The Effect of Gingival Inflammation on Salivary Cytochrome P450 Enzymes in Children: A Case-Control Study
Abstract
Background/Aim: Gingival inflammation in children involves characteristic changes of the salivary composition that reflect not only weakened local defence factors but also increased defensive reflexes. This study aimed to compare the salivary parameters cytochrome concentration, density and flow rate between children with gingival inflammation and clinically healthy gingiva.
Methods: A total of 86 children were included and divided into two groups: 41 with gingival inflammation and 45 with healthy gingiva, which was gender matched for age. Unstimulated saliva was collected and cytochrome concentration, salivary density and flow rate were measured.
Results: Participants with gingival inflammation had significantly lower mean salivary cytochrome concentration and density but showed increased salivary flow rate compared to healthy controls. These differences were found in both sexes, being more marked in boys with respect to the age increase of flow rate. Correlation studies showed a strong negative correlation between salivary density and flow rate in both groups. These results indicate that there is a unique biochemical signature for gingival inflammation in children, which includes lower cytochrome and density, accompanied by an increase in flow rate.
Conclusion: In children, gingival inflammation was associated with reduced salivary CYP450 and density and increased flow rate in saliva, suggesting a unique biochemistry of oral disease.
References
Kragelund C, Hansen C, Torpet LA, Nauntofte B, Brøsen K, Pedersen AML, Buchwald C, Therkildsen MH, Reibel J. Expression of two drug metabolizing cytochrome P450 enzymes in human salivary glands. Oral Dis. 2008;14(6):533–40. doi: 10.1111/j.1601-0825.2007.01415.x.
Slaughter RL, Edwards DJ. Recent advances: the cytochrome P450 enzymes. Ann Pharmacother. 1995;29(6):619–24. doi: 10.1177/106002809502900612.
Wilkinson GR. Drug metabolism and variability among patients in drug response. N Engl J Med. 2005;352(21):2211–21. doi: 10.1056/NEJMra032424.
Lynch T, Price A. The effect of cytochrome P450 metabolism on drug response, interactions, and adverse effects. Am Fam Physician. 2007 Aug 1;76(3):391–6. PMID:17708140.
Zhou Y, Ingelman Sundberg M, Lauschke VM. Worldwide distribution of cytochrome P450 alleles: a meta analysis of population scale sequencing projects. Clin Pharmacol Ther. 2017 Oct;102(4):688–700. doi: 10.1002/cpt.690.
Lenoir C, Rollason V, Desmeules JA, Samer CF. Influence of inflammation on cytochromes P450 activity in adults: a systematic review of the literature. Front Pharmacol. 2021 Nov 16;12:733935. doi: 10.3389/fphar.2021.733935.
Christmas P. Role of cytochrome P450s in inflammation. Adv Pharmacol. 2015;74:163–92. doi: 10.1016/bs.apha.2015.03.005.
Morgan ET. Regulation of cytochrome P450 by inflammatory mediators: why and how? Drug Metab Dispos. 2001 Mar;29(3):207–12. Erratum in: Drug Metab Dispos. 2001 Jun;29(6):932. PMID:11181485.
de Jong LM, Jiskoot W, Swen JJ, Manson ML. Distinct effects of inflammation on cytochrome P450 regulation and drug metabolism: lessons from experimental models and a potential role for pharmacogenetics. Genes (Basel). 2020 Dec 16;11(12):1509. doi: 10.3390/genes11121509.
Stanke Labesque F, Concordet D, Djerada Z, Bouchet S, Solas C, Mériglier E, et al. Neglecting plasma protein binding in COVID 19 patients leads to a wrong interpretation of lopinavir overexposure. Clin Pharmacol Ther. 2021 Apr;109(4):1030–3. doi: 10.1002/cpt.2196.
Aitken AE, Morgan ET. Gene specific effects of inflammatory cytokines on cytochrome P450 2C, 2B6 and 3A4 mRNA levels in human hepatocytes. Drug Metab Dispos. 2007 Sep;35(9):1687–93. doi: 10.1124/dmd.107.015511.
Stavropoulou E, Pircalabioru GG, Bezirtzoglou E. The role of cytochromes P450 in infection. Front Immunol. 2018;9:89. doi: 10.3389/fimmu.2018.00089.
Dikova VR, Principe S, Bagan JV. Salivary inflammatory proteins in patients with oral potentially malignant disorders. J Clin Exp Dent. 2019 Jul;11(7):e659–64. doi: 10.4317/jced.55917.
Diesch T, Filippi C, Fritschi N, Filippi A, Ritz N. Cytokines in saliva as biomarkers of oral and systemic oncological or infectious diseases: a systematic review. Cytokine. 2021 Jul;143:155506. doi: 10.1016/j.cyto.2021.155506.
Tomofuji T, Ekuni D, Irie K, Azuma T, Endo Y, Tamaki N, et al. Preventive effects of a cocoa enriched diet on gingival oxidative stress in experimental periodontitis. J Periodontol. 2009 Nov;80(11):1799–808. doi: 10.1902/jop.2009.090270.
World Health Organization. Oral Health Surveys: Basic Methods. 5th ed. Geneva: WHO; 2013.
Khurshid Z, Zohaib S, Najeeb S, Zafar MS, Slowey PD, Almas K. Human saliva collection devices for proteomics: an update. Int J Mol Sci. 2016 Jun 6;17(6):846. doi: 10.3390/ijms17060846.
Navazesh M, Kumar SK; University of Southern California School of Dentistry. Measuring salivary flow: challenges and opportunities. J Am Dent Assoc. 2008 May;139(Suppl):35S–40S. doi: 10.14219/jada.archive.2008.0353.
Humphrey SP, Williamson RT. A review of saliva: normal composition, flow, and function. J Prosthet Dent. 2001 Feb;85(2):162–9. doi: 10.1067/mpr.2001.113778.
Davidovich E, Ccahuana Vasquez RA, Grender J, Timm H, Gonen H, Zini A. A 4 week randomized controlled trial evaluating plaque and gingivitis effects of an electric toothbrush in a paediatric population. Int J Paediatr Dent. 2024;34(3):246–55. doi: 10.1111/ipd.13130.
Sanchis Sanchis A, Grau MD, Moliner AR, Morales Murillo CP. Effects of age and gender in emotion regulation of children and adolescents. Front Psychol. 2020;11:946. doi: 10.3389/fpsyg.2020.00946.
Ajeel N, Diab B. Dental caries as a health risk for visual acuity in relation to salivary transforming growth factor beta 1 among students aged 8–10 years: a cross sectional study. J Int Soc Prevent Community Dent. 2024;14(2):144–51. doi: 10.4103/jispcd.jispcd_205_23.
Ahmed AA, Diab BS, Razeghi S. Sleep disorders and dental caries related to salivary alpha amylase among dental students. J Baghdad Coll Dent. 2024;36(2). doi: 10.26477/jbcd.v36i2.3679.
Taher AK, Radhi NJMH. Salivary irisin in relation to recurrent aphthous ulcer and weight status in Diyala City, Iraq. J Baghdad Coll Dent. 2024;36(1):19–26. doi: 10.26477/jbcd.v36i1.3587.
Skutnik Radziszewska A, Zalewska A. Salivary redox biomarkers in the course of caries and periodontal disease. Appl Sci. 2020;10(18):6240. doi: 10.3390/app10186240.
Eberhard J, Grote K, Luchtefeld M, Heuer W, Schuett H, Divchev D, et al. Experimental gingivitis induces systemic inflammatory markers in young healthy individuals: a single subject interventional study. PLoS One. 2013;8(2):e55265. doi: 10.1371/journal.pone.0055265.
Sreebny LM. Saliva in health and disease: an appraisal and update. Int Dent J. 2000;50(3):160–71. doi: 10.1111/j.1875-595X.2000.tb00554.x.
Haug SR, Birkeland JM, Olsen I. Acute dental pain and salivary biomarkers for stress and inflammation in patients with pulpal or periapical inflammation. J Oral Facial Pain Headache. 2023;33(2):227–34. doi: 10.3290/j.ofph_33_2_227.
Proctor GB. Disease induced changes in salivary gland function and the composition of saliva. J Dent Res. 2021 Nov;100(11):1201–9. doi: 10.1177/00220345211004842.
Inoue H, Ono K, Masuda W, Morimoto Y, Tanaka T, Yokota M, et al. Gender differences in unstimulated whole saliva flow rate and salivary gland sizes. Arch Oral Biol. 2006;51(12):1055–60. doi: 10.1016/j.archoralbio.2006.06.010.
Gotouda H, Sasai H, Taguchi C, Wang J, Arikawa K, Kuyama K, et al. Study of salivary volumes by the modified ion dilution method. Int J Oral Med Sci. 2004;3(3):121–7. doi: 10.5466/ijoms.3.121.
Tóthová L, Kamodyová N, Červenka T, Celec P. Salivary markers of oxidative stress in oral diseases. Front Cell Infect Microbiol. 2015 Oct 20;5:73. doi: 10.3389/fcimb.2015.00073.
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).
