Abstract
Aim:
To evaluate the effectiveness of subantimicrobial-dose doxycycline (SDD) as an adjunct to scaling and root planing (SRP) treatment against the nitrosative stress of moderate to advanced chronic periodontitis.
Methods:
Adults with untreated chronic periodontitis (n=174) were randomly administered SRP+SDD (n=87) (20 mg of doxycycline twice daily) or SRP+placebo (n=87) treatment for 3 months. At baseline and after 3 months, the probing depths (PD), bleeding on probing (BOP) and clinical attachment level (CAL) were measured, and a gingivomucosal biopsy was collected to assay the induction of nitric oxide synthase (iNOS) and 3-nitrotyrosine (3NT), and blood was collected to assay for total nitrites and nitrates (NOx) and 3NT.
Results:
Compared to baseline, at the completion of treatment, significant decreases in the levels of tissue iNOS and 3NT and serum NOx and 3NT were observed in both groups. SRP+SDD yielded a greater reduction in the gingivomucosal and serum nitrosative stress markers than did SRP+placebo. PD, BOP, and CAL reduction were correlated with the nitrosative stress parameters.
Conclusion:
On a short-term basis, SDD therapy may be used as an adjunct to SRP treatment against nitrosative stress in moderate to advanced chronic periodontitis.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
Kirkwood KL, Cirelli JA, Rogers JE, Giannobile WV . Novel host response therapeutic approaches to treat periodontal diseases. Periodontol 2000 2007; 43: 294–315.
American Academy of Periodontology. Comprehensive periodontal therapy: a statement by the American Academy of Periodontology. J Periodontol 2011; 82: 943–9.
Inaba H, Amano A . Roles of oral bacteria in cardiovascular diseases — from molecular mechanisms to clinical cases: Implication of periodontal diseases in development of systemic diseases. J Pharmacol Sci 2010; 113: 103–9.
Bascones-Martínez A, Muñoz-Corcuera M, Noronha S, Mota P, Bascones-Ilundain C, Campo-Trapero J . Host defence mechanisms against bacterial aggression in periodontal disease: Basic mechanisms. Med Oral Patol Oral Cir Bucal 2009; 14: e680–5.
Ababneh KT, Taha AH, Abbadi MS, Karasneh JA, Khader YS . The association of aggressive and chronic periodontitis with systemic manifestations and dental anomalies in a Jordanian population: a case control study. Head Face Med 2010; 6: 30–7.
Kumar SS, Mittal M, Khanna P . Role of antibiotics in the treatment of periodontal disease-an overview. Int J Microbiol 2012. DOI: 10.5580/2af7.
Golub LM, Greenwald RA . Clinical applications of non-antibacterial tetracyclines. Part II. Pharmacol Res 2011; 64: 549–50.
Sgolastra F, Petrucci A, Gatto R, Giannoni M, Monaco A . Long-term efficacy of subantimicrobial-dose doxycycline as an adjunctive treatment to scaling and root planing: a systematic review and metaanalysis. J Periodontol 2011; 82: 1570–81.
Menaka KB, Ramesh A, Thomas B, Suchetha Kumari N . Estimation of nitric oxide as an inflammatory marker in periodontitis. J Indian Soc Periodontol 2009; 13: 75–8.
Reher VG, Zenóbio EG, Costa FO, Reher P, Soares RV . Nitric oxide levels in saliva increase with severity of chronic periodontitis. J Oral Sci 2007; 49: 271–6.
Simão AN, Lozovoy MA, Simão TN, Venturini D, Barbosa DS, Dichi JB, et al. Immunological and biochemical parameters of patients with metabolic syndrome and the participation of oxidative and nitroactive stress. Braz J Med Biol Res 2011; 44: 707–12.
Lohinai Z, Mabley JG, Fehér E, Marton A, Komjáti K, Szabó C . Role of the activation of the nuclear enzyme poly(ADP-ribose) polymerase in the pathogenesis of periodontitis. J Dent Res 2003; 82: 987–92.
Uğar-Cankal D, Ozmeric N . A multifaceted molecule, nitric oxide in oral and periodontal diseases. Clin Chim Acta 2006; 366: 90–100.
Lohinai Z, Benedek P, Fehér E, Györfi A, Rosivall L, Fazekas A, et al. Protective effects of mercaptoethylguanidine, a selective inhibitor of inducible nitric oxide synthase, in ligature-induced periodontitis in the rat. Br J Pharmacol 1998; 123: 353–60.
Wu YM, Chen LL, Yan J, Zhuang CY, Gu ZY . Effect of Porphyromonas gingivalis PrtC on cytokine expression in ECV304 endothelial cells and its level in subgingival plaques from patients with chronic periodontitis. Acta Pharmacol Sin 2007; 28: 1015–23.
Savage A, Eaton KA, Moles DR, Needleman I . A systematic review of definitions of periodontitis and methods that have been used to identify this disease. J Clin Periodontol 2009; 36: 458–67.
Di Nardo Di Maio F, Lohinai Z, D'Arcangelo C, De Fazio PE, Speranza L, De Lutiis MA, et al. Nitric oxide synthase in healthy and inflamed human dental pulp. J Dent Res 2004; 83: 312–6.
Watarai H, Warita H, Soma K . Effect of nitric oxide on the recovery of the hypofunctional periodontal ligament. J Dent Res 2004; 83: 338–42.
Bezerra MM, Brito GA, Ribeiro RA, Rocha FA . Low-dose doxycycline prevents inflammatory bone resorption in rats. Braz J Med Biol Res 2002; 35: 613–6.
Tian J, Yan Z, Wu Y, Zhang SL, Wang K, Ma XR, et al. Inhibition of iNOS protects endothelial-dependent vasodilation in aged rats. Acta Pharmacol Sin 2010; 31: 1324–8.
Di Paola R, Mazzon E, Maiere D, Zito D, Britti D, De Majo M, et al. Rosiglitazone reduces the evolution of experimental periodontitis in the rat. J Dent Res 2006; 85: 156–61.
Lohinai Z, Stachlewitz R, Virag L, Szekely AD, Hasko G, Szabo C . Evidence for reactive nitrogen species formation in the gingivomucosal tissue. J Dent Res 2001; 80: 470–5.
Ghasemi A, Hedayati M, Biabani H . Protein precipitation methods evaluated for determination of serum nitric oxide end products by the Griess assay. J Med Sci Res 2007; 2: 29–32.
Miranda KM, Espey MG, Wink DA . A rapid, simple spectrophotometric method for simultaneous detection of nitrate and nitrite. Nitric Oxide 2001; 5: 62–71.
Khan J, Brennand DM, Bradley N, Gao B, Bruckdorfer R, Jacobs M . 3-Nitrotyrosine in the proteins of human plasma determined by an ELISA method. Biochem J 1998; 330: 795–801.
Greenstein G . Efficacy of subantimicrobial-dose doxycycline in the treatment of periodontal diseases: a critical evaluation. Int J Periodontics Restorative Dent 2004; 24: 528–43.
Payne JB, Golub LM, Stoner JA, Lee HM, Reinhardt RA, Sorsa T, et al. The effect of subantimicrobial-dose-doxycycline periodontal therapy on serum biomarkers of systemic inflammation: a randomized, double-masked, placebo-controlled clinical trial. J Am Dent Assoc 2011; 142: 262–73.
Lee JY, Lee YM, Shin SY, Seol YJ, Ku Y, Rhyu IC, et al. Effect of subantimicrobial dose doxycycline as an effective adjunct to scaling and root planing. J Periodontol 2004; 75: 1500–8.
Gu Y, Lee HM, Sorsa T, Salminen A, Ryan ME, Slepian MJ, et al. Non-antibacterial tetracyclines modulate mediators of periodontitis and atherosclerotic cardiovascular disease: A mechanistic link between local and systemic inflammation. Pharmacol Res 2011; 64: 573–9.
Gu Y, Lee HM, Sorsa T, Simon SR, Golub LM . Doxycycline inhibits mononuclear cell-mediated connective tissue breakdown. FEMS Immunol Med Microbiol 2010; 58: 218–25.
Emingil G, Gürkan A, Atilla G, Kantarci A . Subantimicrobial-dose doxycycline and cytokine-chemokine levels in gingival crevicular fluid. J Periodontol 2011; 82: 452–61.
Preshaw PM, Novak MJ, Mellonig J, Magnusson I, Polson A, Giannobile WV, et al. Modified-release subantimicrobial dose doxycycline enhances scaling and root planing in subjects with periodontal disease. J Periodontol 2008; 79: 440–52.
Caton J, Ryan ME . Clinical studies on the management of periodontal diseases utilizing subantimicrobial dose doxycycline (SDD). Pharmacol Res 2011; 63: 114–20.
Wink DA, Miranda KM, Espey MG . Cytotoxicity related to oxidative and nitrosative stress by nitric oxide. Exp Biol Med (Maywood) 2001; 226: 621–3.
Wink DA, Miranda KM, Espey MG, Pluta RM, Hewett SJ, Colton C, et al. Mechanisms of the antioxidant effects of nitric oxide. Antioxid Redox Signal 2001; 3: 203–13.
Reher VG, Zenóbio EG, Costa FO, Reher P, Soares RV . Nitric oxide levels in saliva increase with severity of chronic periodontitis. J Oral Sci 2007; 49: 271–6.
Acknowledgements
This work was financially supported by the Ministry of Education, Research and Youth, CNCSIS grant PNII-IDEI 1273/2008. We would like to thank Synevo Romania SRL for providing the blood samples and Mihaela Banciu for editing the text.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Pârvu, A., Alb, S., Crăciun, A. et al. Efficacy of subantimicrobial-dose doxycycline against nitrosative stress in chronic periodontitis. Acta Pharmacol Sin 34, 247–254 (2013). https://doi.org/10.1038/aps.2012.129
Received:
Accepted:
Published:
Issue date:
DOI: https://doi.org/10.1038/aps.2012.129
Keywords
This article is cited by
-
Effect of tetracyclines on pulpal and periodontal healing after tooth replantation: a systematic review of human and animal studies
BMC Oral Health (2021)
-
Systematic review and meta-analysis on the adjunctive use of host immune modulators in non-surgical periodontal treatment in healthy and systemically compromised patients
Scientific Reports (2021)
