Inhibition of rat endotoxin-induced lethality by BN 52021 and BN 52063, compounds with PAF-acether antagonistic effect and protease-inhibitory activity.
Since proteolytic enzymes play a key role in endotoxaemia and anaphylaxis, diseases in which PAF-acether may be involved, we have investigated the activity of BN 52021 and BN 52063, two potent and specific PAF-acether antagonists, on plasma protease activity in the rat. After oral administration, both drugs dose-dependently decreased plasma trypsin-like activity (PTLA) although they did not show any inhibitory effect in vitro. PAF-acether and endotoxin injected into rats increased PTLA, the increase with endotoxin appearing more slowly but to a higher extent than with PAF-acether. Inhibition of the endotoxin-induced increase in PTLA was obtained with BN 52021, BN 52063 and dexamethasone, whereas aprotinin was ineffective. Since BN 52021 and BN 52063 reduced also the endotoxin-induced lethality in the rat, their antiprotease activity may be a consequence of their PAF-antagonistic effect. Further studies will be required with other PAF antagonists to assess fully this assumption.
D000818:Animals; D004224:Diterpenes; D004731:Endotoxins / Q000633:toxicity*; D046934:Ginkgolides; D007783:Lactones; D008297:Male; D010741:Phospholipases A / Q000032:analysis; D010936:Plant Extracts / Q000494:pharmacology*; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D011480:Protease Inhibitors / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012772:Shock, Septic / Q000517:prevention & control; D014357:Trypsin / Q000097:blood
D004224:Diterpenes; D004731:Endotoxins; D046934:Ginkgolides; D007783:Lactones; D010936:Plant Extracts; D010972:Platelet Activating Factor; D011480:Protease Inhibitors; C050422:BN 52063; C045856:ginkgolide B; D010741:Phospholipases A; D014357:Trypsin