Endodontic medicine: interrelationships among apical periodontitis, systemic disorders, and tissue responses of dental materials

Cintra, Luciano Tavares Angelo; Estrela, Carlos; Azuma, Mariane Maffei; Queiroz, Índia Olinta de Azevedo; Kawai, Toshihisa; Gomes-Filho, João Eduardo

doi:10.1590/1807-3107bor-2018.vol32.0068

Acessibilidade / Reportar erro

Brasil

Español English

sumário « anterior atual seguinte »

Sumário

Critical Review, Endodontic Therapy • Braz. oral. res. 32 (suppl 1) • 2018 • https://doi.org/10.1590/1807-3107bor-2018.vol32.0068 copy

Endodontic medicine: interrelationships among apical periodontitis, systemic disorders, and tissue responses of dental materials

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract:

Endodontic medicine, which addresses the bidirectional relationship between endodontic infections and systemic diseases, has gained prominence in the field of endodontics. There is much evidence showing that while systemic disease may influence the pathogenesis of endodontic infection, endodontic infection can also cause systemic alterations. These alterations include more severe bone resorption and inflammation in the periapical area as well as enhanced systemic disease symptoms. Similarly, many reports have described the impact of systemic diseases on the tissue responses to dental materials. Conversely, the local use of dental materials may show systemic effects in the form of altered production of biomarkers. Thus, studies to better understand the mechanisms related to those connections are extremely important. In this context, the objective of this review was to analyze and discuss the current literature regarding the connections among these three factors—systemic diseases, endodontic infection, and endodontic dental materials—and determine how these connections may interfere in the systemic health status and the endodontic treatment outcomes, which are represented by periapical wound healing.

Keywords:
Endodontics; Periapical Periodontitis; Dental Pulp Necrosis; Metabolic Diseases; Dental Materials

Authors (year)	Study type	Systemic condition	Effects
Kohsaka et al.²⁶26. Kohsaka T, Kumazawa M, Yamasaki M, Nakamura H. Periapical lesions in rats with streptozotocin-induced diabetes. J Endod. 1996 Aug;22(8):418-21. https://doi.org/10.1016/S0099-2399(96)80243-3 https://doi.org/10.1016/S0099-2399(96)80... (1996)	Rats	Diabetes	Diabetes increases bone loss and inflammatory response of AP.
Brito et al.³⁹39. Britto LR, Katz J, Guelmann M, Heft M. Periradicular radiographic assessment in diabetic and control individuals. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2003 Oct;96(4):449-52. https://doi.org/10.1016/S1079-2104(03)00034-9 https://doi.org/10.1016/S1079-2104(03)00... (2003)	Humans	Diabetes	Diabetes increases refractory lesions after endodontic treatment in men.
Fouad and Burleson³⁸38. Fouad AF, Burleson J. The effect of diabetes mellitus on endodontic treatment outcome: data from an electronic patient record. J Am Dent Assoc. 2003 Jan;134(1):43-51. https://doi.org/10.14219/jada.archive.2003.0016 https://doi.org/10.14219/jada.archive.20... (2003)	Humans	Diabetes	Diabetes is associated with a reduced successful outcome after endodontic treatment
Iwama et al.²⁷27. Iwama A, Nishigaki N, Nakamura K, Imaizumi I, Shibata N, Yamasaki M et al. The effect of high sugar intake on the development of periradicular lesions in rats with type 2 diabetes. J Dent Res. 2003 Apr;82(4):322-5. https://doi.org/10.1177/154405910308200416 https://doi.org/10.1177/1544059103082004... (2003)	Rats	Diabetes	Diabetes increases bone loss and inflammatory response of AP.
Segura-Egea et al.³²32. Segura-Egea JJ, Jiménez-Pinzón A, Ríos-Santos JV, Velasco-Ortega E, Cisneros-Cabello R, Poyato-Ferrera M. High prevalence of apical periodontitis amongst type 2 diabetic patients. Int Endod J. 2005 Aug;38(8):564-9. https://doi.org/10.1111/j.1365-2591.2005.00996.x https://doi.org/10.1111/j.1365-2591.2005... (2005)	Humans	Diabetes	Type 2 diabetes is associated with the prevalence of AP.
Caplan et al.⁴⁶46. Caplan DJ, Chasen JB, Krall EA, Cai J, Kang S, Garcia RI et al. Lesions of endodontic origin and risk of coronary heart disease. J Dent Res. 2006 Nov;85(11):996-1000. https://doi.org/10.1177/154405910608501104 https://doi.org/10.1177/1544059106085011... (2006)	Humans	Cardiovascular diseases	AP is associated with cardiovascular diseases in patients under 40 years old.
Schulze et al.¹⁷17. Schulze A, Schönauer M, Busse M. Sudden improvement of insulin sensitivity related to an endodontic treatment. J Periodontol. 2007 Dec;78(12):2380-4. https://doi.org/10.1902/jop.2007.070033 https://doi.org/10.1902/jop.2007.070033... (2007)	Humans	Diabetes	AP alters insulin resistance.
Segura-Egea et al.⁵³53. Segura-Egea JJ, Jimenez-Moreno E, Calvo-Monroy C, Ríos-Santos JV, Velasco-Ortega E, Sánchez-Domínguez B et al. Hypertension and dental periapical condition. J Endod. 2010 Nov;36(11):1800-4. https://doi.org/10.1016/j.joen.2010.08.004 https://doi.org/10.1016/j.joen.2010.08.0... (2010)	Humans	Cardiovascular diseases	Endodontic infection associated with hypertension.
Segura-Egea et al.⁵⁴54. Segura-Egea JJ, Castellanos-Cosano L, Velasco-Ortega E, Ríos-Santos JV, Llamas-Carreras JM, Machuca G et al. Relationship between smoking and endodontic variables in hypertensive patients. J Endod. 2011 Jun;37(6):764-7. https://doi.org/10.1016/j.joen.2011.03.004 https://doi.org/10.1016/j.joen.2011.03.0... (2011)	Humans	Cardiovalcular diseases	AP and root canal treatment was higher in smoker hypertensive patients.
López-López et al.³³33. López-López J, Jané-Salas E, Estrugo-Devesa A, Velasco-Ortega E, Martín-González J, Segura-Egea JJ. Periapical and endodontic status of type 2 diabetic patients in Catalonia, Spain: a cross-sectional study. J Endod. 2011 May;37(5):598-601. https://doi.org/10.1016/j.joen.2011.01.002 https://doi.org/10.1016/j.joen.2011.01.0... (2011)	Humans	Diabetes	Diabetes is associated with the prevalence endodontic treatment and AP.
Marotta et al.³⁴34. Marotta PS, Fontes TV, Armada L, Lima KC, Rôças IN, Siqueira Junior JF. Type 2 diabetes mellitus and the prevalence of apical periodontitis and endodontic treatment in an adult Brazilian population. J Endod. 2012 Mar;38(3):297-300. https://doi.org/10.1016/j.joen.2011.11.001 https://doi.org/10.1016/j.joen.2011.11.0... (2012)	Humans	Diabetes	Diabetes is not associated with the prevalence of AP.
Pasqualini et al.⁴⁵45. Pasqualini D, Bergandi L, Palumbo L, Borraccino A, Dambra V, Alovisi M et al. Association among oral health, apical periodontitis, CD14 polymorphisms, and coronary heart disease in middle-aged adults. J Endod. 2012 Dec;38(12):1570-7. https://doi.org/10.1016/j.joen.2012.08.013 https://doi.org/10.1016/j.joen.2012.08.0... (2012)	Humans	Cardiovascular diseases	There is no correlation between AP and cardiovascular diseases.
Astolphi et al.²⁰20. Astolphi RD, Curbete MM, Colombo NH, Shirakashi DJ, Chiba FY, Prieto AK et al. Periapical lesions decrease insulin signal and cause insulin resistance. J Endod. 2013 May;39(5):648-52. https://doi.org/10.1016/j.joen.2012.12.031 https://doi.org/10.1016/j.joen.2012.12.0... (2013)	Rats	Healthy	AP increases the insulin signaling in serum
Cintra et al.⁴¹41. Cintra LT, Facundo ACS, Azuma MM, Sumida DH, Astolphi RD, Bomfim SR et al. Pulpal and periodontal diseases increase triglyceride levels in diabetic rats. Clin Oral Investig. 2013 Jul;17(6):1595-9. https://doi.org/10.1007/s00784-012-0853-7 https://doi.org/10.1007/s00784-012-0853-... (2013)	Rats	Diabetes	Diabetes increases AP bone resorption. AP increases triglycerides levels.
Inchingolo et al.²⁴24. Inchingolo F, Marrelli M, Annibali S, Cristalli MP, Dipalma G, Inchingolo AD et al. Influence of endodontic treatment on systemic oxidative stress. Int J Med Sci. 2013 Dec;11(1):1-6. https://doi.org/10.7150/ijms.6663 https://doi.org/10.7150/ijms.6663... (2013)	Humans	Healthy	AP increases oxidative stress
Cintra et al.²⁸28. Cintra LT, Samuel RO, Facundo AC, Prieto AK, Sumida DH, Bomfim SR et al. Relationships between oral infections and blood glucose concentrations or HbA1c levels in normal and diabetic rats. Int Endod J. 2014 Mar;47(3):228-37. https://doi.org/10.1111/iej.12136 https://doi.org/10.1111/iej.12136... (2014)	Rats	Diabetes	Diabetes increases AP bone resorption. AP increases HbA1 levels.
Cintra et al.²⁹29. Cintra LT, Facundo ACS, Prieto AK, Sumida DH, Narciso LG, Mogami Bomfim SR et al. Blood profile and histology in oral infections associated with diabetes. J Endod. 2014 Aug;40(8):1139-44. https://doi.org/10.1016/j.joen.2014.01.034 https://doi.org/10.1016/j.joen.2014.01.0... (2014)	Rats	Diabetes	Diabetes increases AP bone resorption. AP increases serum inflammatory cells.
Cintra et al.³⁰30. Cintra LT, Samuel RO, Azuma MM, Ribeiro CP, Narciso LG, Lima VM et al. Apical periodontitis and periodontal disease increase serum IL-17 levels in normoglycemic and diabetic rats. Clin Oral Investig. 2014 Dec;18(9):2123-8. https://doi.org/10.1007/s00784-014-1192-7 https://doi.org/10.1007/s00784-014-1192-... (2014)	Rats	Diabetes	Diabetes increases AP bone resorption. AP increases the proinflammatory cytokine IL-17 in blood.
Costa et al.⁵⁰50. Costa TH, Figueiredo Neto JA, Oliveira AE, Maia MFL, Almeida AL. Association between chronic apical periodontitis and coronary artery disease. J Endod. 2014 Feb;40(2):164-7. https://doi.org/10.1016/j.joen.2013.10.026 https://doi.org/10.1016/j.joen.2013.10.0... (2014)	Humans	Cardiovascular diseases	AP increases the risk to develop coronary artery disease.
Astolphi et al.²¹21. Astolphi RD, Curbete MM, Chiba FY, Cintra LT, Ervolino E, Mota MS et al. Periapical lesions decrease insulin signaling in rat skeletal muscle. J Endod. 2015 Aug;41(8):1305-10. https://doi.org/10.1016/j.joen.2015.04.002 https://doi.org/10.1016/j.joen.2015.04.0... (2015)	Rats	Healthy	AP increases the insulin signaling in skeletal muscle.
Gomes-Filho et al.⁶⁰60. Gomes-Filho JE, Wayama MT, Dornelles RC, Ervolino E, Yamanari GH, Lodi CS et al. Raloxifene modulates regulators of osteoclastogenesis and angiogenesis in an oestrogen deficiency periapical lesion model. Int Endod J. 2015 Nov;48(11):1059-68. https://doi.org/10.1111/iej.12403 https://doi.org/10.1111/iej.12403... (2015)	Rats	Hypoestrogenia	Hypoestrogenism increases levels of the local regulators of both osteoclastogenesis and angiogenesis
Gomes-Filho et al.⁶¹61. Gomes-Filho JE, Wayama MT, Dornelles RC, Ervolino E, Coclete GA, Duarte PC et al. Effect of raloxifene on periapical lesions in ovariectomized rats. J Endod. 2015 May;41(5):671-5. https://doi.org/10.1016/j.joen.2014.11.027 https://doi.org/10.1016/j.joen.2014.11.0... (2015)	Rats	Hypoestrogenia	Hypoestrogenism potentiates the progression of AP
Sánchez-Domínguez et al.¹⁸18. Sánchez-Domínguez B, López-López J, Jané-Salas E, Castellanos-Cosano L, Velasco-Ortega E, Segura-Egea JJ. Glycated hemoglobin levels and prevalence of apical periodontitis in type 2 diabetic patients. J Endod. 2015 May;41(5):601-6. https://doi.org/10.1016/j.joen.2014.12.024 https://doi.org/10.1016/j.joen.2014.12.0... (2015)	Humans	Diabetes	AP increases HbA1 levels.
An et al.⁵¹51. An GK, Morse DE, Kunin M, Goldberger RS, Psoter WJ. Association of radiographically diagnosed apical periodontitis and cardiovascular disease: a hospital records-based study. J Endod. 2016 Jun;42(6):916-20. https://doi.org/10.1016/j.joen.2016.03.011 https://doi.org/10.1016/j.joen.2016.03.0... (2016)	Humans	Cardiovascular diseases	Endodontic infection associated with cardiovascular diseases.
Cintra et al.⁷7. Cintra LT, Samuel RO, Azuma MM, Queiróz AO, Ervolino E, Sumida DH et al. Multiple apical periodontitis influences serum levels of cytokines and nitric oxide. J Endod. 2016 May;42(5):747-51. https://doi.org/10.1016/j.joen.2016.01.022 https://doi.org/10.1016/j.joen.2016.01.0... (2016)	Rats	Healthy	AP increases proinflammatory cytokines
Gomes et al.⁴⁹49. Gomes MS, Hugo FN, Hilgert JB, Sant’Ana Filho M, Padilha DM, Simonsick EM et al. Apical periodontitis and incident cardiovascular events in the Baltimore longitudinal study of ageing. Int Endod J. 2016 Apr;49(4):334-42. https://doi.org/10.1111/iej.12468 https://doi.org/10.1111/iej.12468... (2016)	Humans	Cardiovascular diseases	Endodontic infection associated with cardiovascular diseases.
Grønkjær et al.⁵⁹59. Grønkjær L, Holmstrup P, Schou S, Schwartz K, Kongstad J, Jepsen P et al. Presence and consequence of tooth periapical radiolucency in patients with cirrhosis. Hepat Med. 2016 Sep;8:97-103. https://doi.org/10.2147/HMER.S113485 https://doi.org/10.2147/HMER.S113485... (2016)	Humans	Cirrhosis	AP increases the prevalence of cirrhosis-related complications such as ascites, hepatic encephalopathy, and/or variceal bleeding.
Lijestrand et al.⁴4. Liljestrand JM, Mäntylä P, Paju S, Buhlin K, Kopra KA, Persson GR et al. Association of endodontic lesions with coronary artery disease. J Dent Res. 2016 Nov;95(12):1358-65. https://doi.org/10.1177/0022034516660509 https://doi.org/10.1177/0022034516660509... (2016)	Humans	Cardiovascular diseases	Endodontic infection associated with cardiovascular diseases.
Martins et al.⁴⁸48. Martins CM, Sasaki H, Hirai K, Andrada AC, Gomes-Filho JE. Relationship between hypertension and periapical lesion: an in vitro and in vivo study. Braz Oral Res. 2016 Oct;30(1):e78. https://doi.org/10.1590/1807-3107BOR-2016.vol30.0078 https://doi.org/10.1590/1807-3107BOR-201... (2016)	Rats	Cardiovascular diseases	Hypertension did not alter AP progression. Hypertension increases osteoclasts differentiation “in vitro”.
Rudranaik et al.³⁷37. Rudranaik S, Nayak M, Babshet M. Periapical healing outcome following single visit endodontic treatment in patients with type 2 diabetes mellitus. J Clin Exp Dent. 2016 Dec;8(5):e498-504. https://doi.org/10.4317/jced.52859 https://doi.org/10.4317/jced.52859... (2016)	Humans	Diabetes	Diabetes increases the bone loss in AP and decrease the healing capacity.
Segura-Egea et al.⁴⁰40. Segura-Egea JJ, Martín-González J, Cabanillas-Balsera D, Fouad AF, Velasco-Ortega E, López-López J. Association between diabetes and the prevalence of radiolucent periapical lesions in root-filled teeth: systematic review and meta-analysis. Clin Oral Investig. 2016 Jul;20(6):1133-41. https://doi.org/10.1007/s00784-016-1805-4 https://doi.org/10.1007/s00784-016-1805-... (2016)	Systematic review and meta-analysis	Diabetes	Diabetes increases the prevalency of AP in endodontically treated teeth.
Zhang et al.²³23. Zhang J, Huang X, Lu B, Zhang C, Cai Z. Can apical periodontitis affect serum levels of CRP, IL-2, and IL-6 as well as induce pathological changes in remote organs? Clin Oral Investig. 2016 Sep;20(7):1617-24. https://doi.org/10.1007/s00784-015-1646-6 https://doi.org/10.1007/s00784-015-1646-... (2016)	Rats	Healthy	AP increases the levels of CRP, IL-2, and IL-6 in blood. In addition, AP affects organs.
Arya et al.¹⁹19. Arya S, Duhan J, Tewari S, Sangwan P, Ghalaut V, Aggarwal S. Healing of apical periodontitis after nonsurgical treatment in patients with type 2 diabetes. J Endod. 2017 Oct;43(10):1623-7. https://doi.org/10.1016/j.joen.2017.05.013 https://doi.org/10.1016/j.joen.2017.05.0... (2017)	Humans	Diabetes	Diabetes decreases periapical healing after endodontic treatment. AP increases HbA1 levels
Azuma et al.³¹31. Azuma MM, Gomes-Filho JE, Prieto AK, Samuel RO, Lima VM, Sumida DH et al. Diabetes increases interleukin-17 levels in periapical, hepatic, and renal tissues in rats. Arch Oral Biol. 2017 Nov;83:230-5. https://doi.org/10.1016/j.archoralbio.2017.08.001 https://doi.org/10.1016/j.archoralbio.20... (2017)	Rats	Diabetes	Diabetes increases interleukin-17 levels in periapical, hepatic, and renal tissues
Cintra et al.⁴³43. Cintra LT, Samuel RO, Prieto AK, Sumida DH, Dezan-Júnior E, Gomes-Filho JE. Oral health, diabetes, and body weight. Arch Oral Biol. 2017 Jan;73:94-9. https://doi.org/10.1016/j.archoralbio.2016.10.002 https://doi.org/10.1016/j.archoralbio.20... (2017)	Rats	Diabetes	AP alters body weight and weight of organs
Khalighinejad et al.⁵⁶56. Khalighinejad N, Aminoshariae A, Kulild JC, Sahly K, Mickel A. Association of end-stage renal disease with radiographically and clinically diagnosed apical periodontitis: a hospital-based study. J Endod. 2017 Sep;43(9):1438-41. https://doi.org/10.1016/j.joen.2017.04.014PMID:28712633 https://doi.org/10.1016/j.joen.2017.04.0... (2017)	Humans	Renal disease	End-stage renal diseases may possibly alter the pathogenesis of AP. AP increases the levels of urea.
Khalighinejad et al.⁵⁷57. Khalighinejad N, Aminoshariae A, Kulild JC, Mickel A. Apical periodontitis, a predictor variable for preeclampsia: a case-control study. J Endod. 2017 Oct;43(10):1611-4. https://doi.org/10.1016/j.joen.2017.05.021 https://doi.org/10.1016/j.joen.2017.05.0... (2017)	Humans	Preeclampsia	AP is a strong predictor for maternal preeclampsia.
Pereira et al.²²22. Pereira RF, Cintra LT, Tessarin GW, Chiba FY, Mattera MSLC, Scaramele NF, et al. Periapical lesions increase macrophage infiltration and inflammatory signaling in muscle tissue of rats. J Endod. 2017 Jun;43(6):982-8. https://doi.org/10.1016/j.joen.2017.01.030 https://doi.org/10.1016/j.joen.2017.01.0... (2017)	Rats	Healthy	AP promotes an increase in macrophage infiltration and inflammation in muscle tissue
Piras et al.⁵⁸58. Piras V, Usai P, Mezzena S, Susnik M, Ideo F, Schirru E et al. Prevalence of apical periodontitis in patients with inflammatory bowel diseases: a retrospective clinical study. J Endod. 2017 Mar;43(3):389-94. https://doi.org/10.1016/j.joen.2016.11.004 https://doi.org/10.1016/j.joen.2016.11.0... (2017)	Humans	Inflammatory bowel disease	Inflammatory bowel disease increases the prevalence and bone loss of AP.
Prieto et al.⁶6. Prieto AK, Gomes-Filho JE, Azuma MM, Sivieri-Araújo G, Narciso LG, Souza JC et al. Influence of apical periodontitis on stress oxidative parameters in diabetic rats. J Endod. 2017 Oct;43(10):1651-6. https://doi.org/10.1016/j.joen.2017.05.014 https://doi.org/10.1016/j.joen.2017.05.0... (2017)	Rats	Diabetes	Diabetes increases AP bone resorption. AP increase oxidative stress.
Rashmi et al.⁴⁷47. Rashmi N, Galhotra V, Goel P, Rajguru JP, Jha SK, Kulkarni K. Assessment of C-reactive proteins, cytokines, and plasma protein levels in hypertensive patients with apical periodontitis. J Contemp Dent Pract. 2017 Jun;18(6):516-21. https://doi.org/10.5005/jp-journals-10024-2076 https://doi.org/10.5005/jp-journals-1002... (2017)	Humans	Cardiovascular diseases	AP alters systemic inflammatory markers in hypertensive patients.
Smadi et al.³⁵35. Smadi L. Apical Periodontitis and endodontic treatment in patients with type ii diabetes mellitus: comparative cross-sectional survey. J Contemp Dent Pract. 2017 May;18(5):358-62. https://doi.org/10.5005/jp-journals-10024-2046 https://doi.org/10.5005/jp-journals-1002... (2017)	Humans	Diabetes	Diabetes is associated with the prevalence of AP.
Singhal & Rai⁴⁴44. Singhal RK, Rai B. sTNF-R Levels: Apical periodontitis linked to coronary heart disease. Open Access Maced J Med Sci. 2017 Mar;5(1):68-71. https://doi.org/10.3889/oamjms.2017.010 https://doi.org/10.3889/oamjms.2017.010... (2017)	Humans	Cardiovascular diseases	AP alters systemic inflammation.
Tibúrcio-Machado et al.³⁶36. Tibúrcio-Machado CD, Bello MC, Maier J, Wolle CF, Bier CA. Influence of diabetes in the development of apical periodontitis: a critical literature review of human studies. J Endod. 2017 Mar;43(3):370-6. https://doi.org/10.1016/j.joen.2016.11.012 https://doi.org/10.1016/j.joen.2016.11.0... (2017)	Critical literature review	Diabetes	Positive association between diabetes and a larger number of periapical lesions.
Fereira et al.⁴²42. Ferreira LL, Gomes JE, Sumida DH, Bonfim SR, Sivieri-Araújo G, Guimarães G et al. Diabetic rats present high mean platelet count in the presence of oral infections. Braz Dent J. 2017 Sep-Oct;28(5):548-51. https://doi.org/10.1590/0103-6440201701386 https://doi.org/10.1590/0103-64402017013... (2017)	Rats	Diabetes	Oral infections associated with diabetes increases mean platelet count.
Virtanen et al.⁵²52. Virtanen E, Nurmi T, Söder PÖ, Airila-Månsson S, Söder B, Meurman JH. Apical periodontitis associates with cardiovascular diseases: a cross-sectional study from Sweden. BMC Oral Health. 2017 Jul;17(1):107. https://doi.org/10.1186/s12903-017-0401-6 https://doi.org/10.1186/s12903-017-0401-... (2017)	Humans	Cardiovascular diseases	AP is associated with cardiovascular diseases.
Samuel et al.⁵5. Samuel RO, Gomes-Filho JE, Azuma MM, Sumida DH, Oliveira SH, Chiba FY et al. Endodontic infections increase leukocyte and lymphocyte levels in the blood. Clin Oral Investig. 2018 Apr;22(3):1395-401. https://doio.org/10.1007/s00784-017-2222-z. https://doio.org/10.1007/s00784-017-2222... (2018)	Rats	Healthy	AP increases inflammatory cells in blood.

Authors (year)	Study type	Materials	Body organs	Analysis
Elovaara et al.⁶⁹69. Elovaara E, Kivistö H, Vainio H. Effects of methyl methacrylate on non-protein thiols and drug metabolizing enzymes in rat liver and kidneys. Arch Toxicol. 1983 Feb;52(2):109-21. https://doi.org/10.1007/BF00354771 https://doi.org/10.1007/BF00354771... (1983)	Rats	Methyl methacrylate (MMA)	Kidney	Biochemical analysis (NADPH-cytochrome c reductase, 7-ethoxycoumarin 0-deethylase, PPO, GSH, cytochrome P-450)
	Rats	Methyl methacrylate (MMA)	Liver
Raje et al.⁷⁰70. Raje RR, Ahmad S, Weisbroth SH. Methylmethacrylate: tissue distribution and pulmonary damage in rats following acute inhalation. Res Commun Chem Pathol Pharmacol. 1985 Oct;50(1):151-4. https://doi.org/10.1016/0378-4274(83)90539-8 https://doi.org/10.1016/0378-4274(83)905... (1985)	Rats	Methyl methacrylate (MMA)	Blood	Histopathologic
			Brain	Chromatography
			Lungs
Economides et al.⁷⁶76. Economides N, Kotsaki-Kovatsi VP, Poulopoulos A, Kolokuris I, Rozos G, Shore R. Experimental study of the biocompatibility of four root canal sealers and their influence on the zinc and calcium content of several tissues. J Endod. 1995 Mar;21(3):122-7. https://doi.org/10.1016/S0099-2399(06)80436-X https://doi.org/10.1016/S0099-2399(06)80... (1995)	Rats	AH-26	Brain	Biochemical analysis (Zn, Ca)
		Roth 811	Liver
		CRCS	Kidney
		Sealapex	Uterus
Kolokouris et al.⁷⁷77. Kolokouris I, Kotsaki-Kovatsi VP, Economides N, Poulopoulos A, Rozos G, Vlemmas I. Influence of zinc oxide and eugenol sealer on concentration of zinc, calcium and copper in rat tissues. Endod Dent Traumatol. 1998 Oct;14(5):210-3. https://doi.org/10.1111/j.1600-9657.1998.tb00840.x https://doi.org/10.1111/j.1600-9657.1998... (1998)	Rats	Roth 811	Liver	Biochemical analysis (Zn, Ca, Cu)
			Heart
			Kidney
			Brain
Ballestri et al.⁶²62. Ballestri M, Baraldi A, Gatti AM, Furci L, Bagni A, Loria P et al. Liver and kidney foreign bodies granulomatosis in a patient with malocclusion, bruxism, and worn dental prostheses. Gastroenterology. 2001 Nov;121(5):1234-8. https://doi.org/10.1053/gast.2001.29333 https://doi.org/10.1053/gast.2001.29333... (2001)	Humans	Dental prostheses (porcelain)	Liver	Histopathologic
	Humans	Dental prostheses (porcelain)	Kidney	Histopathologic
Al-Hiyasat et al.⁶⁷67. Al-Hiyasat AS, Darmani H, Elbetieha AM. Effects of resin based dental composites on fertility of male mice. Eur J Oral Sci. 2002 Feb;110(1):44-7. https://doi.org/10.1034/j.1600-0722.2002.00163.x https://doi.org/10.1034/j.1600-0722.2002... (2002)	Mice	Dental composite	Testicles	Fertility
	Mice	Resin Z-100	Testicles	Sperm count
Fakhouri et al.⁶⁸68. Fakhouri J, Sarkis R, Chababi-Atallah M, Aftimos G. Toxic effects of methyl methacrylate monomer on male genital tissues: in vitro study in rats. J Med Liban. 2008 Jan-Mar;56(1):22-6. (2008)	Rats	Methyl methacrylate (MMA)	Testicles	Histopathologic
	Rats	Methyl methacrylate (MMA)	Seminal vesicles	Histopathologic
Khalil and Eid⁶⁵65. Khalil WA, Eid NF. Biocompatibility of bioaggregate and mineral trioxide aggregate on the liver and kidney. Int Endod J. 2013 Aug;46(8):730-7. https://doi.org/10.1111/iej.12050 https://doi.org/10.1111/iej.12050... (2013)	Rats	Diaroot	Blood (plasma)	Histopathologic
		Bioaggregate	Kidney	Biochemical analysis (ALT,AST,Urea,Creatinine)
		Grey ProRoot MTA	Liver
Demirkaya et al.¹¹11. Demirkaya K, Can Demirdöğen B, Öncel Torun Z, Erdem O, Çetinkaya S, Akay C. In vivo evaluation of the effects of hydraulic calcium silicate dental cements on plasma and liver aluminium levels in rats. Eur J Oral Sci. 2016 Feb;124(1):75-81. https://doi.org/10.1111/eos.12238 https://doi.org/10.1111/eos.12238... (2016)	Rats	MTA Angelus	Blood (plasma)	Biochemical analysis (Al)
		MTA Fillapex	Liver
		Theracal LC
Simsek et al.¹²12. Simsek N, Bulut ET, Ahmetoğlu F, Alan H. Determination of trace elements in rat organs implanted with endodontic repair materials by ICP-MS. J Mater Sci Mater Med. 2016 Mar;27(3):46. https://doi.org/10.1007/s10856-015-5663-4 https://doi.org/10.1007/s10856-015-5663-... (2016)	Rats	Micro Mega MTA	Kidney	Biochemical analysis (Be, Mg,Al,Ca,Cr,As,Pb)
		Bioaggregate	Liver
		Biodentine
Demirkaya et al.⁶⁴64. Demirkaya K, Demirdöğen BC, Torun ZÖ, Erdem O, Çırak E, Tunca YM. Brain aluminium accumulation and oxidative stress in the presence of calcium silicate dental cements. Hum Exp Toxicol. 2017 Oct;36(10):1071-80. https://doi.org/10.1177/0960327116679713 https://doi.org/10.1177/0960327116679713... (2017)	Rats	MTA Angelus	Brain	Biochemical analysis (Al)
	Rats	MTA Fillapex Theracal LC	Brain	Oxidative stress (TBARS,CAT,SOD,GPx)
Demirkaya et al.⁷³73. Demirkaya K, Demirdöğen BC, Torun ZO, Erdem O, Tunca YM. The effects of hydraulic calcium silicate containing endodontic materials on oxidative stress in erythrocytes and liver. Turkish J Biochem. 2017. https://doi.org/10.1515/tjb-2016-0263. https://doi.org/10.1515/tjb-2016-0263... (2017)	Rats	MTA Angelus	Blood (erythrocytes)	Oxidative stress (TBARS,CAT,SOD,GPx)
	Rats	MTA Fillapex Theracal LC	Liver	Oxidative stress (TBARS,CAT,SOD,GPx)
Garcia et al.⁶⁶66. Garcia LD, Huck C, Magalhães FA, Souza PP, Costa CAS. Systemic effect of mineral aggregate-based cements: histopathological analysis in rats. J Appl Oral Sci. 2017 Nov-Dec;25(6):620-30. https://doi.org/10.1590/1678-7757-2016-0634 https://doi.org/10.1590/1678-7757-2016-0... (2017)	Rats	MTAEndobinder	Blood (plasma)	Histopathologic analysis;
			Kidney	Biochemical analysis (ALT,AST,Urea,Creatinine)
			Liver
Queiroz et al.⁸⁰80. Queiroz IOA, Mello WG, Martins CM, Dal Fabbro R, Narciso LG, Massunari L et al. Systemic bone marker expression induced by grey and white mineral trioxide aggregate in normal and diabetic conditions. Int Endod J. 2018 Jan 19. https://doi.org/10.1111/iej.12900 https://doi.org/10.1111/iej.12900... (2018)	Rats	Gray MTA Angelus white MTA Angelus	Blood (plasma)	Biochemical analysis (Ca, P, ALP)

Authors/year	Study type	Materials	Body organs	Analysis	Systemic Condition
Garber et al.⁹²92. Garber SE, Shabahang S, Escher AP, Torabinejad M. The effect of hyperglycemia on pulpal healing in rats. J Endod. 2009 Jan;35(1):60-2. https://doi.org/10.1016/j.joen.2008.09.010 https://doi.org/10.1016/j.joen.2008.09.0... (2009)	Rats	MTA	Dental pulp	Histopathologic analysis	Diabetes Mellitus
Madani et al.⁹³93. Madani ZS, Haddadi A, Mesgarani A, Seyedmajidi M, Mostafazadeh A, Bijani A et al. Histopathologic responses of the dental pulp to calcium-enriched mixture (CEM) and mineral trioxide aggregate (MTA) in diabetic and non-diabetic rats. Int J Mol Cell Med. 2014;3(4):263-71. (2014)	Rats	MTA	Dental pulp	Histopathologic analysis	Diabetes Mellitus
	Rats	CEM	Dental pulp	Histopathologic analysis	Diabetes Mellitus
Gomes-Filho et al.⁸⁷87. Gomes-Filho JE, Queiroz IOA, Watanabe S, Santos LMS, Lodi CS, Okamoto R et al. Influence of diabetes mellitus on tissue response to MTA and its ability to stimulate mineralization. Dent Traumatol. 2015 Feb;31(1):67-72. https://doi.org/10.1111/edt.12130 https://doi.org/10.1111/edt.12130... (2015)	Rats	MTA	Subcutaneous tissue	Tissue response and	Diabetes Mellitus
	Rats	MTA	Subcutaneous tissue	Mineralization ability	Diabetes Mellitus
Gomes Filho et al.⁹⁴94. Gomes-Filho JE, Queiroz ÍO, Watanabe S, Cintra LT, Ervolino E. Influence of diabetes mellitus on the mineralization ability of two endodontic materials. Braz Oral Res. 2016;30(1):S1806-83242016000100218. https://doi.org/10.1590/1807-3107BOR-2016.vol30.0025 https://doi.org/10.1590/1807-3107BOR-201... (2016)	Rats	MTA Fillapex	Subcutaneous tissue	Tissue response and	Diabetes Mellitus
	Rats	Sealapex	Subcutaneous tissue	Mineralization ability	Diabetes Mellitus
Martins et al.¹⁰¹101. Martins CM, Gomes-Filho JE, de Azevedo Queiroz ÍO, Ervolino E, Cintra LT. Hypertension undermines mineralization-inducing capacity of and tissue response to mineral trioxide aggregate endodontic cement. J Endod. 2016 Apr;42(4):604-9. https://doi.org/10.1016/j.joen.2016.01.003 https://doi.org/10.1016/j.joen.2016.01.0... (2016)	Rats	Gray MTA Angelus White MTA Angelus	Subcutaneous tissue	Tissue response and	Hypertension
	Rats	IRM	Subcutaneous tissue	Mineralization ability	Hypertension
Cintra et al.⁹⁵95. Cintra LT, Ferreira LL, Benetti F, Gastélum AA, Gomes-Filho JE, Ervolino E, et al. The effect of dental bleaching on pulpal tissue response in a diabetic animal model. Int Endod J. 2017 Aug;50(8):790-8. https://doi.org/10.1111/iej.12692 https://doi.org/10.1111/iej.12692... (2017)	Rats	35% hydrogen peroxide (H₂O₂)	Dental pulp	Histopathologic analysis
Ferreira et al.⁹⁶96. Ferreira LL, Gomes-Filho JE, Benetti F, Carminatti M, Ervolino E, Briso AL et al. The effect of dental bleaching on pulpal tissue response in a diabetic animal model: a study of immunoregulatory cytokines. Int Endod J. 2018 Mar;51(3):347-56. https://doi.org/10.1111/iej.12852 https://doi.org/10.1111/iej.12852... (2017)	Rats	35% hydrogen peroxide (H₂O₂)	Dental pulp	Immunohistochemistry
	Rats	35% hydrogen peroxide (H₂O₂)	Dental pulp	(IL-6, TNF-α, IL-17)
Martins et al.¹⁰³103. Martins CM, Queiroz IOA, Ervolino E, Cintra LT, Gomes-Filho JE. RUNX-2, OPN and OCN expression induced by grey and white mineral trioxide aggregate in normal and hypertensive rats. Int Endod J. 2018 Jun;51(6):641-8. https://doi.org/10.1111/iej.12876 https://doi.org/10.1111/iej.12876... (2018)	Rats	Gray MTA Angelus White MTA Angelus	Subcutaneous tissue	Immunohistochemistry	Hypertension
	Rats	IRM	Subcutaneous tissue	(Runx-2, OCN, OPN)	Hypertension
Queiroz et al.⁸⁰80. Queiroz IOA, Mello WG, Martins CM, Dal Fabbro R, Narciso LG, Massunari L et al. Systemic bone marker expression induced by grey and white mineral trioxide aggregate in normal and diabetic conditions. Int Endod J. 2018 Jan 19. https://doi.org/10.1111/iej.12900 https://doi.org/10.1111/iej.12900... (2018)	Rats	Gray MTA Angelus White MTA Angelus	Blood (plasma)	Biochemical analysis	Diabetes Mellitus
			Subcutaneous tissue	(Ca, P, ALP)
				Immunohistochemistry
				(Runx-2, OCN, OPN)

Sociedade Brasileira de Pesquisa Odontológica - SBPqO Av. Prof. Lineu Prestes, 2227, 05508-000 São Paulo SP - Brazil, Tel. (55 11) 3044-2393/(55 11) 9-7557-1244 - São Paulo - SP - Brazil
E-mail: office.bor@ingroup.srv.br

Acompanhe os números deste periódico no seu leitor de RSS

[1] Corresponding Author: Luciano Tavares Angelo Cintra E-mail: lucianocintra@foa.unesp.br