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Effects of systemic hydroxytyrosol application in experimental periodontitis of rats

Yıl 2022, Cilt: 2 Sayı: 1, 42 - 50, 15.06.2022

Öz

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.

Destekleyen Kurum

Bolu Abant Izzet Baysal University Scientific Research Center

Proje Numarası

Project number 2017.06.05.1144

Teşekkür

The authors would like to thank Dr. Buket Tekçe for her kind assistance in biochemical analysis

Kaynakça

  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • Berezow, A.B., Darveau, R.P., 2011. Microbial shift and periodontitis. Periodontology 2000, 55(1), 36-47.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • Formica, J.V., Regelson, W., 1995. Review of the biology of quercetin and related bioflavonoids. Food and Chemical Toxicology, 33(12), 1061-1080.
  • Foti, M.C., 2007. Antioxidant properties of phenols. Journal of Pharmacy and Pharmacology, 59(12), 1673-1685.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • Kinane, D.F., 2001. Causation and pathogenesis of periodontal disease. Periodontology 2000, 25(1), 8-20.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • Schroeder, H.E., Listgarten, M.A., 1997. The gingival tissues: the architecture of periodontal protection. Periodontology 2000, 13(1), 91-120.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • Young, I.S., Woodside, J.V., 2001. Antioxidants in health and disease. Journal of Clinical Pathology, 54(3), 176-186.
  • 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.
  • 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.
Yıl 2022, Cilt: 2 Sayı: 1, 42 - 50, 15.06.2022

Öz

Proje Numarası

Project number 2017.06.05.1144

Kaynakça

  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • Berezow, A.B., Darveau, R.P., 2011. Microbial shift and periodontitis. Periodontology 2000, 55(1), 36-47.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • Formica, J.V., Regelson, W., 1995. Review of the biology of quercetin and related bioflavonoids. Food and Chemical Toxicology, 33(12), 1061-1080.
  • Foti, M.C., 2007. Antioxidant properties of phenols. Journal of Pharmacy and Pharmacology, 59(12), 1673-1685.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • Kinane, D.F., 2001. Causation and pathogenesis of periodontal disease. Periodontology 2000, 25(1), 8-20.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • Schroeder, H.E., Listgarten, M.A., 1997. The gingival tissues: the architecture of periodontal protection. Periodontology 2000, 13(1), 91-120.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • Young, I.S., Woodside, J.V., 2001. Antioxidants in health and disease. Journal of Clinical Pathology, 54(3), 176-186.
  • 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.
  • 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.
Toplam 39 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Eczacılık ve İlaç Bilimleri
Bölüm Research Articles
Yazarlar

Mehmet Cihan Şengün 0000-0002-9293-2117

Şadiye Günpınar 0000-0001-6100-322X

Proje Numarası Project number 2017.06.05.1144
Yayımlanma Tarihi 15 Haziran 2022
Gönderilme Tarihi 9 Aralık 2021
Yayımlandığı Sayı Yıl 2022 Cilt: 2 Sayı: 1

Kaynak Göster

APA Şengün, M. C., & Günpınar, Ş. (2022). Effects of systemic hydroxytyrosol application in experimental periodontitis of rats. International Journal of Plant Based Pharmaceuticals, 2(1), 42-50.
AMA Şengün MC, Günpınar Ş. Effects of systemic hydroxytyrosol application in experimental periodontitis of rats. Int. J. Plant Bas. Pharm. Haziran 2022;2(1):42-50.
Chicago Şengün, Mehmet Cihan, ve Şadiye Günpınar. “Effects of Systemic Hydroxytyrosol Application in Experimental Periodontitis of Rats”. International Journal of Plant Based Pharmaceuticals 2, sy. 1 (Haziran 2022): 42-50.
EndNote Şengün MC, Günpınar Ş (01 Haziran 2022) Effects of systemic hydroxytyrosol application in experimental periodontitis of rats. International Journal of Plant Based Pharmaceuticals 2 1 42–50.
IEEE M. C. Şengün ve Ş. Günpınar, “Effects of systemic hydroxytyrosol application in experimental periodontitis of rats”, Int. J. Plant Bas. Pharm., c. 2, sy. 1, ss. 42–50, 2022.
ISNAD Şengün, Mehmet Cihan - Günpınar, Şadiye. “Effects of Systemic Hydroxytyrosol Application in Experimental Periodontitis of Rats”. International Journal of Plant Based Pharmaceuticals 2/1 (Haziran 2022), 42-50.
JAMA Şengün MC, Günpınar Ş. Effects of systemic hydroxytyrosol application in experimental periodontitis of rats. Int. J. Plant Bas. Pharm. 2022;2:42–50.
MLA Şengün, Mehmet Cihan ve Şadiye Günpınar. “Effects of Systemic Hydroxytyrosol Application in Experimental Periodontitis of Rats”. International Journal of Plant Based Pharmaceuticals, c. 2, sy. 1, 2022, ss. 42-50.
Vancouver Şengün MC, Günpınar Ş. Effects of systemic hydroxytyrosol application in experimental periodontitis of rats. Int. J. Plant Bas. Pharm. 2022;2(1):42-50.