ISSN:
1600-0765
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
The four principal metabolites of cyclooxygenase (CO) were examined during the progression of experimental periodontitis in the rhesus monkey Macaca mulalla. Thirty-two monkeys were divided in four disease-matched groups. Three groups were treated with flurbiprofen a potent CO inhibitor, at either 0.027, 0.27 or 7.1 mg/kg/day delivered systemically by a subcutaneously-implanted osmotic mini-pump. We have previously described the findings indicating that flurbiprofen treatment significantly retarded clinical attachment loss (ALOSS), redness and radiographic bone loss (BLOSS). This investigation focuses on the changes in CO metabolites which occur during disease progression of ligature-induced periodontitis and on the dose-response relationship of flurbiprofen, as it relates to disease inhibition and the suppression of ARA metabolites within the crevicular fluid (CF). In untreated animals there was a statistically significant 3-fold increase in CF levels of prostaglandin E2 (PGE2) and thromboxane B2 (TxB2) at 3 months, as compared to baseline, which positively correlated with increases in redness, bleeding, ALOSS and BLOSS. CF-PGE2 and TxB2 levels reached a 6-fold peak at 6 months and returned to baseline by 12 months. Flurbiprofen (Fb) prevented the 3-month rise in TxB2, but did not affect the increase in PGE2. At 6 months, Fb administration caused a dosedependent inhibition of both PGE2 and TxB2. Probit analysis of the doseresponse data revealed that the concentration of Fb which caused a 50% inhibition of CF-TxB2 level (the IC50 value for TxB2 synthesis) was approximately two logs lower than the IC50 value for PGE2 synthesis, i.e. TxA2-IC50= 0.013 vs. PGE2-IC50 1.35 mg flurbiprofen/kg/d. The slopes of the PGE2, and TxB2 inhibition curves were identical, consistent with a similar mechanism or singular enzyme for the site of action of Fb inhibition of CO activity. However, the kinetics and sensitivity of Fb inhibition were significantly different for the CO activity responsible for TxB2 and PGE2 synthesis, perhaps due to different compartmentalization of CO within different cell types.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1111/j.1600-0765.1989.tb00859.x
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