Metal accumulation and nephron heterogeneity in mercuric chloride-induced acute renal failure.
The present study was designed to assess the effects of mercury on glomerular integrity during the early phase of acute renal failure. The silver amplification method showed distribution of mercury in midcortical and juxtamedullary glomeruli and on the brush border of the S2 segment of the proximal tubule 15 min after treatment. At 30 min, there was a decrease in glomerular staining and increased mercury in the proximal tubule. After 3 hr, mercury was no longer detectable in glomeruli but was widespread in the lumen of the proximal tubule. By 24 hr, mercury was prominent in all proximal tubular segments throughout the cortex. The presence of mercury in glomeruli was not related to hemodynamic changes, as there was no evidence for blood redistribution toward juxtamedullary glomeruli as assessed by the filling of the microvascular system with Monastral Blue B. The reduced activity of horseradish peroxidase (administered i.v. 90 sec and 10 min before sacrifice) in juxtamedullary glomeruli 30 min after mercury administration suggests a decreased uptake of horseradish peroxidase or an increased glomerular protein filtration. These data support glomerular filtration as the predominant excretory route for mercury, highlight the marked nephron heterogeneity in the distribution of this metal, and show that impairment of glomerular integrity occurs before necrosis of the proximal tubules and acute renal failure.
Wilks
M F
MF
Drug Development and Chemical Safety Research Unit, Faculty of Science, University of East London, United Kingdom.
Gregg
N J
NJ
Bach
P H
PH
D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000503:physiopathology; D000818:Animals; D005919:Glomerular Filtration Rate / Q000502:physiology; D007211:Indoles; D007678:Kidney Glomerulus / Q000378:metabolism; D008297:Male; D008627:Mercuric Chloride / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity*; D009399:Nephrons / Q000502:physiology*; D009942:Organometallic Compounds; D051381:Rats; D017208:Rats, Wistar; D013194:Staining and Labeling
D007211:Indoles; D009942:Organometallic Compounds; C015445:copper phthalocyanine; D008627:Mercuric Chloride