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2019, vol. 58, iss. 2, pp. 135-144
Effect of curcumin and p53 signaling pathway in rat thymocytes toxicity induced by Mancozeb
aUniveristy of Niš, Faculty of Medicine, Department of Physiology
bClinical Centre Niš, Clinic of Eye Diseases
Mancozeb, as a dithiocarbamate fungicide, is widely used in agriculture due to its low acute toxicity and short environmental persistence. We examined the protective role of curcumin on Mancozeb-induced toxicity in rat thymocytes and potential mechanisms involved. Rat thymocytes were exposed to Mancozeb (0.01 μg/ml) and/or curcumin (0.3, 1, 3 μM) and levels of cell viability, caspase-3, caspase-9 activity, cytochrome C oxidase, catalase activity, reactive oxygen species (ROS) production and p53 signaling involvement were evaluated after 24 h of incubation. Cells treated with Mancozeb showed increased toxicity, caspase-3, 9 activity and ROS production with decreased cytochrome C oxidase and catalase activity. Inhibition of caspase-3 and 9 activity resulted with reduced rat thymocytes toxicity while inhibition of p53 signaling pathway suppressed caspase-3 activity in cells. Co-treatment with curcumin (1, 3 μM) displayed significantly reduced toxicity, caspase-3, 9 activity and ROS production, together with increased cytochrome C and catalase activity in cells. These findings propose that Mancozeb-induced apoptosis in rat thymocytes is caspase dependent and is partially attributed to p53 signaling pathway. Certain curcumin concentrations may modulate Mancozeb-induced rat thymocytes toxicity, due to its anti-oxidative effect, and may be useful for providing potential therapeutic strategy in immunomodulation induced by Mancozeb.
Al-Gayyar, M.M.H., Al, Y.A., Sherif, I.O., Shams, M.E.E., Abbas, A.E. (2014) Protective effects of arjunolic acid against cardiac toxicity induced by oral sodium nitrite: Effects on cytokine balance and apoptosis. Life Sciences, 111(1-2), 18-26
Amaral, J.D., Xavier, J.M., Steer, C.J., Rodrigues, C.M. (2010) The role of p53 in apoptosis. Discov Med, 9(45), 145-152
Badr, R., Hashemi, M., Javadi, G., Movafagh, A., Mahdian, R. (2016) Assessment of global ischemic/reperfusion and Tacrolimus administration on CA1 region of hippocampus: gene expression profiles of BAX and BCL2 genes. Bratislava Medical Journal, 117(06), 358-362
Banerjee, A., Kunwar, A., Mishra, B., Priyadarsini, K.I. (2008) Concentration dependent antioxidant/prooxidant activity of curcumin studies from AAPH induced hemolysis of RBCs. ChemBiol Interact, 174(2), 134-139
Brady, C.A., Attardi, L.D. (2010) p53 at a glance. Journal of Cell Science, 123(15), 2527-2532
Calviello, G., Piccioni, E., Boninsegna, A., Tedesco, B., Maggiano, N., Serini, S., Wolf, F., Palozza, P. (2006) DNA damage and apoptosis induction by the pesticide Mancozeb in rat cells: Involvement of the oxidative mechanism. Toxicology and Applied Pharmacology, 211(2), 87-96
Chen, J., Xu, T., Chen, C. (2015) The critical roles of miR-21 in anti-cancer effects of curcumin. Ann Transl Med, 3(21), 330-330
Choi, E.Y., Shin, K.C., Lee, J., Kwon, T.K., Kim, S., Park, J.W. (2015) Treatment with a small synthetic compound, KMU-193, induces apoptosis in A549 human lung carcinoma cells through p53 up-regulation. Asian Pacific Journal of Cancer Prevention, 16(14), 5883-5887
Colosio, C., Barcellini, W., Maroni, M., Alcini, D., Bersani, M., Cavallo, D., Galli, A., Meroni, P., Pastorelli, R., Rizzardi, G., Soleo, L., Foà, V. (1996) Immunomodulatory effects of occupational exposure to Mancozeb. Archives of Environmental Health: An International Journal, 51(6), 445-451
Dastjerdi, M.N., Valiana, A., Mardani, M., Ra, M.Z. (2016) Adenosine A1 receptor modifies P53 expression and apoptosis in breast cancer cell line Mcf-7. Bratislava Medical Journal, 116(04), 242-246
Demir, E.A., Oz, M., Alp, M.I., Gergerlioglu, H.S., Nurullahoglu, K.E., Yerlikaya, F.H. (2016) Co-administration of cisplatin and curcumin does not alter mood-associated behaviors. Bratislava Medical Journal, 116(02), 106-111
Domico, L.M., Zeevalk, G.D., Bernard, L.P., Cooper, K.R. (2006) Acute neurotoxic effects of mancozeb and maneb in mesencephalic neuronal cultures are associated with mitochondrial dysfunction. NeuroToxicology, 27(5), 816-825
Guan, F., Ding, Y., Zhang, Y., Zhou, Y., Li, M., Wang, C. (2016) Curcumin suppresses proliferation and migration of MDA-MB-231 breast cancer cells through autophagy-dependent Akt degradation. PLoS One, 11(1), e0146553-e0146553
Guo, L.D., Chen, X.J., Hu, Y.H., Yu, Z.J., Wang, D., Liu, J.Z. (2013) Curcumin inhibits proliferation and induces apoptosis of human colorectal cancer cells by activating the mitochondria apoptotic pathway. Phytotherapy Research, 27(3), 422-430
Hori, R., Kashiba, M., Toma, T., Yachie, A., Goda, N., Makino, N., Soejima, A., Nagasawa, T., Nakabayashi, K., Suematsu, M. (2002) Gene transfection of H25A mutant heme oxygenase-1 protects cells against hydroperoxide-induced cytotoxicity. Journal of Biological Chemistry, 277(12), 10712-10718
Kaur, H., Bal, A., Sandhir, R. (2014) Curcumin supplementation improves mitochondrial and behavioral deficits in experimental model of chronic epilepsy. Pharmacology Biochemistry and Behavior, 125, 55-64
Kaushik, S., Kaur, J. (2003) Chronic cold exposure affects the antioxidant defense system in various rat tissues. Clinica Chimica Acta, 333(1), 69-77
Koizumi, K., Kawanai, T., Hashimoto, E., Kanbara, Y., Masuda, T., Kanemaru, K., Okano, Y., Oyama, Y. (2011) Cytometric analysis on cytotoxicity of curcumin on rat thymocytes: Proapoptotic and antiapoptotic actions of curcumin. Toxicology in Vitro, 25(4), 985-990
Kotipatruni, R.P., Ren, X., Thotala, D., Jaboin, J.J. (2015) NDRG4 is a novel oncogenic protein and p53 associated regulator of apoptosis in malignant meningioma cells. Oncotarget, 6(19), 17594-17604
Leadsham, J.E., Sanders, G., Giannaki, S., Bastow, E.L., Hutton, R., Naeimi, W.R., Breitenbach, M., Gourlay, C.W. (2013) Loss of cytochrome C oxidase promotes RAS-dependent ROS production from the ER resident NADPH oxidase, Yno1p, in yeast. Cell Metabolism, 18(2): 279-286
Li, X., Liu, X. (2005) Effect of curcumin on immune function of mice. J Huazhong Univ Sci Technolog Med Sci, 25(2), 137-140
Liao, Y.F., Hung, H.C., Hour, T.C., Hsu, P.C., Kao, M.C., Tsay, G.J., Liu, G. (2008) Curcumin induces apoptosis through an ornithine decarboxylase-dependent pathway in human promyelocytic leukemia HL-60 cells. Life Sciences, 82(7-8), 367-375
Mackenzie, G.G., Queisser, N., Wolfson, M.L., Fraga, C.G., Adamo, A.M., Oteiza, P.I. (2008) Curcumin induces cell-arrest and apoptosis in association with the inhibition of constitutively active NF-κB and STAT3 pathways in Hodgkin's lymphoma cells. International Journal of Cancer, 123(1), 56-65
Mandarapu, R., Ajumeera, R., Venkatesan, V., Prakhya, B.M. (2014) Proliferation and TH1/TH2 cytokine production in human peripheral blood mononuclear cells after treatment with cypermethrin and mancozebin vitro. Journal of Toxicology, 2014, 308286
Medjdoub, A., Merzouk, S.A., Merzouk, H., Chiali, F.Z., Narce, M. (2011) Effects of Mancozeb and Metribuzin on in vitro proliferative responses and oxidative stress of human and rat spleen lymphocytes stimulated by mitogens. Pesticide Biochemistry and Physiology, 101(1), 27-33
Meslin, F., Thiery, J., Richon, C., Jalil, A., Chouaib, S. (2007) Granzyme B-induced cell death involves induction of p53 tumor suppressor gene and its activation in tumor target cells. Journal of Biological Chemistry, 282(45), 32991-32999
Nishimura, Y., Oyama, T.B., Sakanashi, Y., Oyama, T.M., Matsui, H., Okano, Y., Oyama, Y.B. (2008) Some characteristics of quercetin-induced cytotoxicity on rat thymocytes under in vitro condition. Toxicology in Vitro, 22(4), 1002-1007
Park, G.B., Choi, Y., Kim, Y.S., Lee, H.K., Kim, D.S., Hur, D.Y. (2013) ROS and ERK1/2-mediated caspase-9 activation increases XAF1 expression in Dexamethasone-induced apoptosis of EBV-transformed B cells. International Journal of Oncology, 43(1), 29-38
Pavlović, V., Cekić, S., Sokolović, D., Đinđić, B. (2006) Modulatory effect of monosodium glutamate on rat thymocuyes proliferation and apoptosis. Bratisl Lek Listy, 107(5), 185-191
Pavlović, V., Cekić, S., Kamenov, B., Cirić, M., Krtinić, D. (2015) The effect of ascorbic acid on Mancozeb-induced toxicity in rat thymocytes. Folia Biol, 61(3), 116-123
Pavlović, V., Cekić, S., Cirić, M., Krtinić, D., Jovanović, J. (2016) Curcumin attenuates Mancozeb-induced toxicity in rat thymocytes through mitochondrial survival pathway. Food and Chemical Toxicology, 88, 105-111
Rohm (1995) Dithane fungicide. Philadelphia: Material Safety Data Sheetpp, X, p. 1-11
Schüll, S., Günther, S.D., Brodesser, S., Seeger, J.M., Tosetti, B., Wiegmann, K., Pongratz, C., Diaz, F., Witt, A., Andree, M., Brinkmann, K., Krönke, M., Wiesner, R.J., Kashkar, H. (2015) Cytochrome c oxidase deficiency accelerates mitochondrial apoptosis by activating ceramide synthase 6. Cell Death & Disease, 6(3), e1691-e1691
Slovackova, J., Smarda, J., Smardova, J. (2012) Roscovitine-induced apoptosis of H1299 cells depends on functional status of p53. Neoplasma, 59(06), 606-612
Srinivasan, A., Menon, V.P., Periaswamy, V., Rajasekaran, K.N. (2003) Protection of pancreatic beta-cell by the potential antioxidant bis-o-hydroxycinnamoyl methane, analogue of natural curcuminoid in experimental diabetes. J Pharm PharmSci, 6(3), 327-333
Srinivasan, S., Avadhani, N.G. (2012) Cytochrome c oxidase dysfunction in oxidative stress. Free Radical Biology and Medicine, 53(6), 1252-1263
Srivastava, A.K., Ali, W., Singh, R., Bhui, K., Tyagi, S., Al-Khedhairy, A.A., Srivastava, P.K., Musarrat, J., Shukla, Y. (2012) Mancozeb-induced genotoxicity and apoptosis in cultured human lymphocytes. Life Sciences, 90(21-22), 815-824
Tripathy, M.K., Mitra, D. (2010) Differential modulation of mitochondrial OXPHOS system during HIV-1 induced T-cell apoptosis: up regulation of Complex-IV subunit COX-II and its possible implications. Apoptosis, 15(1), 28-40
Tu, C.T., Han, B., Liu, H.C., Zhang, S.C. (2011) Curcumin protects mice against concanavalin a-induced hepatitis by inhibiting intrahepatic intercellular adhesion molecule-1 (ICAM-1) and CXCL10 expression. Molecular and Cellular Biochemistry, 358(1-2), 53-60
Vaccari, A., Saba, P., Mocci, I., Ruiu, S. (1999) Dithiocarbamate pesticides affect glutamate transport in brain synaptic vesicles. J PharmacolExpTher, 288(1), 1-5
Vine, M.F., Stein, L., Weigle, K., Schroeder, J., Degnan, D., Tse, C.K., Hanchette, C., Backer, L. (2000) Effects on the immune system associated with living near a pesticide dump site. Environmental Health Perspectives, 108(12), 1113-1124
Zahm, S.H., Blair, A. (1993) Cancer among migrant and seasonal farmworkers: An epidemiologic review and research agenda. American Journal of Industrial Medicine, 24(6), 753-766


article language: English
document type: Original Scientific Paper
DOI: 10.5633/amm.2019.0221
published in SCIndeks: 09/09/2019
peer review method: double-blind
Creative Commons License 4.0

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