Protective Effect of Hydroxytyrosol Against Oxidative Stress Mediated by Arsenic-Induced Neurotoxicity in Rats
- 169 Downloads
The present study reports beneficial effect of hydroxytyrosol (HT) against arsenic (As)-induced oxidative stress in the rat brain. Rats were orally administered with sodium arsenite dissolved in distilled water (25 ppm, by oral gavage) for 8 weeks or HT (10 mg/kg b. wt.) in combination with As. Results showed increase in protein oxidation and lipid peroxidation, while catalase and superoxide dismutase (SOD) activities as well as GSH content were decreased after As exposure in rat brain. Fourier transform infrared analysis showed significant alteration in peak area values that also validated the oxidative damage to lipids and proteins. In addition, As exposure caused increase in protein expression of caspase-3 and Bax, while Bcl-2 expression was downregulated resulting in translocation of cytochrome c from mitochondria to cytosol. Treatment of HT with As reversed protein oxidation, lipid peroxidation, and increased GSH content as well as catalase and SOD activities. Administration of HT also prevented translocation of cytochrome c from mitochondria and increased mitochondria/cytosol ratio of cytochrome c. Hence, treatment of HT with As improved antioxidant system and efficiently lowered the generation of oxidative stress in rat brain.
KeywordsArsenic Hydroxytyrosol Oxidative stress FTIR Neurotoxicity
The financial assistance for the present work was provided by Indian Council of Medical Research, New Delhi, India (grant No 58/51/2011-BMS), in the form of ad hoc scheme project sanctioned to Vijay Kumar. Authors also acknowledge Department of Science and Technology, New Delhi, for providing research infrastructural facilities in the form of FIST program (grant no. SR/FST/LSI-534/2012).
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflict of interest.
- 1.Chowdhury, U. K., Biswas, B. K., Chowdhury, T. R., Samanta, G., Mandal, B. K., Basu, G. C., Chanda, C. R., Lodh, D., Saha, K. C., Mukherjee, S. K., & Roy, S. (2000). Groundwater arsenic contamination in Bangladesh and West Bengal, India. Environmental Health Perspectives, 108(5), 393–397.CrossRefPubMedPubMedCentralGoogle Scholar
- 3.Rodriguez-Barranco, M., Lacasana, M., Aguilar-Garduno, C., Alguacil, J., Gil, F., Gonzalez-Alzaga, B., & Rojas-Garcia, A. (2013). Association of arsenic, cadmium and manganese exposure with neurodevelopment and behavioural disorders in children: a systematic review and meta-analysis. Sci Total Environ, 454-455, 562–577.CrossRefPubMedGoogle Scholar
- 4.Yen, C. C., Ho, T. J., Wu, C. C., Chang, C. F., Su, C. C., Chen, Y. W., Jinn, T. R., Lu, T. H., Cheng, P. W., Su, Y. C., & Liu, S. H. (2011). Inorganic arsenic causes cell apoptosis in mouse cerebrum through an oxidative stress-regulated signaling pathway. Archives of Toxicology, 85(6), 565–575.CrossRefPubMedGoogle Scholar
- 9.Rios, R., Zarazua, S., Santoyo, M. E., Sepulveda-Saavedra, J., Romero-Diaz, V., Jimenez, V., Perez-Severiano, F., Vidal-Cantu, G., Delgado, J. M., & Jimenez-Capdeville, M. E. (2009). Decreased nitric oxide markers and morphological changes in the brain of arsenic-exposed rats. Toxicology, 261(1–2), 68–75.CrossRefPubMedGoogle Scholar
- 16.Zou, X., Feng, Z., Li, Y., Wang, Y., Wertz, K., Weber, P., Fu, Y., & Liu, J. (2012). Stimulation of GSH synthesis to prevent oxidative stress-induced apoptosis by hydroxytyrosol in human retinal pigment epithelial cells: activation of Nrf2 and JNK-p62/SQSTM1 pathways. The Journal of Nutritional Biochemistry, 23(8), 994–1006.CrossRefPubMedGoogle Scholar
- 20.Zheng, A., Li, H., Xu, J., Cao, K., Li, H., Pu, W., Yang, Z., Peng, Y., Long, J., Liu, J., & Feng, Z. (2015). Hydroxytyrosol improves mitochondrial function and reduces oxidative stress in the brain of db/db mice: role of AMP-activated protein kinase activation. The British Journal of Nutrition, 113(11), 1667–1676.CrossRefPubMedGoogle Scholar
- 21.Ristagno, G., Fumagalli, F., Porretta-Serapiglia, C., Orru, A., Cassina, C., Pesaresi, M., Masson, S., Villanova, L., Merendino, A., Villanova, A., & Cervo, L. (2012). Hydroxytyrosol attenuates peripheral neuropathy in streptozotocin-induced diabetes in rats. Journal of Agricultural and Food Chemistry, 60(23), 5859–5865.CrossRefPubMedGoogle Scholar
- 22.De La Cruz, J. P., Ruiz-Moreno, M. I., Guerrero, A., Reyes, J. J., Benitez-Guerrero, A., Espartero, J. L., & Gonzalez-Correa, J. A. (2015). Differences in the neuroprotective effect of orally administered virgin olive oil (Olea europaea) polyphenols tyrosol and hydroxytyrosol in rats. Journal of Agricultural and Food Chemistry, 63(25), 5957–5963.CrossRefGoogle Scholar
- 29.da Rocha, P. D. S., Campos, J. F., Nunes-Souza, V., do Carmo Vieira, M., de Araujo Boleti, A. P., Rabelo, L. A., dos Santos, E. L., & de Picoli Souza, K. (2017). Antioxidant and protective effects of Schinus terebinthifolius raddi against doxorubicin-induced toxicity. Applied Biochemistry and Biotechnology, 1–16.Google Scholar
- 40.Moraes, T. B., Jacques, C. E. D., Rosa, A. P., Dalazen, G. R., Terra, M., Coelho, J. G., & Dutra-Filho, C. S. (2013). Role of catalase and superoxide dismutase activities on oxidative stress in the brain of a phenylketonuria animal model and the effect of lipoic acid. Cellular and Molecular Neurobiology, 33(2), 253–260.CrossRefPubMedGoogle Scholar
- 43.Arunsundar, M., Shanmugarajan, T. S., & Ravichandran, V. (2015). 3,4-Dihydroxyphenylethanol attenuates spatio-cognitive deficits in an Alzheimer’s disease mouse model: modulation of the molecular signals in neuronal survival-apoptotic programs. Neurotoxicity Research, 27(2), 143–155.CrossRefPubMedGoogle Scholar