Abstract
Protective effect of the natural dipeptide carnosine on the antioxidant system of rats under conditions of oxidative stress caused by chronic cadmium administration was investigated. Oxidative status of experimental animals were evaluated based on a number of informative parameters of iron-induced chemiluminescence. It was shown that the introduction of cadmium for 7 days reduces the duration of the latent period of chemiluminescence in the brain, liver, and blood plasma suggesting the depletion of endogenous antioxidant defense. Coexposure to carnosine and cadmium led to significant increase in the level of antioxidant protection in plasma, liver, and brain of animals. Carnosine also prevented the increase of lipid hydroperoxides in the brain and prevented the development of lipid peroxidation content in liver and plasma of animals. Mechanism of the protective effect of carnosine under conditions of oxidative stress induced by cadmium administration was shown on human neuroblastoma SH-SY5Y cell culture. Addition of the cadmium to the incubation medium to a final concentration of 5 μM reduced cell viability of a culture, as was determined by MTT assay; simultaneous addition of carnosine (0.25 mM final concentration) with cadmium resulted in increased cell viability during 24 hours of incubation. Thus, carnosine in a final concentration of 1 mM effectively prevented the development of necrotic lesions of neuroblastoma cells, inhibiting the formation of reactive oxygen species as measured by flow cytometry. The results indicate the ability of carnosine to prevent the development of oxidative stress under the toxic action of cadmium.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Brzoska, M.M., Majewska, K., and Kupraszewicz, E., Effects of low, moderate and relatively high chronic exposure to cadmium on long bones susceptibility to fractures in male rats, Environ. Toxicol. Pharmacol., 2010, vol. 29, no. 3, pp. 235–245.
Hammond, P.B. and Foulkes, E.C., Metal ion toxicity in man and animals, in Metal Ions in Biological Systems, Sigel, H., Ed., New York: Marcel Dekker, 1986, pp. 157–200.
Satoh, M., Koyama, H., Kaji, T., Kito, H., and Tohyama, C., Perspectives on cadmium toxicity research, Tohoku J. Exp. Med., 2002, vol. 196, no. 1, pp. 23–32.
Thompson, J. and Bannigan, J., Cadmium: Toxic effects on the reproductive system and the embryo, Reprod. Toxicol., 2008, vol. 25, no. 3, pp. 304–315.
Jiang, L.F., Yao, T.M., Zhu, Z.L., Wang, C., and Ji, L.N., Impacts of Cd(II) on the conformation and selfaggregation of Alzheimer’s tau fragment corresponding to the third repeat of microtubule-binding domain, Biochim. Biophys. Acta, 2007, no. 1774, pp. 1414–1421.
Lukawski, K., Nieradko, B., and Sieklucka-Dziuba, M., Effects of cadmium on memory processes in mice exposed to transient cerebral oligemia, Neurotoxicol. Teratol., 2005, no. 27, pp. 575–584.
Inozemtsev, A.N., Bokieva, S.B., Karpukhina, O.V., and Gumarkalieva, K.Z., Effects of combined treatment with heavy metals and piracetam on learning and memory in rats, Dokl. Biol. Sci., 2008, vol. 422, no. 1, pp. 301–304.
Frolova, N.A., The biological effect of cadmium under chronic exposure during antenatal and postnatal development in rats, Toksikol. Vestn., 2007, no. 1, pp. 11–14.
Watjen, W. and Beyersmann, D., Cadmium-induced apoptosis in C6 glioma cells: Influence of oxidative stress, Biometals, 2004, vol. 17, no. 1, pp. 65–78.
Abu-Taweel, G.M., Ajarem, J.S., and Ahmad, M., Protective effect of curcumin on anxiety, learning behavior, neuromuscular activities, brain neurotransmitters and oxidative stress enzymes in cadmium intoxicated mice, J. Behav. Brain Sci., 2013, no. 3, pp. 74–84.
Jomova, K. and Valko, M., Advances in metal-induced oxidative stress and human disease, Toxicology, 2011, vol. 283, nos. 2–3, pp. 65–87.
Nishimura, Y., Yamaguchi, J.Y., Kanada, A., Horimoto, K., Kanemaru, K., Satoh, M., and Oyama, Y., Increase in intracellular Cd2+ concentration of rat cerebellar granule neurons incubated with cadmium chloride: Cadmium cytotoxicity under external Ca2+-free condition, Toxicol. In Vitro, 2006, vol. 20, no. 2, pp. 211–216.
Jimi, S., Uchiyama, M., Takaki, A., Suzumiya, J., and Hara, S., Mechanisms of cell death induced by cadmium and arsenic, Ann. N. Y. Acad. Sci., 2004, vol. 1011, no. 1, pp. 325–331.
Halliwell, B. and Gutteridge, J.M.C., Free Radical in Biology and Medicine, New York: Oxford Univ. Press, 1999, 3rd ed., pp. 617–783.
Fedorova, T.N., Maksimova, M.Yu., Varakin, Yu.Ya., Logvinenko, A.A., Gnedovskaya, E.V., and Suslina, Z.A., Oxidation of blood lipoproteins in patients with impaired cerebral circulation, Ann. Klin. Eksp. Nevrol., 2014, vol. 8, no. 1, pp. 30–33.
Boldyrev, A.A., Karnozin i zashchita tkanei ot okislitel’nogo stressa (Carnosine and Protection of Tissues from Oxidative Stress), Moscow: Dialog-MGU, 1999.
Berezhnoy, D.S., Bokieva, S.B., Stvolinskii, S.L., Fedorova, T.N., and Inozemtsev, A.N., Effect of carnosine on conditioned passive avoidance response in the norm and under hypoxia conditions, Moscow Univ. Biol. Sci. Bull., 2015, vol. 70, no. 3, pp. 105–109.
Boldyrev, A.A., Carnosine: New concept for the function of an old molecule, Biochemistry (Moscow), 2012, vol. 77, no. 4, pp. 313–326.
Abaimov, D.A., Sariev, A.K., Tankevich, M.V., Pantyukhova, E.Yu., Prokhorov, D.I., Fedorova, T.N., Lopachev, A.V., Stvolinskii, S.L., Konovalova, E.V., and Seifulla, R.D., The study of basic pharmacokinetic characteristics and efficiency of penetration of dipeptide carnosine into the brain in the experiment, Eksp. Klin. Farmakol., 2015, vol. 78, no. 3, pp. 30–35.
Fedorova, T.N., Rebrova, O.Yu., and Larskii, E.G., Micro modification of the method for determining the activity of free radical oxidation processes, Lab. Delo, 1991, no. 3, pp. 37–39.
Akkuratov, E.E., Lopacheva, O.M., Kruusmägi, M., Lopachev, A.V., Shah, Z.A., Boldyrev, A.A., and Liu, L., Functional interaction between Na/K-ATPase and NMDA receptor in cerebellar neurons, Cell. Mol. Neurobiol., 2015, vol. 52, no. 3, pp. 1726–1734.
Boldyrev, A., Song, R., Djatlov, V., Lawrence, D., and Carpenter, D., Neuronal cell death and reactive oxigen species, Cell Mol. Neurobiol., 2000, vol. 20, no. 4, pp. 433–450.
Fedorova, T.N., Kulikova, O.I., Stvolinsky, S.L., and Orlova, V.S., The protective effect of (S)-trolox–carnosine on a human neuroblastoma SH-SY5Y cell culture under the impact of heavy metals, Neurochem. J., 2016, vol. 10, no. 1, pp. 53–58.
Fedorova, T.N., Stvolinskii, S.L., Kulikova, O.I., Konovalova, E.V., Levacheva, I.S., Samsonova, O., and Bakovskii, U., The effectiveness of neuroprotective action of novel derivatives of natural antioxidant carnosine in conditions of oxidative stress in vitro and in vivo, Ann. Klin. Eksp. Nevrol., 2016, vol. 10, no. 1, pp. 47–52.
Stvolinsky, S.L., Bulygina, E.R., Fedorova, T.N., Meguro, K., Sato, T., Tyulina, O.V., Abe, H., and Boldyrev, A.A., Biological activity of novel synthetic derivatives of carnosine, Cell. Mol. Neurobiol., 2010, vol. 30, no. 3, pp. 395–404.
Author information
Authors and Affiliations
Corresponding author
Additional information
Original Russian Text © O.I. Kulikova, T.N. Fedorova, S.L. Stvolinsky, V.S. Orlova, A.N. Inozemtsev, 2016, published in Vestnik Moskovskogo Universiteta, Seriya 16: Biologiya, 2016, No. 4, pp. 66–71.
About this article
Cite this article
Kulikova, O.I., Fedorova, T.N., Stvolinsky, S.L. et al. Carnosine prevents the development of oxidative stress under the conditions of toxic action of cadmium. Moscow Univ. Biol.Sci. Bull. 71, 240–244 (2016). https://doi.org/10.3103/S0096392516040064
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.3103/S0096392516040064