Nephrology Dialysis Transplantation, Vol 13, Issue 6 1406-1411, Copyright © 1998 by Oxford University Press
M Potier, A Wolf and J Cambar
Background: One adverse side-effect of the
immunosuppressive drug cyclosporin A (CsA) is a decrease in glomerular
filtration rate (GFR). This effect might be the result of increased
glomerular contractions. The present study compared the contractile effects
of CsA, cyclosporin G (CsG) and the novel cyclosporin derivative IMM 125 in
isolated rat glomeruli and primary cultures of rat mesangial cells.
Methods: Interactive image analysis was used to
measure glomerular and mesangial cell contraction.
Results: CsA, CsG, and IMM 125 at concentrations of 0,
10-9, 10-8,
10-7, 10-6 and
10-5 M caused a time-dependent and a
concentration-dependent contraction of isolated glomeruli and mesangial
cells 30 min after incubation. In glomeruli, CsA was more potent than CsG
and IMM 125. In mesangial cells, IMM 125 also exhibited the lowest
contractile activity, while CsA and CsG were almost equally moyreactive.
The absolute degree of the glomerular contraction was proportional to the
number of contracting mesangial cells in one glomeruli. The number of
responding cells after incubation with IMM 125 and CsG were lower compared
to CsA, which might explain the different response with CsG and CsA in both
models. Conclusions: Since the concentrations used in
these experiments were close to that reached in rat serum after treatment
with CsA, the present results suggest that the contractile effects of IMM
125 and CsG in isolated glomeruli were clearly smaller compared to CsA,
which might reflect the cyclosporins induced GFR changes in
vivo. Key words: contraction analysis;
cultured mesangial cells; cyclosporins; isolated glomeruli; rat
ORIGINAL ARTICLES
Comparative study of cyclosporin A, cyclosporin G, and the novel cyclosporin derivative IMM 125 in isolated glomeruli and cultured rat mesangial cells: a morphometric analysis
Laboratoire de Biologie Cellulaire, Faculté des Sciences Pharmaceutiques, 146 rue Léo Saignat,F-33076 Bordeaux Cedex, France; Novartis Pharma AG, Toxicology/Pathology, Basel, Switzerland
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