Development of liver disease caused by chronic periodontitis in rats
DOI:
https://doi.org/10.1590/Keywords:
Fatty liver, Histopathology, Periodontal disease, Oxidative stress, SteatosisAbstract
Periodontitis is an inflammatory disease characterized by producing alterations in periodontal tissues, but it has been associated with the manifestation of systemic alterations, related to those produced in liver tissue. This study aims to evaluate the progression of liver damage caused by ligation-induced periodontitis in rats with time intervals of ten to 80 days. Methodology Overall, 40 rats were divided into five groups: control (no ligatures), P10, P20, P40, and P80 (teeth with ligatures at intervals of ten, 20, 40, and 80 days) in which we verified liver disease caused by periodontitis. Oral parameters were evaluated: gingival bleeding index (GBI), probing pocket depth (PPD), dental mobility (TM), myeloperoxidase activity (MPO), alveolar bone height (ABH). Liver parameters were evaluated: liver weight, histopathological scores for steatosis, inflammation, and necrosis in the liver; glutathione (GSH) and malondialdehyde (MDA). Serum parameters were also evaluated: concentrations in liver tissues, blood levels of albumin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), glucose, total cholesterol, and total proteins.
Results The results showed that the hepatic steatosis score gradually increased (P<0.05) in rats with induced periodontitis for up to 20 days (P20); and the rats with ligatures for 40 (P40) and 80 days (P80) had stable scores compared to the P20, without any further worsening, similarly occurred with GSH, MDA, and total cholesterol.
Conclusions This study indicated that liver alterations caused by ligature-induced periodontitis are progressive in early stages (0-20 days) and reach a plateau in later stages (40-80 days).
Downloads
References
- Wolf TG, Cagetti MG, Fisher JM, Seeberger GK, Campus G. Non-communicable diseases and oral health: an overview. Front Oral Health. 2021;2:725460. doi: 10.3389/froh.2021.725460
» https://doi.org/10.3389/froh.2021.725460
- Silva FR, Guimarães-Vasconcelos AC, Carvalho-França LF, di-Lenardo D, Rodrigues LS, Barreto-do-Nascimento ML, et al. Relationship between -889 C/T polymorphism in interleukin-1A gene and risk of chronic periodontitis: evidence from a meta-analysis with new published findings. Med Oral Patol Oral Cir Bucal. 2017;22(1):e7-e14. doi: 10.4317/medoral.21233
» https://doi.org/10.4317/medoral.21233
- Carvajal P, Carrer FC, Galante ML, Vernal R, Solis CB. Prevalence of periodontal diseases: Latin America and the Caribbean Consensus 2024. Braz Oral Res. 2024;38(suppl 1):e116. doi: 10.1590/1807-3107bor-2024.vol38.0116
» https://doi.org/10.1590/1807-3107bor-2024.vol38.0116
- Eke PI, Thornton-Evans GO, Wei L, Borgnakke WS, Dye BA, Genco RJ. Periodontitis in US adults: National Health and Nutrition Examination Survey 2009-2014. J Am Dent Assoc. 2018;149(7):576-88.e6. doi: 10.1016/j.adaj.2018.04.023
» https://doi.org/10.1016/j.adaj.2018.04.023
- Kocher T, Holtfreter B, Pitchika V, Kuhr K, Jordan RA. Entwicklung der Zahn- und Mundgesundheit in Deutschland von 1997 bis 2014 [Trends in dental and oral health status in Germany between 1997 and 2014]. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz. 2021;64(7):782-92. German. doi: 10.1007/s00103-021-03345-6
» https://doi.org/10.1007/s00103-021-03345-6
- Villoria GE, Fischer RG, Tinoco EM, Meyle J, Loos BG. Periodontal disease: a systemic condition. Periodontol 2000. 2024;96(1):7-19. doi: 10.1111/prd.12616
» https://doi.org/10.1111/prd.12616
- Herrera D, Molina A, Buhlin K, Klinge B. Periodontal diseases and association with atherosclerotic disease. Periodontol 2000. 2020;83(1):66-89. doi: 10.1111/prd.12302
» https://doi.org/10.1111/prd.12302
- Shinjo T, Nishimura F. The bidirectional association between diabetes and periodontitis, from basic to clinical. Jpn Dent Sci Rev. 2024;60:15-21. doi: 10.1016/j.jdsr.2023.12.002
» https://doi.org/10.1016/j.jdsr.2023.12.002
- Yang L, Fang S, Zhang R, Xia R. Associations between different triglyceride glucose index-related obesity indices and periodontitis: results from NHANES 2009-2014. Lipids Health Dis. 2024;23(1):213. doi: 10.1186/s12944-024-02192-z
» https://doi.org/10.1186/s12944-024-02192-z
- Joo K, Kang YW, Moon SY, Baek YH, Son M. Association between nonalcoholic fatty liver disease scores and chronic periodontitis: a retrospective cohort study. J Periodontol. 2025;96(5):490-8. doi: 10.1002/JPER.24-0171
» https://doi.org/10.1002/JPER.24-0171
- Caetano VD, Andrade RS, França LF, Pessoa LD, Rodrigues AA, Alves EH, et al. Food restriction reduces hepatic alterations associated with experimental periodontitis. J Periodontol. 2022;93(1):156-65. doi: 10.1002/JPER.20-0772
» https://doi.org/10.1002/JPER.20-0772
- Pessoa LS, Pereira-da Silva FR, Alves EH, França LF, di Lenardo D, Carvalho JS, et al. One or two ligatures inducing periodontitis are sufficient to cause fatty liver. Med Oral Patol Oral Cir Bucal. 2018;23(3):e269-e276. doi: 10.4317/medoral.22204
» https://doi.org/10.4317/medoral.22204
- Carvalho JS, Vasconcelos AC, Alves EH, Carvalho AS, Silva FR, França LF, et al. Steatosis caused by experimental periodontitis is reversible after removal of ligature in rats. J Periodontal Res. 2017;52(5):883-92. doi: 10.1111/jre.12459
» https://doi.org/10.1111/jre.12459
- Scheres N, Laine ML, Sipos PM, Bosch-Tijhof CJ, Crielaard W, de Vries TJ, et al. Periodontal ligament and gingival fibroblasts from periodontitis patients are more active in interaction with Porphyromonas gingivalis. J Periodontal Res. 2011;46(4):407-16. doi: 10.1111/j.1600-0765.2011.01353.x
» https://doi.org/10.1111/j.1600-0765.2011.01353.x
- França LF, Vasconcelos AC, Silva FR, Alves EH, Carvalho JS, Lenardo DD, et al. Periodontitis changes renal structures by oxidative stress and lipid peroxidation. J Clin Periodontol. 2017;44(6):568-76. doi: 10.1111/jcpe.12729
» https://doi.org/10.1111/jcpe.12729
- Andrade RS, França LF, Pessoa LD, Landim BA, Rodrigues AA, Alves EH, et al. High-fat diet aggravates the liver disease caused by periodontitis in rats. J Periodontol. 2019;90(9):1023-31. doi: 10.1002/JPER.18-0564
» https://doi.org/10.1002/JPER.18-0564
- Liu R, Li N, Liu N, Zhou X, Dong ZM, Wen XJ, et al. Effects of systemic ornidazole, systemic and local compound ornidazole and pefloxacin mesylate on experimental periodontitis in rats. Med Sci Monit. 2012;18(3):BR95-102. doi: 10.12659/msm.882514
» https://doi.org/10.12659/msm.882514
- Vasconcelos DF, Pereira da Silva FR, Pinto ME, Santana LA, Souza IG, Miranda de Souza LK, et al. Decrease of pericytes is associated with liver disease caused by ligature-induced periodontitis in rats. J Periodontol. 2017;88(2):e49-e57. doi: 10.1902/jop.2016.160392
» https://doi.org/10.1902/jop.2016.160392
- Chaves LS, Nicolau LA, Silva RO, Barros FC, Freitas AL, Aragão KS, et al. Antiinflammatory and antinociceptive effects in mice of a sulfated polysaccharide fraction extracted from the marine red algae Gracilaria caudata. Immunopharmacol Immunotoxicol. 2013;35(1):93-100. doi: 10.3109/08923973.2012.707211
» https://doi.org/10.3109/08923973.2012.707211
- Miller PD Jr, McEntire ML, Marlow NM, Gellin RG. An evidenced-based scoring index to determine the periodontal prognosis on molars. J Periodontol. 2014;85(2):214-25. doi: 10.1902/jop.2013.120675
» https://doi.org/10.1902/jop.2013.120675
- Turlin B, Ramm GA, Purdie DM, Lainé F, Perrin M, Deugnier Y, et al. Assessment of hepatic steatosis: comparison of quantitative and semiquantitative methods in 108 liver biopsies. Liver Int. 2009;29(4):530-5. doi: 10.1111/j.1478-3231
» https://doi.org/10.1111/j.1478-3231
- Sedlak J, Lindsay RH. Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman's reagent. Anal Biochem. 1968;25(1):192-205. doi: 10.1016/0003-2697(68)90092-4
» https://doi.org/10.1016/0003-2697(68)90092-4
- Mihara M; Uchiyama M. Determination of malonaldehyde precursor in tissues by thiobarbituric acid test. Analytic Biochemistry. 1978;86(1):271. doi: 10.1016/0003-2697(78)90342-1
- Tomofuji T, Ekuni D, Irie K, Azuma T, Tamaki N, Maruyama T, et al. Relationships between periodontal inflammation, lipid peroxide and oxidative damage of multiple organs in rats. Biomed Res. 2011;32(5):343-9. doi: 10.2220/biomedres.32.343
» https://doi.org/10.2220/biomedres.32.343
- Hajishengallis G, Chavakis T, Hajishengallis E, Lambris JD. Neutrophil homeostasis and inflammation: novel paradigms from studying periodontitis. J Leukoc Biol. 2015;98(4):539-48. doi: 10.1189/jlb.3VMR1014-468R
» https://doi.org/10.1189/jlb.3VMR1014-468R
- Vegda HS, Patel B, Girdhar GA, Pathan MS, Ahmad R, Haque M, et al. Role of nonalcoholic fatty liver disease in periodontitis: a bidirectional relationship. Cureus. 2024;16(7):e63775. doi: 10.7759/cureus.63775
» https://doi.org/10.7759/cureus.63775
- Mohideen K, Chandrasekar K, Ramsridhar S, Rajkumar C, Ghosh S, Dhungel S. Assessment of oxidative stress by the estimation of lipid peroxidation Marker Malondialdehyde (MDA) in patients with chronic periodontitis: a systematic review and meta-analysis. Int J Dent. 2023;2023:6014706. doi: 10.1155/2023/6014706
» https://doi.org/10.1155/2023/6014706
- Pais R, Pascale A, Fedchuck L, Charlotte F, Poynard T, Ratziu V, et al. Progression from isolated steatosis to steatohepatitis and fibrosis in nonalcoholic fatty liver disease. Clin Res Hepatol Gastroenterol. 2011;35(1):23-8. doi: 10.1016/j.gcb.2010.06.004
» https://doi.org/10.1016/j.gcb.2010.06.004
- Oh RC, Hustead TR, Ali SM, Pantsari MW. Mildly elevated liver transaminase levels: causes and evaluation. Am Fam Physician. 2017;96(11):709-15.
- Wieckowska A, McCullough AJ, Feldstein AE. Noninvasive diagnosis and monitoring of nonalcoholic steatohepatitis: present and future. Hepatology. 2007;46(2):582-9. doi: 10.1002/hep.21768
» https://doi.org/10.1002/hep.21768
- Xu J, Zhang R, Lin S, Li W, Li T, Li Z, et al. Association between periodontitis with the all-cause and cause specific mortality among the population with hyperlipidemia. BMC Oral Health. 2024;24(1):1246. doi: 10.1186/s12903-024-05055-2
» https://doi.org/10.1186/s12903-024-05055-2
- Silva FR, Conceição Pinto MS, França LF, Alves EH, Carvalho JS, Di Lenardo D, et al. Sulfated polysaccharides from the marine algae Gracilaria caudata prevent tissue damage caused by ligature-induced periodontitis. Int J Biol Macromol. 2019;132:1-8. doi: 10.1016/j.ijbiomac.2019.03.194
» https://doi.org/10.1016/j.ijbiomac.2019.03.194
- Suh JS, Kim SY, Lee SH, Kim RH, Park NH. Hyperlipidemia is necessary for the initiation and progression of atherosclerosis by severe periodontitis in mice. Mol Med Rep. 2022;26(2):273. doi: 10.3892/mmr.2022.12789
» https://doi.org/10.3892/mmr.2022.12789
- Kim SY, Kim YJ, Kim S, Momeni M, Lee A, Treanor A, et al. GV1001 Inhibits the Severity of the ligature-induced periodontitis and the vascular lipid deposition associated with the periodontitis in mice. Int J Mol Sci. 2023;24(16):12566. doi: 10.3390/ijms241612566
Downloads
Published
Issue
Section
License
Copyright (c) 2025 Karen Neisman Rodriguez Ayala, Vinícius da Silva Caetano, Any Carolina Cardoso Guimarães Vasconcelos, Maria Vitoria Pereira de Sousa, Nikaely Brandão Barbosa, Luanna Maria Soares Mesquita, Paulo Roberto Carneiro Gomes, André Luis dos Reis Barbosa, Hélio Mateus Silva Nascimento , Daniel Fernando Pereira Vasconcelos

This work is licensed under a Creative Commons Attribution 4.0 International License.
Todo o conteúdo do periódico, exceto onde está identificado, está licenciado sob uma Licença Creative Commons do tipo atribuição CC-BY.