Individual and combined effects of selective cyclooxygenase-2 inhibitor and omega-3 fatty acid on endotoxin-induced periodontitis in rats.
BACKGROUND
The present study was planned to evaluate the individual and combined effects of selective cyclooxygenase-2 (COX-2) inhibitor, celecoxib, and omega-3 fatty acid on the gingival tissue levels of prostaglandin E2 (PGE2), prostaglandin F2alpha (PGF2alpha), leukotriene B4 (LTB4), and platelet activating factor (PAF) in endotoxin-induced periodontitis in rats.


METHODS
Experimental periodontitis was induced by repeated injection of Escherichia coli endotoxin (LPS). Forty-four adult male Sprague-Dawley rats were divided into five study groups: saline control, LPS, celecoxib, omega-3 fatty acid, and combination celecoxib and omega-3 fatty acid. Celecoxib and omega-3 fatty acid were given either as a single agent or as a combination therapy during 14 days of the study period. At the end of the 2-week protocol, the rats were sacrificed, the gingival tissues were dissected and extracted, and the extracts were analyzed for PGE2, PGF2alpha, and LTB4 levels by enzyme immunoassay and for PAF levels by radioimmunoassay. The defleshed jaws were analyzed morphometrically for alveolar bone loss. Data were evaluated statistically by using parametric tests.


RESULTS
LPS injection resulted in significantly more bone loss than the saline controls (P<0.05) and significant elevations in the gingival tissue levels of all the analyzed mediators except PGF2alpha. Individual administration of celecoxib revealed significant reductions in PGE2 and PAF levels (P <0.05), while omega-3 fatty acid provided significant reduction in PGE2, PGF2alpha, and LTB4 levels compared to the LPS group (P <0.05). Combined administration of celecoxib and omega-3 fatty acid exhibited significantly lower values than those of the LPS group in all the analyzed membrane phospholipid mediators (P <0.05), which approximated the levels in the saline control group (P>0.05).


CONCLUSIONS
The results of the present study indicate that celecoxib and omega-3 fatty acid, when used individually, show a rather partial effect on the control of the analyzed mediators, but when combined they show a synergic effect and provide significant reductions in the gingival tissue levels of PGE2, PGF2alpha, LTB4, and PAF in LPS-induced experimental periodontitis. These findings may pioneer further clinical human studies investigating the possible place of celecoxib and omega-3 fatty acid in periodontal treatment.
Vardar
Saynur
S
School of Dentistry, Department of Periodontology, Ege University, Izmir, Turkey. saynurvardar@yahoo.com
Buduneli
Eralp
E
Baylas
Haluk
H
Berdeli
Afig Hüseyinov
AH
Buduneli
Nurcan
N
Atilla
Gül
G
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D000068579:Celecoxib; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D015237:Dinoprost / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D004195:Disease Models, Animal; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004731:Endotoxins; D015525:Fatty Acids, Omega-3 / Q000627:therapeutic use*; D007975:Leukotriene B4 / Q000378:metabolism; D008297:Male; D010518:Periodontitis / Q000139:chemically induced / Q000188:drug therapy*; D010972:Platelet Activating Factor / Q000378:metabolism; D011720:Pyrazoles / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides / Q000627:therapeutic use*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D004731:Endotoxins; D015525:Fatty Acids, Omega-3; D010972:Platelet Activating Factor; D011720:Pyrazoles; D013449:Sulfonamides; D007975:Leukotriene B4; C044101:endotoxin, Escherichia coli; D015237:Dinoprost; D000068579:Celecoxib; D015232:Dinoprostone