In vivo anti-allergic and anti-inflammatory effects of drugs that inhibit lipoxygenase activity in vitro.
Studies in vitro have already shown that the chemotactic effect of leukotriene LTB4, as well as its pro-aggregatory effect on a suspension of leukocytes, could be inhibited by the lipoxygenase (LO) inhibitor ETYA; moreover a beneficial effect of another LO-inhibitor, diethylcarbamazine, has been shown on experimental asthma. To explore a possible therapeutic application of substances that inhibit 15-LO of soybean in vitro, we have tested several active compounds, namely nordihydroguaiaretic acid (NDGA), phenidone, diethylcarbamazine and mefenamic acid, on the following in vivo inflammation models in the rat: plantar oedema induced by carrageenin; cutaneous vascular hyperpermeability induced by pafacether; pleurisy induced by carrageenin. The correlation between the LO-inhibitor effect of these compounds in vitro and their beneficial effects in the different tests that were performed, as well as the mechanisms of action induced in the different experimental models, are discussed.
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001091:Arachidonate Lipoxygenases; D002199:Capillary Permeability; D002396:Catechols / Q000494:pharmacology / Q000627:therapeutic use; D003907:Dexamethasone / Q000494:pharmacology / Q000627:therapeutic use; D004049:Diethylcarbamazine / Q000494:pharmacology / Q000627:therapeutic use; D006967:Hypersensitivity / Q000188:drug therapy* / Q000201:enzymology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology / Q000627:therapeutic use; D007249:Inflammation / Q000188:drug therapy* / Q000201:enzymology; D016859:Lipoxygenase Inhibitors; D008297:Male; D009637:Masoprocol; D009930:Organic Chemicals; D010323:Passive Cutaneous Anaphylaxis; D010998:Pleurisy / Q000188:drug therapy; D011720:Pyrazoles / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D011919:Rats, Inbred Strains; D013440:Sulfides
D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D002396:Catechols; D016859:Lipoxygenase Inhibitors; D009930:Organic Chemicals; D011720:Pyrazoles; D013440:Sulfides; C047172:BM 15501; C047171:methyl-2-butylmercapto-4-catechol; D009637:Masoprocol; D003907:Dexamethasone; D001091:Arachidonate Lipoxygenases; C015429:phenidone; D004049:Diethylcarbamazine; D007213:Indomethacin