Protective Effect of Three Xanthine Derivatives (Theophylline, Caffeine and Pentoxifylline) against the Cyclosporin A-lnduced Glomerular Contraction in Isolated Glomeruli and Cultured Mesangial Cells

1. Nephron. 1997;77(4):427-34. doi: 10.1159/000190320.

Protective effect of three xanthine derivatives (theophylline, caffeine and
pentoxifylline) against the cyclosporin A-induced glomerular contraction in
isolated glomeruli and cultured mesangial cells.

Potier M(1), Aparicio M, Cambar J.

Author information:
(1)Laboratoire de Biologie Cellulaire, Faculté de Pharmacie, et Hôpital
Pellegrin, Bordeaux, France.

Cyclosporin A (CyA), an immunosuppressive agent, induces in vivo a severe
nephrotoxicity with large decrease in renal hemodynamics correlated with in
vitro glomerular contraction. The aim of this study is to show the ability of
three xanthine derivatives, caffeine, theophylline and pentoxifylline, to
diminish the CyA-induced in vitro glomerular contraction. The use of isolated
glomeruli and cultured rat mesangial cells permits us to evaluate by
quantitative and qualitative morphometric analysis the contraction elicited
either with CyA alone or with previous treatment with nontoxic concentrations of
xanthine derivatives. Indirect immunofluorescence of actin filaments makes it
possible to appreciate qualitative morphometric changes in mesangial cells. A
10-min pretreatment with caffeine, theophylline or pentoxifylline (10(-4) to
10(-9) M) abolishes the contraction elicited with 10(-6) M CyA. CyA alone
induces -13.9% compared to CyA with 10(-6) M pentoxifylline which induces only
-3.2% of reduction of planar glomerulus surface area after 30 min. Similar
results were provided with cultured rat mesangial cells. As shown by indirect
immunofluorescence xanthine derivatives prevent the cytoskeletal reorganization
(alpha-actin) of cultured mesangial cells which occurs with CyA. The marked
constriction induced by CyA in isolated glomeruli and mesangial cells can be
prevented by xanthine derivatives.

DOI: 10.1159/000190320
PMID: 9434065 [Indexed for MEDLINE]

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