title: Periodontitis in rats induces systemic oxidative stress that is controlled by bone-targeted antiresorptives.
abstract: BACKGROUND
  Periodontitis is a chronic, polymicrobial inflammatory disease that degrades connective tissue and alveolar bone and results in tooth loss. Oxidative stress has been linked to the onset of periodontal tissue breakdown and systemic inflammation, and the success of antiresorptive treatments will rely on how effectively they can ameliorate periodontal disease-induced oxidative stress during oral infection.
  
  
  METHODS
  Rats were infected with polybacterial inoculum consisting of Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia, as an oral lavage every other week for 12 weeks. Daily subcutaneous injections of enoxacin, bis-enoxacin, alendronate, or doxycycline were administered for 6 weeks after 6 weeks of polybacterial infection in rats. The serum levels of oxidative stress parameters and antioxidant enzymes, including glutathione peroxidase, superoxide dismutase, and catalase, were evaluated in each of the infected, treated, and sham-infected rats.
  
  
  RESULTS
  Rats infected with the periodontal pathogens displayed a five-fold increase in the oxidative stress index compared with controls as a result of increased levels of serum oxidants and decreases in total antioxidant activity. The overall decrease in antioxidant activity occurred despite increases in three important antioxidant enzymes, suggesting an imbalance between antioxidant macromolecules/small molecules production and antioxidant enzyme levels. Surprisingly, the bone-targeted antiresorptives bis-enoxacin and alendronate inhibited increases in oxidative stress caused by periodontitis. Bis-enoxacin, which has both antiresorptive and antibiotic activities, was more effective than alendronate, which acts only as an antiresorptive.
  
  
  CONCLUSIONS
  To the best of the authors' knowledge, this is the first study to demonstrate that the increased oxidative stress induced by periodontal infection in rats can be ameliorated by bone-targeted antiresorptives.
authors.affiliation: Department of Periodontology, College of Dentistry, University of Florida, Gainesville, FL.
authors.forename: Sehkar
authors.initials: S
authors.lastname: Oktay
authors.forename: Sasanka S
authors.initials: SS
authors.lastname: Chukkapalli
authors.forename: Mercedes F
authors.initials: MF
authors.lastname: Rivera-Kweh
authors.forename: Irina M
authors.initials: IM
authors.lastname: Velsko
authors.forename: L Shannon
authors.initials: LS
authors.lastname: Holliday
authors.forename: Lakshmyya
authors.initials: L
authors.lastname: Kesavalu
mesh_terms: D019386:Alendronate / Q000627:therapeutic use; D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D000975:Antioxidants / Q000032:analysis; D016866:Bacteroidaceae Infections / Q000378:metabolism; D001442:Bacteroides Infections / Q000378:metabolism; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D002374:Catalase / Q000097:blood; D060085:Coinfection / Q000382:microbiology; D004318:Doxycycline / Q000627:therapeutic use; D015365:Enoxacin / Q000627:therapeutic use; D005260:Female; D016166:Free Radical Scavengers / Q000097:blood; D005979:Glutathione Peroxidase / Q000097:blood; D016905:Gram-Negative Bacterial Infections / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D016877:Oxidants / Q000097:blood; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D010518:Periodontitis / Q000378:metabolism* / Q000382:microbiology / Q000517:prevention & control; D016966:Porphyromonas gingivalis / Q000502:physiology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000097:blood; D048373:Treponema denticola / Q000502:physiology
chemical_list: D000900:Anti-Bacterial Agents; D000975:Antioxidants; D050071:Bone Density Conservation Agents; D016166:Free Radical Scavengers; D016877:Oxidants; D015365:Enoxacin; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D004318:Doxycycline; D019386:Alendronate
keywords: Alendronate; bacteria; enoxacin; lipid peroxidation; oxidative stress; periodontal; periodontal diseases
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