Inhibition of human periodontal prostaglandin E2 synthesis with selected agents

Abstract

Considerable evidence has demonstrated the importance of PGE2 synthesis in the pathogenesis of periodontal disease. Although various cyclooxygenase inhibitors have been known to block periodontal PGE2 synthesis and prevent disease progression in animal models, there are few reports comparing relative efficacies of various inhibitors of arachidonic acid (ARA) metabolism. We have developed a sensitive in vitro assay to measure PGE2 synthesis in periodontal tissues. The apparent IC50 values (i.e. the concentration of drug which causes 50% inhibition of maximum PGE2 synthesis) have been determined for a series of arachidonic acid analogues as well as competitive and non-competitive cyclooxygenase inhibitors. Periodontal tissue homogenates were incubated in the presence of 3H-arachidonic acid for 45 min at 37 degrees C. Inhibitors were tested at 10(-10)-10(-4) M and at zero concentration to measure conversion of 3H-arachidonate to 3H-PGE2. Log or half log dilutions of inhibitors were tested in triplicate for each assay. Radiolabeled PGE2 was extracted from homogenates, purified by reverse phase chromatography and quantitated by double antibody capture. RIA was performed on each homogenate to determine the amount of endogenous unlabeled PGE2 present in the sample to correct for antibody capture recovery. The apparent IC50 values were determined for each drug by averaging two or more replicate assays. Specific total enzymatic activity of periodontal tissue homogenates was typically 5-11 pg PGE2/min/mg tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

1‐Tetradecanol Complex: Therapeutic Actions in Experimental Periodontitis

“…The topical application of omega‐3 (ω‐3) polyunsaturated fatty acid (PUFA) was successful in the treatment of inflammatory diseases, such as psoriasis, as well as experimental periodontitis in animal models by decreasing leukocyte chemotaxis, adhesion molecule expression, and inflammatory cytokine production 16–18 . Offenbacher et al 19 showed that eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) can inhibit the production of PGE 2 to an extent similar to ibuprofen when added to human periodontal homogenates. Pilot clinical and animal studies 20–24 with ω‐3 and ω‐6 PUFA supplementation also showed beneficial results on periodontal inflammation and bone loss, indicating an anti‐inflammatory role for these fatty acids without any evidence of the side effects often reported with the long‐term use of non‐steroidal anti‐inflammatory drugs and other anti‐inflammatory agents.…”

Formulation development of novel in situ nanoemulgel (NEG) of ketoprofen for the treatment of periodontitis

“…Ketoprofen (KP), a congener of the 2-arylpropionic acid class of non-steroidal anti-inflammatory drugs (NSAIDs), has been shown to have therapeutic value in the treatment of periodontal disease via inhibition of the cyclooxegenase enzyme, which is responsible for the biosynthesis of prostaglandins (Offenbacher et al, 1990). Over the past several years there has been increasing interest in the use of nonsteroidal anti-inflammatory agents to prevent or control periodontal disease (Howell et al, 1993;Pauletto et al, 1997).…”

Pharmacokinetic and Safety Evaluations of Ketoprofen Gels in Subjects with Adult Periodontitis

“…Prostaglandin E2 (PGE2), which is present in gingival crevicular fluid (GCF), is associated with alveolar bone resorption, periodontal attachment loss, and inflammation in periodontal tissues (Offenbacher et al, 1984(Offenbacher et al, , 1986(Offenbacher et al, , 1990(Offenbacher et al, , 1991(Offenbacher et al, , 1993). An initial six-month pre-clinical pharmacology study demonstrated significant reductions in crevicular fluid prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) in monkeys treated for ligature-induced periodontal bone loss with a 1.0% ketoprofen cream formulation (Li et al, 1996).…”

“…A previous study, investigating the application of ketoprofen gel to maxillary dentures in 37 edentulous subjects, found no physical evidence of oral irritation, no changes in blood chemistry or complete blood count, and urinalysis results to be within the normal range of biological variability (Papas et al, 1997). Finally, among various NSAID agents that could potentially be efficacious in treating periodontal diseases in topical formulations, ketoprofen is one of the more potent in blocking PGE2 synthesis in inflamed gingival homogenates in in vitro assays (Offenbacher et al, 1990).…”

“…Ketoprofen, a congener of the 2-arylpropionic acid class of non-steroidal anti-inflammatory drugs (NSAIDs), has been shown to have therapeutic value in the treatment of periodontal disease via the inhibition of the cyclooxygenase enzyme, which is responsible for the biosynthesis of prostaglandins (Offenbacher et al, 1990). Prostaglandin E2 (PGE2), which is present in gingival crevicular fluid (GCF), is associated with alveolar bone resorption, periodontal attachment loss, and inflammation in periodontal tissues (Offenbacher et al, 1984(Offenbacher et al, , 1986(Offenbacher et al, , 1990(Offenbacher et al, , 1991(Offenbacher et al, , 1993).…”