Different effects of non-steroidal antiinflammatory drugs on human gallbladder cyclooxygenase and lipoxygenase.

FRANCHI ANA MARIA; DI GIROLAMO GUILLERMO; FARINA MARIANA; DE LOS SANTOS AR; MARTI ML; GIMENO MARTA ALICIA

MEDICINA (BUENOS AIRES)

MEDICINA (BUENOS AIRES)

Lugar: Buenos Aires; Año: 2000 vol. 60 p. 580 - 586

0025-7680

Lysine clonixinate (LC) is a non-steroidal antiinflammatory agent (NSAID) with only few adverse effects. This characteristic has prompted us to suggest that its administration, at levels equivalent to those found in human plasma following therapeutic doses, slightly inhibitis cyclooxygenase I (COX I). Three experiments were performed. Experiment 1: to study the in vitro effect of LC at concentrations of 4 and 6 µg/ml, comparable with those found in plasma following an oral therapeutic dose of 125 mg. Gallbladder tissue segments were incubated with 0.25 µCi of 14C-arachidonic acid and the production of prostaglandin E2 (PGE2), prostaglandin F2a (PGF2a) and 6-keto prostaglandin F1a (6-keto PGF1a) was measured. LC did not affect basal production of any of the 3 prostaglandins (PGs) but at 6 µg/ml slightly reduced the levels of 5-hidroxyeicosatetraenoic acid (5-HETE). Experiment 2: LC was administered preoperatively to 6 patients by continuous perfusion, to achieve a steady-state concentration between 4 and 6 µg/ml. Gallbladder segments from the 6 treated and another 6 control patients were incubated in 14C-arachidonic acid. Gallbladder segments treated with LC did not show a decreased production of any of the three PGs whereas 5-HETE released to the medium was significantly lower. Experiment 3: 18 patients received an IV bolus of LC 100 mg (n1 = 6) or LC 200 mg (n2 = 6) or indomethacin (INDO) 50 mg (n3 = 6). Unlike the administration of INDO bolus, LC in the above doses did not inhibit PG synthesis. Both NSAIDs showed different effects when the production of 5-HETE synthesis was assessed. Treatment with INDO did not alter the production of 5-HETE while LC elicited significant inhibition. The three studies conducted, namely in vitro and in vivo continuous perfusion and IV bolus, revealed that LC had no effect on prostaglandin synthesis while reducing significantly the levels of 5-HETE.