Potential use of isolated glomeruli and cultured mesangial cells as in vitro models to assess nephrotoxicity |
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Authors: | A Rodriguez-Barbero B L'Azou J Cambar JM López-Novoa |
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Institution: | (1) Instituto Reina Sofía de Investigación Nefrológica, Departamento de Fisiología y Farmacología, Universidad de Salamanca, Salamanca, Spain;(2) Groupe d'Etude de Physiologie et Physiopathologie Rénales, Départment de Biologie Cellulaire, Université Victor Segalen Bordeaux 2, Bordeaux, France |
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Abstract: | The purpose of this short review is to present the potential of using isolated glomeruli and cultured mesangial cells as two
differentin vitro models to assess the glomerular effect of molecules with nephrotoxic properties. The advantage of using isolated renal glomeruli
is that they conserve the architecture of this anatomical region of the kidney; moreover, they are free of any vascular, nervous
or humoral influences derived from other regions of the kidney. Mesangial cells are perivascular pericytes located within
the central portion of the glomerular tuft between capillary loops. Mesangial cells have a variety of functions including
synthesis and assembly of the mesangial matrix, endocytosis and processing of plasma macromolecules, and control of glomerular
hemodynamics, mainly the ultrafiltration coefficient K
f, via mesangial cell contraction or release of vasoactive hormones. Most authors agree that mesangial cells play a major role
in glomerular contraction, filtration surface area, and K
f regulation. One of the major effects of toxicants on glomerular structures is contraction. We can assess quantitatively the
degree of toxicant-induced mesangial cell contraction or glomerular contraction by measuring the changes in planar cell surface
area or apparent glomerular cross-sectional area after exposition to the toxicant. Thesein vitro models can also reveal glomerular effects of xenobiotics that are difficult or impossible to observe in vivo. In addition, these studies permit a fundamental examination of the mechanism of action of xenobiotics on glomerular cells,
including the possibility that at least a part of their effects are mediated by local mediators released by glomerular cells.
We review the effects and the mechanisms of action of several toxicants such as gentamicin, cyclosporin, cisplatin, and cadmium
on isolated glomeruli or cultured mesangial cells. As suchin vitro results confirmin vivo renal hemodynamic changes caused by toxicants, we conclude that these models are fruitful tools for the study of renal toxicity.
Thesein vitro systems might also serve as a predictive tool in the evaluation of drugs inducing changes in glomerular filtration rate and
as a way to propose protective agents against these dramatic hemodynamic effects.
This revised version was published online in July 2006 with corrections to the Cover Date. |
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Keywords: | glomeruli kidney mesangial cells nephrotoxicity |
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