Changes in prostaglandin E2 (PGE2) levels in paw exudate, stomach and kidney of arthritic rats: effects of flosulide.
To further examine the organ-specific toxic effects of selective and non-selective COX-2 inhibitors in adjuvant arthritis (CAA), we assessed the PGE2 concentration in various organs. AA was induced by intradermal injection of Mycobacterium butyricum. Fourteen days after inoculation, AA rats were selected and treated orally every day for two weeks with the selective COX-2 inhibitor, flosulide, or the COX-1-COX-2 inhibitor, indomethacin. The time-course of paw swelling was determined. At the end of treatments, PGE2 was extracted from paw, stomach (wall and mucosa) and kidney and its concentration was determined by ELISA. Paw edema increase was accompanied by a rise in PGE2 concentration. PGE2 also increased in stomach (mucosa and wall) and kidney. The anti-inflammatory treatment with flosulide (5 mg/kg x day), and indomethacin (1 mg/kg x day), reduced plantar edema by 98.0% and 74.4% respectively. Both drugs greatly decreased PGE2 levels in paw (73.7-53.2%), stomach wall (84.5-80.3%), stomach mucosa (109.9-110.9%) and kidney (92.9-97.5% respectively). However, PGE2 reductions in AA rats did not fall significantly below control values.
Turull
A
A
Departament de Fisiologia, Facultat de Farmàcia, Universitat de Barcelona, Spain.
Queralt
J
J
D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy / Q000378:metabolism*; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D015232:Dinoprostone / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000188:drug therapy / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005528:Foot; D005753:Gastric Mucosa / Q000378:metabolism; D007189:Indans / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D009928:Organ Specificity / Q000187:drug effects; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013270:Stomach / Q000187:drug effects*; D013997:Time Factors
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007189:Indans; D007527:Isoenzymes; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C059178:flosulide; D015232:Dinoprostone; D007213:Indomethacin