Superoxide–Mediated Glomerulopathy in the Endotoxin–Treated Pregnant Rat

Abstract

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 pregnancy, 12 rats were infused for 1 h with 1.0 μg/kg bw endotoxin via a permanent 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 (14,000 U/kg) after the start of the infusion (SOD rats). The other 6 rats received no SOD treatment (endotoxin rats). Control pregnant rats were infused 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 specimens were snap–frozen. Cryostat kidney sections were stained for fibrinogen, ecto–ATP diphosphohydrolase (e–ATPase) activity, polymorphonuclear cells, monocytes and various adhesion molecules on the endothelium and the leukocytes. SOD treatment appeared to significantly prevent the increased urinary albumin excretion and the decrease of glomerular e–ATPase activity which were observed in endotoxin–treated rats. This effect of SOD treatment after endotoxin infusion was associated with a significant inhibition of glomerular monocyte influx and a significant inhibition of adhesion molecule expression (glomerular ICAM–1 and VCAM–1 and leukocyte LFA–1 and VLA–4).The present data suggest that in the endotoxin–infused pregnant rat, production of superoxide in the first few hours after the infusion plays a role in the induction of glomerular damage, leading to albuminuria and diminished e–ATPase expression during the following days.