Association of Serum Antioxidant Enzymes and Nervous Tissue Markers in Hypertensive Patients

DOI: 10.4236/wjcd.2014.44024   PDF   HTML     3,858 Downloads   5,441 Views   Citations


Background and Purpose: Hypertension has serious effects on cerebral blood vessels. Oxidative stress seems to be implicated in blood pressure elevation, through increased reactive oxygen species and/or decreased antioxidant capacity. Recently blood markers indicating damage to the central nervous system were reported to be increased in hypertensive patients. However, it is unknown whether antioxidant capacity is related to these changes. This study was designed to explore if the concentration of blood markers for nervous tissue damage was associated to antioxidant capacity in hypertensive patients. Methods: Twenty hypertensive patients and 23 healthy controls were studied. They were paired by age, sex, ethnicity, or risk factors. Serum neuron specific enolase (NSE) and S100 calcium binding protein B (S100B) were measured as nervous tissue damage markers, as well as the activity of antioxidant enzymes (catalase, glutathione peroxidase, glutathione reductase and gamma-glutamyltransferase). Results: Serum neuronal specific enolase (NSE) and S100 calcium binding protein B (S100B) concentrations determined by immunoassay were significantly increased in patients vs. controls. The activities of antioxidant enzymes measured by spectrophotometry showed that plasmatic catalase and erythrocytic glutathione peroxidase were significantly increased in patients, but erythocytic catalase was decreased. Gamma-glutamyltransferase activity was significantly correlated with S100B in hypertensive patients, while erythrocytic catalase activity was decreased in subjects with higher NSE levels. Conclusion: This preliminary investigation suggested that antioxidant status might be modulated through changes in antioxidant enzymatic activity in hypertensive patients. The association of some of these changes with peripheral markers of damage to the central nervous system could indicate that the increased levels of these proteins in hypertension are partly related to oxidative stress.

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Peña-Sánchez, M. , González-García, S. , Riverón-Forment, G. , Fernández-Concepción, O. , Martínez-Bonne, O. , Lemus-Molina, G. , Fernández-Almirall, I. , Menéndez-Sainz, M. , González-Quevedo, A. and Eells, J. (2014) Association of Serum Antioxidant Enzymes and Nervous Tissue Markers in Hypertensive Patients. World Journal of Cardiovascular Diseases, 4, 160-168. doi: 10.4236/wjcd.2014.44024.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Briones, A.M. and Touyz, R.M. (2010) Oxidative Stress and Hypertension: Current Concepts. Current Hypertension Reports, 12, 135-142.
[2] Ward, N.C., Hodgson, J.M., Puddey, I.B., Mori, T.A., Beilin, L.J. and Croft, K.D. (2004) Oxidative Stress in Human Hypertension: Association with Anti-hypertensive Treatment, Gender, Nutrition, and Lifestyle. Free Radical Biology & Medicine, 36, 26-32.
[3] Khullar, J., Relan, V. and Sherawat, B.S. (2004) Antioxidant Activities and Oxidative Stress by Products in Human Hypertension. Hypertension, 43, e7-e8.
[4] Tandon, R., Sinha, M.K., Garg, H., Khanna, R. and Khanna, H.D. (2005) Oxidative Stress in Patients with Essential Hypertension. National Medical Journal of India, 18, 297-299.
[5] Bessa, S.S., Ali, E.M. and Hamdy, S.M. (2009) The Role of Glutathione S-Transferase M1 and T1 Gene Polymorphisms and Oxidative Stress-Related Parameters in Egyptian Patients with Essential Hypertension. European Journal of Internal Medicine, 20, 625-630.
[6] Amirkhizi, F., Siassi, F., Djalali, M. and Foroushani, A.R. (2010) Assessment of Antioxidant Enzyme Activities in Erythrocytes of Pre-Hypertensive and Hypertensive Women. Journal of Research in Medical Sciences, 15, 270-278.
[7] Kashyap, M.K., Yadav, V., Sherawat, B.S., Jain, S., Kumari, S., Khullar, M., et al. (2005) Different Antioxidants Status, Total Antioxidant Power and Free Radicals in Essential Hypertension. Molecular and Cellular Biochemistry, 277, 89-99.
[8] Simic, D.V., Mimic-Oka, J., Pljesa-Ercegovac, M., Savic-Radojevic, A., Opacic, M., Matic, D., et al. (2006) By Products of Oxidative Protein Damage and Antioxidant Enzyme Activities in Plasma of Patients with Different Degrees of Essential Hypertension. Journal of Human Hypertension, 20, 149-155.
[9] Sathiyapriya, V., Nandeesha, H., Bobby, Z., Selvaraj, N. and Pavithran, P. (2007) Perturbation of Oxidant-Antioxidant Status in Non-Obese Prehypertensive Male Subjects. Journal of Human Hypertension, 21, 176-178.
[10] Nandeesha, H., Sathiyapriya, V., Bobby, Z., Pavithran, P., Agrawal, A. and Selvaraj, N. (2007) Altered Oxidant Antioxidant Status in Non-Obese Men with Moderate Essential Hypertension. Indian Journal of Medical Sciences, 61, 326-331.
[11] Montezano, A.C. and Touyz, R.M. (2012) Molecular Mechanisms of Hypertension—Reactive Oxygen Species and Antioxidants: A Basic Science Update for the Clinician. Canadian Journal of Cardiology, 28, 288-295.
[12] Yu, J.G., Zhou, R.R. and Cai, G.J. (2011) From Hypertension to Stroke: Mechanisms and Potential Prevention Strategies. CNS Neuroscience & Therapeutics, 17, 577-584.
[13] González-Quevedo, A., García, S.G., Concepción, O.F., Freixas, R.S., Sotolongo, L.Q., Menéndez, M.C., et al. (2011) Increased Serum S-100B and Neuron Specific Enolase—Potential Markers of Early Nervous System Involvement in Essential Hypertension. Clinical Biochemistry, 44, 154-159.
[14] Andreazza, A.C., Cassini, C., Rosa, A.R., Leite, M.C., de Almeida, L.M., Nardin, P., et al. (2007) Serum S100B and Antioxidant Enzymes in Bipolar Patients. Journal of Psychiatric Research, 41, 523-529.
[15] Sulaj, M., Saniova, B., Drobna, E. and Schudichova, J. (2009) Serum Neuron Specific Enolase and Malondialdehyde in Patients after Out-Of-Hospital Cardiac Arrest. Cellular and Molecular Neurobiology, 29, 807-810.
[16] Chobanian, A.V., Bakris, G.L., Black, H.R., Cushman, W.C., Green, L.A., Izzo Jr., J.L., et al. (2003) The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: The JNC 7 Report. Journal of the American Medical Association, 289, 2560-2572.
[17] Perloff, D., Grim, C., Flack, J., Frohlich, E.D., Hill, M., McDonald, M., et al. (1993) Human Blood Pressure Determination by Sphygmomanometry. Circulation, 88, 2460-2470.
[18] Aebi, H. (1984) Catalase in Vitro. Methods in Enzymology, 105, 121-126.
[19] Paglia, D.E. and Valentine, W.N. (1967) Studies on the Quantitative and Qualitative Characterization of Erythrocyte Glutathione Peroxidase. Journal of Laboratory and Clinical Medicine, 70, 158-169.
[20] Carlberg, I. and Mannervik, B. (1985) Glutathione Reductase. Methods in Enzymology, 113, 485-490.
[21] Pasqualetti, P., Festuccia, V., MacCarone, C., Di Lauro, G. and Casale, R. (1995) Diagnostic Value of Gamma Glutamyltranspeptidase and the Mean Corpuscular Volume in Chronic Hepatitis of Alcoholic Etiology. Minerva Medica, 86, 395-402.
[22] Halliwell, B. and Gutteridge, J.M. (2007) Free Radicals in Biology and Medicine. Oxford University Press, Oxford.
[23] Mansego, M.L., Solar, Gde, M., Alonso, M.P., Martínez, F., Sáez, G.T., Escudero, J.C., et al. (2011) Polymorphisms of Antioxidant Enzymes, Blood Pressure and Risk of Hypertension. Journal of Hypertension, 29, 492-500.
[24] Kedziora-Kornatowska, K., Czuczejko, J., Pawluk, H., Kornatowski, T., Motyl, J., Szadujkis-Szadurski, L., et al. (2004) The Markers of Oxidative Stress and Activity of the Antioxidant System in the Blood of Elderly Patients with Essential Arterial Hypertension. Cellular and Molecular Biology Letters, 9, 635-641.
[25] Chaves, F.J., Mansego, M.L., Blesa, S., Gonzalez-Albert, V., Espinosa, O., Giner, V., et al. (2007) Inadequate Cytoplasmic Antioxidant Enzymes Response Contributes to the Oxidative Stress in Human Hypertension. American Journal of Hypertension, 20, 62-69.
[26] Wassmann, S., Wassmann, K. and Nickenig, G. (2004) Modulation of Oxidant and Antioxidant Enzyme Expression and Function in Vascular Cells. Hypertension, 44, 381-386.
[27] Rybka, J., Kupczyk, D., Kedziora-Kornatowska, K., Czuczejko, J., Szewczyk-Golec, K., Motyl, J., et al. (2011) Glutathione-Related Antioxidant Defense System in Elderly Patients Treated for Hypertension. Cardiovascular Toxicology, 11, 1-9.
[28] Kedziora-Kornatowska, K., Czuczejko, J., Szewczyk-Golec, K., Motyl, J., Szadujkis-Szadurski, L., Kornatowski, T., et al. (2006) Effects of Perindopril and Hydrochlorothiazide on Selected Indices of Oxidative Stress in the Blood of Elderly Patients with Essential Hypertension. Clinical and Experimental Pharmacology and Physiology, 33, 751-756.
[29] Kaminsky, Y., Suslikov, A. and Kosenko, E. (2010) Specific and Pronounced Impacts of Lisinopril and Lisinopril plus Simvastatin on Erythrocyte Antioxidant Enzymes. The Journal of Clinical Pharmacology, 50, 180-187.
[30] Hashimoto, R., Umemoto, S., Guo, F., Umeji, K., Itoh, S., Kishi, H., et al. (2010) Nifedipine Activates PPAR Gamma and Exerts Antioxidative Action through Cu/ZnSOD Independent of Blood-Pressure Lowering in SHRSP. Journal of Atherosclerosis and Thrombosis, 17, 785-795.
[31] Weseler, A.R. and Bast, A. (2010) Oxidative Stress and Vascular Function: Implications for Pharmacologic Treatments. Current Hypertension Reports, 12, 154-161.
[32] Jiang, Z., Akey, J.M., Shi, J., Xiong, M., Wang, Y., Shen, Y., et al. (2001) A Polymorphism in the Promoter Region of Catalase is Associated with Blood Pressure Levels. Human Genetics, 109, 95-98.
[33] Medina-Hernández, V., Ramos-Loyo, J., Luquin, S., Sánchez, L.F., García-Estrada, J. and Navarro-Ruiz, A. (2007) Increased Lipid Peroxidation and Neuron Specific Enolase in Treatment Refractory Schizophrenics. Journal of Psychiatric Research, 41, 652-658.
[34] Góth, L. (1991) A Simple Method for Determination of Serum Catalase Activity and Revision of Reference Range. Clinica Chimica Acta, 196, 143-152.
[35] Zhou, X.F., Cui, J., DeStefano, A.L., Chazaro, I., Farrer, L.A., Manolis, A.J., et al. (2005) Polymorphisms in the Promoter Region of Catalase Gene and Essential Hypertension. Disease Markers, 21, 3-7.
[36] Onat, A., Hergenç, G., Karabulut, A., Türkmen, S., Dogan, Y., Uyarel, H., et al. (2006) Serum Gamma Glutamyltransferase as a Marker of Metabolic Syndrome and Coronary Disease Likelihood in Nondiabetic Middle-Aged and Elderly Adults. Preventive Medicine, 43, 136-139.
[37] Cheung, B.M., Ong, K.L., Tso, A.W., Cherny, S.S., Sham, P.C., Lam, T.H., et al. (2011) Gamma-Glutamyltransferase Level Predicts the Development of Hypertension in Hong Kong Chinese. Clinica Chimica Acta, 412, 1326-1331.
[38] Mason, J.E., Starke, R.D. and Van Kirk, J.E. (2010) Gamma-Glutamyltransferase: A Novel Cardiovascular Risk Biomarker. Preventive Cardiology, 13, 36-41.
[39] Shimizu, Y., Imano, H., Ohira, T., Kitamura, A., Kiyama, M., Okada, T., et al. (2010) Gamma-Glutamyltranspeptidase and Incident Stroke among Japanese Men and Women: The Circulatory Risk in Communities Study (CIRCS). Stroke, 41, 385-388.
[40] Lee, D.H., Jacobs Jr., D.R., Gross, M., Steffes, M., et al. (2003) Gamma-Glutamyltransferase is a Predictor of Incident Diabetes and Hypertension: The Coronary Artery Risk Development in Young Adults (CARDIA) Study. Clinical Chemistry, 49, 1358-1366.
[41] Shankar, A. and Li, J. (2007) Association between Serum Gamma-Glutamyltransferase Level and Prehypertension among US Adults. Circulation Journal, 71, 1567-1572.
[42] Juranek, J.K., Aleshin, A., Rattigan, E.M., Johnson, L., Qu, W., Song, F., et al. (2010) Morphological Changes and Immunohistochemical Expression of RAGE and Its Ligands in the Sciatic Nerve of Hyperglycemic Pig (Sus Scrofa). Biochemistry Insights, 1, 47-59.
[43] Aviles-Reyes, R.X., Angelo, M.F., Villarreal, A., Rios, H., Lazarowski, A. and Ramos, A.J. (2010) Intermittent Hypoxia during Sleep Induces Reactive Gliosis and Limited Neuronal Death in Rats: Implications for Sleep Apnea. Journal of Neurochemistry, 112, 854-869.
[44] Sorci, G., Riuzzi, F., Agneletti, A.L., Marchetti, C. and Donato, R. (2004) S100B Causes Apoptosis in a Myoblast Cell Line in a RAGE-Independent Manner. Journal of Cellular Physiology, 199, 274-283.
[45] Hamed, S.A., Hamed, E.A. and Zakary, M.M. (2009) Oxidative Stress and S-100B Protein in Children with Bacterial Meningitis. BMC Neurology, 9, 51.
[46] Tskitishvili, E., Sharentuya, N., Temma-Asano, K., Mimura, K., Kinugasa-Taniguchi, Y., Kanagawa, T., et al. (2010) Oxidative Stress-Induced S100B Protein from Placenta and Amnion Affects Soluble Endoglin Release from Endothelial Cells. Molecular Human Reproduction, 16, 188-199.

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