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...

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Published in:	Archives of oral biology Vol. 56; no. 6; pp. 540 - 548
Main Authors:	Bastos, Jasílio Vilela, Queiroz-Junior, Celso Martins, Caliari, Marcelo Vidigal, Francischi, Janetti Nogueira, Pacheco, Cinthia Mara da Fonseca, Maltos, Kátia Lucy de Melo
Format:	Journal Article
Language:	English
Published:	England Elsevier Ltd 01-06-2011
Subjects:	3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer - pharmacology Advanced Basic Science Alveolar bone loss Alveolar Bone Loss - prevention & control Analysis of Variance Animals Dentistry Disease Models, Animal IL-10 IL-6 Interleukin-10 - agonists Interleukin-6 - antagonists & inhibitors Interleukin-8 - antagonists & inhibitors Male Opioids Osteoclasts - drug effects Peroxidase - antagonists & inhibitors Rats Rats, Sprague-Dawley Receptors, Opioid, kappa - agonists Tumor Necrosis Factor-alpha - antagonists & inhibitors Alveolar bone loss IL-6 IL-10 Opioids
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Summary:	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. Design 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. Conclusion 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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0003-9969 1879-1506
DOI:	10.1016/j.archoralbio.2010.11.012