Metal Accumulation and Nephron Heterogeneity in Mercuric Chloride-Induced Acute Renal Failure

Abstract

h S T R A ( J TThe present siudy 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 iv 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.

Ischemic and nephrotoxic acute renal failure are distinguished by their broad transcriptomic responses

“…Alternately, the initial injury occurs in the cortical proximal tubules, and this transient injury travels down the nephron to induce further injury in the S3 segment of the proximal tubule, leading to the manifestation of acute renal failure. The latter model is consistent with electron microscopy studies that show a progression of injury along the nephron with a similar time course (10,11,24,34,39).…”

Bioaccumulation of inorganic and methylated mercury by the gills of the shore crab Carcinus maenas: transepithelial fluxes and histochemical localization

“…The peripheral pedicels of nephrocytes are similar to those of the podocytes of the cells lining the Bowman space in the kidney of vertebrates and through which a plasma ultrafiltrate is formed (Ruppert 1994). Those cells have in fact been shown to accumulate mercury (Baatrup et al 1986, Wilks et al 1994) and thus have also been identified as important target sites for Hg-induced nephrotoxicity in vertebrates (Prasada Rao et al 1989, Bano & Hasan 1990, Artese et al 1993, Girardi et al 1996. In crustaceans, nephrocytes have long been considered to be phagocytic (Drach 1930, Doughtie & Rao 1981, Smith & Ratcliffe 1981, Taylor & Taylor 1992, ridding the hemolymph of any cell debris or foreign substances.…”