Effects of systemic hydroxytyrosol application in experimental periodontitis of rats

Mehmet Cihan Sengun; Sadiye Gunpinar

doi:10.62313/ijpbp.2022.15

Authors

Mehmet Cihan Sengun Bolu Abant Izzet Baysal University, Faculty of Dentistry, Department of Periodontology, Bolu, Turkey https://orcid.org/0000-0002-9293-2117
Sadiye Gunpinar Bolu Abant Izzet Baysal University, Faculty of Dentistry, Department of Periodontology, Bolu, Turkey https://orcid.org/0000-0001-6100-322X

DOI:

https://doi.org/10.62313/ijpbp.2022.15

Keywords:

Alveolar bone loss, Antioxidant, Experimental periodontitis, Hydroxytyrosol, Oxidative stress

Abstract

This study aimed to determine the effects of systemically administered hydroxytyrosol (HT) on alveolar bone resorption and oxidative stress parameters in experimental periodontitis (EP). Thirty-two rats were divided randomly into four groups; 1) periodontally healthy + serum physiologic (PH-SP), 2) PH + hydroxytyrosol (PH-HT), 3) experimental periodontitis + SP (EP-SP), and 4) EP-HT. Following induction of EP, 10 mg/kg of systemic HT (test)/SP (control) was administered and continued for 14 days. The animals were euthanized on the 15th day, and the jaws were removed for histopathologic, histomorphometric, and immunohistochemical analyses. Enzyme-linked immunosorbent assay (ELISA) was used to analyze serum and gingival tissue malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) levels. The receptor activator of NF-kB ligand (RANKL), osteoprotegerin (OPG) levels, and RANKL/OPG ratio were analyzed via immunolabeling. Serum and tissue MDA, SOD, and GSH-Px levels did not differ between the groups. The immunohistochemical evaluation showed that RANKL levels and RANKL/OPG ratio in HT applied groups were significantly lower than SP applied groups. Within the limits of this study, daily administration of hydroxytyrosol at a dose of 10 mg/kg for 14 days could prevent alveolar bone destruction in experimental periodontitis. Besides, the antioxidant effect of HT could not be revealed.

References

Akalin, F.A., Toklu, E., Renda, N., 2005. Analysis of superoxide dismutase activity levels in gingiva and gingival crevicular fluid in patients with chronic periodontitis and periodontally healthy controls. Journal of Clinical Periodontology, 32(3), 238-243. DOI: https://doi.org/10.1111/j.1600-051X.2005.00669.x

Akalιn, F.A., Baltacιoğlu, E., Alver, A., Karabulut, E., 2007. Lipid peroxidation levels and total oxidant status in serum, saliva and gingival crevicular fluid in patients with chronic periodontitis. Journal of Clinical Periodontology, 34(7), 558-565. DOI: https://doi.org/10.1111/j.1600-051X.2007.01091.x

Arabacı, T., Kermen, E., Özkanlar, S., Köse, O., Kara, A., Kızıldağ, A., Ibişoğlu, E., 2015. Therapeutic effects of melatonin on alveolar bone resorption after experimental periodontitis in rats: a biochemical and immunohistochemical study. Journal of Periodontology, 86(7), 874-881. DOI: https://doi.org/10.1902/jop.2015.140599

Baltacıoğlu, E., Yuva, P., Aydın, G., Alver, A., Kahraman, C., Karabulut, E., Akalın, F.A., 2014. Lipid peroxidation levels and total oxidant/antioxidant status in serum and saliva from patients with chronic and aggressive periodontitis. Oxidative stress index: a new biomarker for periodontal disease?. Journal of Periodontology, 85(10), 1432-1441. DOI: https://doi.org/10.1902/jop.2014.130654

Bartold, P.M., Cantley, M.D., Haynes, D.R., 2010. Mechanisms and control of pathologic bone loss in periodontitis. Periodontology 2000, 53(1), 55-69. DOI: https://doi.org/10.1111/j.1600-0757.2010.00347.x

Berezow, A.B., Darveau, R.P., 2011. Microbial shift and periodontitis. Periodontology 2000, 55(1), 36-47. DOI: https://doi.org/10.1111/j.1600-0757.2010.00350.x

Brezani, V., Smejkal, K., Hosek, J., Tomasova, V., 2018. Anti-inflammatory natural prenylated phenolic compounds-potential lead substances. Current Medicinal Chemistry, 25(10), 1094-1159. DOI: https://doi.org/10.2174/0929867324666170810161157

Chapple, I.L., Matthews, J.B., 2007. The role of reactive oxygen and antioxidant species in periodontal tissue destruction. Periodontology 2000, 43(1), 160-232. DOI: https://doi.org/10.1111/j.1600-0757.2006.00178.x

Dalcico, R., de Menezes, A.M., Deocleciano, O.B., Oriá, R.B., Vale, M.L., Ribeiro, R.A., Brito, G.A.D.C., 2013. Protective mechanisms of simvastatin in experimental periodontal disease. Journal of Periodontology, 84(8), 1145-1157. DOI: https://doi.org/10.1902/jop.2012.120114

Di Paola, R., Mazzon, E., Rotondo, F., Dattola, F., Britti, D., De Majo, M., Cuzzocrea, S., 2005. Reduced development of experimental periodontitis by treatment with M40403, a superoxide dismutase mimetic. European Journal of Pharmacology, 516(2), 151-157. DOI: https://doi.org/10.1016/j.ejphar.2005.04.039

Ellis, S.D., Tucci, M.A., Serio, F.G., Johnson, R.B., 1998. Factors for progression of periodontal diseases. Journal of Oral Pathology & Medicine, 27(3), 101-105. DOI: https://doi.org/10.1111/j.1600-0714.1998.tb01923.x

Fabiani, R., Rosignoli, P., De Bartolomeo, A., Fuccelli, R., Servili, M., Montedoro, G.F., Morozzi, G., 2008. Oxidative DNA damage is prevented by extracts of olive oil, hydroxytyrosol, and other olive phenolic compounds in human blood mononuclear cells and HL60 cells. The Journal of Nutrition, 138(8), 1411-1416. DOI: https://doi.org/10.1093/jn/138.8.1411

Fedchenko, N., Reifenrath, J., 2014. Different approaches for interpretation and reporting of immunohistochemistry analysis results in the bone tissue–a review. Diagnostic Pathology, 9(1), 1-12. DOI: https://doi.org/10.1186/s13000-014-0221-9

Formica, J.V., Regelson, W., 1995. Review of the biology of quercetin and related bioflavonoids. Food and Chemical Toxicology, 33(12), 1061-1080. DOI: https://doi.org/10.1016/0278-6915(95)00077-1

Foti, M.C., 2007. Antioxidant properties of phenols. Journal of Pharmacy and Pharmacology, 59(12), 1673-1685. DOI: https://doi.org/10.1211/jpp.59.12.0010

França, L.F.C., Vasconcelos, A.C.C., da Silva, F.R., Alves, E.H., Carvalho, J.S., Lenardo, D.D., Vasconcelos, D.F., 2017. Periodontitis changes renal structures by oxidative stress and lipid peroxidation. Journal of Clinical Periodontology, 44(6), 568-576. DOI: https://doi.org/10.1111/jcpe.12729

Hornef, M.W., Wick, M.J., Rhen, M., Normark, S., 2002. Bacterial strategies for overcoming host innate and adaptive immune responses. Nature Immunology, 3(11), 1033-1040. DOI: https://doi.org/10.1038/ni1102-1033

Huang, P., Su, T., Wang, H., 2000. The relationship between GPx activity in gingival fluid and clinical parameters of adult periodontitis. Hua xi kou qiang yi xue za zhi= Huaxi kouqiang yixue zazhi= West China Journal of Stomatology, 18(2), 106-108.

Karakan, N.C., Akpınar, A., Göze, F., Poyraz, Ö., 2017. Investigating the effects of systemically administered strontium ranelate on alveolar bone loss histomorphometrically and histopathologically on experimental periodontitis in rats. Journal of Periodontology, 88(2), e24-e31. DOI: https://doi.org/10.1902/jop.2016.160227

Kassebaum, N.J., Bernabé, E., Dahiya, M., Bhandari, B., Murray, C.J.L., Marcenes, W., 2014. Global burden of severe tooth loss: a systematic review and meta-analysis. Journal of Dental Research, 93(7_suppl), 20S-28S. DOI: https://doi.org/10.1177/0022034514537828

Khurana, S., Venkataraman, K., Hollingsworth, A., Piche, M., Tai, T.C., 2013. Polyphenols: benefits to the cardiovascular system in health and in aging. Nutrients, 5(10), 3779-3827. DOI: https://doi.org/10.3390/nu5103779

Kinane, D.F., 2001. Causation and pathogenesis of periodontal disease. Periodontology 2000, 25(1), 8-20. DOI: https://doi.org/10.1034/j.1600-0757.2001.22250102.x

Kose, O., Arabaci, T., Kara, A., Yemenoglu, H., Kermen, E., Kizildag, A., Ozkanlar, S., 2016. Effects of melatonin on oxidative stress index and alveolar bone loss in diabetic rats with periodontitis. Journal of Periodontology, 87(5), e82-e90. DOI: https://doi.org/10.1902/jop.2016.150541

Mnafgui, K., Hajji, R., Derbali, F., Khlif, I., Kraiem, F., Ellefi, H., Gharsallah, N., 2016. Protective effect of hydroxytyrosol against cardiac remodeling after isoproterenol-induced myocardial infarction in rat. Cardiovascular Toxicology, 16(2), 147-155. DOI: https://doi.org/10.1007/s12012-015-9323-1

Pirozzi, C., Lama, A., Simeoli, R., Paciello, O., Pagano, T.B., Mollica, M.P., Meli, R., 2016. Hydroxytyrosol prevents metabolic impairment reducing hepatic inflammation and restoring duodenal integrity in a rat model of NAFLD. The Journal of Nutritional Biochemistry, 30, 108-115. DOI: https://doi.org/10.1016/j.jnutbio.2015.12.004

Reyes, J.J., Villanueva, B., López-Villodres, J.A., De La Cruz, J.P., Romero, L., Rodríguez-Pérez, M.D., González-Correa, J.A., 2017. Neuroprotective effect of hydroxytyrosol in experimental diabetes mellitus. Journal of Agricultural and Food Chemistry, 65(22), 4378-4383. DOI: https://doi.org/10.1021/acs.jafc.6b02945

Saglam, E., Canakci, C. F., Sebin, S. O., Saruhan, N., Ingec, M., Canakci, H., & Sezer, U. (2018). Evaluation of oxidative status in patients with chronic periodontitis and polycystic ovary syndrome: A cross‐sectional study. Journal of Periodontology, 89(1), 76-84. DOI: https://doi.org/10.1902/jop.2017.170129

Sağlam, M., Köseoğlu, S., Hatipoğlu, M., Esen, H.H., Köksal, E., 2015. Effect of sumac extract on serum oxidative status, RANKL/OPG system and alveolar bone loss in experimental periodontitis in rats. Journal of Applied Oral Science, 23, 33-41. DOI: https://doi.org/10.1590/1678-775720140288

Schroeder, H.E., Listgarten, M.A., 1997. The gingival tissues: the architecture of periodontal protection. Periodontology 2000, 13(1), 91-120. DOI: https://doi.org/10.1111/j.1600-0757.1997.tb00097.x

Silva, S., Sepodes, B., Rocha, J., Direito, R., Fernandes, A., Brites, D., Figueira, M.E., 2015. Protective effects of hydroxytyrosol-supplemented refined olive oil in animal models of acute inflammation and rheumatoid arthritis. The Journal of Nutritional Biochemistry, 26(4), 360-368. DOI: https://doi.org/10.1016/j.jnutbio.2014.11.011

Sobaniec, H., Sobaniec-Lotowska, M.E., 2000. Morphological examinations of hard tissues of paradontium and evaluation of selected processes of lipid peroxidation in blood serum of rats in the course of experimental periodontitis. Medical Science Monitor, 6(5), 875-881.

Tamaki, N., Orihuela-Campos, R.C., Inagaki, Y., Fukui, M., Nagata, T., Ito, H.O., 2014. Resveratrol improves oxidative stress and prevents the progression of periodontitis via the activation of the Sirt1/AMPK and the Nrf2/antioxidant defense pathways in a rat periodontitis model. Free Radical Biology and Medicine, 75, 222-229. DOI: https://doi.org/10.1016/j.freeradbiomed.2014.07.034

Tas, U., Ayan, M., Sogut, E., Kuloglu, T., Uysal, M., Tanriverdi, H.I., Sarsilmaz, M., 2015. Protective effects of thymoquinone and melatonin on intestinal ischemia–reperfusion injury. Saudi Journal of Gastroenterology: Official Journal of the Saudi Gastroenterology Association, 21(5), 284-289. DOI: https://doi.org/10.4103/1319-3767.166203

Tsai, C.C., Chen, H.S., Chen, S.L., Ho, Y.P., Ho, K.Y., Wu, Y.M., Hung, C.C., 2005. Lipid peroxidation: a possible role in the induction and progression of chronic periodontitis. Journal of Periodontal Research, 40(5), 378-384. DOI: https://doi.org/10.1111/j.1600-0765.2005.00818.x

Wang, H., Xue, L., Yan, R., Zhou, Y., Wang, M.S., Cheng, M.J., Huang, H.J., 2013. Comparison of histologic characteristics of Chinese chronic hepatitis B patients with persistently normal or mildly elevated ALT. PloS One, 8(11), e80585. DOI: https://doi.org/10.1371/journal.pone.0080585

Wang, X.L., Li, T., Li, J.H., Miao, S.Y., Xiao, X.Z., 2017. The effects of resveratrol on inflammation and oxidative stress in a rat model of chronic obstructive pulmonary disease. Molecules, 22(9), 1529. DOI: https://doi.org/10.3390/molecules22091529

Young, I.S., Woodside, J.V., 2001. Antioxidants in health and disease. Journal of Clinical Pathology, 54(3), 176-186. DOI: https://doi.org/10.1136/jcp.54.3.176

Zhang, X., Jiang, Y., Mao, J., Ren, X., Ji, Y., Mao, Y., Huang, S., 2021. Hydroxytyrosol prevents periodontitis-induced bone loss by regulating mitochondrial function and mitogen-activated protein kinase signaling of bone cells. Free Radical Biology and Medicine, 176, 298-311. DOI: https://doi.org/10.1016/j.freeradbiomed.2021.09.027

Zhou, T., Chen, D., Li, Q., Sun, X., Song, Y., Wang, C., 2013. Curcumin inhibits inflammatory response and bone loss during experimental periodontitis in rats. Acta Odontologica Scandinavica, 71(2), 349-356. DOI: https://doi.org/10.3109/00016357.2012.682092