Endotoxin-induced acute renal failure in mice. Effects of indomethacin and the thromboxane-synthetase antagonist UK 38.485.

Abstract

Functional acute renal failure (ARF) was induced within 24 h following i.p. injection of 200 micrograms E. coli endotoxins (ET) into C3H/HeHan mice. Pre- and post-treatment with either UK 38.485, a selective thromboxane (TX)-synthetase inhibitor, or with the cyclo-oxigenase inhibitor, indomethacin (IM), does not prevent acute renal failure in these mice. Histologically, only very little fibrin degradation and few microthrombi are present 24 h later in the kidneys, so that disseminated intravascular coagulation (DIC) mechanisms cannot have caused the significant azotemia. Slight histological changes are accentuated in the UK 38.485-treated group. Only the indomethacin group has a significantly increased mortality as compared to all other groups. We conclude from our study that with low dosages of endotoxins functional ARF can be induced in mice without a circulatory shock and early mortality and that both UK 38.485 and IM are of little value in preventing it.