Biosafety and Protective Effects of Tyrosol from Olea europaea L. in Gingivitis: In Vitro and in Vivo Studies
Keywords:
Anti-Inflammatory Agents, Antioxidants, Biological Products, Complementary TherapiesAbstract
Objective: To evaluate tyrosol's biosafety in cytotoxicity, genotoxicity, mutagenicity, and acute toxicity studies in an experimental gingivitis model. Material and Methods: Tyrosol was extracted from a freeze-dried and ultra-processed extract of olive oil (Olea europaea L.). Antioxidant activity was determined by the DPPH˙ radical scavenging method. Genotoxicity and mutagenicity were examined using ten mice divided into three groups: Group 1 received a solution containing 2,000 mg/kg of tyrosol; Group 2 (negative control) received distilled water, and Group 3 (positive control) received cyclophosphamide intraperitoneally. Antioxidant enzymes catalase (CAT) and superoxide dismutase (SOD) were also evaluated. Statistical analysis employed the Student t-test and ANOVA (p<0.05). Results: DPPH radical scavenging activity was evident at all tested concentrations. Over 14 days, tyrosol caused no deaths, toxicity, or adverse effects, with weight gain in all animals. Tyrosol was found to be safe in the toxicity tests. Histologically, the animals treated with 30 mg/kg of tyrosol decreased inflammatory infiltrate, and their tissue repair was similar to the control group. Moreover, compared to the positive control, there was an increase in CAT and SOD in the tyrosol gingivitis treatment groups. Conclusion: Tyrosol is safe, not genotoxic, and mildly mutagenic at high doses. Additionally, tyrosol reduces gingivitis through its anti-inflammatory and antioxidant properties and the weight gain of animals treated with the compound, indicating tyrosol's therapeutic potential.References
Hashmi MA, Khan A, Hanif M, Farooq U, Perveen S. Traditional uses, phytochemistry, and pharmacology of olea europaea (olive). Evid Based Complement Alternat Med 2015; 2015:541591. https://doi.org/10.1155/2015/541591
Cheurfa M, Abdallah HH, Allem R, Noui A, Picot-Allain CMN, Mahomoodally F. Hypocholesterolaemic and antioxidant properties of Olea europaea L. leaves from Chlef province, Algeria using in vitro, in vivo and in silico approaches. Food Chem Toxicol 2019; 123:98-105. https://doi.org/10.1016/j.fct.2018.10.002
Elnahas RA, Elwakil BH, Elshewemi SS, Olama ZA. Egyptian Olea europaea leaves bioactive extract: Antibacterial and wound healing activity in normal and diabetic rats. J Tradit Complement Med 2021; 11(5):427-434. https://doi.org/10.1016/j.jtcme.2021.02.008
Mougiou N, Trikka F, Trantas E, Ververidis F, Makris A, Argiriou A, et al. Expression of hydroxytyrosol and oleuropein biosynthetic genes are correlated with metabolite accumulation during fruit development in olive, Olea europaea, cv. Koroneiki. Plant Physiol Biochem 2018; 128:41-49. https://doi.org/10.1016/j.plaphy.2018.05.004
Paulo F, Santos L. New insights in the in vitro release of phenolic antioxidants: The case study of the release behavior of tyrosol from tyrosol-loaded ethylcellulose microparticles during the in vitro gastrointestinal digestion. Colloids Surf B Biointerfaces 2020; 196:111339. https://doi.org/10.1016/10.1016/j.colsurfb.2020.111339
Ramos AC, Negreiros JHCN, Lima AKM, Cordeiro MA, Godoy GP. The therapeutic applicability of tyrosol and hydroxytyrosol for Dentistry. Res Soc Dev 2020; 9(8):e830986420-e830986420. https://doi.org/10.33448/rsd-v9i8.6420
Christofoli BR, Rios FS, Costa RSA, Wagner TP, Goergen J, Izquierdo C, et al. Changes in gingivitis and protective factors among adults: A 4-year prospective population-based study. Community Dent Oral Epidemiol 2021; 49(5):437-444. https://doi.org/10.1111/cdoe.12619
Cirkel LL, Jacob L, Smith L, López-Sánchez GF, Konrad M, Kostev K. Relationship between chronic gingivitis and subsequent depression in 13,088 patients followed in general practices. J Psychiatr Res 2021; 138:103-106. https://doi.org/10.1016/j.jpsychires.2021.03.059
Lamster IB, Lalla E, Borgnakke WS, Taylor GW. The relationship between oral health and diabetes mellitus. J Am Dent Assoc 2008; 139(Suppl):19S-24S. https://doi.org/10.14219/jada.archive.2008.0363
Liccardo D, Cannavo A, Spagnuolo G, Ferrara N, Cittadini A, Rengo C, et al. Periodontal disease: A risk factor for diabetes and cardiovascular disease. Int J Mol Sci 2019; 20(6):1414. https://doi.org/10.3390/ijms20061414
Borovskaya TG, Vychuzhanina AV, Grigor'eva VA, Kollantay OV, Goldberg VE, Dygai AM. Evaluation of the effect of p-tyrosol on the level of DNA damage in the DNA comet assay in vivo. Bull Exp Biol Med 2020; 169(2):233-236. https://doi.org/ 10.1007/s10517-020-04857-y
Brand-Williams W, Cuvelier ME, Berset C. Use of a free radical method to evaluate antioxidant activity. LWT - Food Sci Technol 1995; 28(1):25-30. https://doi.org/10.1016/S0023-6438(95)80008-5
Organisation for Economic Co-operation and Development. Test No. 423: Acute Oral Toxicity - Acute Toxic Class Method. OECD Guidelines for the Testing of Chemicals, Section 4, OECD Publishing, Paris; 2002. https://doi.org/10.1787/9789264071001-en
Collins AR, Oscoz AA, Brunborg G, Gaivão I, Giovannelli L, Kruszewski M, et al. The comet assay: Topical issues. Mutagenesis 2008; 23(3):143-151. https://doi.org/10.1093/mutage/gem051
Schimid W. The micronucleus test. Mutat Res 1975; 31(1):9-15. https://doi.org/10.1016/0165-1161(75)90058-8
Organisation for Economic Co-operation and Development. Test No. 474: Mammalian Erythrocyte Micronucleus Test, OECD Guidelines for the Testing of Chemicals, Section 4, OECD Publishing, Paris; 2016. https://doi.org/10.1787/9789264264762-en
Akashi A. Effect of ramipril on periodontal disease experimentally induced in rats. PhD thesis – Bauru School of Dentistry, University of São Paulo, Bauru; 2016.
Lohinai Z, Benedek P, Fehér E, Györfi A, Rosivall L, Fazekas A, et al. Protective effects of mercaptoethylguanidine, a selective inhibitor of inducible nitric oxide synthase, in ligature-induced periodontitis in the rat. Br J Pharmacol 1998; 123(3):353-360. https://doi.org/10.1038/sj.bjp.0701604
Peixoto RF, Pereira JS, Nonaka CF, Silveira EJ, Miguel MC. Immunohistochemical analysis of FoxP3+ cells in periapical granulomas and radicular cysts. Arch Oral Biol 2012; 57(9):1159-1164. https://doi.org/10.1016/j.archoralbio.2012.02.005
Brianezi L, Ornelas E, Gehrke FS, Fonseca FLA, Alves BDCA, Sousa LVA, et al. Effects of physical training on the myocardium of oxariectomized LDLr knockout mice: MMP 2/9, collagen I/III, inflammation and oxidative stress. Arq Bras Cardiol 2020; 114(1):100-105. https://doi.org/10.5935/abc.20190223
Sinha, UK, Gallagher LA. Effects of steel scalpel, ultrasonic scalpel, CO2 laser, and monopolar and bipolar electrosurgery on wound healing in guinea pig oral mucosa. Laryngoscope 2003; 36(8):228-236. https://doi.org/10.1097/00005537-200302000-00007
Sinha AK. Colorimetric assay of catalase. Anal Biochem 1972; 47(2):389-394. https://doi.org/10.1016/0003-2697(72)90132-7
Misra HP, Fridovich I. The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase. J Biol Chem 1972; 247(10):3170-3175.
Karković Marković A, Torić J, Barbarić M, Jakobušić Brala C. Hydroxytyrosol, tyrosol and derivatives and their potential effects on human health. Molecules 2019; 24(10):2001. https://doi.org/10.1016/10.3390/molecules24102001
Dos Santos Souza TG, Silva MM, Feitoza GS, Melo Alcântara LF, Silva MA, Oliveira AM, et al. Biological safety of Syagrus coronata (Mart.) Becc. Fixed oil: Cytotoxicity, acute oral toxicity, and genotoxicity studies. J Ethnopharmacol 2021; 272:113941. https://doi.org/10.1016/j.jep.2021.113941
Ighodaro O, Akinloye O. First line defence antioxidants-superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX): Their fundamental role in the entire antioxidant defence grid. Alexandria J Med 2018; 54(4):287-293. https://doi.org/10.1016/j.ajme.2017.09.001
Garlet GP, Martins W Jr, Fonseca BA, Ferreira BR, Silva JS. Matrix metalloproteinases, their physiological inhibitors and osteoclast factors are differentially regulated by the cytokine profile in human periodontal disease. J Clin Periodontol 2004; 31(8):671-679. https://doi.org/10.1111/j.1600-051X.2004.00545.x
Halliwell B. “Free radicals and antioxidants - quo vadis?.” Trends Pharmacol Sci 2011; 32(3):125-130. https://doi.org/0.1016/j.tips.2010.12.002
Bunte K, Hensel A, Beikler T. Polyphenols in the prevention and treatment of periodontal disease: A systematic review of in vivo, ex vivo and in vitro studies. Fitoterapia 2019; 132:30-39. https://doi.org/10.1016/j.fitote.2018.11.012
Qi F, Huang H, Wang M, Rong W, Wang J. Applications of antioxidants in dental procedures. Antioxidants 2022; 11(12):2492. https://doi.org/10.3390/antiox11122492
Kim YY, Lee S, Kim MJ, Kang BC, Dhakal H, Choi YA, et al. Tyrosol attenuates lipopolysaccharide-induced acute lung injury by inhibiting the inflammatory response and maintaining the alveolar capillary barrier. Food Chem Toxicol 2017; 109(Pt 1):526-533. https://doi.org/10.1016/j.fct.2017.09.053
Barbaro B, Toietta G, Maggio R, Arciello M, Tarocchi M, Galli A, et al. Effects of the olive-derived polyphenol oleuropein on human health. Int J Mol Sci 2014; 15(10):18508-18524. https://doi.org/10.3390/ijms151018508
Luo G, Huang Y, Mo D, Ma N, Gao F, Song L, et al. Tyrosol attenuates proinflammatory cytokines from cultured astrocytes and NF-κB activation in in vitro oxygen glucose deprivation. Neurochem Int 2018; 121:140-145. https://doi.org/10.1016/j.neuint.2018.10.006
Fortes C, García-Vilas JÁ, Quesada AR, Medina MA. Evaluation of the anti-angiogenic potential of hydroxytyrosol and tyrosol, two bio-active phenolic compounds of extra virgin olive oil, in endothelial cell cultures. Food Chem 2012; 134(1):134-140. https://doi.org/10.1016/j.foodchem.2012.02.079
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