DNA damage levels in systemic lupus erythematosus patients with low disease activity: An evaluation by comet assay

Abstract

Oxidative stress has been implicated in the inflammatory process of Systemic Lupus Erythematosus (SLE), particularly by the formation of anti-DNA autoantibodies, which can lead to DNA damage. The aim of this study was to investigate, through comet assay, whether the level of DNA damage in SLE patients is different from that of healthy subjects. Twenty-five adult SLE patients with SLEDAI up to ten, and 25 healthy subjects were paired according to age, gender and Body Mass Index (BMI). Other anthropometric variables were also assessed. Comet assay was assessed as the marker of oxidative stress described as DNA Damage (DD) percentage. Waist Circumference (WC), Hip Circumference (HC) and BMI were also performed. Exclusion criteria for patients and controls comprised smoking and other chronic disorders. Level of damage index was remarkably higher in SLE patients than in controls, and no significant differences between the groups were found for age, BMI, WC and HC. No stratification concerning gender was performed, since there were just two males per group. No correlation was observed between BMI and DD (%). DD increased in SLE, which reflects the oxidant/antioxidant imbalance in these patients. These findings support an association between oxidative stress and SLE. This stronger correlation observed in patients with low disease activity may be useful in elucidating the mechanisms of disease pathogenesis.

Share and Cite:

Montalvão, T. , Miranda-Vilela, A. , Roll, M. , Grisolia, C. and Santos-Neto, L. (2012) DNA damage levels in systemic lupus erythematosus patients with low disease activity: An evaluation by comet assay. Advances in Bioscience and Biotechnology, 3, 983-988. doi: 10.4236/abb.2012.327121.

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1] Mathis, K., Venegas-Pont, M., Masterson, W., Stewart, N., Wasson, K. and Ryan, M. (2012) Oxidative stress promotes hypertension and albuminuria during autoimmune disease systemic lupus erythematosus. Hypertension, 59, 673-679. doi:10.1161/HYPERTENSIONAHA.111.190009
[2] Grammatikos, A. and Tsokos, C. (2012) Immunodeficiency and autoimmunity: Lessons from systemic lupus erythematosus. Trends in Molecular Medicine, 18, 101-108. doi:10.1016/j.molmed.2011.10.005
[3] Hassan, S., Gheita, T., Kenawy, S., Fahim, A., El-sorougy, I. and Abdou, M. (2011) Oxidative stress in systemic lupus erythematosus and arthritis patients: Relationship to disease manifestations and activity. International Journal of Rheumatic Diseases, 14, 325-331. doi:10.1111/j.1756-185X.2011.01630.x
[4] Lozovoy, M., Simao, A., Panis, C., Rotter, M., Reiche, E., Morimoto, H., Lavado, E., Cecchini, R. and Dichi, I. (2011) Oxidative stress is associated with liver damage, inflammatory status, and corticosteroid therapy in patients with systemic lupus erythematosus. Lupus, 20, 1250-1259. doi:10.1177/0961203311411350
[5] Wang, G., Pierangeli, S., Papalardo, E., Ansari, G. and Khan, M. (2010) Markers of oxidative and nitrosative stress in systemic lupus erythematosus: Correlation with disease activity. Arthritis & Rheumatism, 62, 2064-2072.
[6] Kyttaris, V. (2010) Systemic lupus erythematosus: From genes to organ damage. Methods in Molecular Biology, 662, 265-283. doi:10.1007/978-1-60761-800-3_13
[7] Janicki-Deverts, D., Cohen, S., Matthews, K., Gross, M. and Jacobs, D. (2009) Socioeconomic status, antioxidant micronutrients, ad correlates of oxidative damage: The coronary artery risk development in young adults (CAR-DIA) study. Psychosomatic Medicine, 71, 541-548. doi:10.1097/PSY.0b013e31819e7526
[8] Bayir, H. and Kagan, V. (2008) Bench-to-bedside review: Mitochondrial injury, oxidative stress and apoptosis: There is nothing more practical than a good theory. Critical Care, 12, 206. doi:10.1186/cc6779
[9] Pérez, Y., Pérez, L., Netto, R., Lima, D. and Lima, E. (2012) Malondialdehyde and the sulfhydryl groups as biomarkers of oxidative stress in patients with systemic lupus erythematosus. Revista Brasileira de Reumatologia, 52, 656-660.
[10] Zhang, Q., Ye, D., Chen, G. and Zheng, Y. (2010) Oxidative protein damage and antioxidant status in systemic lupus erythematosus. Clinical and Experimental Dermatology, 35, 287-294. doi:10.1111/j.1365-2230.2009.03437.x
[11] Kurien, B. and Scofield, R. (2003) Free radical mediated peroxidative damage in systemic lupus erythematosus. Life Sciences, 73, 1655-1666. doi:10.1016/S0024-3205(03)00475-2
[12] Rastmanesh, R. and Baer, A. (2011) Possible augmentation of photosensitivity by dietary fuanocoumarins in patients with systemic lupus erythematosus. Lupus, 20, 1005-1009. doi:10.1177/0961203311414099
[13] Kotani, K. and Taniguchi, N. (2012) Correlation between high-sensitivity c-reactive protein and reactive oxygen metabolites during a one-year period among asymptomatic subjects. Journal of Clinical Medicine and Research, 4, 52-55.
[14] Ostling, O. and Johanson, K. (1984) Microeletrophoretic study of radiation-indeced DNA damages in individual mammalian cells. Biochemical and Biophysical Research Communications, 123, 291-298. doi:10.1016/0006-291X(84)90411-X
[15] Singh, N., McCoy, M., Tice, R. and Schneider, E. (1988) A simple technique for quantitation of levels of DNA damage in individual cells. Experimental Cell Research, 175, 184-191. doi:10.1016/0014-4827(88)90265-0
[16] Fairbairn, D., Olive, P. and O’Neill, K. (1995) The comet assay: A comprehensive review. Mutation Research, 339, 37-59. doi:10.1016/0165-1110(94)00013-3
[17] Collins, A.R. (2009) Investigating oxidative DNA damage and its repair using the comet assay. Mutation Research, 681, 24-32.
[18] Andreoli, C., Leopardi, P., Rossi, S. and Crebelli, R. (1999) Processing of DNA damage induced by hydrogen peroxide and methyl methanesulfonate in human lymphocytes: Analysis by alkaline single cell gel electrophoresis and cytogenetic methods. Mutagenesis, 14, 497-503.
[19] Dusinska, M. and Collins, A.R. (2008) The comet assay in human biomonitoring: Gene-environment interactions. Mutagenesis, 23, 191-205.
[20] McKenna, D.J., Stephanie, R., McKeown, S.R. and McKelvey-Martin, V.J. (2008) Potential use of the comet assay in the clinical management of cancer. Mutagenesis, 23, 183-190.
[21] Bombardier, C., Gladman, D., Urowitz, M., Caron, D. and Chang, C. (1992) Derivation of the SLEDAI: A disease activity index for lupus patients. The Committee on prognosis studies in SLE. Arthritis & Rheumatism, 35, 630-640. doi:10.1002/art.1780350606
[22] Hochberg, M., et al. (1997) Updating the american college of rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis & Rheumatism, 40, 1725. doi:10.1002/art.1780400928
[23] Miranda-Vilela, A., Akimoto, A., Alves, P., Pereira, L., Goncalves, C., Klautau-Guimaraes, M. and Grisolia, C. (2009) Dietary carotenoid-rich pequi oil reduces plasma lipid peroxidation and DNA damage in runners and evidence for an association with MnSOD genetic variant-Val9Ala. Genetics and Molecular Research, 8, 1481-1495. doi:10.4238/vol8-4gmr684
[24] Miranda-Vilela, A., Alves, P., Akimoto, A., Pereira, L., Klautau-Guimara, M. and Grisolia, C. (2010) The effect of hydrogen peroxide-induced oxidative stress on leucocytes depends on age and physical training in healthy human subjects carrying the same genotypes of antioxidant enzymes’ gene polymorphisms. American Journal of Human Biology, 22, 807-812. doi:10.1002/ajhb.21086
[25] Collins, A.R., Ai-guo, M. and Duthie, S.J. (1995) The kinetics of oxidative DNA damage (strand breaks and oxidised pyrimidines) human cells. Mutation Research, 336, 69-77.
[26] Jalonszynski, P., Kujawski, M., Czub-Swierczek, M., Markowska, J. and Szyfter, K. (1997) Bleomicin-induced DNA damage and its removal in lymphocytes of breast cancer patients studied by comet assay. Mutation Research, 385, 223-233.
[27] Keaney, J., Lasson, M., Vasan, R., Wilson, P., Lipinska, I., Corey, D., Massaro, J., Sutherland, P., Vita, J. and Benjamin, E. (2003) Obesity and systemic oxidative stress clinical correlates of oxidative stress in the Framinghan study. Arteriosclerosis, Thrombosis and Vascular Biology, 23, 434-439. doi:10.1161/01.ATV.0000058402.34138.11
[28] Crist, B., Alekel, L., Ritland, L., Hanson, L., Genschel, U. and Reddy, M. (2009) Association of oxidative stress, iron, and centralizes fat mass in healthy postmenopausal women. Journal of Women's Health, 18, 795-801. doi:10.1089/jwh.2008.0988
[29] Florencio, G., Goncalves, A., Canário, A. and Silva, M. (2011) Aging: A reflection about physical activity and oxidative stress in woman. Acta Médica Portuguesa, 4, 983-988.
[30] Furukawa, S., Fujita, T., Shimabukuro, M., Iwaki, M., Yamada, Y., Nakajima, Y., Nakayama, O., Makishimo, M., Matsuda, M. and Shimomura, I. (2004) Increased oxidative stress in obesity and its impact on metabolic syndrome. The Journal of Clinical Investigation, 114, 1752-1761.
[31] Oeser, A., Chung, C., Asanuma, Y., Avalos, I. and Stein, M. (2005) Obesity is a independent contributor to functional capacity and inflammation in systemic lupus erythematosus. Arthritis & Rheumatism, 52, 3651-3659. doi:10.1002/art.21400
[32] Avalos, I., Chung, C., Oeser, A., et al. (2007) Oxidative stress in systemic lupus erythematosus: Relationship to disease activity and symptoms. Lupus, 16, 195-200.

Copyright © 2024 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.