ABSORPTION, RETENTION AND URINARY-EXCRETION OF CHROMIUM-51 IN RATS PRETREATED WITH INDOMETHACIN AND DOSED WITH DIMETHYLPROSTAGLANDIN E(2), MISOPROSTOL OR PROSTACYCLIN

Drug-nutrient interactions affecting chromium were investigated in thi s study. Rats were injected with indomethacin to reduce endogenous pro staglandin synthesis and dosed with prostaglandin analogues or prostac yclin. Effects on absorption, tissue distribution and urinary excretio n of Cr-51 from (CrCl3)-Cr-51 were evaluated using a 2 x 4 factorial e xperimental design. Forty-eight adult male rats were food deprived for 12 h and then injected intraperitoneally with indomethacin (5 mg/kg b ody wt) or placebo. Thirty minutes later, rats were intubated and dose d with one of four treatments: a prostaglandin E(1) analogue (misopros tol) at 50 mu g/kg body wt; a prostaglandin E(2) analogue (16,16-dimet hylprostaglandin E(2)) at 7.5 mu g/kg body wt; prostacyclin at 20 mu g /kg body wt; or control (7.64 mmol/L Tween-80 suspended in 0.15 mol/L NaCl containing 0.48 mol/L ethanol). Immediately after intubation, rat s were dosed with 3.7 mBq of (CrCl3)-Cr-51 by micropipette. Blood was collected from the tail at intervals after Cr-51 dosing. Six hours aft er dosing, 51Cr rats were exsanguinated by cardiac puncture. Indometha cin, an inhibitor of prostaglandin synthesis, significantly increased (P < 0.05) Cr-51 in blood at all time periods tested except at 15 min. In tissues, indomethacin significantly increased Cr-51 retention. Uri nary Cr-51 excretion at 6 h was higher (P < 0.05) in indomethacin-pret reated rats than in control rats. Administration of indomethacin, whic h blocks prostaglandin synthesis, enhanced Cr-51 absorption, whereas d osing with 16,16-dimethylprostaglandin E(2) decreased Cr-51 absorption .