A new test for evaluating nonsteroidal anti-inflammatory drugs in vitro: inhibition of prostaglandin E2 production in minced intestinal tissue

Arch Int Pharmacodyn Ther. 1992 Mar-Apr:316:114-23.

Abstract

A new method for evaluating the inhibitory effect of nonsteroidal anti-inflammatory drugs on prostaglandin E2 production is presented. Minced rat intestinal tissue was incubated with a nonsteroidal anti-inflammatory drug and homogenized. After centrifugation, prostaglandin E2 in the supernatant was measured by radioimmunoassay. The production of prostaglandin E2 was decreased by nonsteroidal anti-inflammatory drugs, in a concentration-dependent manner, the order of potency being diclofenac greater than loxoprofen greater than indomethacin greater than ibuprofen greater than TA-847 (imidazole derivative). Loxoprofen, a prodrug, inhibited the prostaglandin E2 production. In a classical enzyme assay with sheep seminal vesicle microsomal prostaglandin endoperoxide synthase, the order of inhibitory potency was TA-847 greater than diclofenac greater than indomethacin greater than ibuprofen. The inhibitory effect of loxoprofen was very weak. On the other hand, the potency order of these nonsteroidal anti-inflammatory drugs, with regard to their anti-inflammatory effect as determined in the rat carrageenin-induced paw edema model, was loxoprofen greater than indomethacin greater than diclofenac greater than ibuprofen greater than TA-847. The results of the new method with intestinal tissue showed thus a good correlation with the anti-inflammatory activity in vivo.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Carrageenan
  • Dinoprostone / biosynthesis*
  • Drug Evaluation, Preclinical
  • Edema / chemically induced
  • Edema / drug therapy
  • Gastric Mucosa / metabolism
  • In Vitro Techniques
  • Intestinal Mucosa / metabolism*
  • Male
  • Microsomes / drug effects
  • Microsomes / metabolism
  • Prostaglandin-Endoperoxide Synthases / metabolism
  • Rats
  • Rats, Inbred Strains
  • Seminal Vesicles / metabolism
  • Sheep
  • Stomach / drug effects

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Carrageenan
  • Prostaglandin-Endoperoxide Synthases
  • Dinoprostone