Effects of Ethylthiosulfanylate and Chromium (VI) on the State of Glutathione Antioxidant System and Oxidative Stress Marker Content in Rat Kidneys

Main Article Content

Bohdan Kotyk*
Ruslana Iskra


Hexavalent chromium (Cr(VI)) is a heavy metal and powerful toxicant with strong oxidative properties. Antioxidant defense system plays a key role in the processes of elimination and prevention of the negative effects of Cr(VI)-induced oxidative stress in biological systems. Prolonged action of Cr(VI)-induced oxidative stress leads to dysfunction of the antioxidant defense system and as a result provokes cell apoptosis. Ethylthiosulfanylate is synthetic sulfur-containing organic compound that belongs to the class of thiosulfonates. Structurally, thiosulfonates are synthetic analogues of natural organosulfur biologically active substances obtained from garlic, onion, cauliflower and broccoli. Thiosulfonates have antioxidant properties and activate the processes of reactive oxygen species (ROS) utilization. Therefore, the aim of this study was to examine the effect of ethylthiosulfanylate as a synthetic analogue of natural biologically active substances on the state of glutathione antioxidant system and oxidative stress marker content in the kidneys of rats under the condition of Cr(VI)-induced oxidative stress. Our results report that 14 days of ethylthiosulfanylate pretreatment (100 mg/kg body weight) caused attenuation of the intensity of Cr(VI)-induced lipid and protein peroxidation processes (P < 0.05). Moreover, previous impact of ethylthiosulfanylate prevented depletion of the total reduced glutathione (GSH) pool after 14 days of potassium dichromate action in kidneys of rats (P < 0.05). The present study indicates that ethylthiosulfanylate had antioxidant properties and partially inhibited Cr(VI)-induced oxidative damage in kidneys of rats. The obtained results may become a part of the background for the creation of effective methods of prevention and correction of the antioxidant and pro-oxidant states in kidneys affected by the action of Сr(VI)-induced oxidative stress.

Keywords: rats; antioxidant system; kidneys; oxidative stress; ethylthiosulfanylate; hexavalent chromium

*Corresponding author: Tel.: (+38) 0934179385

                                             E-mail: [email protected]

Article Details

Original Research Articles


Saha, R., Nandi, R. and Saha, B., 2011. Sources and toxicity of hexavalent chromium. Journal of Coordination Chemistry, 64(10), 1782-1806.

Mehany, H.A., Abo-youssef, A.M., Ahmed, L.A., El-Shaimaa, A. and El-Latif, H.A.A., 2013. Protective effect of vitamin E and atorvastatin against potassium dichromate-induced nephrotoxicity in rats. Beni-Suef University Journal of Basic and Applied Sciences, 2(2), 96-102.

Boşgelmez, I.I. and Güvendik, G., 2004. Effects of taurine on oxidative stress parameters and chromium levels altered by acute hexavalent chromium exposure in mice kidney tissue. Biological Trace Element Research, 102(1-3), 209-225.

Atmaca, G., 2004. Antioxidant effects of sulfur-containing amino acids. Yonsei Medical Journal, 45(5), 776-788.

Asatiani, N., Kartvelishvili, T., Abuladze, M., Asanishvili, L. and Sapojnikova, N., 2011. Chromium (VI) can activate and impair antioxidant defense system. Biological Trace Element Research, 142, 388-397.

Stanley, J.A., Sivakumar, K.K., Nithy, T.K., Arosh, J.A., Hoyer, P.B., Burghardt, R.C. and Banu, S.K., 2013. Postnatal exposure to chromium through mother’s milk accelerates follicular atresia in F1 offspring through increased oxidative stress and depletion of antioxidant enzymes. Free Radical Biology and Medicine, 61, 179-196.

Parveen, K., Khan, M.R. and Siddiqui, W.A., 2009. Pycnogenol® prevents potassium dichromate (K2Cr2O7)-induced oxidative damage and nephrotoxicity in rats. Chemico-Biological Interactions, 181(3), 343-350.

Sahu, B.D., Koneru, M., Bijargi, S.R., Kota, A. and Sistla, R., 2014. Chromium-induced nephrotoxicity and ameliorative effect of carvedilol in rats: Involvement of oxidative stress, apoptosis and inflammation. Chemico-Biological Interactions, 223, 69-79.

Zeid, E.H.A., Hussein, M.M.A. and Ali, H., 2018. Ascorbic acid protects male rat brain from oral potassium dichromate-induced oxidative DNA damage and apoptotic changes: the expression patterns of caspase-3, P 53, Bax, and Bcl-2 genes. Environmental Science and Pollution Research, 25(13), 13056-13066.

Lubenets, V., Havryliak, V., Pylypets, A. and Nakonechna, A., 2018. Changes in the spectrum of proteins and phospholipids in tissues of rats exposed to thiosulfonates. Regulatory Mechanisms in Biosystems, 9(4), 495-500.

Zenkov, N.K., Menshchikova, E.B., Kandalintseva, N.V., Oleynik, A.S., Prosenko, A.E., Gusachenko, O.N., Shklyaeva, O.A., Vavilin, V.A. and Lyakhovich, V.V., 2007. Antioxidant and antiinflammatory activity of new water-soluble sulfur-containing phenolic compounds. Biochemistry (Moscow), 72(6), 644-651.

Vavilin, V.A., Shintyapina, A.B., Safronova, O.G., Antontseva, E.V., Mordvinov, V.A., Nikishina, M.V., Kandalintseva, N.V., Prosenko, A.E. and Lyakhovich, V.V., 2014. Position of an active thiosulfonate group in new phenolic antioxidants is critical for ARE-mediated induction of GSTP1 and NQO1. Journal of Pharmaceutical Sciences and Research, 6(4), 178-183.

Acharya, M. and Lau-Cam, C.A., 2013. Comparative evaluation of the effects of taurine and thiotaurine on alterations of the cellular redox status and activities of antioxidant and glutathione-related enzymes by acetaminophen in the rat. Advances in Experimental Medicine and Biology, 776, 199-215.

Chung, L.Y., 2006. The antioxidant properties of garlic compounds: allyl cysteine, alliin, allicin, and allyl disulfide. Journal of Medicinal Food, 9(2), 205-213.

Li, X.-H., Li, C.-Y., Lu, J.-M., Tian, R.-B. and Wei, J., 2012. Allicin ameliorates cognitive deficits ageing-induced learning and memory deficits through enhancing of Nrf2 antioxidant signaling pathways. Neuroscience Letters, 514(1), 46-50.

Li, X.-H., Li, C.-Y., Xiang, Z.-G., Hu, J.-J., Lu, J.-M., Tian, R.-B. and Jia, W., 2012. Allicin ameliorates cardiac hypertrophy and fibrosis through enhancing of Nrf2 antioxidant signaling pathways. Cardiovascular Drugs and Therapy, 26(6), 457-465.

Lubenets, V., Karpenko, O., Ponomarenko, M., Zahoriy, G., Krychkovska, A. and Novikov, V., 2013. Development of new antimicrobial compositions of thiosulfonate structure. Chemistry & Chemical Technology, 7(2), 119-124.

Vlizlo, V.V., Fedoruk, R.S., Ratych, I.B., Vishchur, O.I., Sharan, M.M., Vudmaska, I.V., Fedorovych, Y.I., Ostapiv, D.D., Stapai, P.V., Buchko, O.M., Hunchak, A.V., Salyha, Y.T., Stefanyshyn, O.M., Hevkan, I.I., Lesyk, Y.V., Simonov, M.R., Nevostruieva, I.V., Khomyn, M.M., Smolianinov, K.B., Havryliak, V.V., Kolisnyk, H.V., Petrukh, I.M., Broda, N.A., Luchka, I.V., Kovalchuk, I.I., Kropyvka, S.Y., Paraniak, N.M., Tkachuk, V.M., Khrabko, M.I., Shtapenko, O.V., Dzen, Y.O., Maksymovych, I.Y., Fedorovych, V.V., Yuskiv, L.L., Dolaichuk, O.P., Ivanytska, L.A., Sirko, Y.M., Kystsiv, V.O., Zahrebelnyi, O.V., Simonov, R.P., Stoianovska, H.M., Kyryliv, B.Y., Kuziv, M.I., Maior, K.Y., Kuzmina, N.V., Talokha, N.I., Lisna, B.B., Klymyshyn, D.O., Chokan, T.V., Kaminska, M.V., Kozak, M.R., Oliinyk, A.V., Holova, N.V., Dubinskyi, V.V., Iskra, R.Y., Rivis, Y.F., Tsepko, N.L., Kyshko, V.I., Oleksiuk, N.P., Denys, H.H., Slyvchuk, Y.I. and Martyn, Y.V., 2012. Laboratory Methods of Investigation in Biology, Stockbreeding and Veterinary. 2nd ed. Lviv: Spolom.

Rosalovsky, V.P., Grabovska, S.V. and Salyha, Y.T., 2015 Changes in glutathione system and lipid peroxidation in rat blood during the first hour after chlorpyrifos exposure. The Ukrainian Biochemical Journal, 87(5), 124-132.

Lowry, O.H., Rosebrough, N.J., Farr, A.L. and Randall, R.J., 1951. Protein measurement with the Folin phenol reagent. The Journal of Biological Chemistry, 193(1), 265-275.

Soleimani, M., Dehabadi, L., Wilson, L.D. and Tabil, L.G., 2018. Antioxidants classification and applications in lubricants. In: D. Johnson, ed. Lubrication-Tribology, Lubricants and Additives. Saskatoon: Intech Open, pp. 23-42.

Chauvin, J.R., Griesser, M. and Pratt, D.A., 2019. The antioxidant activity of polysulfides: it's radical! Chemical Science, 10, 4999-5010.

Yaremkevych, O., Polischuk, I., Mandzynets, S., Bura, M., Sanagurskyi, D., Lubenec, V. and Novikov, V., 2011. Analysis of variance of influence of thiosulphonic acid deriva-tives on the Na+, K+-ATP-ase activity of loach embryos in vitro. Visnyk of the Lviv University, Series Biology, 57, 38-46.

Pylypets, A.Z., Iskra, R.Y., Havryliak, V.V., Nakonechna, A.V., Novikov, V.P. and Lubenets, V.I., 2017. Effects of thiosulfonates on the lipid composition of rat tissues. The Ukrainian Biochemical Journal, 89, 56-62.

Reyes, J.L., Molina-Jijón, E., Rodríguez-Muñoz, R., Bautista-García, P., Debray-García, Y. and Namorado, M., 2013. Tight junction proteins and oxidative stress in heavy metals-induced nephrotoxicity. BioMed Research International, 2013, https://doi.org/10.1155/2013/730789

Kotyzova, D., Hodkova, A., Bludovska, M. and Eybl, V., 2015. Effect of chromium (VI) exposure on antioxidant defense status and trace element homeostasis in acute experiment in rat. Toxicology and Industrial Health, 31(11), 1044-1050.

Geetha, S., Sai Ram, M., Mongia, S., Singh, V., Ilavazhagan, G. and Sawhney, R., 2003. Evaluation of antioxidant activity of leaf extract of Seabuckthorn (Hippophae rhamnoides L.) on chromium(VI) induced oxidative stress in albino rats. Journal of Ethnopharmacology, 87(2-3), 247-251.

Saber, T.M., Farag, M.R. and Cooper, R.G., 2015. Ameliorative effect of extra virgin olive oil on hexavalent chromium-induced nephrotoxicity and genotoxicity in rats. Revue de Médecine Véterinaire, 166(1-2), 11-19.

Franklina, C.C., Backosa, D.S., Moharb, I., Whiteb, C.C., Formanc, H. J. and Kavanagh, T.J., 2009. Structure, function, and post-translational regulation of the catalytic and modifier subunits of glutamate cysteine ligase. Molecular Aspects of Medicine, 30(1-2), 86-98.

Schütt, F., Aretz, S., Auffarth, G.U. and Kopitz, J., 2012. Moderately reduced ATP levels promote oxidative stress and debilitate autophagic and phagocytic capacities in human RPE cells. Investigative Ophthalmology & Visual Science, 53(9), 5354-5361.

Kurata, M., Suzuki, M. and Agar, N.S., 2000. Glutathione regeneration in mammalian erythrocytes. Comparative Haematology International, 10, 59-67.

Pratheeshkumar, P., Son, Y.O., Divya, S.P., Roy, R.V., Hitron, J.A., Wang, L., Kim, D., Dai, J., Asha, P., Zhang, Z., Wang, Y. and Shi, X., 2014. Luteolin inhibits Cr(VI)-induced malignant cell transformation of human lung epithelial cells by targeting ROS mediated multiple cell signaling pathways. Toxicology and Applied Pharmacology, 281(2), 230-241.

Mampuys, P., McElroy, C.R., Clark, J.H., Orru, R.V.A. and Maes, B.U.W., 2020. Thiosulfonates as emerging reactants: Synthesis and applications. Advanced Synthesis and Catalysis, 362(1), 3-64.