Effect of combination of misoprostol and indomethacin on eicosanoid production in carrageenan-induced air pouch inflammation in rats.
The effect of single or combined administration of indomethacin and misoprostol on the exudate leukocyte count and thromboxane B2, a stable metabolite of thromboxane A2, and on the leukotriene B4 level, as cyclooxygenase and lipoxygenase metabolites of arachidonic acid, was investigated in acute carrageenan-induced air pouch inflammation in rats. Administration of indomethacin (0.25 to 4 mg/kg) 1 h before carrageenan given by the orogastric route reduced the exudate leukocyte count and thromboxane B2 level whereas it increased the exudate leukotriene B4 level dose dependently. Administration of misoprostol, a synthetic prostaglandin E1 analogue, (12.5 to 100 microg/kg) twice daily for two days before carrageenan given by the orogastric route increased the exudate leukocyte count. Combined misoprostol and indomethacin did not change the effect of indomethacin alone on exudate leukocyte count. Misoprostol, when used alone, decreased exudate thromboxane B2 level significantly. However, misoprostol did not change the exudate leukotriene B4 level, while its combination with indomethacin prevented the indomethacin-induced increase in exudate leukotriene B4 level. In conclusion, although misoprostol can be combined with non-steroidal anti-inflammatory drugs in many chronic inflammatory situations, our results indicate that misoprostol may also be combined with indomethacin in acute inflammation without producing any change on the antiinflammatory efficacy of indomethacin in rats.
Sayar
K
K
Department of Pharmacology and Clinical Pharmacology, Medical Faculty of Ankara University, Turkey.
Melli
M
M
D000704:Analysis of Variance; D000818:Animals; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002351:Carrageenan; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005079:Excipients; D005260:Female; D007124:Immunoenzyme Techniques; D007213:Indomethacin / Q000008:administration & dosage / Q000627:therapeutic use*; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D007958:Leukocyte Count / Q000187:drug effects; D007975:Leukotriene B4 / Q000378:metabolism*; D016595:Misoprostol / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D013929:Thromboxane B2 / Q000378:metabolism*
D000897:Anti-Ulcer Agents; D016861:Cyclooxygenase Inhibitors; D005079:Excipients; D016595:Misoprostol; D007975:Leukotriene B4; D013929:Thromboxane B2; D002351:Carrageenan; D007213:Indomethacin