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

M Potier
Nephrology Dialysis Transplantation. 1998-06-01; 13(6): 1406-1411
DOI: 10.1093/ndt/13.6.1406

PubMed

1. Nephrol Dial Transplant. 1998 Jun;13(6):1406-11. doi: 10.1093/ndt/13.6.1406.

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.

Potier M(1), Wolf A, Cambar J.

Author information:
(1)Laboratoire de Biologie Cellulaire, Faculté des Sciences Pharmaceutiques,
Bordeaux, France.

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 myoreactive. 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.