Effects of isoxicam and other non-steroidal anti-inflammatory drugs on arachidonic acid metabolism by rat peritoneal leucocytes

Abstract

Inhibition of prostaglandin formation from [14C]arachidonic acid by rat peritoneal leucocytes occurred with nonsteroidal anti-inflammatory drugs, their order of potency being indomethacin greater than piroxicam greater than naproxen greater than ibuprofen greater than isoxicam. At the lowest concentration tested (1 microgram ml-1), indomethacin markedly increased the accumulation of lipoxygenase products in the cell incubates. Naproxen, ibuprofen or piroxicam 1 or 10 micrograms ml-1 resulted in smaller increases of lipoxygenase products, and there was only a small rise with these concentrations of isoxicam.

The combination of naproxen and citral reduces nociception and gastric damage in rats

“…In the present study, the systemic administration of naproxen was able to decrease the nociceptive effect induced by formalin. The anti-inflammatory and antinociceptive properties of naproxen have been attributed to the inhibition of cyclooxygenase, in both the central nervous system and peripheral tissues, and the consequent inhibition of prostaglandin biosynthesis (Tavares et al, 1985). Therefore, it is probable that inhibition of prostaglandin synthesis is responsible for the antinociceptive effect observed with the formalin.…”

Modulation of eicosanoid and histamine release from human dispersed lung cells by terfenadine

“…The differences between these in vivo studies and our study may derive from the heterogeneity of mast cells between the nose and the lung, from a different cellular environment, and also from the difference in the model used. There was no evidence of substrate shunting, a phenomenon reported by a number of researchers, although several other groups have not observed this action (1,7,8,28,31,38,40).…”

Studies on the mechanism by which indomethacin increases the anticancer effect of methotrexate

“…Differences in the extents to which indomethacin and flur-biprofen inhibit prostaglandin synthesis or divert substrate metabolism into lipoxygenase products might affect the response. We found that the formation of lipoxygenase products from ['4C]-arachidonic acid by rat peritoneal leucocytes differed when indomethacin, piroxicam or isoxicam were used (Tavares et al, 1985).…”

“…After incubating 1-2 x 106 NC cells for 1 h at 370C, 5% CO2 in air, either alone or in the presence of either bradykinin 5 tyg ml' or the calcium ionophore A23 187 1 pg ml-', no PGE2 or thromboxane B2 (TXB2) was detected by radioimmunoassay (RIA, limits of detection 300 and 100pgml-' respectively). Nevertheless, cells incubated with ['4C]-arachidonic produced small amounts of substances chromatographing (Tavares et al, 1985) with cyclo-oxygenase and lipoxygenase products (mean percentage incorporations into prostaglandins and LTB4 1.3 ± 0.07% and 1.04 ± 0.07% respectively, unpublished). Another question about the importance ofprostaglandin synthesis inhibition is raised by the finding that although the mean accumulation of radiolabel was somewhat higher with flurbiprofen, this may well have arisen by chance (P < 0.3).…”

“…We do not know if the increased accumulation of label represents increased uptake of methotrexate or a degradation product, or decreased release of methotrexate or its products such as polyglutamates (Jolivet et al, 1983 (Tavares et al, 1985).…”