TY  - JOUR
T1  - Inflammatory mediators’ essence in apical periodontitis
TT  - Apikal periodontitiste inflamatuar mediatörlerin özü
AU  - Jakovljevic, Aleksandar
AU  - Milojević, Nikola
AU  - Krdzovic Lazic, Ema
AU  - Lukic, Lazar
AU  - Puresevic, Dobroslav
AU  - Mirkovic, Milana
PY  - 2024
DA  - September
Y2  - 2024
DO  - 10.26650/eor.20241423117
JF  - European Oral Research
JO  - EOR
PB  - Istanbul University
WT  - DergiPark
SN  - 2630-6158
SP  - 160
EP  - 168
VL  - 58
IS  - 3
LA  - en
AB  - Apical periodontitis (AP) represents chronic inflammatory reaction of periradicular tissues of teeth with necrotic pulp. Although AP has been considered as a multifactorial disease, different microorganisms and their virulence factors from infected root canals are considered to be the primary cause of periradicular inflammatory process. The interplay between microbes and host leads to an inflammatory cascade of events that includes activation of innate and adaptive components of immunity. Activation of different immune cells in AP is intermediated by different molecules known as mediators of inflammation. These molecules establish various network interrelationships in the inflamed periapical area and induce alveolar bone resorption. This narrative review aimed to explore and present the current knowledge of selected inflammatory mediators, including cytokines, matrix metalloproteinases, bone resorption regulators and components of oxidative stress involved in the alveolar bone resorption in AP.
KW  - periapical periodontitis
KW  - cytokines
KW  - oxidative stress
KW  - matrix metalloproteinases
KW  - bone resorption
N2  - Apikal periodontitis (AP), dişlerin periradiküler dokularının nekrotik pulpa ile kronik inflamatuar reaksiyonunu ifade eder. AP çok faktörlü bir hastalık olarak kabul edilmesine rağmen, enfekte kök kanallarından farklı mikroorganizmalar ve bunların virülans faktörlerinin periradiküler inflamatuar sürecin birincil nedeni olduğu düşünülmektedir. Mikroplar ve konakçı arasındaki etkileşim, bağışıklığın doğuştan gelen ve adaptif bileşenlerinin aktivasyonunu içeren inflamatuar bir olaylar dizisine yol açar. AP'de farklı bağışıklık hücrelerinin aktivasyonuna, inflamasyon aracıları olarak bilinen farklı moleküller aracılık eder. Bu moleküller iltihaplı periapikal bölgede çeşitli ağ ilişkileri kurar ve alveolar kemik emilimini indükler. Bu derleme makalesi, sitokinler, matriks metalloproteinazlar, kemik rezorpsiyon düzenleyicileri ve AP'de alveoler kemik rezorpsiyonunda rol oynayan oksidatif stres bileşenleri dahil olmak üzere bazı inflamatuar mediatörlerle ilgili mevcut bilgileri sunmayı amaçlamaktadır.
CR  - 1. Nair, P.N. On the causes of persistent apical periodontitis: a review. Int Endod J 2006; 39: 249281. google scholar
CR  - 2. Siqueira JF Jr, Röças IN. Present status and future directions: Microbiology of endodontic infections. Int Endod J 2022; 55: 512-530. google scholar
CR  - 3. Marton, I.J., Kiss, C. Overlapping protective and destructive regulatory pathways in apical periodontitis. J Endod 2014; 40: 155-163. google scholar
CR  - 4. Fouad AF. Molecular mediators of pulpal inflammation. In: Franklin RT, Seltzer S, Hargreaves KM, Goodis HE, editors. Seltzer and Bender's Dental Pulp. Chicago: Quintessence Publishing, 2012, p. 241-75. google scholar
CR  - 5. Liu C, Chu D, Kalantar-Zadeh K, George J, Young HA, Liu G. Cytokines: From Clinical Significance to Quantification. Adv Sci (Weinh) 2021; 8: 2004433. google scholar
CR  - 6. Lee SK, Lorenzo J. Cytokines regulating osteoclast formation and function. Curr Opin Rheumatol 2006; 18: 411-8. google scholar
CR  - 7. Idriss HT, Naismith JH. TNF alpha and the TNF receptor superfamily: structure-function relationship(s). Microsc Res Tech 2000; 50: 184-95. google scholar
CR  - 8. Bradley JR. TNF-mediated inflammatory disease. J Pathol 2008; 214: 149-60. google scholar
CR  - 9. Gazivoda D, Dzopalic T, Bozic B, Tatomirovic Z, Brkic Z, Colic M. Production of proinflammatory and immunoregulatory cytokines by inflammatory cells from periapical lesions in culture. J Oral Pathol Med 2009; 38: 605-11. google scholar
CR  - 10. Artese L, Piattelli A, Quaranta M, Colasante A, Musani P. Immunoreactivity for interleukin 1-beta and tumor necrosis factor-alpha and ultrastructural features of monocytes/macrophages in periapical granulomas. J Endod 1991; 17: 483-7. google scholar
CR  - 11. Graves DT, Oskoui M, Volejnikova S, Naguib G, Cai S, Desta T, Kakouras A, Jiang Y. Tumor necrosis factor modulates fibroblast apoptosis, PMN recruitment, and osteoclast formation in response to P. gingivalis infection. J Dent Res 2001; 80: 1875-9. google scholar
CR  - 12. Samuel RO, Gomes-Filho JE, Azuma MM, Sumida DH, de Oliveira SHP, Chiba FY, Bomfim SRM, Ciarlini PC, Narciso LG, Cintra LTA. Endodontic infections increase leukocyte and lymphocyte levels in the blood. Clin Oral Investig 2018; 22: 1395-1401. google scholar
CR  - 13. Safavi KE, Rossomando EF. Tumor necrosis factor identified in periapical tissue exudates of teeth with apical periodontitis. J Endod 1991; 17: 12-4. google scholar
CR  - 14. Nunez N, Erdogan O, Casey SM, Hernandez R, Tan S, Gibbs JL. Elevated Cytokine Levels in Gingival Crevicular Fluid of Teeth with Apical Periodontitis. J Endod 2023; 49: 657-63. google scholar
CR  - 15. Pezelj-Ribaric S, Magasic K, Prpic J, Miletic I, Karlovic Z. Tumor necrosis factor-alpha in peripical tissue exudates of teeth with apical periodontitis. Mediators Inflamm 2007; 2007: 69416. google scholar
CR  - 16. Teixeira-Salum TB, Rodrigues DB, Gervasio AM, Souza CJ, Rodrigues V Jr, Loyola AM. Distinct Th1, Th2 and Treg cytokines balance in chronic periapical granulomas and radicular cysts. J Oral Pathol Med 2010; 39: 250-6. google scholar
CR  - 17. Ataoglu T, Ungor M, Serpek B, Haliloglu S, Ataoglu H, Ari H. Interleukin-1beta and tumour necrosis factor alpha levels in periapical exudates. Int Endod J 2002; 35: 181-5. google scholar
CR  - 18. Prso IB, Kocjan W, Simic H et al. Tumor necrosis factor alpha and interleukin 6 in human periapical lesions. Mediators Inflamm 2007; 2007: 38210. google scholar
CR  - 19. Jakovljevic A, Knezevic A, Karalic D, Soldatovic I, Popovic B, Milasin J, Andric M. Pro-inflammatory cytokine levels in human apical periodontitis: Correlation with clinical and histological findings. Aust Endod J 2015; 41: 72-7. google scholar
CR  - 20. Palomo J, Dietrich D, Martin P, Palmer G, Gabay C. The interleukin (IL)-1 cytokine family--Balance between agonists and antagonists in inflammatory diseases. Cytokine 2015; 76: 25-37. google scholar
CR  - 21. Gabay C, Lamacchia C, Palmer G. IL-1 pathways in inflammation and human diseases. Nat Rev Rheumatol 2010; 6: 232-41. google scholar
CR  - 22. Hamachi T, Anan H, Akamine A, Fujise O, Maeda K. Detection of interleukin-1 beta mRNA in rat periapical lesions. J Endod 1995; 21: 118-21. google scholar
CR  - 23. Matsumoto A, Anan H, Maeda K. An immunohistochemical study of the behavior of cells expressing interleukin-1 alpha and interleukin-1 beta within experimentally induced periapical lesions in rats. J Endod 1998; 24: 811-6. google scholar
CR  - 24. Barkhordar RA, Hussain MZ, Hayashi C. Detection of interleukin-1 beta in human periapical lesions. Oral Surg Oral Med Oral Pathol 1992; 73: 334-6. google scholar
CR  - 25. Kuo ML, Lamster IB, Hasselgren G. Host mediators in endodontic exudates. I. Indicators of inflammation and humoral immunity. J Endod 1998; 24: 598-603. google scholar
CR  - 26. Lim GC, Torabinejad M, Kettering J, Linkhardt TA, Finkelman RD. Interleukin 1-beta in symptomatic and asymptomatic human periradicular lesions. J Endod 1994; 20: 225-7. google scholar
CR  - 27. Tazawa K, Azuma Presse MM, Furusho H, Stashenko P, Sasaki H. Revisiting the role of IL-1 signaling in the development of apical periodontitis. Front Dent Med 2022; 3: 985558. google scholar
CR  - 28. Tanaka T, Narazaki M, Kishimoto T. IL-6 in inflammation, immunity, and disease. Cold Spring Harb Perspect Biol 2014; 6: a016295. google scholar
CR  - 29. Matsushita K, Tajima T, Tomita K, Abeyama K, Maruyama I, Takada H, Nagaoka S. Inflammatory cytokine production and specific antibody responses against possible causative bacteria in patients with multilesional periapical periodontitis. J Endod 1998; 24: 817-21. google scholar
CR  - 30. Kawashima N, Stashenko P. Expression of bone-resorptive and regulatory cytokines in murine periapical inflammation. Arch Oral Biol 1999; 44: 55-66. google scholar
CR  - 31. Huang GT, Do M, Wingard M, Park JS, Chugal N. Effect of interleukin-6 deficiency on the formation of periapical lesions after pulp exposure in mice. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2001; 92: 83-8. google scholar
CR  - 32. Balto K, Sasaki H, Stashenko P. Interleukin-6 deficiency increases inflammatory bone destruction. Infect Immun 2001; 69: 744-50. google scholar
CR  - 33. Barkhordar RA, Hayashi C, Hussain MZ. Detection of interleukin-6 in human dental pulp and periapical lesions. Endod Dent Traumatol 1999; 15: 26-7. google scholar
CR  - 34. Radics T, Kiss C, Tar I, Marton IJ. Interleukin-6 and granulocyte-macrophage colony stimulating factor in apical periodontitis: correlation with clinical and histologic findings of the involved teeth. Oral Microbiol Immunol 2003; 18: 9-13. google scholar
CR  - 35. Abdolsamadi HR, Vahedi M, Esmaeili F, Nazari S, Abdollahzadeh S. Serum Interleukin-6 as a Serologic Marker of Chronic Periapical Lesions: A Case-control Study. J Dent Res Dent Clin Dent Prospects 2008; 2: 43-7. google scholar
CR  - 36. Alvarez C, Monasterio G, Cavalla F, Cordova LA, Hernandez M, Heymann D, Garlet GP, Sorsa T, Parnanen P, Lee HM, Golub LM, Vernal R, Kantarci A. Osteoimmunology of Oral and Maxillofacial Diseases: Translational Applications Based on Biological Mechanisms. Front Immunol. 2019; 18: 1664. google scholar
CR  - 37. Okamoto K, Nakashima T, Shinohara M, Negishi-Koga T, Komatsu N, Terashima A, Sawa S, Nitta T, Takayanagi H. Osteoimmunology: The Conceptual Framework Unifying the Immune and Skeletal Systems. Physiol Rev 2017; 97: 1295-349. google scholar
CR  - 38. Terashima A, Takayanagi H. Overview of Osteoimmunology. Calcif Tissue Int 2018; 102: 50311. google scholar
CR  - 39. Zhang X, Peng B. Immunolocalization of receptor activator ofNF kappa B ligand in rat periapical lesions. J Endod 2005; 31: 574-7. google scholar
CR  - 40. Kawashima N, Suzuki N, Yang G, Ohi C, Okuhara S, Nakano-Kawanishi H, Suda H. Kinetics of RANKL, RANK and OPG expressions in experimentally induced rat periapical lesions. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2007; 103: 707-11. google scholar
CR  - 41. Chuang FH, Tsai CC, Chen JH, Chen KK, Chen YK, Lin YC. Long-term sequential receptor activator of NF-kB ligand (RANKL) and osteoprotegrin (OPG) expression in lipopolysaccharide-induced rat periapical lesions. J Oral Pathol Med 2012; 41: 186-93. google scholar
CR  - 42. Tay JY, Bay BH, Yeo JF, Harris M, Meghji S, Dheen ST. Identification of RANKL in osteolytic lesions of the facial skeleton. J Dent Res 2004; 83: 349-53. google scholar
CR  - 43. Sabeti M, Simon J, Kemani V, Valles Y, Rostein I. Detection of receptor activator of NF-kappa beta ligand in apical periodontitis. J Endod 2005; 31: 17-8. google scholar
CR  - 44. Fukada SY, Silva TA, Garlet GP, Rosa AL, da Silva JS, Cunha FQ. Factors involved in the T helper type 1 and type 2 cell commitment and osteoclast regulation in inflammatory apical diseases. Oral Microbiol Immunol 2009; 24: 25-31. google scholar
CR  - 45. Menezes R, Bramante CM, da Silva Paiva KB, Letra A, Carneiro E, Fernando Zambuzzi W, Granjeiro JM. Receptor activator NFkappaB-ligand and osteoprotegerin protein expression in human periapical cysts and granulomas. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2006; 102: 4049. google scholar
CR  - 46. Salinas-Munoz M, Garrido-Flores M, Baeza M, Huamân-Chipana P, Gartfa-Sesnich J, Bologna R, Vernal R, Hernandez M. Bone resorptive activity in symptomatic and asymptomatic apical lesions of endodontic origin. Clin Oral Investig 2017; 21: 2613-2618. google scholar
CR  - 47. Duka M, Erakovic M, Dolicanin Z, Stefanovic D, Ğolic M. Production of Soluble Receptor Activator of Nuclear Factor Kappa-B Ligand and Osteoprotegerin by Apical Periodontitis Cells in Culture and Their Modulation by Cytokines. Mediators Inflamm 2019; 18: 8325380. google scholar
CR  - 48. Nikolic N, Jakovljevic A, Carkic J, Beljic-Ivanovic K, Miletic M, Soldatovic I, Andric M, Ivanovic V, Milasin J. Notch Signaling Pathway in Apical Periodontitis: Correlation with Bone Resorption Regulators and Proinflammatory Cytokines. J Endod 2019; 45: 123-8. google scholar
CR  - 49. Cabral-Pacheco GA, Garza-Veloz I, Castruita-De la Rosa C, Ramirez-Acuna JM, Perez-Romero BA, Guerrero-Rodriguez JF, et al. The roles of matrix metalloproteinases and their inhibitors in human diseases. Int J Mol Sci 2020; 21: 9739. google scholar
CR  - 50. Monea M, Pop AM. The use of salivary levels of matrix metalloproteinases as an adjuvant method in the early diagnosis of oral squamous cell carcinoma: A narrative literature review. Curr Issues Mol Biol 2022; 44: 6306-22. google scholar
CR  - 51. Loffek S, Schilling O, Franzke C-W. Biological role of matrix metalloproteinases: A critical balance. Eur Respir J 2010; 38: 191-208. google scholar
CR  - 52. Anshida VP, Kumari RA, Murthy CS, Samuel A. Extracellular matrix degradation by host matrix metalloproteinases in restorative dentistry and endodontics: An overview. J Oral Maxillofac Pathol 2020; 24: 352-60. google scholar
CR  - 53. Hannas AR, Pereira JC, Granjeiro JM, Tjaderhane L. The role of matrix metalloproteinases in the oral environment. Acta Odontol Scand 2007; 65: 1-13. google scholar
CR  - 54. Sorsa T, Tjaderhane L, Salo T. Matrix metalloproteinases (MMPs) in oral diseases. Oral Dis 2004; 10: 311-8. google scholar
CR  - 55. Panagakos FS, O'Boskey JF Jr, Rodriguez E. Regulation of pulp cell matrix metalloproteinase production by cytokines and lipopolysaccharides. J Endod 1996; 22: 358-61. google scholar
CR  - 56. O'Boskey FJ Jr, Panagakos FS. Cytokines stimulate matrix metalloproteinase production by human pulp cells during long-term culture. J Endod 1998; 24: 7-10. google scholar
CR  - 57. Wang G, Fan WT, Zhang Z, Huang SG. Expression of matrix metalloproteinase-8 and matrix metalloproteinase-13 in mast cells of human periapical lesions. Int J Clin Exp Pathol 2018; 11: 25306. google scholar
CR  - 58. Corotti MV, Willian Fernando Zambuzzi, Paiva S, Menezes R, Pinto LC, Vanessa Soares Lara, et al. Immunolocalization of matrix metalloproteinases-2 and -9 during apical periodontitis development. Arch Oral Biol 2009; 54: 764-71. google scholar
CR  - 59. Wan CY, Li L, Liu LS, Jiang CM, Zhang HZ, Wang JX. Expression of Matrix Metalloproteinases and Tissue Inhibitor of Matrix Metalloproteinases during Apical Periodontitis Development. J Endod 2021; 47: 1118-25. google scholar
CR  - 60. Shin SJ, Lee JI, Baek SH, Lim SS. Tissue levels of matrix metalloproteinases in pulps and periapical lesions. J Endod 2002; 28: 313-5. google scholar
CR  - 61. Leonardi R, Caltabiano R, Loreto C. Collagenase-3 (MMP-13) is expressed in periapical lesions: an immunohistochemical study. Int Endod J 2005; 38: 297-301. google scholar
CR  - 62. Martinho FC, Teixeira FF, Cardoso FG, Ferreira NS, Nascimento GG, Carvalho CA, Valera MC. Clinical Investigation of Matrix Metalloproteinases, Tissue Inhibitors of Matrix Metalloproteinases, and Matrix Metalloproteinase/Tissue Inhibitors of Matrix Metalloproteinase Complexes and Their Networks in Apical Periodontitis. J Endod 2016; 42: 1082-8. google scholar
CR  - 63. Letra A, Ghaneh G, Zhao M, Ray H Jr, Francisconi CF, Garlet GP, Silva RM. MMP-7 and TIMP-1, new targets in predicting poor wound healing in apical periodontitis. J Endod 2013; 39: 1141-6. google scholar
CR  - 64. Hadziabdic N, Kurtovic-Kozaric A, Pojskic N, Sulejmanagic N, Todorovic L. Gene-expression analysis of matrix metalloproteinases 1 and 2 and their tissue inhibitors in chronic periapical inflammatory lesions. J Oral Pathol Med 2016; 45: 224-30. google scholar
CR  - 65. Pereira Faustino IS, Azevedo RS, Takahama A Jr. Metalloproteinases 2 and 9 Immunoexpression in Periapical Lesions from Primary Endodontic Infection: Possible Relationship with the Histopathological Diagnosis and the Presence of Pain. J Endod 2016; 42: 547-51. google scholar
CR  - 66. Georgiou AC, Cornejo Ulloa P, Van Kessel GMH, Crielaard W, Van der Waal SV. Reactive oxygen species can be traced locally and systemically in apical periodontitis: A systematic review. Arch Oral Biol 2021; 129: 105167. google scholar
CR  - 67. Xiang M, Fan J, Fan J. Association of Toll-like receptor signaling and reactive oxygen species: a potential therapeutic target for posttrauma acute lung injury. Mediators Inflamm 2010; 2010: 916425. google scholar
CR  - 68. Chapple IL. Reactive oxygen species and antioxidants in inflammatory diseases. J Clin Periodontol 1997; 24: 287-96. google scholar
CR  - 69. Trivedi S, Lal N. Antioxidant enzymes in periodontitis. J Oral Biol Craniofac Res 2017; 7: 5457. google scholar
CR  - 70. Biswas SK. Does the Interdependence between Oxidative Stress and Inflammation Explain the Antioxidant Paradox? Oxid Med Cell Longev 2016; 2016: 5698931. google scholar
CR  - 71. Halliwell B, Whiteman M. Measuring reactive species and oxidative damage in vivo and in cell culture: how should you do it and what do the results mean? Br J Pharmacol 2004; 142: 231-55. google scholar
CR  - 72. Babior BM. The respiratory burst of phagocytes. J Clin Invest 1984; 73: 599-601. google scholar
CR  - 73. Halliwell B. Reactive oxygen species in living systems: source, biochemistry, and role in human disease. Am J Med 1991; 91: 14-22. google scholar
CR  - 74. Hernândez-Rios P, Pussinen PJ, Vernal R, Hernândez M. Oxidative Stress in the Local and Systemic Events of Apical Periodontitis. Front Physiol 2017; 8: 869. google scholar
CR  - 75. Frazâo DR, Santos Mendes PF, Baia-da-Silva DC, Mendonça de Moura JD, Neves Dos Santos VR, Matos-Sousa JM, de Souza Balbinot G, Guimarâes DM, Collares FM, Lima RR. Modulation of blood redox status by the progression of induced apical periodontitis in rats. Front Physiol 2023; 14: 1214990. google scholar
CR  - 76. Prieto AKC, Gomes-Filho JE, Azuma MM, Sivieri-Araujo G, Narciso LG, Souza JC, Ciarlini PC, Cintra LTA. Influence of Apical Periodontitis on Stress Oxidative Parameters in Diabetic Rats. J Endod 2017; 43: 1651-56. google scholar
CR  - 77. Milojevic Samanovic A, Jakovljevic V, Vasovic M, Mitrovic S, Rankovic M, Mihajlovic K, Bolevich S, Zivkovic V. Cardiac, biochemical and histopathological analysis reveals impaired heart function in hypertensive rats with apical periodontitis. Int Endod J 2021; 54: 1581-96. google scholar
CR  - 78. Tsosura TVS, Dos Santos RM, Chaves Neto AH, Chiba FY, Carnevali ACN, Mattera MSLC, Belardi BE, Cintra LTÂ, da Silva Machado NE, Matsushita DH. Maternal Apical Periodontitis Increases Insulin Resistance and Modulates the Antioxidant Defense System in the Gastrocnemius Muscle of Adult Offspring. J Endod 2021; 47: 1126-31. google scholar
CR  - 79. Cotti E, Zedda A, Deidda M, Piras A, Flore G, Ideo F, Madeddu C, Pau VM, Mercuro G. Endodontic infection and endothelial dysfunction are associated with different mechanisms in men and women. J Endod 2015; 41: 594-600. google scholar
CR  - 80. Gomes C, Martinho FC, Barbosa DS, Antunes LS, Povoa HCC, Baltus THL, Morelli NR, Vargas HO, Nunes SOV, Anderson G, Maes M. Increased Root Canal Endotoxin Levels are Associated with Chronic Apical Periodontitis, Increased Oxidative and Nitrosative Stress, Major Depression, Severity of Depression, and a Lowered Quality of Life. Mol Neurobiol 2018; 55: 2814-2827. google scholar
CR  - 81. Inchingolo F, Marrelli M, Annibali S, Cristalli MP, Dipalma G, Inchingolo AD, Palladino A, Inchingolo AM, Gargari M, Tatullo M. Influence of endodontic treatment on systemic oxidative stress. Int J Med Sci 2013; 11: 1-6. google scholar
CR  - 82. Giebultowicz J, Wroczynski P, Samolczyk-Wanyura D. Comparison of antioxidant enzymes activity and the concentration of uric acid in the saliva of patients with oral cavity cancer, odontogenic cysts and healthy subjects. J Oral Pathol Med 2011; 40: 726-30. google scholar
CR  - 83. Vengerfeldt V, Mandar R, Saag M, Piir A, Kullisaar T. Oxidative stress in patients with endodontic pathologies. J Pain Res 2017; 10: 2031-40. google scholar
CR  - 84. Dezerega A, Madrid S, Mundi V, Valenzuela MA, Garrido M, Paredes R, Gartfa-Sesnich J, Ortega AV, Gamonal J, Hernandez M. Pro-oxidant status and matrix metalloproteinases in apical lesions and gingival crevicular fluid as potential biomarkers for asymptomatic apical periodontitis and endodontic treatment response. J Inflamm (Lond) 2012; 9: 8. google scholar
CR  - 85. Cotti E, Zedda A, Deidda M, Piras A, Flore G, Ideo F, Madeddu C, Pau VM, Mercuro G. Endodontic infection and endothelial dysfunction are associated with different mechanisms in men and women. J Endod 2015; 41: 594-600. google scholar
CR  - 86. Miller AA, De Silva TM, Jackman KA, Sobey CG. Effect of gender and sex hormones on vascular oxidative stress. Clin Exp Pharmacol Physiol 2007; 34: 1037-43. google scholar
CR  - 87. Lamster IB, Novak MJ. Host mediators in gingival crevicular fluid: implications for the pathogenesis of periodontal disease. Crit Rev Oral Biol Med 1992; 3: 31-60. google scholar
CR  - 88. Mody N, Parhami F, Sarafian TA, Demer LL. Oxidative stress modulates osteoblastic differentiation of vascular and bone cells. Free Radic Biol Med 2001; 31: 509-19. google scholar
CR  - 89. Yoon SO, Park SJ, Yoon SY, Yun CH, Chung AS. Sustained production of H(2)O(2) activates pro-matrix metalloproteinase-2 through receptor tyrosine kinases/phosphatidylinositol 3-kinase/NF-kappa B pathway. J Biol Chem 2002; 277: 30271-82. google scholar
CR  - 90. Binker MG, Binker-Cosen AA, Gaisano HY, de Cosen RH, Cosen-Binker LI. TGF-Ş1 increases invasiveness of SW1990 cells through Rac1/ROS/NF-KB/IL-6/MMP-2. Biochem Biophys Res Commun 2011; 405: 140-5. google scholar
CR  - 91. Kakehashi S, Stanley HR, Fitzgerald RJ. The Effects Of Surgical Exposures Of Dental Pulps In Germ-Free And Conventional Laboratory Rats. Oral Surg Oral Med Oral Pathol 1965; 20: 340-9. google scholar
CR  - 92. Jakovljevic A, Andric M, Nikolic N, Coric V, Krezovic S, Carkic J, Knezevic A, Beljic-Ivanovic K, Pljesa-Ercegovac M, Miletic M, Soldatovic I, Radosavljevic T, Jovanovic T, Simic T, Ivanovic V, Milasin J. Levels of oxidative stress biomarkers and bone resorption regulators in apical periodontitis lesions infected by Epstein-Barr virus. Int Endod J 2018; 51: 593-604. google scholar
CR  - 93. Huang X, Browngardt CM, Jiang M, Ahn SJ, Burne RA, Nascimento MM. Diversity in Antagonistic Interactions between Commensal Oral Streptococci and Streptococcus mutans. Caries Res 2018; 52: 88-101. google scholar
CR  - 94. Shetty P, Kumari, S. Serum total anti-oxidants, super oxide dismutase (SOD), myeloperoxidase and vitamin C levels in periapical inflammation-A Original Study. Res J Pharm Biol Chem Sci 2012; 3: 934-9. google scholar
CR  - 95. Inchingolo F, Marrelli M, Annibali S, Cristalli MP, Dipalma G, Inchingolo AD, Palladino A, Inchingolo AM, Gargari M, Tatullo M. Influence of endodontic treatment on systemic oxidative stress. Int J Med Sci 2013; 11: 1-6. google scholar
CR  - 96. Guo TZ, Wei T, Huang TT, Kingery WS, Clark JD. Oxidative Stress Contributes to Fracture/Cast-Induced Inflammation and Pain in a Rat Model of Complex Regional Pain Syndrome. J Pain 2018; 19: 1147-1156. google scholar
UR  - https://doi.org/10.26650/eor.20241423117
L1  - https://dergipark.org.tr/en/download/article-file/3764218
ER  -