Biphasic effects of nonsteroidal anti-inflammatory drugs on prostaglandin production by cultured rat calvariae

Prostaglandins
L G RaiszP M Fall

Abstract

We have studied the effects on bone of three structurally dissimilar non-steroidal anti-inflammatory drugs which inhibit prostaglandin cyclo-oxygenase activity (PGH synthase); indomethacin, flurbiprofen, and piroxicam. We used cultures of half calvaria from neonatal or fetal rats to measure effects on PGE2 production, measured by radioimmunoassay. In four day neonatal rat calvaria, indomethacin inhibited PGE2 release into the medium by 80% at 10(-8) M, while flurbiprofen and piroxicam produced similar inhibition at 10(-6) M. However, at 10(-10) M, treatment with all three compounds resulted in an increase in medium PGE2 concentration of 60 to 120%. To assess the mechanism of this effect, bones were labeled with [3H]-arachidonic acid, washed and cultured in the presence or absence of piroxicam. At 10(-6) M, piroxicam inhibited production of cyclo-oxygenase products and arachidonic acid release. However, at 10(-10) M, there was a substantial increase in labeled products, particularly PGE2, despite a further decrease in arachidonic acid release. In 21 day fetal rat cultures, flurbiprofen was found to increase PGE2 release both in control cultures and cultures which had been incubated with cortisol (10(-8) M) to reduce endogenous a...Continue Reading

Citations

Oct 1, 1990·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·N LaneD B Kimmel
Dec 1, 1991·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·H A Simmons, L G Raisz
Dec 1, 1993·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·L G Raisz
Mar 1, 1995·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·A Scutt, P Bertram
Jan 1, 1993·Osteoporosis International : a Journal Established As Result of Cooperation Between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA·L G RaiszP M Fall
Jan 1, 1992·Agents and Actions·G W Cannon, D S Harper
Jan 1, 1995·Research in Experimental Medicine. Zeitschrift Für Die Gesamte Experimentelle Medizin Einschliesslich Experimenteller Chirurgie·M LeunigR K Jain
Mar 10, 1995·Life Sciences·M G SergeevaS D Varfolomeyev
Aug 16, 2001·Critical Reviews in Toxicology·E J Calabrese
Oct 13, 2012·Human & Experimental Toxicology·E J CalabreseV Calabrese

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