Surperoxide-mediated glomerulopathy in the endotoxin-treated pregnant rat

In the present study the role of superoxide in the glomerular damage in the low-dose endotoxin-infused pregnant rats was investigated. On day 14 of pr egnancy, 12 rats were infused for 1 h with 1.0 mu g/kg bw endotoxin via a p ermanent jugular vein cannula. Of these rats, 6 were treated with SOD both prior to endotoxin infusion (7,000 U/kg) and 30 min (7,000 U/kg) and 4 h (1 4,000 U/kg) after the start of the infusion (SOD rats). The other 6 rats re ceived no SOD treatment (endotoxin rats). Control pregnant rats were infuse d for 1 h with saline (saline rats; n = 6). Urinary albumin was measured on days 15 and 19 of pregnancy. On day 21, rats were sacrificed and kidney sp ecimens were snap-frozen. Cryostat kidney sections were stained for fibrino gen, ecto-ATP diphosphohydrolase (e-ATPase) activity, polymorphonuclear cel ls, monocytes and various adhesion molecules on the endothelium and the leu kocytes. SOD treatment appeared to significantly prevent the increased urin ary albumin excretion and the decrease of glomerular e-ATPase activity whic h were observed in endotoxin-treated rats. This effect of SOD treatment aft er endotoxin infusion was associated with a significant inhibition of glome rular monocyte influx and a significant inhibition of adhesion molecule exp ression (glomerular ICAM-1 and VCAM-1 and leukocyte LFA-1 and VLA-4). The present data suggest that in the endotoxin-infused pregnant rat, produc tion of superoxide in the first few hours after the infusion plays a role i n the induction of glomerular damage, leading to albuminuria and diminished e-ATPase expression during the following days.