title: Peripheral kappa opioid receptors activation reduces alveolar bone loss in rats by modulating interleukin-6 and -10.
abstract: OBJECTIVE
  The beneficial effects of kappa opioid agonist U-50,488 in preventing periodontal disease (PD) progression in rats have already been described, but its mechanism of action is unknown. The present study evaluated the expression of TNF-α, IL-6, IL-8 and IL-10 in the gingival tissues of rats with ligature-induced PD, treated with U-50,488. It also correlated the effects of this agonist with myeloperoxidase (MPO) activity and the presence of osteoclasts.
  
  
  METHODS
  Male Holtzman rats weighing 250-300 g were divided into four groups: (1) control, (2) ligature, (3) ligature+saline and (4) ligature+kappa agonist. Experimental PD was induced by placing a sterile silk ligature around the 2nd left upper molar. Rats from groups 3 to 4 were locally administered with either saline or U-50,488, respectively, from day 3 to day 5 following ligation. After 5 or 11 days, the rats were euthanized and periodontal tissue samples were collected for histological and morphometric analysis and for determination of TNF-α, IL-6, IL-8, IL-10 and MPO.
  
  
  RESULTS
  Ligature placement induced significant alveolar bone loss. The number of osteoclasts, degree of MPO activity, IL-6, IL-8 and TNF-α expression were also increased by PD. U-50,488 reduced both bone loss and the number of osteoclasts, but did not alter histological inflammatory infiltrate or MPO activity. U-50,488 significantly reduced IL-6 and increased IL-10 levels, but did not affect TNF-α and IL-8.
  
  
  CONCLUSIONS
  Lowering the levels of IL-6 and increasing IL-10 are important mechanisms by which U-50,488 reduces alveolar bone loss in ligature-induced periodontal disease.
authors.affiliation: Department of Dental Clinics, Pathology and Surgery, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Jasílio Vilela
authors.initials: JV
authors.lastname: Bastos
authors.forename: Celso Martins
authors.initials: CM
authors.lastname: Queiroz-Junior
authors.forename: Marcelo Vidigal
authors.initials: MV
authors.lastname: Caliari
authors.forename: Janetti Nogueira
authors.initials: JN
authors.lastname: Francischi
authors.forename: Cinthia Mara da Fonseca
authors.initials: CM
authors.lastname: Pacheco
authors.forename: Kátia Lucy de Melo
authors.initials: KL
authors.lastname: Maltos
mesh_terms: D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000494:pharmacology*; D016301:Alveolar Bone Loss / Q000517:prevention & control*; D000704:Analysis of Variance; D000818:Animals; D004195:Disease Models, Animal; D016753:Interleukin-10 / Q000819:agonists*; D016209:Interleukin-8 / Q000037:antagonists & inhibitors; D008297:Male; D010010:Osteoclasts / Q000187:drug effects; D009195:Peroxidase / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D017473:Receptors, Opioid, kappa / Q000819:agonists*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors; D000093242:Interleukin-6 Inhibitors
chemical_list: D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D016753:Interleukin-10; D016209:Interleukin-8; D009195:Peroxidase; D017473:Receptors, Opioid, kappa; D014409:Tumor Necrosis Factor-alpha; D000093242:Interleukin-6 Inhibitors