovery, classes, regulation and potential applications, Redox Biol., 2018, vol. 17, pp. 297–314.
Ma, Q., Role of Nrf2 in oxidative stress and toxicity, Annu. Rev. Pharm. Toxicol., 2013, vol. 53, pp. 401–426.
Menshchikova, E.B., Tkachev, V.O., and Zenkov, N.K., Redox-dependent signaling system Nrf2/ARE in inflammation, Mol. Biol. (Moscow), 2010, vol. 44, no. 3, pp. 343–358.
Ahmed, S.M.U., Luo, L., and Namani, A., Nrf2 signaling pathway: pivotal roles in inflammation, Biochim. Biophys. Acta, 2017, vol. 863, pp. 585–597.
Lu, M.C., Ji, J.A., Jiang, Z.Y., and You, Q.D., The Keap1-Nrf2-ARE pathway as a potential preventive and therapeutic target: an update, Med. Res. Rev, 2016, vol. 36, no. 5, pp. 924–963.
Zenkov, N.K., Menshchikova, E.B., and Tkachev, V.O., Keap1/Nrf2/ARE redox-sensitive signaling system as a pharmacological target, Biochemistry (Moscow), 2013, vol. 78, no. 1, pp. 19–36.
Hayes, J.D. and Dinkova-Kostova, A.T., The Nrf2 regulatory network provides an interface between redox and intermediary metabolism, Trends Biochem. Sci., 2014, vol. 39, no. 4, pp. 199–216.
Cai, Z., Lou, Q., Wang, F., et al., N-acetylcysteine protects against liver injure induced by carbon tetrachloride via activation of the Nrf2/HO-1 pathway, Int. J. Clin. Exp. Pathol., 2015, vol. 8, no. 7, pp. 8655–8662.
Ajit, D., Simonyi, A., Li, R., et al., Phytochemicals and botanical extracts regulate NF-kB and Nrf2/ARE, Neurochem. Int., 2016, vol. 97, pp. 49–56.
Smith, R.E., Tran, K., and Smith, C.C., The role of the Nrf2/ARE antioxidant system in preventing cardiovascular diseases, Diseases, 2016, vol. 4, pp. 1–20.
Ben-Dor, A., Steiner, M., Gheber, L., et al., Carotenoids activate the antioxidant response element transcription system, Mol. Cancer Ther., 2005, vol. 4, no. 1, pp. 177–186.
Cao, W., Xu, X., Jia, G., et al., Roles of spermine in modulating the antioxidant status and Nrf2 signalling molecules expression in the thymus and spleen of suckling piglets—new insight, Anim. Physiol. Anim. Nutr., 2018, vol. 102, pp. e183–e192.
Zhai, X., Lin, M., Zhang, F., et al., Dietary flavonoid genistein induces Nrf2 and phase II detoxification gene expression via ERKs and PKC pathways and protects against oxidative stress in Caco-2 cells, Mol. Nutr. Food Res., 2013, vol. 57, no. 2, pp. 249–259.
Pilar Valdecantos, M., Prieto-Hontoria, P.L., Pardo, V., et al., Essential role of Nrf2 in the protective effect of lipoic acid against lipoapoptosis in hepatocytes, Free Radic. Biol. Med., 2015, vol. 84, pp. 263–278.
Li, L., Du, J., Lian, Y., et al., Protective effects of coenzyme Q10 against hydrogen peroxide-induced oxidative stress in PC12 cell: the role of Nrf2 and antioxidant enzymes, Cell Mol. Neurobiol., 2016, vol. 36, no. 1, pp. 103–111.
Mikhailenko, A.A., Bazanov, G.A., Pokorovsky, V.I., and Konenkov, V.I., Profilakticheskaya immunologiya (Preventive Immunology), Moscow: OOO Triada, pp. 272–278.
Sokolova, G.V., Sinicyn, M.B., Kozhemyakin, L.A., and Perel’man, M.I., Glutoxim in the treatment of tuberculosis, Antibiot. Khimioter., 2002, no. 7, pp. 20–23.
Grebenyuk, A.N., Rejnyuk, V.L., Antushevich, A.E., et al., The effectiveness of neuropeptide and hepatoprotectors of peptide and nonpeptide nature in the treatment of acute extremely severe poisoning with ethanol, Vestn. Ross. Voen.-Med. Akad., 2014, vol. 45, no. 1, pp. 136–145.
Bakulin, I.S. and Zaharova, M.N., Lipoic acid in pathogenetic therapy of diabetic polyneuropathy: a review of clinical and experimental studies, Nervn. Bolezni, 2017, no. 2, pp. 3–9.
Böhm, V., Lycopene and heart health, Mol. Nutr. Food Res., 2012, vol. 56, no. 2, pp. 296–303.
Patt, H.M., Tyree, E.B., and Straube, R.L., Cysteine protection against X-irradiation, Science, 1949, vol. 110, pp. 213–214.
D’Autr’eaux, B. and Toledano, M.B., ROS as signalling molecules: mechanisms that generate specificity in ROS homeostasis, Nat. Rev. Mol. Cell Biol., 2007, vol. 8, no. 10, pp. 813–824.
Milvy, P., On the mechanism of radioprotection by cysteine and cysteamine: ESR studies of irradiated binary and ternary systems of DNA and TMP, Radiat. Res., 1971, vol. 48, no. 2, pp. 206–215.
Schmidt, E.E., Interplay between cytosolic disulfide reductase systems and the Nrf2/Keap1 pathway, Biochem. Soc. Trans., 2015, vol. 43, no. 4, pp. 632–638.
Tkachenko, A.G. and Fedotova, M.V., Dependence of protective functions of Escherichia coli polyamines on strength of stress caused by superoxide radicals, Biochemistry (Moscow), 2007, vol. 72, no. 1, pp. 109–116.
Kuznetsov, V.V., Radyukina, N.L., and Shevyakova, N.I., Polyamines and stress: biological role, metabolism, and regulation, Russ. J. Plant Physiol., 2006, vol. 53, pp. 583–604.
Weiss, J.F. and Landauer, M.R., Protection against ionizing radiation by antioxidant nutrients and phytochemicals, Toxicology, 2003, vol. 189, nos. 1–2, pp. 1–20.
Tarumov, R.A., Basharin, V.A., and Grebenyuk, A.N., Radioprotective properties of modern antioxidants, Rentgenol. Radiol., 2012, vol. 13, pp. 682–700.
Motahari, M., Sadeghizadeh, M., Behmanesh, M., et al., Generation of stable ARE-driven reporter system for monitoring oxidative stress, DARU J. Pharm. Sci., 2015, vol. 23, pp. 1–7.
Wang, X.J., Hayes, J.D., and Wolf, C.R., Generation of a stable antioxidant response element-driven reporter gene cell line and its use to show redox-dependent activation of Nrf2 by cancer chemotherapeutic agents, Cancer Res., 2006, vol. 66, no. 15, pp. 10983–10994.
Funding
This study was performed within the framework of a State Assignment, project no. 0112-2019-0002.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
The authors declare that they have no conflict of interest. This article does not contain any studies involving animals or human participants performed by any of the authors.
Additional information
Translated by M. Batrukova
Rights and permissions
About this article
Cite this article
Abilev, S.K., Sviridova, D.A., Grebenyuk, A.N. et al. Study of the Prooxidant and Antioxidant Activity of Anti-Radiation Agents with LUX-Biosensors. Biol Bull Russ Acad Sci 46, 1646–1656 (2019). https://doi.org/10.1134/S106235901912001X
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1134/S106235901912001X