Markers of Oxidative Stress in the Saliva of Type 2 Diabetic Patients

Main Article Content

Olatunde Olayanju
Victory Edem
Chika Okwor
Gabriel Odok
Nnaemeka Awah

Abstract

Objective: Diabetes mellitus is associated with increased prevalence of oral diseases for which reactive oxygen species have been implicated. The saliva contains protective antioxidants which statutorily curtail these destructive oxygen molecules. A functional compromise of the antioxidants may precipitate oxidative stress leading to the increased oral disease susceptibility. However, salivary markers of oxidative stress have not been sufficiently studied in the diabetics. Methods: A total of 166 adults were recruited for this study. They comprised of 95 Type 2 diabetic patients and 71 healthy non-diabetic controls. About 3 ml of unstimulated saliva samples were collected from participants and processed, levels of salivary H2O2, NO and MDA were measured using spectrophotometry method and compared between the two groups. Data was analysed using t-test, logistic regression and receiver operating characteristics (ROC) with statistical significance set at p<0.05. Results: Salivary H2O2 (p=0.024) and NO (p=0.002) were significantly higher in the diabetic patients when compared to the healthy non-diabetic control group. Binary logistic regression showed that patients with Type 2 diabetic mellitus are more likely to have elevated salivary H2O2 (OR= 1.013; p=0.025) and NO (OR=1.016; p=0.003) levels. ROC analysis showed statistically significant performance of salivary NO levels in distinguishing between T2DM patients and healthy controls. Conclusions: Higher levels of oxidative stress markers including salivary H2O2 and NO in the diabetic groups could be a pointer to the characteristic high prevalence of oral diseases in diabetes mellitus, given that oxidative stress predisposes to disease vulnerability. This calls for increased attention to oral health in diabetes management to minimise co-morbidity.

Downloads

Download data is not yet available.

Metrics

Metrics Loading ...

Article Details

Section
Articles

References

Abadi, P. A., Koopaie, M., & Montazeri, R. (2020). Comparison of salivary nitric oxide and oral health in diabetic patients with and without xerostomia. Diabetes & Metabolic Syndrome: Clinical Research & Reviews, 14, 11-15.

Al-Maskari, A. Y., Al-Maskari, M. Y., & Al-Sudairy, S. (2011). Oral manifestations and complications of diabetes mellitus: a review. Sultan Qaboos University Medical Journal, 11(2), 179.

Asmat, U., Abad, K., & Ismail, K. (2016). Diabetes mellitus and oxidative stress?A concise review. Saudi Pharmaceutical Journal, 24(5), 547-553.

Astaneie, F., Afshari, M., Mojtahedi, A., Mostafalou, S., Zamani, M. J., Larijani, B., & Abdollahi, M. (2005). Total Antioxidant Capacity and Levels of Epidermal Growth Factor and Nitric Oxide in Blood and Saliva of Insulin-Dependent Diabetic Patients. Arch Med Res, 36(4), 376- 381.

Awatef, M., Abdelh, È., & Asma, K. (2013). Hydrogen peroxide: An oxidant stress indicator in type 2 diabetes. BCAIJ, 7(4), 166-172.

Bajaj, S., & Khan, A. (2012). Antioxidants and diabetes Indian J of Endocrinol Metab, Dec; 16 (Suppl 2): S267- S271.

Bentur, L., Mansour, Y., Brik, R., Eizenberg, Y., & Nagler, R. M. (2006). Salivary oxidative stress in children during acute asthmatic attack and during remission. Respiratory Medicine, 100, 1195- 1201.

Bentz, B. G., Haines, G. K. I., Hanson, D. G., & Radosevich, J. A. (1998). Endothelial constitutive nitric oxide synthase (ecNOS) localization in normal and neoplastic salivary tissue. Head Neck, 20(4), 304-309.

Berbudi, A., Rahmadika, N., Cahyadi, A., & Ruslami, R. (2019). Type 2 diabetes and its impact on the immune system [published ahead of print, 2019 Oct 23]. Curr Diabetes Rev 2019;10.2174/15733998156661910240858.

Bhutia, Y., Ghosh, A., Sherpa, M. L., Pal, R., & Mohanta, P. K. (2011). Serum malondialdehyde level: Surrogate stress marker in the Sikkimese diabetics. Journal of natural science, biology, and medicine, 2(1), 107.

Blasiak, J., Arabski, M., Krupa, R., Wozniak, K., Zadrozny, M., Kasznicki, J., . . . Drzewoski, J. (2004). DNA damage and repair in type 2 diabetes mellitus. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 554(1-2), 297-304.

Bozovic, D., Racic, M., & Ivkovic, N. (2013). Salivary cortisol levels as a biological marker of stress reaction. Med Arch, 67(5), 374- 377.

Ceriello, A., Quagliaro, L., Catone, B., Pascon, R., Piazzola, M., Bais, B., . . . Motz, E. (2002). Role of Hyperglycemia in Nitrotyrosine Postprandial Generation. Diabetes care, 25(8), 1439-1443.

Choromanska, M., Klimiuk, A., Kostecka-Sochon, P., Wilczynska, K., Kwiatkowski, M., Okuniewska, N., . . . Maciejczyk, M. (2017). Antioxidant defence, oxidtive stress, and oxidative damage in saliva,plasma and erythrocyte of dementia patients. Can Salivary AGE be a marker of Dementia? Int J Mol Sci, 18(10).

Cosentino, F., Hishikawa, K., Katusic, Z. S., & Lüscher, T. F. (1997). High glucose in?creases nitric oxide synthase expression and superoxide anion generation in humanaortic endothelial cells. Circulation, 96, 25- 28.

Daghigh, F., Borghaei, R. C., Thornton, R. D., & Bee, J. H. (2002). Human gingival fibroblasts produce nitric oxide in response to proinflammatory cytokines. . J Periodontol, 73(4), 392- 400.

Demircan, N., Gurel, A., Armutcu, F., Unalacak, M., Aktunc, E., & Atmaca, H. (2008). The evaluation of serum cystatin C, malondialdehyde, and total antioxidant status in patients with metabolic syndrome. Med Sci Monit, 14(2), CR97-101. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/18227768

Desmond Jay, Hirofumi Hitomi, & Griendling, K. K. (2006). Oxidative stress and diabetic cardiovascular complications. Free Radical Biology & Medicine 40, 40, 183- 192. doi:10.1016/j.freeradbiomed.2005.06.018

Gallou, G., Ruelland, A., Legras, B., Maugendre, D., Allannic, H., & Cloarec, L. (1993). Plasma malondialdehyde in type 1 and type 2 diabetic patients. Clinica chimica acta, 214(2), 227-234.

Hoang, H. H., Padgham, S. V., & Meininger, C. J. (2013). L-arginine, tetrahydrobiopterin, nitric oxide and diabetes. Current Opinion in Clinical Nutrition & Metabolic Care, 16(1), 76-82.

Indurkar, M. S., Maurya, A. S., & Indurkar, S. (2016). Oral Manifestations of Diabetes. Clinical diabetes, 34, 54-57.

Kadir, T., Pisiriciler, R., Akyüz, S., Yarat, A., Emekli, N., & Ipbüker, A. (2002). Mycological and cytological examination of oral candidal carriage in diabetic patients and non-diabetic control subjects: Thorough analysis of local aetiologic and systemic factors. J Oral Rehabil., 29, 452-457.

Kosoko, A. M., Olayanju, O. A., Rahamon, S. K., & Arinola, O. G. (2017). Salivary lipid peroxidation and antioxidant status in Nigerian cigarette smokers with or without periodontitis. Asian Journal of Medicine and Health, 3(3), 1-9. doi:10.9734/AJMAH/2017/30749

Leoncini, G., Signorello, M. G., Piana, A., Carrubba, M., & U, A. (1997). Hyperactivity and increased hydrogen peroxide formation in platelets of NIDDM patients. Thrombosis Research, 86(2), 153- 160.

Maciejczyk, M., Zalewska, A., & Ladny, J. R. (2019). Salivary antioxidant barrier, redox status, and oxidative damage to proteins and lipids in healthy children, adults and the elderly. oxidative medicine and cellular longevity, 2019, 1- 12.

Maritim, A. C., Sanders, R. A., & Watkins, J. B., 3rd. (2003). Diabetes, oxidative stress, and antioxidants: a review. J Biochem Mol Toxicol, 17(1), 24-38. doi:10.1002/jbt.10058

Nakhjavani, M., Esteghamati, A., Nowroozi, S., Asgarani, F., Rashidi, A., & Khalilzadeh, O. (2010). Type 2 diabetes mellitus duration: an independent predictor of serum malondialdehyde levels. Singapore medical journal, 51(7), 582.

Papanicolaou, D. A., Mullen, N., Kyrou, I., & Nieman, L. K. (2002). Nighttime salivary cortisol: a useful test for the diagnosis of cushing's syndrome. J Clin Endocrinol Metab, 87, 4515- 4521.

Paquette, D. W., & Williams, R. C. (2000). Modulation of host inflammatory mediators as a treatment strategy for periodontal diseases. Periodontol, 24(1), 239- 252.

Pitocco, D., Tesauro, M., Alessandro, R., Ghirlanda, G., & Cardillo, C. (2013). Oxidative Stress in Diabetes Implications for Vascular and Other Complications. Int. J. Mol. Sci., 14, 21525-21550. doi:10.3390/ijms141121525

Pitocco, D., Zaccardi, F., Di Stasio, E., Romitelli, F., Santini, S. A., Zuppi, C., & Ghirlanda, G. (2010). Oxidative stress, nitric oxide, and diabetes. The review of diabetic studies: RDS, 7(1), 15.

Rehman, K., & Akash, M. S. H. (2017). Mechanism of Generation of Oxidative Stress and Pathophysiology of Type 2 Diabetes Mellitus: How Are They Interlinked? J Cell Biochem, 118(11), 3577-3585. doi:10.1002/jcb.26097

Slatter, D. A., C.H. Bolton, C. H., & Bailey, A. J. (2000). The importance of lipid-derived malondialdehude in diabetes mellitus. Diabetologia, 43, 550- 557.

Sunitha, M., & Shanmugam, S. (2006). Evaluation of salivary nitric oxide levels in oral mucosal diseases: a controlled clinical trial Indian J Dent Res, 17, 117-120.

Takeichi, O., Hayashi, M., Tsurumachi, T., Tomita, T., Ogihara, H., Ogiso, B., & Saito, T. (1999). Inducible nitric oxide synthase activity by interferon-gamma-producing cells in human radicular cysts. Int Endod J 1999; 32(2): 124-30. Int Endod J, 32(2), 124- 130.

Thomas, B., Ramesh, A., Suresh, S., & Prasad, B. R. (2013). A comparative evaluation of antioxidant enzymes and selenium in the serum of periodontitis patients with diabetes mellitus type 2. Contemp Clin Dent, 4, 176-180.

Trivedi, S., Lal, N., Mahdi, A. A., Mittal, M., Singh, B., & Pandey, S. (2014). Evaluation of antioxidant enzymes activity and malondialdehyde levels in patients with chronic periodontitis and diabetes mellitus. Journal of periodontology, 85(5), 713-720.

Zygula, A., Kosinski, P., Zwierzchowska, A., Sochacka, M., Wroczynski, P., Makarewicz-Wujec, M., . . . Giebultowicz, J. (2019). Oxidative stress markers in saliva and plasma differ between diet-controlled and insulin-controlled gestational diabetes mellitus. Diabetes Res Clin Pract, 148, 72-80. doi:10.1016/j.diabres.2018.11.021