{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T03:48:14Z","timestamp":1787024894923,"version":"build-2736575974"},"reference-count":94,"publisher":"Bentham Science Publishers Ltd.","issue":"1","license":[{"start":{"date-parts":[[2008,1,22]],"date-time":"2008-01-22T00:00:00Z","timestamp":1200960000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":["opendentistryjournal.com","benthamopen.com"],"crossmark-restriction":true},"short-container-title":["TODENTJ"],"published-print":{"date-parts":[[2008,1,22]]},"abstract":"<jats:p>This review addresses the role of adjunctive tetracycline therapy in the management of periodontal diseases and its efficacy in reducing inflammatory burden, oxidative stress and its sequelae in patients with coexisting features of metabolic syndrome. Removal of the dimethylamine group at C4 of the tetracycline molecule reduces its antibiotic properties, enhancing its non-antimicrobial actions; this strategy has aided the development of several chemically modified tetracyclines such as minocycline and doxycycline, by altering different regions of the molecule for focused action on biological targets. Tetracyclines are effective in reducing inflammation by inhibiting matrix metalloproteinases, preventing excessive angiogenesis, inhibiting apoptosis and stimulating bone formation. There are important applications for tetracyclines in the management of diabetic, dyslipidaemic periodontal patients who smoke. The diverse mechanisms of action of tetracyclines in overcoming oxidative stress and enhancing matrix synthesis are discussed in this review.<\/jats:p>","DOI":"10.2174\/1874210600802010005","type":"journal-article","created":{"date-parts":[[2008,10,31]],"date-time":"2008-10-31T11:57:52Z","timestamp":1225454272000},"page":"5-12","update-policy":"https:\/\/doi.org\/10.2174\/crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["A Role for Non-Antimicrobial Actions of Tetracyclines in Combating Oxidative Stress in Periodontal and Metabolic Diseases: A Literature Review"],"prefix":"10.2174","volume":"2","author":[{"given":"M","family":"Soory","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"965","reference":[{"key":"refR1","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1111\/j.1834-7819.2004.tb00070.x","volume":"49","author":"Georgiou TO","year":"2004","unstructured":"Georgiou TO, Marshall RI, Bartold PM. \n                    Prevalence of systemic diseases in Brisbane general and periodontal practice patients \n                    Aust Dent J  \n                    2004; \n                    49\n                    : 177-84.","journal-title":"Aust Dent J"},{"key":"refR2","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1111\/j.1600-051X.2004.00539.x","volume":"31","author":"Molloy J","year":"2004","unstructured":"Molloy J, Wolff LF, Lopez-Guzman A, Hodges JS. \n                    The association of periodontal disease parameters with systemic medical conditions and tobacco use \n                    J Clin Periodontol  \n                    2004; \n                    31\n                    : 625-34.","journal-title":"J Clin Periodontol"},{"key":"refR3","doi-asserted-by":"crossref","first-page":"13","DOI":"10.2174\/1568005310202010013","volume":"2","author":"Soory M","year":"2002","unstructured":"Soory M. \n                    Hormone mediation of immune responses in the progression of diabetes, rheumatoid arthritis and periodontal diseases \n                    Curr Drug Targets-Immun, Endocr Metab Disord  \n                    2002; \n                    2\n                    : 13-25.","journal-title":"Curr Drug Targets-Immun, Endocr Metab Disord"},{"key":"refR4","volume":"4","author":"Soory M","year":"2004","unstructured":"Soory M. \n                    Biomarkers of diabetes mellitus and rheumatoid arthritis associated with oxidative stress, applicable to periodontal diseases \n                    Curr Top Steroid Res  \n                    2004; \n                    4","journal-title":"Curr Top Steroid Res"},{"key":"refR5","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1034\/j.1600-0528.2002.300304.x","volume":"30","author":"Tsai C","year":"2002","unstructured":"Tsai C, Hayes C, Taylor GW. \n                    Glycaemic control of Type 2 diabetes and severe periodontal disease in the US adult population \n                    Community Dent Oral  \n                    2002; \n                    30\n                    : 182-92.","journal-title":"Community Dent Oral"},{"key":"refR6","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1111\/j.1600-0765.1991.tb01646.x","volume":"26","author":"Socransky S","year":"1991","unstructured":"Socransky S, Haffajee A. \n                    Microbial mechanisms in the pathogenesis of destructive periodontal diseases a critical assessment \n                    J Periodont Res  \n                    1991; \n                    26\n                    : 95-212.","journal-title":"J Periodont Res"},{"key":"refR7","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1902\/annals.1998.3.1.108","volume":"3","author":"Page RC","year":"1998","unstructured":"Page RC. \n                    The pathobiology of periodontal diseases may affect systemic diseases inversion of a paradigm \n                    Ann Periodontol  \n                    1998; \n                    3\n                    : 108-20.","journal-title":"Ann Periodontol"},{"key":"refR8","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1111\/j.1600-0765.2004.00771.x","volume":"40","author":"Chun YH","year":"2005","unstructured":"Chun YH, Chun KR, Olguin D, Wang HL. \n                    Biological foundation for periodontitis as a potential risk factor for atherosclerosis \n                    J Periodont Res  \n                    2005; \n                    40\n                    : 87-95.","journal-title":"J Periodont Res"},{"key":"refR9","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s10266-004-0043-4","volume":"92","author":"Bergstrom J","year":"2004","unstructured":"Bergstrom J. \n                    Tobacco smoking and chronic destructive disease \n                    Odontol  \n                    2004; \n                    92\n                    : 1-8.","journal-title":"Odontol"},{"key":"refR10","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1034\/j.1600-051X.2001.280801.x","volume":"28","author":"Scott DA","year":"2001","unstructured":"Scott DA, Palmer RM, Stapleton JA. \n                    Validation of smoking status in clinical research into inflammatory periodontal disease \n                    J Clin Periodontol  \n                    2001; \n                    28\n                    : 715-22.","journal-title":"J Clin Periodontol"},{"key":"refR11","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1016\/S0011-8532(03)00023-5","volume":"47","author":"Holmstrup P","year":"2003","unstructured":"Holmstrup P, Poulsen AH, Andersen L, Skuldbol T, Fiehn NE. \n                    Oral infections and systemic diseases \n                    Dent Clin North Am  \n                    2003; \n                    47\n                    : 575-98.","journal-title":"Dent Clin North Am"},{"key":"refR12","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/S1079-2104(99)70214-3","volume":"87","author":"Taylor GW","year":"1999","unstructured":"Taylor GW. \n                    Periodontal treatment and its effects on glycaemic control: a review of the evidence \n                    Oral Surg Oral Med Oral Pathol Oral Radiol Endod  \n                    1999; \n                    87\n                    : 311-16.","journal-title":"Oral Surg Oral Med Oral Pathol Oral Radiol Endod"},{"key":"refR13","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1016\/j.ahj.2003.12.022","volume":"147","author":"Deliargyris EN","year":"2004","unstructured":"Deliargyris EN, Madianos PN, Kadoma W, et al. \n                    Periodontal disease in patients with acute myocardial infarction prevalence and contribution to elevated C-reactive protein levels \n                    Am Heart J  \n                    2004; \n                    147\n                    : 1005-9.","journal-title":"Am Heart J"},{"key":"refR14","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1111\/j.1600-051X.2005.00641.x","volume":"32","author":"Montebugnoli L","year":"2005","unstructured":"Montebugnoli L, Servidio D, Miaton RA, et al. \n                    Periodontal health improves systemic inflammatory and haemostatic status in subjects with coronary heart disease \n                    J Clin Periodontol  \n                    2005; \n                    32\n                    : 188-92.","journal-title":"J Clin Periodontol"},{"key":"refR15","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1161\/CIRCULATIONAHA.104.511998","volume":"112","author":"Beck JD","year":"2005","unstructured":"Beck JD, Eke P, Heiss G, Madianos P, et al. \n                    Periodontal disease and coronary heart disease a reappraisal of the exposure \n                    Circulation  \n                    2005; \n                    112\n                    : 19-24.","journal-title":"Circulation"},{"key":"refR16","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1111\/j.1600-0757.2006.00166.x","volume":"43","author":"Kirkwood KL","year":"2007","unstructured":"Kirkwood KL, Cirelli JA, Rogers JE, Giannobile WV. \n                    Novel host response therapeutic approaches to treat periodontal diseases \n                    Periodontology 2000  \n                    2007; \n                    43\n                    : 294-315.","journal-title":"Periodontology 2000"},{"key":"refR17","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1016\/j.jaad.2005.10.004","volume":"54","author":"Sapadin AN","year":"2006","unstructured":"Sapadin AN, Fleischmajer R. \n                    Tetracyclines Nonantibiotic properties and their implications \n                    J Am Acad Dermatol  \n                    2006; \n                    54\n                    : 258-65.","journal-title":"J Am Acad Dermatol"},{"key":"refR18","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1177\/08959374980120011901","volume":"12","author":"Nelson ML","year":"1998","unstructured":"Nelson ML. \n                    Chemical and biological dynamics of tetracyclines \n                    Adv Dent Res  \n                    1998; \n                    12\n                    : 5-11.","journal-title":"Adv Dent Res"},{"key":"refR19","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1111\/j.1600-051X.2007.01122.x","volume":"34","author":"Kaner D","year":"2007","unstructured":"Kaner D, Bernimoulin JP, Hopfenmuller W, Kleber BM, Friedmann A. \n                    Controlled delivery chlorhexidine chip versus amoxicillin\/ metronidazole as adjunctive antimicrobial therapy for generalised aggressive periodontitis a randomised controlled clinical trial \n                    J Clin Periodontol  \n                    2007; \n                    34\n                    : 880-91.","journal-title":"J Clin Periodontol"},{"key":"refR20","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1586\/14787210.5.4.703","volume":"5","author":"Horz HP","year":"2007","unstructured":"Horz HP, Conrads G. \n                    Diagnosis and anti-infective therapy of periodontitis \n                    Expert Rev Anti infect Ther  \n                    2007; \n                    5\n                    : 703-15.","journal-title":"Expert Rev Anti infect Ther"},{"key":"refR21","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1902\/jop.2005.76.3.426","volume":"76","author":"Mascarenhas P","year":"2005","unstructured":"Mascarenhas P, Gapski R, Al-Shammari K, et al. \n                    Clinical response of azithromycin as an adjunct to non-surgical periodontal therapy in smokers \n                    J Periodontol  \n                    2005; \n                    76\n                    : 426-36.","journal-title":"J Periodontol"},{"key":"refR22","doi-asserted-by":"crossref","first-page":"1741","DOI":"10.1902\/jop.2007.070118","volume":"78","author":"Grossi SG","year":"2007","unstructured":"Grossi SG, Goodson JM, Gunsolley JC, et al. \n                    Mechanical therapy with adjunctive minocycline microspheres reduces red complex bacteria in smokers \n                    J Periodontol  \n                    2007; \n                    78\n                    : 1741-50.","journal-title":"J Periodontol"},{"key":"refR23","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1902\/annals.2003.8.1.79","volume":"8","author":"Hanes PJ","year":"2003","unstructured":"Hanes PJ, Purvis JP. \n                    Local anti-infective therapy Pharmacological agents. A systematic review \n                    Ann Periodontol  \n                    2003; \n                    8\n                    : 79-98.","journal-title":"Ann Periodontol"},{"key":"refR24","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1902\/jop.2004.75.4.531","volume":"75","author":"Paquette DW","year":"2004","unstructured":"Paquette DW, Hanlon A, Lessem J, Williams RC. \n                    Clinical relevance of adjunctive minocycline microspheres in patients with chronic periodontitis: secondary analysis of a phase 3 trial \n                    J Periodontol  \n                    2004; \n                    75\n                    : 531-6.","journal-title":"J Periodontol"},{"key":"refR25","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1111\/j.1600-0765.2004.00763.x","volume":"40","author":"Lu H-K","year":"2005","unstructured":"Lu H-K, Chei C-J. \n                    Efficacy of subgingivally applied minocycline in the treatment of chronic periodontitis \n                    J Periodont Res  \n                    2005; \n                    40\n                    : 20-7.","journal-title":"J Periodont Res"},{"key":"refR26","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1111\/j.1600-0501.2006.01269.x","volume":"17","author":"Persson RG","year":"2006","unstructured":"Persson RG, Salvi GE, Heitz-Mayfield LJA, Lang NP. \n                    Antimicrobial therapy using a local drug delivery system Arestin in the treatment of peri-implantitis. 1: microbiological outcomes  \n                    Clin Oral Implants Res  \n                    2006; \n                    17\n                    : 386-93.","journal-title":"Clin Oral Implants Res"},{"key":"refR27","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1111\/j.1365-2710.2007.00853.x","volume":"32","author":"Heaton PC","year":"2007","unstructured":"Heaton PC, Fenwick SR, Brewer DE. \n                    Association between tetracycline or doxycycline and hepatotoxicity a population based case-control study \n                    J Clin Pharm Ther  \n                    2007; \n                    32\n                    : 483-7.","journal-title":"J Clin Pharm Ther"},{"key":"refR28","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1111\/j.1600-0765.2005.00843.x","volume":"41","author":"Suzuki A","year":"2006","unstructured":"Suzuki A, Yagisawa J, Kumakura S, Tsutsui T. \n                    Effects of minocycline and doxycycline on cell survival and gene expression in human gingival and periodontal ligament cells \n                    J Periodont Res  \n                    2006; \n                    41\n                    : 124-31.","journal-title":"J Periodont Res"},{"key":"refR29","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.det.2007.01.012","volume":"25","author":"Webster G","year":"2007","unstructured":"Webster G, Del Rosso JQ. \n                    Anti-inflammatory activity of tetracyclines \n                    Dermatol Clin  \n                    2007; \n                    25\n                    : 133-5.","journal-title":"Dermatol Clin"},{"key":"refR30","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1111\/j.1368-5031.2006.00825.x","volume":"60","author":"Wright Jr E","year":"2006","unstructured":"Wright Jr E, Scism-Bacon JL. \n                    Glass LC 2006. Oxidative stress in type 2 diabetes the role of fasting and postprandial glycaemia \n                     Int J Clin Pract  \n                    2006; \n                    60\n                    : 308-14.","journal-title":"Int J Clin Pract"},{"key":"refR31","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1093\/ajcn\/83.6.1248","volume":"83","author":"Grundy SM","year":"2006","unstructured":"Grundy SM. \n                    Does a diagnosis of metabolic syndrome have value in clinical practice \n                    Am J Clin Nutr  \n                    2006; \n                    83\n                    : 1237-47.","journal-title":"Am J Clin Nutr"},{"key":"refR32","doi-asserted-by":"crossref","first-page":"1690","DOI":"10.1177\/00220345010800080201","volume":"80","author":"Nishimura F","year":"2001","unstructured":"Nishimura F, Murayama Y. \n                    Periodontal inflammation and insulin resistance - lessons from obesity \n                    J Dent Res  \n                    2001; \n                    80\n                    : 1690-4.","journal-title":"J Dent Res"},{"key":"refR33","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1111\/j.1601-0825.2005.01119.x","volume":"11","author":"Promsudthi A","year":"2005","unstructured":"Promsudthi A, Pimapansri S, Deerochanawong C, Kanchanavasita W. \n                    The effect of periodontal therapy on uncontrolled type 2 diabetes mellitus in older subjects \n                    Oral disease  \n                    2005; \n                    11\n                    : 293- 298.","journal-title":"Oral disease"},{"key":"refR34","doi-asserted-by":"crossref","first-page":"1559","DOI":"10.2337\/diabetes.54.5.1559","volume":"54","author":"Krady JK","year":"2005","unstructured":"Krady JK, Basu A, allen CM, et al. \n                    Minocycline reduces proinflammatory cytokine expression2005. microglial activation and caspase-3 activation in a rodent model of diabetic retinopathy \n                    Diabetes  \n                    2005; \n                    54\n                    : 1559-65.","journal-title":"Diabetes"},{"key":"refR35","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.neuint.2005.04.018","volume":"47","author":"Wang AL","year":"2005","unstructured":"Wang AL, Yu AC, Lau LT, et al. \n                    Minocycline inhibits LPS-induced retinal microglia activation \n                    Neurochem Int  \n                    2005; \n                    47\n                    (1-2)\n                    : 152-8.","journal-title":"Neurochem Int"},{"key":"refR36","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1016\/j.neuint.2006.10.008","volume":"50","author":"Yao JS","year":"2007","unstructured":"Yao JS, Shen F, Young WL, Yang GY. \n                    Comparison of doxycycline and minocycline in the inhibition of VEGF-induced smooth muscle cell migration \n                    Neurochem Int  \n                    2007; \n                    50\n                    : 524-30.","journal-title":"Neurochem Int"},{"key":"refR37","first-page":"77","volume":"55","author":"Kol R","year":"2006","unstructured":"Kol R, Palattella A. \n                    The use of doxycycline in periodontology. Histologic in vivo study on mice affected by diabetes mellitus \n                    Minerva Stomatol  \n                    2006; \n                    55\n                    : 77-86.","journal-title":"Minerva Stomatol"},{"key":"refR38","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1111\/j.1600-051X.2005.00736.x","volume":"32","author":"Llambes F","year":"2005","unstructured":"Llambes F, Silvestre FJ, Hernandez-Mijares A, Guiha R, Caffesse R. \n                    Effect of non-surgical periodontal treatment with or without doxycycline on the periodontium of type 1 diabetic patients \n                    J Clin Periodontol  \n                    2005; \n                    32\n                    : 915-20.","journal-title":"J Clin Periodontol"},{"key":"refR39","first-page":"160","volume":"6","author":"Skaleric U","year":"2004","unstructured":"Skaleric U, Schara R, Medvescek M, Hanlon A, Doherty F, Lessem J. \n                    Periodontal treatment by Arestin and its effects on glycaemic control in Type 1 diabetic patients \n                    J Int Acad Periodontol  \n                    2004; \n                    6\n                    : 160-5.","journal-title":"J Int Acad Periodontol"},{"key":"refR40","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1902\/jop.2006.050087","volume":"77","author":"Machion L","year":"2006","unstructured":"Machion L, Andia DC, Lecio G, et al. \n                     Locally delivered doxycycline as an adjunctive therapy to scaling and root planing in the treatment of smokers a 2-year follow up \n                    J Periodontol  \n                    2006; \n                    77\n                    : 606-13.","journal-title":"J Periodontol"},{"key":"refR41","doi-asserted-by":"crossref","first-page":"1927","DOI":"10.1902\/jop.2005.76.11.1927","volume":"76","author":"Buduneli E","year":"2005","unstructured":"Buduneli E, Buduneli N, Vardar-Sengul S, et al. \n                    Systemic low-dose doxycycline and alendronate administration and serum interleukin-1 beta, osteocalcin and C-reactive protein levels in rats \n                    J Periodontol  \n                    2005; \n                    76\n                    : 1927-33.","journal-title":"J Periodontol"},{"key":"refR42","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/j.archoralbio.2006.10.005","volume":"52","author":"Gomes PS","year":"2007","unstructured":"Gomes PS, Fernandes MH. \n                    Effect of therapeutic levels of doxycycline and minocycline in the proliferation and differentiation of human bone marrow osteoblastic cells \n                    Arch Oral Biol  \n                    2007; \n                    52\n                    : 251-9.","journal-title":"Arch Oral Biol"},{"key":"refR43","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.jdiacomp.2004.10.001","volume":"19","author":"Hirsh IB","year":"2005","unstructured":"Hirsh IB, Brownlee M. \n                    Should minimal blood glucose variability become the gold standard of glycaemic control? \n                    J Diabetes Complicat  \n                    2005; \n                    19\n                    : 178-81.","journal-title":"J Diabetes Complicat"},{"key":"refR44","doi-asserted-by":"crossref","first-page":"21S","DOI":"10.1016\/j.amjmed.2005.04.011","volume":"118","author":"Hirsh IB","year":"2005","unstructured":"Hirsh IB. \n                    Intensifying insulin therapy in patients with Type 2 diabetes mellitus \n                    Am J Med  \n                    2005; \n                    118\n                    (5A)\n                    : 21S-6S.","journal-title":"Am J Med"},{"key":"refR45","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1016\/j.cardiores.2004.05.001","volume":"63","author":"Basta G","year":"2004","unstructured":"Basta G, Schmidt AM, DeCaterina R. \n                    Advanced glycation end products and vascular inflammation implications for accelerated atherosclerosis in diabetes \n                    Cardiovasc Res  \n                    2004; \n                    63\n                    : 582-92.","journal-title":"Cardiovasc Res"},{"key":"refR46","doi-asserted-by":"crossref","first-page":"2067","DOI":"10.1161\/01.CIR.0000034509.14906.AE","volume":"106","author":"Esposito K","year":"2002","unstructured":"Esposito K, Nappo F, Marfella R, et al. \n                    Inflammatory cytokine concentrations are acutely increased by hyperglycaemia in humans role of oxidative stress \n                    Circulation  \n                    2002; \n                    106\n                    : 2067-72.","journal-title":"Circulation"},{"key":"refR47","doi-asserted-by":"crossref","first-page":"F760","DOI":"10.1152\/ajprenal.00050.2004","volume":"287","author":"Kelly KJ","year":"2004","unstructured":"Kelly KJ, Sutton TA, Weathered N, et al. \n                    Minocycline inhibits apoptosis and inflammation in a rat model of ischaemic renal injury \n                    Am J Physiol Renal Physiol  \n                    2004; \n                    287\n                    : F760-6.","journal-title":"Am J Physiol Renal Physiol"},{"key":"refR48","doi-asserted-by":"crossref","first-page":"225","DOI":"10.2174\/156720107781023938","volume":"4","author":"Jordan J","year":"2007","unstructured":"Jordan J, Fernandez-Gomez FJ, Ramos M, Ikuta I, Aguirre N, Galindo MF. \n                    Minocycline and cytoprotection shedding new light on a shadowy controversy \n                    Curr Drug Deliv  \n                    2007; \n                    4\n                    : 225-31.","journal-title":"Curr Drug Deliv"},{"key":"refR49","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1111\/j.1600-0757.2007.00207.x","volume":"44","author":"Ritchie CS","year":"2007","unstructured":"Ritchie CS. \n                    Obesity and periodontal disease \n                    Periodontology 2000  \n                    2007; \n                    44\n                    : 154-63.","journal-title":"Periodontology 2000"},{"key":"refR50","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1111\/j.1600-0757.2006.00186.x","volume":"43","author":"Saito T","year":"2007","unstructured":"Saito T, Shimazaki Y. \n                    Metabolic disorders related to obesity and periodontal disease \n                    Periodontology 2000  \n                    2007; \n                    43\n                    : 254-66.","journal-title":"Periodontology 2000"},{"key":"refR51","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1136\/thorax.55.12.987","volume":"55","author":"West R","year":"2000","unstructured":"West R, McNeill A, Raw M. \n                    Smoking cessation guidelines for health professionals an update. Health Education Authority \n                     Thorax  \n                    2000; \n                    55\n                    : 987-99.","journal-title":"Thorax"},{"key":"refR52","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1902\/annals.1998.3.1.51","volume":"3","author":"Grossi SG","year":"1998","unstructured":"Grossi SG, Genco RJ. \n                    Periodontal disease and diabetes mellitus a two-way relationship \n                    Ann Periodontol  \n                    1998; \n                    3\n                    : 51-61.","journal-title":"Ann Periodontol"},{"key":"refR53","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1111\/j.1600-0757.2006.00193.x","volume":"44","author":"Mealey BL","year":"2007","unstructured":"Mealey BL, Ocampo GL. \n                    Diabetes mellitus and periodontal disease \n                    Periodontology 2000  \n                    2007; \n                    44\n                    : 127-53.","journal-title":"Periodontology 2000"},{"key":"refR54","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1177\/08959374980120010501","volume":"12","author":"Golub LM","year":"1998","unstructured":"Golub LM, Lee HM, Ryan ME, Giannobile WV, Payne J, Sorsa T. \n                    Tetracyclines inhibit connective tissue breakdown by multiple non-antimicrobial mechanisms \n                    Adv Dent Res  \n                    1998; \n                    12\n                    : 12-26.","journal-title":"Adv Dent Res"},{"key":"refR55","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1016\/0006-291X(92)91118-A","volume":"188","author":"Guerin C","year":"1992","unstructured":"Guerin C, Laterra J, Masnyk T, Golub LM, Brem H, et al. \n                    Selective endothelial growth inhibition by tetracyclines that inhibit collagenase \n                    Biochem Biophys Res Commun  \n                    1992; \n                    188\n                    : 740-5.","journal-title":"Biochem Biophys Res Commun"},{"key":"refR56","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1177\/08959374980120010301","volume":"12","author":"Hanemaaijer R","year":"1998","unstructured":"Hanemaaijer R, Visser H, Koolwijk P, et al. \n                    Inhibition of MMP synthesis by doxycycline and chemically modified tetracyclines in human endothelial cells \n                    Adv Dent Res  \n                    1998; \n                    12\n                    : 114-8.","journal-title":"Adv Dent Res"},{"key":"refR57","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1016\/S0741-5214(98)70367-2","volume":"27","author":"Boyle JR","year":"1998","unstructured":"Boyle JR, McDermott E, Crowther M, Wills AD, Bell PR, Thompson MM. \n                    Doxycycline inhibits elastin degradation and reduces metalloproteinase activity in a model of aneurismal disease \n                    J Vasc Surg  \n                    1998; \n                    27\n                    : 354-61.","journal-title":"J Vasc Surg"},{"key":"refR58","first-page":"2544","volume":"41","author":"Solomon A","year":"2000","unstructured":"Solomon A, Rosenblatt M, Li DQ, et al. \n                    Doxycycline inhibition of interleukin-1 in the corneal epithelium \n                    Invest Ophth Vis Sci  \n                    2000; \n                    41\n                    : 2544-57.","journal-title":"Invest Ophth Vis Sci"},{"key":"refR59","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1128\/AAC.41.1.117","volume":"41","author":"Milano S","year":"1997","unstructured":"Milano S, Arcoleo F, D'Agostino P, Cillari E. \n                    Intraperitoneal injection of tetracyclines protects mice from lethal endotoxemia downregulating inducible nitric oxide synthase in various organs and cytokine nitrate secretion in blood \n                    Antimicrob Agents Ch  \n                    1997; \n                    41\n                    : 117-21.","journal-title":"Antimicrob Agents Ch"},{"key":"refR60","doi-asserted-by":"crossref","first-page":"3630","DOI":"10.1128\/AAC.47.11.3630-3633.2003","volume":"47","author":"Krakauer T","year":"2003","unstructured":"Krakauer T, Buckley M. \n                    Doxycycline is anti-inflammatory and inhibits Staphylococcal exotoxin-indued cytokines and chemokines \n                    Anitimicrob Agents Chemother  \n                    2003; \n                    47\n                    : 3630-3.","journal-title":"Anitimicrob Agents Chemother"},{"key":"refR61","doi-asserted-by":"crossref","first-page":"2949","DOI":"10.2741\/2024","volume":"11","author":"Varghese S","year":"2006","unstructured":"Varghese S. \n                    Matrix metalloproteinases and their inhibitors in bone an overview of regulation and functions \n                    Front Biosci  \n                    2006; \n                    11\n                    : 2949-66.","journal-title":"Front Biosci"},{"key":"refR62","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1902\/jop.2004.75.3.453","volume":"75","author":"Lee HM","year":"2004","unstructured":"Lee HM, Ciancio SG, Tuter G, Ryan ME, Komaroff E, Golub  M. \n                    Subantimicrobial dose doxycycline efficacy as a matrix metalloproteinase inhibitor in chronic periodontitis patients is enhanced when combined with a non-steroidal anti-inflammatory drug \n                    J Periodontol  \n                    2004; \n                    75\n                    : 453-63.","journal-title":"J Periodontol"},{"key":"refR63","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1111\/j.1600-051X.2005.00785.x","volume":"32","author":"Salvi GE","year":"2005","unstructured":"Salvi GE, Lang NP. \n                    Host response modulation in the management of periodontal diseases \n                    J Clin Periodontol  \n                    2005; \n                    32\n                    (Suppl 6)\n                    : 108-29.","journal-title":"J Clin Periodontol"},{"key":"refR64","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1111\/j.1600-051X.2005.00728.x","volume":"32","author":"Preshaw PM","year":"2005","unstructured":"Preshaw PM, Hefti AF, Bradshaw MH. \n                    Adjunctive subantimicrobial dose doxycycline in smokers and non-smokers with chronic periodontitis \n                    J Clin Periodontol  \n                    2005; \n                    32\n                    : 610-6.","journal-title":"J Clin Periodontol"},{"key":"refR65","doi-asserted-by":"crossref","first-page":"1252","DOI":"10.2460\/ajvr.67.7.1252","volume":"67","author":"Raulo SM","year":"2006","unstructured":"Raulo SM, Sorsa T, Maisi P. \n                    In vitro inhibition of matrixmetallo-proteinase activity in tracheal epithelial lining fluid from horses with recurrent airway obstruction \n                    Am J Vet Res  \n                    2006; \n                    67\n                    : 1252-7.","journal-title":"Am J Vet Res"},{"key":"refR66","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1097\/01.shk.0000180619.06317.2c","volume":"24","author":"Steinberg J","year":"2005","unstructured":"Steinberg J, Halter J, Schiller H, et al. \n                    Chemically modified tetracycline prevents the development of septic shock and acute respiratory distress syndrome in a chemically applicable porcine model \n                    Shock  \n                    2005; \n                    24\n                    (4)\n                    : 348-56.","journal-title":"Shock"},{"key":"refR67","doi-asserted-by":"crossref","first-page":"608","DOI":"10.2741\/1557","volume":"10","author":"Kagawa N","year":"2005","unstructured":"Kagawa N, Senbonmatsu TA, Satoh K, et al. \n                    Tetracycline protects myocardium against ischaemic injury \n                    Front Biosci  \n                    2005; \n                    10\n                    : 608-19.","journal-title":"Front Biosci"},{"key":"refR68","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s11010-005-2540-3","volume":"270","author":"Griffin MO","year":"2005","unstructured":"Griffin MO, Jinno M, Miles LA, Villarreal FJ. \n                    Reduction of myocardial infarct size by doxycycline a role for plasmin inhibition \n                    Mol Cell Biochem  \n                    2005; \n                    270\n                    : 1-11.","journal-title":"Mol Cell Biochem"},{"key":"refR69","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1007\/s11010-006-9379-0","volume":"300","author":"Garcia RA","year":"2007","unstructured":"Garcia RA, Go KV, Villarreal FJ. \n                    Effects of timed administration of doxycycline or methylprednisolone on post-myocardial infarction inflammation and left ventricular remodelling in the rat heart \n                    Mol Cell Biochem  \n                    2007; \n                    300\n                    : 159-69.","journal-title":"Mol Cell Biochem"},{"key":"refR70","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1902\/jop.2004.75.10.1387","volume":"75","author":"Emingil G","year":"2004","unstructured":"Emingil G, Atilla G, Sorsa T, Savolainen P, Baylas H. \n                    Effectiveness of adjunctive low-dose doxycycline therapy on clinical parameters and gingival crevicular fluid laminin-5 gamma2 chain levels in chronic periodontitis \n                    J Periodontol  \n                    2004; \n                    75\n                    : 1387-96.","journal-title":"J Periodontol"},{"key":"refR71","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1016\/j.bone.2004.02.028","volume":"35","author":"Holmes SG","year":"2004","unstructured":"Holmes SG, Still K, Buttle DJ, Bishop NJ, Grabowski PS. \n                    Chemically modified tetracyclines act through multiple mechanisms directly on osteoclast precursors \n                    Bone  \n                    2004; \n                    35\n                    : 471-8.","journal-title":"Bone"},{"key":"refR72","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1046\/j.1524-475X.2002.10605.x","volume":"10","author":"Pirila E","year":"2002","unstructured":"Pirila E, Parikka M, Ramamurthy NS, et al. \n                    Chemically modified tetracycline (CMT-8) and oestrogen promote wound healing in ovariectomised rats effects on matrix metalloproteinase-2 membrane type1 matrixmetalloproteinase, and laminin-5 gamma2-chain \n                    Wound Repair Regen  \n                    2002; \n                    10\n                    : 38-51.","journal-title":"Wound Repair Regen"},{"key":"refR73","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1902\/jop.2004.75.3.441","volume":"75","author":"Gapski R","year":"2004","unstructured":"Gapski R, Barr JL, Sarment DP, Layher MG, Socransky SS, Giannobile WV. \n                    Effect of systemic matrix metalloproteinase inhibition on periodontal wound repair a proof of concept trial \n                    J Periodontol  \n                    2004; \n                    75\n                    : 493-4.","journal-title":"J Periodontol"},{"key":"refR74","doi-asserted-by":"crossref","first-page":"1809","DOI":"10.1016\/S0006-2952(03)00450-7","volume":"66","author":"Kirkwood K","year":"2003","unstructured":"Kirkwood K, Martin T, Andreadis ST, Kim YJ. \n                    Chemically modified tetracyclines selectively inhibit IL-6 expression in osteoblasts by decreasing mRNA stability \n                    Biochem Pharmacol  \n                    2003; \n                    66\n                    : 1809-19.","journal-title":"Biochem Pharmacol"},{"key":"refR75","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1111\/j.1471-4159.2005.03219.x","volume":"94","author":"Kraus RL","year":"2005","unstructured":"Kraus RL, Pasieczny R, Lariosa-Willingham K, Turner MS, Jiang A, Trauger JW. \n                    Antioxidant properties of minocycline neuroprotection in an oxidative stress assay and direct radical-scavenging activity \n                    J Neurochem  \n                    2005; \n                    94\n                    : 819-27.","journal-title":"J Neurochem"},{"key":"refR76","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/1471-2377-4-7","volume":"4","author":"Xu L","year":"2004","unstructured":"Xu L, Fagan SC, Waller JL, et al. \n                    Low dose intravenous minocycline is neuroprotective after middle cerebral artery occlusion-reperfusion in rats \n                    BMC Neurol  \n                    2004; \n                    4\n                    : 7.","journal-title":"BMC Neurol"},{"key":"refR77","doi-asserted-by":"crossref","first-page":"2182","DOI":"10.1523\/JNEUROSCI.5275-03.2004","volume":"24","author":"Stirling DP","year":"2004","unstructured":"Stirling DP, Khodarahmi K, Liu J, et al. \n                    Minocycline treatment reduces delayed oligodendrocycte death, attenuates axonal dieback and improves functional outcome after spinal cord injury \n                    J Neurosci  \n                    2004; \n                    24\n                    : 2182-90.","journal-title":"J Neurosci"},{"key":"refR78","doi-asserted-by":"crossref","first-page":"1835","DOI":"10.1016\/j.neuroscience.2006.05.043","volume":"141","author":"Ryu JK","year":"2006","unstructured":"Ryu JK, Choi HB, McLarnon JG. \n                    Combined minocycline plus pyruvate treatment enhances effects of each agent to inhibit inflammation, oxidative damage and neuronal loss in an excitotoxic animal model of Huntington's disease \n                    Neuroscience  \n                    2006; \n                    141\n                    : 1835-48.","journal-title":"Neuroscience"},{"key":"refR79","doi-asserted-by":"crossref","first-page":"567","DOI":"10.4049\/jimmunol.176.1.567","volume":"176","author":"Hoyt JC","year":"2006","unstructured":"Hoyt JC, Ballering J, Numanami H, Hayden JM, Robbins RA. \n                    Doxycycline modulates nitric oxide production in murine lung epithelial cells \n                    J Immunol  \n                    2006; \n                    176\n                    : 567-72.","journal-title":"J Immunol"},{"key":"refR80","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1111\/1523-1747.ep12285793","volume":"86","author":"Miyachi Y","year":"1986","unstructured":"Miyachi Y, Yoshioka A, Imamura S, Niwa Y. \n                    Effect of antibiotics on the generation of reactive oxygen species \n                    J Invest Dermatol  \n                    1986; \n                    86\n                    : 449-53.","journal-title":"J Invest Dermatol"},{"key":"refR81","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1111\/j.1600-0765.2005.00818.x","volume":"40","author":"Tsai CC","year":"2005","unstructured":"Tsai CC, Chen HS, Chen SL, et al. \n                    Lipid peroxidation: a possible role in the induction and progression of chronic periodontitis \n                    J Periodont Res  \n                    2005; \n                    40\n                    (5)\n                    : 378-84.","journal-title":"J Periodont Res"},{"key":"refR82","first-page":"135","volume":"50","author":"Krol K","year":"2004","unstructured":"Krol K. \n                    Reactive oxygen species and antioxidant mechanisms in the pathogenesis of periodontitis \n                    Ann Acad Med Stetin  \n                    2004; \n                    50\n                    : 135-48.","journal-title":"Ann Acad Med Stetin"},{"key":"refR83","first-page":"255","volume":"10","author":"Panjamurthy K","year":"2005","unstructured":"Panjamurthy K, Manoharan S, Ramachandran CR. \n                    Lipid peroxidation and antioxidant status in patients with periodontitis \n                    Cell Mol Biol Lett  \n                    2005; \n                    10\n                    : 255-64.","journal-title":"Cell Mol Biol Lett"},{"key":"refR84","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1111\/j.1601-5037.2006.00197.x","volume":"4","author":"Chapple ILC","year":"2006","unstructured":"Chapple ILC. \n                    Oxidative stress, nutrition and neutrogenomics in periodontal health and disease \n                    Int J Dent Hyg  \n                    2006; \n                    4\n                    (Suppl 1)\n                    : 15-21.","journal-title":"Int J Dent Hyg"},{"key":"refR85","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1111\/j.0303-6979.2004.00576.x","volume":"31","author":"Martorelli de Lima AF","year":"2004","unstructured":"Martorelli de Lima AF, Cury CC, Palioto DB, Duro AM, da Silva RC, Wolff LF. \n                    Therapy with adjunctive doxycycline local delivery in patients with type 1 diabetes mellitus and periodontitis \n                    J Clin Periodontol  \n                    2004; \n                    31\n                    : 648-53.","journal-title":"J Clin Periodontol"},{"key":"refR86","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1902\/jop.2001.72.8.1069","volume":"72","author":"Llavaneras A","year":"2001","unstructured":"Llavaneras A, Ramamurthy NS, Heikkila P, et al. \n                    A combination of a chemically modified doxycycline and a biphosphonate synergistically inhibits endotoxin-induced periodontal breakdown in rats \n                    J Periodontol  \n                    2001; \n                    72\n                    : 1069-77.","journal-title":"J Periodontol"},{"key":"refR87","doi-asserted-by":"crossref","first-page":"750","DOI":"10.2174\/138920007782798162","volume":"8","author":"Soory M","year":"2007","unstructured":"Soory M. \n                    Periodontal diseases and rheumatoid arthritis. A coincident model for therapeutic intervention? \n                    Curr Drug Metab  \n                    2007; \n                    8\n                    : 750-7.","journal-title":"Curr Drug Metab"},{"key":"refR88","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1902\/jop.2005.76.2.229","volume":"76","author":"Ramamurthy NS","year":"2005","unstructured":"Ramamurthy NS, Greenwald RA, Celiker MY, Shi EY. \n                    Experimental arthritis in rats induces biomarkers of periodontitis which are ameliorated by gene therapy with tissue inhibitor of matrix metalloproteinases \n                    J Periodontol  \n                    2005; \n                    76\n                    : 229-33.","journal-title":"J Periodontol"},{"key":"refR89","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1902\/jop.2006.050419","volume":"77","author":"Houde V","year":"2006","unstructured":"Houde V, Grenier D, Chandad F. \n                    protective effects of grape seed proanthocyanidins against oxidative stress induced by lipopolysaccharides of periodontopathogens \n                    J Periodontol  \n                    2006; \n                    77\n                    : 1371-9.","journal-title":"J Periodontol"},{"key":"refR90","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1111\/j.1600-051X.2004.00531.x","volume":"31","author":"Wood N","year":"2004","unstructured":"Wood N, Johnson RB. \n                    The relationship between tomato intake and congestive heart failure risk in periodontitis subjects \n                    J Clin Periodontol  \n                    2004; \n                    31\n                    : 574-80.","journal-title":"J Clin Periodontol"},{"key":"refR91","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.phrs.2006.11.006","volume":"55","author":"Kampkotter A","year":"2007","unstructured":"Kampkotter A, Pielarski T, Rohrig R, et al. \n                    The Ginkgo biloba extract EGb761 reduces stress sensitivity, ROS accumulation and expression of catalase and glutathione S-transferase 4 in Caenorhabditis elegans \n                    Pharmacol Res  \n                    2007; \n                    55\n                    : 139-47.","journal-title":"Pharmacol Res"},{"key":"refR92","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1016\/j.fct.2006.07.024","volume":"45","author":"Sener G","year":"2007","unstructured":"Sener G, Sehirli O, Tozan A, Velioglu-Ovunc A, Gedik N, Omurtag GZ. \n                    Ginkgo biloba extract protects against mercury (ll)-induced oxidative tissue damage in rats \n                    Food Chem Toxicol  \n                    2007; \n                    45\n                    : 543-50.","journal-title":"Food Chem Toxicol"},{"key":"refR93","doi-asserted-by":"crossref","first-page":"279","DOI":"10.2174\/187153006778250037","volume":"6","author":"Rahman ZA","year":"2006","unstructured":"Rahman ZA, Soory M. \n                    Antioxidant effects of glutathione and IGF in a hyperglycaemic cell culture model of fibroblasts: Some actions of advanced glycaemic end products (AGE) and nicotine \n                    Endocr, Metab Immune Disord - Drug Targets  \n                    2006; \n                    6\n                    : 279-86.","journal-title":"Endocr, Metab Immune Disord - Drug Targets"},{"key":"refR94","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1016\/j.steroids.2006.09.003","volume":"71","author":"Figuero E","year":"2006","unstructured":"Figuero E, Soory M, Cerero R, Bascones A. \n                    Oxidant \/ antioxidant interactions of nicotine, Coenzyme Q10, Pycnogeneol and phytoestorgens in oral periosteal fibroblasts and MG63 osteoblasts \n                    Steroids  \n                    2006; \n                    71\n                    : 1062-72.","journal-title":"Steroids"}],"container-title":["The Open Dentistry Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/opendentistryjournal.com\/contents\/volumes\/V2\/TODENTJ-2-5\/TODENTJ-2-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/opendentistryjournal.com\/contents\/volumes\/V2\/TODENTJ-2-5\/TODENTJ-2-5.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/opendentistryjournal.com\/contents\/volumes\/V2\/TODENTJ-2-5\/TODENTJ-2-5.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,3,25]],"date-time":"2019-03-25T05:56:53Z","timestamp":1553493413000},"score":1,"resource":{"primary":{"URL":"https:\/\/opendentistryjournal.com\/VOLUME\/2\/PAGE\/5\/"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,1,22]]},"references-count":94,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2008,1,22]]}},"alternative-id":["TODENTJ-2-5"],"URL":"https:\/\/doi.org\/10.2174\/1874210600802010005","relation":{},"ISSN":["1874-2106"],"issn-type":[{"value":"1874-2106","type":"print"}],"subject":[],"published":{"date-parts":[[2008,1,22]]},"assertion":[{"value":"Peer Reviewed","order":0,"name":"review_status","label":"Review Status","group":{"name":"peer_review_details","label":"Peer Review Details"}},{"value":"Single blind","order":1,"name":"review_process","label":"Review Process","group":{"name":"peer_review_details","label":"Peer Review Details"}},{"value":"Checked with iThenticate","order":0,"name":"screening_status","label":"Screening Status","group":{"name":"plagiarism_screening","label":"Plagiarism Screening"}},{"value":"2007-10-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2007-12-18","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2008-1-22","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}