Skip to main content

Advertisement

SpringerLink
Log in

Experimental apical periodontitis alters salivary biochemical composition and induces local redox state disturbances in the salivary glands of male rats

  • Research
  • Published:
Clinical Oral Investigations Aims and scope Submit manuscript

Abstract

Objectives

The objective was to evaluate the effects of experimental apical periodontitis on the inflammatory, functional, biochemical, and redox parameters of the parotid and submandibular glands in rats.

Materials and methods

Twenty 12-week-old male Wistar rats were randomly divided into two groups (n = 10): a control group and apical periodontitis group. After 28 days, the saliva was collected for salivary flow rate and biochemistry composition. Both glands were sampled for quantification of the tumor necrosis factor-alpha (TNF-α) and biochemical analyses of redox state.

Results

TNF-α concentrations were higher in both salivary glands adjacent to the periapical lesions in animals with apical periodontitis and also compared to the control group. The apical periodontitis group increased the salivary amylase, chloride, potassium, calcium, and phosphate. The total oxidant capacity increased in the parotid gland adjacent to the periapical lesions in the same rat and compared to the control group. Conversely, the total antioxidant capacity of the parotid glands on both sides in the apical periodontitis group was lower than that in the control group. Furthermore, glutathione peroxidase activity increased in the submandibular gland adjacent to the apical periodontitis group compared to the control group.

Conclusions

Experimental apical periodontitis alters salivary biochemical composition, in addition to increasing inflammatory marker and inducing local disturbances in the redox state in the parotid and submandibular glands of male rats.

Clinical relevance

Apical periodontitis could exacerbate the decline in oral health by triggering dysfunction in the salivary glands.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Data availability

No datasets were generated or analyzed during the current study.

References

  1. Bag AK, Curé JK, Chapman PR et al (2018) Imaging of inflammatory disorders of salivary glands. Neuroimaging Clin N Am 28:255–272. https://doi.org/10.1016/J.NIC.2018.01.006

    Article  PubMed  Google Scholar 

  2. Proctor GB, Shaalan AM (2021) Disease-induced changes in salivary gland function and the composition of saliva. J Dent Res 100:1201–1209. https://doi.org/10.1177/00220345211004842

    Article  PubMed  CAS  Google Scholar 

  3. Busch L, Miozza V, Sterin-Borda L, Borda E (2009) Increased leukotriene concentration in submandibular glands from rats with experimental periodontitis. Inflamm Res 58:423–430. https://doi.org/10.1007/S00011-009-0008-8

    Article  PubMed  CAS  Google Scholar 

  4. Ekuni D, Endo Y, Irie K et al (2010) Imbalance of oxidative/anti-oxidative status induced by periodontitis is involved in apoptosis of rat submandibular glands. Arch Oral Biol 55:170–176. https://doi.org/10.1016/J.ARCHORALBIO.2009.11.013

    Article  PubMed  CAS  Google Scholar 

  5. Shikayama T, Fujita-Yoshigaki J, Sago-Ito M et al (2020) Hematogenous apoptotic mechanism in salivary glands in chronic periodontitis. Arch Oral Biol 117. https://doi.org/10.1016/j.archoralbio.2020.104775

  6. Miozza V, Borda E, S-Borda LS, Busch L (2010) Increase nitric oxide synthase activity in parotid glands from rats with experimental periodontitis. Oral Dis 16:801–806.https://doi.org/10.1111/J.1601-0825.2010.01691.X

  7. Miozza V, Borda E, Sterin-Borda L, Busch L (2009) Experimental periodontitis induces a cAMP-dependent increase in amylase activity in parotid glands from male rats. Inflammation 32:357–363. https://doi.org/10.1007/S10753-009-9142-2

    Article  PubMed  CAS  Google Scholar 

  8. Miozza V, Sánchez G, Sterin-Borda L, Busch L (2011) Enhancement of carbachol-induced amylase secretion in parotid glands from rats with experimental periodontitis. Arch Oral Biol 56:1514–1520. https://doi.org/10.1016/J.ARCHORALBIO.2011.06.006

    Article  PubMed  CAS  Google Scholar 

  9. Busch L, Sterin-Borda L, Borda E (2008) Beta-adrenoceptor alterations coupled with secretory response and experimental periodontitis in rat submandibular glands. Arch Oral Biol 53:509–516. https://doi.org/10.1016/J.ARCHORALBIO.2007.12.010

    Article  PubMed  CAS  Google Scholar 

  10. Nakamura-Kiyama M, Ono K, Masuda W et al (2014) Changes of salivary functions in experimental periodontitis model rats. Arch Oral Biol 59:125–132. https://doi.org/10.1016/j.archoralbio.2013.11.001

    Article  PubMed  CAS  Google Scholar 

  11. Segura-Egea JJ, Martín-González J, Castellanos-Cosano L (2015) Endodontic medicine: connections between apical periodontitis and systemic diseases. Int Endod J 48:933–951. https://doi.org/10.1111/IEJ.12507

    Article  PubMed  CAS  Google Scholar 

  12. Jakovljevic A, Nikolic N, Jacimovic J et al (2020) Prevalence of apical periodontitis and conventional nonsurgical root canal treatment in general adult population: an updated systematic review and meta-analysis of cross-sectional studies published between 2012 and 2020. J Endod 46:1371–1386. https://doi.org/10.1016/J.JOEN.2020.07.007

    Article  PubMed  Google Scholar 

  13. Cantiga-Silva C, Estrela C, Segura-Egea JJ et al (2021) Inflammatory profile of apical periodontitis associated with liver fibrosis in rats: histological and immunohistochemical analysis. Int Endod J 54:1353–1361. https://doi.org/10.1111/IEJ.13519

    Article  PubMed  CAS  Google Scholar 

  14. Sasaki H, Hirai K, Martins MC et al (2016) Interrelationship between periapical lesion and systemic metabolic disorders. Curr Pharm Des 22:2204–2215.https://doi.org/10.2174/1381612822666160216145107

  15. Tibúrcio-Machado CS, Michelon C, Zanatta FB et al (2021) The global prevalence of apical periodontitis: a systematic review and meta-analysis. Int Endod J 54:712–735. https://doi.org/10.1111/IEJ.13467

    Article  PubMed  Google Scholar 

  16. Gomes MS, Blattner TC, Sant’Ana Filho M et al (2013) Can apical periodontitis modify systemic levels of inflammatory markers? A systematic review and meta-analysis. J Endod 39:1205–1217.https://doi.org/10.1016/j.joen.2013.06.014

  17. Rashmi N, Galhotra V, Goel P et al (2017) Assessment of C-reactive proteins, cytokines, and plasma protein levels in hypertensive patients with apical periodontitis. J Contemp Dent Pract 18:516–521. https://doi.org/10.5005/jp-journals-10024-2076

    Article  PubMed  CAS  Google Scholar 

  18. Stys LPA, Böttcher DE, Scarparo RK et al (2022) Serum levels of inflammatory markers and HbA1c in patients with type 2 diabetes and apical periodontitis: preliminary findings. Aust Endod J 48:105–115. https://doi.org/10.1111/AEJ.12569

    Article  PubMed  Google Scholar 

  19. Astolphi RD, Curbete MMH, Colombo NH et al (2013) Periapical lesions decrease insulin signal and cause insulin resistance. J Endod 39:648–652. https://doi.org/10.1016/j.joen.2012.12.031

    Article  PubMed  Google Scholar 

  20. Conti LC, Segura-Egea JJ, Cardoso CBM et al (2020) Relationship between apical periodontitis and atherosclerosis in rats: lipid profile and histological study. Int Endod J 53:1387–1397. https://doi.org/10.1111/iej.13350

    Article  PubMed  CAS  Google Scholar 

  21. Astolphi RD, Curbete MM, Chiba FY et al (2015) Periapical lesions decrease insulin signaling in rat skeletal muscle. J Endod 41:1305–1310. https://doi.org/10.1016/j.joen.2015.04.002

    Article  PubMed  Google Scholar 

  22. Tsosura TVS, dos Santos RM, Chaves Neto AH et al (2021) Maternal apical periodontitis increases insulin resistance and modulates the antioxidant defense system in the gastrocnemius muscle of adult offspring. J Endod 47:1126–1131. https://doi.org/10.1016/j.joen.2021.04.003

    Article  PubMed  Google Scholar 

  23. dos Santos RM, Tsosura TVS, Belardi BE et al (2023) Melatonin decreases plasma TNF-α and improves nonenzymatic antioxidant defence and insulin sensitivity in rats with apical periodontitis fed a high-fat diet. Int Endod J 56:164–178. https://doi.org/10.1111/iej.13852

    Article  PubMed  Google Scholar 

  24. Barcelos RCS, Rosa HZ, Roversi K et al (2020) Apical periodontitis induces changes on oxidative stress parameters and increases Na+/K+-ATPase activity in adult rats. Arch Oral Biol 118. https://doi.org/10.1016/j.archoralbio.2020.104849

  25. MilojevicSamanovic A, Jakovljevic V, Vasovic M et al (2021) Cardiac, biochemical and histopathological analysis reveals impaired heart function in hypertensive rats with apical periodontitis. Int Endod J 54:1581–1596. https://doi.org/10.1111/iej.13562

    Article  Google Scholar 

  26. Xiao S, Lei H, Li P et al (2023) Is oxidative stress involved in the hepatic inflammatory response to apical periodontitis? A comparative study in normal and hyperlipidaemic rat. Int Endod J 56:722–733. https://doi.org/10.1111/IEJ.13907

    Article  PubMed  Google Scholar 

  27. Yoon YJ, Kim D, Tak KY et al (2022) Salivary gland organoid culture maintains distinct glandular properties of murine and human major salivary glands. Nat Commun 13. https://doi.org/10.1038/s41467-022-30934-z

  28. Miranda LFB, Lima CV, Pagin R et al (2023) Effect of processing methods of human saliva on the proteomic profile and protein-mediated biological processes. J Proteome Res 22:857–870. https://doi.org/10.1021/acs.jproteome.2c00652

    Article  PubMed  CAS  Google Scholar 

  29. Maciejczyk M, Skutnik-Radziszewska A, Zieniewska I et al (2019) Antioxidant defense, oxidative modification, and salivary gland function in an early phase of cerulein pancreatitis. Oxid Med Cell Longev 2019. https://doi.org/10.1155/2019/8403578

  30. Skutnik-Radziszewska A, Maciejczyk M, Fejfer K et al (2020) Salivary antioxidants and oxidative stress in psoriatic patients: can salivary total oxidant status and oxidative status index be a plaque psoriasis biomarker? Oxid Med Cell Longev 2020. https://doi.org/10.1155/2020/9086024

  31. Zukowski P, Maciejczyk M, Matczuk J et al (2018) Effect of N-acetylcysteine on antioxidant defense, oxidative modification, and salivary gland function in a rat model of insulin resistance. Oxid Med Cell Longev 2018. https://doi.org/10.1155/2018/6581970

  32. Ibuki FK, Bergamaschi CT, da Silva Pedrosa M, Nogueira FN (2020) Effect of vitamin C and E on oxidative stress and antioxidant system in the salivary glands of STZ-induced diabetic rats. Arch Oral Biol 116. https://doi.org/10.1016/J.ARCHORALBIO.2020.104765

  33. Özgür A, Terzi S, Özdemir D et al (2019) Protective effect of whortleberry extract on salivary gland damage induced by neck irradiation in rats. Ear Nose Throat J 98:64–69. https://doi.org/10.1177/0145561319846868

    Article  Google Scholar 

  34. Bhattarai KR, Lee HY, Kim SH et al (2018) Potential application of Ixeris dentata in the prevention and treatment of aging-induced dry mouth. Nutrients 10. https://doi.org/10.3390/NU10121989

  35. Fagundes NCF, Fernandes LMP, Paraense RSDO et al (2016) Binge drinking of ethanol during adolescence induces oxidative damage and morphological changes in salivary glands of female rats. Oxid Med Cell Longev 2016. https://doi.org/10.1155/2016/7323627

  36. Takahashi A, Inoue H, Mishima K et al (2015) Evaluation of the effects of quercetin on damaged salivary secretion. PLoS One 10. https://doi.org/10.1371/JOURNAL.PONE.0116008

  37. Bomfin LE, Braga CM, Oliveira TA et al (2017) 5-Fluorouracil induces inflammation and oxidative stress in the major salivary glands affecting salivary flow and saliva composition. Biochem Pharmacol 145:34–45. https://doi.org/10.1016/J.BCP.2017.08.024

    Article  PubMed  CAS  Google Scholar 

  38. Cintra LTA, Samuel RO, Azuma MM et al (2016) Multiple apical periodontitis influences serum levels of cytokines and nitric oxide. J Endod 42:747–751. https://doi.org/10.1016/j.joen.2016.01.022

    Article  PubMed  Google Scholar 

  39. Tsosura TVS, Chiba FY, Mattera MSLC et al (2019) Maternal apical periodontitis is associated with insulin resistance in adult offspring. Int Endod J 52:1040–1050. https://doi.org/10.1111/iej.13096

    Article  PubMed  CAS  Google Scholar 

  40. Cypriano ML, dos Santos Ramos GHA, de Oliveira ACF et al (2021) Effect of testosterone replacement therapy and mate tea (Ilex paraguariensis) on biochemical, functional and redox parameters of saliva in orchiectomized rats. Arch Oral Biol 132. https://doi.org/10.1016/j.archoralbio.2021.105289

  41. de Oliveira ACF, Brito VGB, Ramos GHA dos S et al (2023) Analysis of salivary flow rate, biochemical composition, and redox status in orchiectomized spontaneously hypertensive rats. Arch Oral Biol 152. https://doi.org/10.1016/J.ARCHORALBIO.2023.105732

  42. dos Santos DR, Fiais GA, de Oliveira Passos A et al (2022) Effects of orchiectomy and testosterone replacement therapy on redox balance and salivary gland function in Wistar rats. J Steroid Biochem Mol Biol 218. https://doi.org/10.1016/j.jsbmb.2021.106048

  43. Hartree EF (1972) Determination of protein: a modification of the Lowry method that gives a linear photometric response. Anal Biochem 48:422–427. https://doi.org/10.1016/0003-2697(72)90094-2

    Article  PubMed  CAS  Google Scholar 

  44. Erel O (2005) A new automated colorimetric method for measuring total oxidant status. Clin Biochem 38:1103–1111. https://doi.org/10.1016/j.clinbiochem.2005.08.008

    Article  PubMed  CAS  Google Scholar 

  45. Buege JA, Aust SD (1978) Microsomal lipid peroxidation. Methods Enzymol 52:302–310. https://doi.org/10.1016/S0076-6879(78)52032-6

    Article  PubMed  CAS  Google Scholar 

  46. Mesquita CS, Oliveira R, Bento F et al (2014) Simplified 2,4-dinitrophenylhydrazine spectrophotometric assay for quantification of carbonyls in oxidized proteins. Anal Biochem 458:69–71. https://doi.org/10.1016/J.AB.2014.04.034

    Article  PubMed  CAS  Google Scholar 

  47. Benzie IFF, Strain JJ (1996) The ferric reducing ability of plasma (FRAP) as a measure of “antioxidant power”: the FRAP assay. Anal Biochem 239:70–76. https://doi.org/10.1006/ABIO.1996.0292

    Article  PubMed  CAS  Google Scholar 

  48. Beutler E, Duron O, Kelly BM (1963) Improved method for the determination of blood glutathione. J Lab Clin Med 61:882–888

    PubMed  CAS  Google Scholar 

  49. Marklund S, Marklund G (1974) Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur J Biochem 47:469–474. https://doi.org/10.1111/J.1432-1033.1974.TB03714.X

    Article  PubMed  CAS  Google Scholar 

  50. Aebi H (1984) Catalase in vitro. Methods Enzymol 105:121–126. https://doi.org/10.1016/S0076-6879(84)05016-3

    Article  PubMed  CAS  Google Scholar 

  51. Wendel A (1981) Glutathione peroxidase. Methods Enzymol 77:325–333. https://doi.org/10.1016/S0076-6879(81)77046-0

    Article  PubMed  CAS  Google Scholar 

  52. Cintra LTA, da Silva Facundo AC, Azuma MM et al (2013) Pulpal and periodontal diseases increase triglyceride levels in diabetic rats. Clin Oral Investig 17:1595–1599. https://doi.org/10.1007/s00784-012-0853-7

    Article  PubMed  Google Scholar 

  53. Justo MP, Cardoso C de BM, Cantiga-Silva C et al (2022) Curcumin reduces inflammation in rat apical periodontitis. Int Endod J 55:1241–1251.https://doi.org/10.1111/iej.13819

  54. Cintra LTA, Da Silva Facundo AC, Prieto AKC et al (2014) Blood profile and histology in oral infections associated with diabetes. J Endod 40:1139–1144. https://doi.org/10.1016/j.joen.2014.01.034

    Article  PubMed  Google Scholar 

  55. Cintra LTA, Samuel RO, Facundo ACS et al (2014) Relationships between oral infections and blood glucose concentrations or HbA1c levels in normal and diabetic rats. Int Endod J 47:228–237. https://doi.org/10.1111/iej.12136

    Article  PubMed  CAS  Google Scholar 

  56. Samuel RO, Ervolino E, de AzevedoQueiroz ÍO et al (2019) Th1/Th2/Th17/Treg balance in apical periodontitis of normoglycemic and diabetic rats. J Endod 45:1009–1015. https://doi.org/10.1016/j.joen.2019.05.003

    Article  PubMed  Google Scholar 

  57. do Nascimento IV, Rodrigues MI de Q, Isaias PHC et al (2022) Chronic systemic corticosteroid therapy influences the development of pulp necrosis and experimental apical periodontitis, exacerbating the inflammatory process and bone resorption in rats. Int Endod J 55:646–659.https://doi.org/10.1111/IEJ.13724

  58. Azuma MM, Gomes-Filho JE, Ervolino E et al (2018) Omega-3 fatty acids reduce inflammation in rat apical periodontitis. J Endod 44:604–608. https://doi.org/10.1016/j.joen.2017.12.008

    Article  PubMed  Google Scholar 

  59. Vasques AMV, da Silva ACR, Bueno CRE et al (2023) Inflammatory profile of apical periodontitis exacerbated by cigarette smoke inhalation: histological and immunohistochemical analysis in rats. Int Endod J 56:465–474. https://doi.org/10.1111/iej.13883

    Article  PubMed  Google Scholar 

  60. Zhou J, Kawai T, Yu Q (2017) Pathogenic role of endogenous TNF-α in the development of Sjögren’s-like sialadenitis and secretory dysfunction in non-obese diabetic mice. Lab Invest 97:458–467. https://doi.org/10.1038/labinvest.2016.141

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  61. Fukuoka CY, Vicari HP, Sipert CR et al (2020) Early effect of laser irradiation in signaling pathways of diabetic rat submandibular salivary glands. PLoS One 15. https://doi.org/10.1371/JOURNAL.PONE.0236727

  62. Pereira RF, Cintra LTA, Tessarin GWL et al (2017) Periapical lesions increase macrophage infiltration and inflammatory signaling in muscle tissue of rats. J Endod 43:982–988. https://doi.org/10.1016/j.joen.2017.01.030

    Article  PubMed  Google Scholar 

  63. Dal-Fabbro R, Marques-de-Almeida M, Cosme-Silva L et al (2019) Chronic alcohol consumption increases inflammation and osteoclastogenesis in apical periodontitis. Int Endod J 52:329–336. https://doi.org/10.1111/iej.13014

    Article  PubMed  CAS  Google Scholar 

  64. Kramer PR, He J, Puri J, Bellinger LL (2012) A non-invasive model for measuring nociception after tooth pulp exposure. J Dent Res 91:883–887. https://doi.org/10.1177/0022034512454297

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  65. Bhattarai KR, Lee HY, Kim SH et al (2018) Ixeris dentata extract increases salivary secretion through the regulation of endoplasmic reticulum stress in a diabetes-induced xerostomia rat model. Int J Mol Sci 19. https://doi.org/10.3390/ijms19041059

  66. Lee HJ, Lee YJ, Kwon HC et al (2006) Radioprotective effect of heat shock protein 25 on submandibular glands of rats. Am J Pathol 169:1601–1611. https://doi.org/10.2353/AJPATH.2006.060327

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  67. Nagler RM, Laufer D (1998) Protection against irradiation-induced damage to salivary glands by adrenergic agonist administration. Int J Radiat Oncol Biol Phys 40:477–481. https://doi.org/10.1016/S0360-3016(97)00574-9

    Article  PubMed  CAS  Google Scholar 

  68. González CR, Amer MAR, Vitullo AD et al (2016) Immunolocalization of the TGFB1 system in submandibular gland fibrosis after experimental periodontitis in rats. Acta Odontol Latinoam 29:138–143

    PubMed  Google Scholar 

  69. Lee JH, Lin JD, Fong JI et al (2013) The adaptive nature of the bone-periodontal ligament-cementum complex in a ligature-induced periodontitis rat model. Biomed Res Int 2013. https://doi.org/10.1155/2013/876316

  70. Dal-Fabbro R, Cosme-Silva L, Capalbo LC et al (2021) Excessive caffeine intake increases bone resorption associated with periapical periodontitis in rats. Int Endod J 54:1861–1870. https://doi.org/10.1111/iej.13578

    Article  PubMed  Google Scholar 

  71. Shabani E, Kalantari H, Kalantar M et al (2021) Berberine ameliorates testosterone-induced benign prostate hyperplasia in rats. BMC Complement Med Ther 21. https://doi.org/10.1186/s12906-021-03472-2

  72. Tenovuo J (1997) Community Dentistry and Oral Epidemiology Salivary parameters of relevance for assessing caries activity in individuals and populations. Community Dent Oral Epidemiol 25:82–86. https://doi.org/10.1111/j.1600-0528.1997.tb00903.x

  73. Almståhl A, Wikström M (2003) Electrolytes in stimulated whole saliva in individuals with hyposalivation of different origins. Arch Oral Biol 48:337–344. https://doi.org/10.1016/S0003-9969(02)00200-5

    Article  PubMed  CAS  Google Scholar 

  74. Amer M, Elverdin JC, Fernández-Solari J et al (2011) Reduced methacholine-induced submandibular salivary secretion in rats with experimental periodontitis. Arch Oral Biol 56:421–427. https://doi.org/10.1016/j.archoralbio.2010.11.004

    Article  PubMed  CAS  Google Scholar 

  75. Haug S, Marthinussen M (2019) Acute dental pain and salivary biomarkers for stress and inflammation in patients with pulpal or periapical inflammation. J Oral Facial Pain Headache 33:227–233. https://doi.org/10.11607/ofph.2007

  76. Arce-Franco M, Dominguez-Luis M, Pec MK et al (2017) Functional effects of proinflammatory factors present in Sjogren’s syndrome salivary microenvironment in an in vitro model of human salivary gland. Sci Rep 7. https://doi.org/10.1038/s41598-017-12282-x

  77. Henskens YMC, van der Weijden FA, van den Keijbus PAM et al (1996) Effect of periodontal treatment on the protein composition of whole and parotid saliva. J Periodontol 67:205–212. https://doi.org/10.1902/JOP.1996.67.3.205

    Article  PubMed  CAS  Google Scholar 

  78. Ahmad P, Hussain A, Carrasco-Labra A, Siqueira WL (2022) Salivary proteins as dental caries biomarkers: a systematic review. Caries Res 56:385–398. https://doi.org/10.1159/000526942

    Article  PubMed  Google Scholar 

  79. Mohammadi Z (2008) Chlorhexidine gluconate, its properties and applications in endodontics. Iran Edond J 2:113–125

    Google Scholar 

  80. Kuo ML, Lamster IB, Hasselgren G (1998) Host mediators in endodontic exudates. II. Changes in concentration with sequential sampling. J Endod 24:636–640. https://doi.org/10.1016/S0099-2399(98)80144-1

    Article  PubMed  CAS  Google Scholar 

  81. Pezelj-Ribarić S, Magašić K, Prpić J et al (2007) Tumor necrosis factor-alpha in peripical tissue exudates of teeth with apical periodontitis. Mediators Inflamm 2007. https://doi.org/10.1155/2007/69416

  82. Shimauchi H, Miki Y, Takayama S-I et al (1996) Development of a quantitative sampling method for periapical exudates from human root canals. J Endod 22:612–615. https://doi.org/10.1016/s0099-2399(96)80032-x

    Article  PubMed  CAS  Google Scholar 

  83. Melvin JE, Yule D, Shuttleworth T, Begenisich T (2005) Regulation of fluid and electrolyte secretion in salivary gland acinar cells. Annu Rev Physiol 67:445–469. https://doi.org/10.1146/annurev.physiol.67.041703.084745

    Article  PubMed  CAS  Google Scholar 

  84. Sneyd J, Rugis J, Su S et al (2022) Simulation of calcium dynamics in realistic three-dimensional domains. Biomolecules 12. https://doi.org/10.3390/biom12101455

  85. Sneyd J, Crampin E, Yule D (2014) Multiscale modelling of saliva secretion. Math Biosci 257:69–79. https://doi.org/10.1016/J.MBS.2014.06.017

    Article  MathSciNet  PubMed  PubMed Central  CAS  Google Scholar 

  86. Roussa E (2011) Channels and transporters in salivary glands. Cell Tissue Res 343:263–287. https://doi.org/10.1007/S00441-010-1089-Y

    Article  PubMed  CAS  Google Scholar 

  87. Patterson K, Catalán MA, Melvin JE et al (2012) A quantitative analysis of electrolyte exchange in the salivary duct. Am J Physiol Gastrointest Liver Physiol 303:1153–1163. https://doi.org/10.1152/ajpgi.00364.2011.-A

    Article  Google Scholar 

  88. Homann V, Kinne-Saffran E, Arnold WH et al (2006) Calcium transport in human salivary glands: a proposed model of calcium secretion into saliva. Histochem Cell Biol 125:583–591. https://doi.org/10.1007/s00418-005-0100-2

    Article  PubMed  CAS  Google Scholar 

  89. Ikuta K, Segawa H, Hanazaki A et al (2019) Systemic network for dietary inorganic phosphate adaptation among three organs. Pflugers Arch 471:123–136. https://doi.org/10.1007/s00424-018-2242-9

    Article  PubMed  CAS  Google Scholar 

  90. Miozza VA, Sánchez GA, Busch L (2012) Influence of experimental periodontitis on cholinergic stimulation of K + release in rat parotid glands. Auton Neurosci 169:43–48. https://doi.org/10.1016/j.autneu.2012.03.004

    Article  PubMed  CAS  Google Scholar 

  91. Carpenter GH, Osailan SM, Correia P et al (2007) Rat salivary gland ligation causes reversible secretory hypofunction. Acta Physiol 189:241–249. https://doi.org/10.1111/J.1365-201X.2006.01662.X

    Article  CAS  Google Scholar 

  92. Correia PN, Carpenter GH, Osailan SM et al (2008) Acute salivary gland hypofunction in the duct ligation model in the absence of inflammation. Oral Dis 14:520–528. https://doi.org/10.1111/j.1601-0825.2007.01413.x

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  93. Brown AE, Rogers JD, Haase EM et al (1999) Prevalence of the amylase-binding protein A gene (abpA) in oral streptococci. J Clin Microbiol 37:4081–4085. https://doi.org/10.1128/JCM.37.12.4081-4085.1999

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  94. Scannapieco FA (1994) Saliva-bacterium interactions in oral microbial ecology. Crit Rev Oral Biol Med 5:203–248. https://doi.org/10.1177/10454411940050030201

    Article  PubMed  CAS  Google Scholar 

  95. Larsen MJ, Fejerkov O (1989) Chemical and structural challenges in remineralization of dental enamel lesions. Scand J Dent Res 97:285–296. https://doi.org/10.1111/J.16000722.1989.TB01615.X

    Article  PubMed  CAS  Google Scholar 

  96. Gaffar A, Blake-Haskins J, Mellberg J (1993) In vivo studies with a dicalcium phosphate dihydrate/MFP system for caries prevention. Int Dent J 43:81–88

    PubMed  CAS  Google Scholar 

  97. White DJ (1997) Dental calculus: recent insights into occurrence, formation, prevention, removal and oral health effects of supragingival and subgingival deposits. Eur J Oral Sci 105:508–522. https://doi.org/10.1111/J.1600-0722.1997.TB00238.X

    Article  PubMed  CAS  Google Scholar 

  98. Zalewska A, Knä M, Maciejczyk M et al (2015) Antioxidant profile, carbonyl and lipid oxidation markers in the parotid and submandibular glands of rats in different periods of streptozotocin induced diabetes. Arch Oral Biol 60:1375–1386. https://doi.org/10.1016/j.archoralbio.2015.06.012

    Article  PubMed  CAS  Google Scholar 

  99. Peralta I, Marrassini C, Arcos MLB, et al (2019) Larrea divaricata Cav. aqueous extract and nordihydroguariaretic acid modulate oxidative stress in submandibular glands of diabetic rats: a buccal protective in diabetes. BMC Complement Altern Med 19. https://doi.org/10.1186/s12906-019-2636-z

  100. Prieto AKC, Gomes-Filho JE, Azuma MM et al (2017) Influence of apical periodontitis on stress oxidative parameters in diabetic rats. J Endod 43:1651–1656. https://doi.org/10.1016/j.joen.2017.05.014

    Article  PubMed  Google Scholar 

  101. Wu YH, Yao QT, Liu SH et al (2021) Effect of ischemic preconditioning on radiation damage to the submandibular gland in rats. Eur J Oral Sci 129:12785–12785. https://doi.org/10.1111/EOS.12785

    Article  Google Scholar 

  102. Lorenzen I, Mullen L, Bekeschus S, Hanschmann EM (2017) Redox regulation of inflammatory processes is enzymatically controlled. Oxid Med Cell Longev 2017. https://doi.org/10.1155/2017/8459402

  103. Bhattarai KR, Junjappa R, Handigund M et al (2018) The imprint of salivary secretion in autoimmune disorders and related pathological conditions. Autoimmun Rev 17:376–390. https://doi.org/10.1016/j.autrev.2017.11.031

    Article  PubMed  CAS  Google Scholar 

  104. Nater UM, Rohleder N (2009) Salivary alpha-amylase as a non-invasive biomarker for the sympathetic nervous system: current state of research. Psychoneuroendocrinology 34:486–496. https://doi.org/10.1016/j.psyneuen.2009.01.014

    Article  PubMed  CAS  Google Scholar 

  105. Inchingolo F, Marrelli M, Annibali S et al (2013) Influence of endodontic treatment on systemic oxidative stress. Int J Med Sci 11:1–6. https://doi.org/10.7150/ijms.6663

    Article  PubMed  PubMed Central  Google Scholar 

  106. Frazão DR, Santos Mendes PF, Baia-da-Silva DC, et al (2023) Modulation of blood redox status by the progression of induced apical periodontitis in rats. Front Physiol 14. https://doi.org/10.3389/fphys.2023.1214990

  107. Gomes C, Martinho FC, Barbosa DS et al (2018) 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 55:2814–2827. https://doi.org/10.1007/S12035-017-0545-Z

    Article  PubMed  CAS  Google Scholar 

  108. Wolle CFB, Zollmann LA, Bairros PO et al (2013) Outcome of periapical lesions in a rat model of type 2 diabetes: refractoriness to systemic antioxidant therapy. J Endod 39:643–647. https://doi.org/10.1016/j.joen.2012.12.030

    Article  PubMed  Google Scholar 

  109. Tibúrcio-Machado C dos S, Lang PM, Campos MM, et al (2021) High-fat diet effect on periapical lesions and hepatic enzymatic antioxidant in rats. Life Sci 264. https://doi.org/10.1016/J.LFS.2020.118637

  110. Kang WS, Jung WK, Bin PS et al (2021) Gemigliptin suppresses salivary dysfunction in streptozotocin-induced diabetic rats. Biomed Pharmacother 137:111297. https://doi.org/10.1016/j.biopha.2021.111297

    Article  PubMed  CAS  Google Scholar 

  111. Fiais GA, Ferreira DS de B, de Freitas RN et al (2023) Assessment of the toxic effects of levetiracetam on biochemical, functional, and redox parameters of salivary glands in male Wistar rats. Toxicology 496. https://doi.org/10.1016/J.TOX.2023.153615

  112. Cheng R, Feng Y, Zhang R et al (2018) The extent of pyroptosis varies in different stages of apical periodontitis. Biochim Biophys Acta Mol Basis Dis 1864:226–237. https://doi.org/10.1016/j.bbadis.2017.10.025

    Article  PubMed  CAS  Google Scholar 

  113. Gomes-Filho JE, Wayama MT, Dornelles RCM et al (2015) Effect of raloxifene on periapical lesions in ovariectomized rats. J Endod 41:671–675. https://doi.org/10.1016/j.joen.2014.11.027

    Article  PubMed  Google Scholar 

  114. Paula-Silva FWG, Ribeiro-Santos FR, Petean IBF et al (2020) Root canal contamination or exposure to lipopolysaccharide differentially modulate prostaglandin E 2 and leukotriene B 4 signaling in apical periodontitis. J Appl Oral Sci 28:1–9. https://doi.org/10.1590/1678-7757-2019-0699

    Article  CAS  Google Scholar 

  115. Minczykowski A, Woszczyk M, Szczepanik A et al (2001) Hydrogen peroxide and superoxide anion production by polymorphonuclear neutrophils in patients with chronic periapical granuloma, before and after surgical treatment. Clin Oral Investig 5:6–10. https://doi.org/10.1007/S007840000095

    Article  PubMed  CAS  Google Scholar 

  116. Guerrero-Bobadilla C, Yáñez-Sánchez I, Franco-Ávila T et al (2020) Reduction of NrF2 as coadjuvant during the development of persistent periapical lesions. Med Oral Patol Oral Cir Bucal 28:404–411. https://doi.org/10.4317/medoral.25815

    Article  Google Scholar 

  117. Marton IJ, Balla G, Hegedus C et al (1993) The role of reactive oxygen intermediates in the pathogenesis of chronic apical periodontitis. Oral Microbiol Immunol 8:254–257. https://doi.org/10.1111/j.1399-302x.1993.tb00570.x

    Article  PubMed  CAS  Google Scholar 

  118. Zalewska A, Joanna K, Sara Z et al (2021) N-Acetylcysteine supplementation did not reverse mitochondrial oxidative stress, apoptosis, and inflammation in the salivary glands of hyperglycemic rats. Nutr Diabetes 11. https://doi.org/10.1038/s41387-021-00177-w

  119. Chen S, Wang Y, Zhang C, Yang Z (2020) Decreased basal and stimulated salivary parameters by histopathological lesions and secretory dysfunction of parotid and submandibular glands in rats with type 2 diabetes. Exp Ther Med 19:2707–2719. https://doi.org/10.3892/etm.2020.8505

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  120. Mostafa OAA, Ibrahim F, Borai E (2023) Protective effects of hesperidin in cyclophosphamide-induced parotid toxicity in rats. Sci Rep 13:158. https://doi.org/10.1038/s41598-022-26881-w

    Article  ADS  PubMed  PubMed Central  CAS  Google Scholar 

  121. Nair PN (2000) (1997) Apical periodontitis: A dynamic encounter between root canal infection and host response. Periodontol 13:121–148. https://doi.org/10.1111/j.1600-0757.1997.tb00098.x

    Article  Google Scholar 

  122. Rechenberg DK, Held U, Burgstaller JM et al (2016) Pain levels and typical symptoms of acute endodontic infections: a prospective, observational study. BMC Oral Health 16:61. https://doi.org/10.1186/s12903-016-0222-z

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

A.H.C.N. acknowledges financial support through a grant from the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior —Brasil (CAPES)—Finance Code 001; Pro-Rectory of Research of UNESP (PROPe – Unesp – Process nº 2022-5529-4) and Grant no. 2022/11532-2, São Paulo Research Foundation (FAPESP). A.R.V. was supported by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brasil (CAPES)—Finance Code 001; L.C. was supported by the Pro-Rectory of Research of UNESP (PROPe – Unesp – Process nº 2022-5529-4) and P.P.P. was supported by Grant no. 2022/11532-2, São Paulo Research Foundation (FAPESP).

Funding

This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (CAPES) - Finance Code 001; Grant no. 2022/11532-2, São Paulo Research Foundation (FAPESP); and Pro-Rectory of Research of Unesp (PROPe-Unesp-Process no. 2022–5529-4-PIBIC).

Author information

Authors and Affiliations

  1. Programa de Pós-Graduação em Ciências, School of Dentistry of Araçatuba–UNESP–Universidade Estadual Paulista, Araçatuba, São Paulo, Brazil

    Arieli Raymundo Vazão, Rayara Nogueira de Freitas, Mariana Pagliusi Justo, Luciano Tavares Ângelo Cintra & Antonio Hernandes Chaves-Neto

  2. Department of Basic Sciences, School of Dentistry of Araçatuba–UNESP–Universidade Estadual Paulista, Araçatuba, São Paulo, Brazil

    Arieli Raymundo Vazão, Lívia Claudino, Pedro Penati Pimpinato, Larissa Victorino Sampaio, Gabriela Alice Fiais, Rayara Nogueira de Freitas, Sandra Helena Penha Oliveira & Antonio Hernandes Chaves-Neto

  3. Programa de Pós-Graduação Multicêntrico em Ciências Fisiológicas–SBFis, School of Dentistry of Araçatuba–UNESP–Universidade Estadual Paulista, Araçatuba, São Paulo, Brazil

    Larissa Victorino Sampaio, Gabriela Alice Fiais, Victor Gustavo Balera Brito, Sandra Helena Penha Oliveira & Antonio Hernandes Chaves-Neto

  4. Department of Preventive and Restorative Dentistry, School of Dentistry of Araçatuba–UNESP–Universidade Estadual Paulista, Araçatuba, São Paulo, Brazil

    Mariana Pagliusi Justo & Luciano Tavares Ângelo Cintra

  5. Laboratory of Functional and Structural Biology, Institute of Biological Sciences, Federal University of Pará (UFPA), Belém, Pará, Brazil

    Rafael Rodrigues Lima

Authors
  1. Arieli Raymundo Vazão
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lívia Claudino
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Pedro Penati Pimpinato
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Larissa Victorino Sampaio
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Gabriela Alice Fiais
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Rayara Nogueira de Freitas
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Mariana Pagliusi Justo
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Victor Gustavo Balera Brito
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Sandra Helena Penha Oliveira
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Rafael Rodrigues Lima
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Luciano Tavares Ângelo Cintra
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Antonio Hernandes Chaves-Neto
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conceptualization: A.R.V., R.R.L., S.H.P.O., L.T.Â.C., and A.H.C.N.; methodology: A.R.V., L.C., P.P.P., L.V.S., G.A.F., R.N.F., M.P.J., V.G.B.B., and A.H.C.N.; formal analysis: A.R.V., L.C., P.P.P., L.V.S., G.A.F., R.N.F., M.P.J., V.G.B.B., and A.H.C.N.; investigation: A.R.V., L.C., P.P.P., and A.H.C.N.; resources: S.H.P.O., L.T.Â.C., and A.H.C.N.; writing original draft: A.R.V., L.C., P.P.P., L.V.S., G.A.F., R.N.F., M.P.J., V.G.B.B. R.R.L., L.T.Â.C., and A.H.C.N.; supervision: A.H.C.N.; project administration: A.H.C.N.; funding acquisition: A.H.C.N.; visualization. All authors reviewed the manuscript.

Corresponding author

Correspondence to Antonio Hernandes Chaves-Neto.

Ethics declarations

Competing interests

The authors declare no competing interests.

Ethics approval

All procedures performed in studies involving animals were in accordance with the standards ARRIVE guideline. The study was approved by the Local Ethics Committee on the Use of Animals, of the Faculdade de Odontologia de Araçatuba, UNESP (No. 0374–2022).

Consent to participate

Not applicable.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Vazão, A.R., Claudino, L., Pimpinato, P.P. et al. Experimental apical periodontitis alters salivary biochemical composition and induces local redox state disturbances in the salivary glands of male rats. Clin Oral Invest 28, 154 (2024). https://doi.org/10.1007/s00784-024-05540-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s00784-024-05540-6

Keywords

Search

Navigation