Absorption, retention and urinary excretion of chromium-51 in rats pretreated with indomethacin and dosed with dimethylprostaglandin E2, misoprostol or prostacyclin.
Drug-nutrient interactions affecting chromium were investigated in this study. Rats were injected with indomethacin to reduce endogenous prostaglandin synthesis and dosed with prostaglandin analogues or prostacyclin. Effects on absorption, tissue distribution and urinary excretion of 51Cr from 51CrCl3 were evaluated using a 2 x 4 factorial experimental design. Forty-eight adult male rats were food deprived for 12 h and then injected intraperitoneally with indomethacin (5 mg/kg body wt) or placebo. Thirty minutes later, rats were intubated and dosed with one of four treatments: a prostaglandin E1 analogue (misoprostol) at 50 microg/kg body wt; a prostaglandin E2 analogue (16,16-dimethylprostaglandin E2) at 7.5 microg/kg body wt; prostacyclin at 20 microg/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, rats were dosed with 3.7 mBq of 51CrCl3 by micropipette. Blood was collected from the tail at intervals after 51Cr dosing. Six hours after dosing, 51Cr rats were exsanguinated by cardiac puncture. Indomethacin, an inhibitor of prostaglandin synthesis, significantly increased (P < 0.05) 51Cr in blood at all time periods tested except at 15 min. In tissues, indomethacin significantly increased 51Cr retention. Urinary 51Cr excretion at 6 h was higher (P < 0.05) in indomethacin-pretreated rats than in control rats. Administration of indomethacin, which blocks prostaglandin synthesis, enhanced 51Cr absorption, whereas dosing with 16,16-dimethylprostaglandin E2 decreased 51Cr absorption.
Kamath
S M
SM
Department of Nutritional Sciences, Oklahoma State University, Stillwater 74078-6141, USA.
Stoecker
B J
BJ
Davis-Whitenack
M L
ML
Smith
M M
MM
Adeleye
B O
BO
Sangiah
S
S
D015064:16,16-Dimethylprostaglandin E2 / Q000008:administration & dosage / Q000494:pharmacology*; D000042:Absorption; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology*; D002857:Chromium / Q000493:pharmacokinetics* / Q000652:urine; D002860:Chromium Radioisotopes; D004750:Enteral Nutrition; D011464:Epoprostenol / Q000008:administration & dosage / Q000494:pharmacology*; D018565:Food-Drug Interactions; D007213:Indomethacin / Q000008:administration & dosage / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D008297:Male; D016595:Misoprostol / Q000008:administration & dosage / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002860:Chromium Radioisotopes; D016595:Misoprostol; D002857:Chromium; D011464:Epoprostenol; D015064:16,16-Dimethylprostaglandin E2; D007213:Indomethacin