Abstract

The author studied the morphologic changes on the glomeruli and tubular structures to clarify the mechanism of nephrotoxicty induced by endotoxin. Also studied was the changes in the permeability of microvasculature at the electron microscopic level using peroxidase as enzymatic electron tracer by the vascular clearance method. Male Sprague-Dawley rats were received 3 mg per kg of body weight of E. coli endotoxin and then sacrified 30, 60, 120, 180, and 300 minutes after injections of the endotoxin, respectively. Another groups of animals were received additionally intravenous injection of peroxidase 5 minutes before their sacrifices in each group. The results obtained were summarized as follows: Light microscopically, the glomeruli showed mild congestion and infiltration of leukocytes, which remained in the same degree throughout. The tubular epithelial cells showed intracellular edema from the early stages and regenerative changes appeared in later times. Electron microscopically, endothelilal cells of the glomeruli and peritubular capillaries showed vacuolization and protrusion of cytoplasmic process toward luminal spaces. The tubular epithelial cells showed intracellular edema from the early stages and regenerative changes appeared in later times. Electron microscopically, endothelial cells of the glomeruli and peritubular capillaries showed vacuolization and protrusion of cytoplasmic process toward luminal spaces. The tubular epithelial cells showed swelling of mitochondria, detachmetnt of ribosomes, swelling of RER and attenuation of basal infolding structures, which were more prominent in later times. Lysosomes appeared from the time 3 hours after injections of endotoxin, and increased in later stages. Some epithelial cells were detached out from the basement membrane in later time, but the basement membrane itself seemed to be intact until the time 5 hours after injection of endotoxin. Peroxidase treated groups showed reactive products to peroxidase in the luminal spaces in both of control and experimental groups until 3 hours, but they were remained within basal layer of the cell in the experimental group after 5 hours, which indicated inhibition of permeability of the particulated material in endotoxin treated group in later time. The results of this study suggested that tubular structures were more severly affected by endotoxin in earlier stage, which indicated that injury to the tubule did participate in the role initiating renal injury which therefore in thought to be the basis for acute renal insufficiency than glomerular injury in endotoxemia.