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Prednisolone and azathioprine worsen the cyclosporine A-induced oxidative phosphorylation decrease of kidney mitochondria.

N Simon·R Zini·C Morin·F Bree·J P Tillement
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Abstract

We investigated the effects of cyclosporine A, prednisolone and azathioprine on respiration rates, Ca2+-induced swelling and Ca2+ fluxes of rat kidney mitochondria. The three drugs significantly decreased the succinate induced-respiration rates according to concentration-dependent processes. Each drug inhibited about 10% of the respiratory control ratio, with EC50 of 3.7 x 10(-7) M, 5.8 x 10(-9) M for cyclosporine A and azathioprine respectively. Prednisolone was the most effective (19.2%) acting by a two-step process with EC50 of 9.2 x 10(-12) M and 1.9 x 10(-8) M. The combination of the three drugs developed a higher significant decrease of respiratory control ratio than that of each drug but lower than the sum of their respective effects. Inhibitions of swelling and Ca2+ fluxes through mitochondrial membrane due to the combination were not different from those induced by cyclosporine A alone. The action mechanisms of cyclosporine A and prednisolone were total and partial Ca2+ dependent respectively. Azathioprine appears to act by a Ca2+-independent one. It is concluded that azathioprine and prednisolone may worsen cyclosporine A-induced renal mitochondrial alteration of oxidative phosphorylation.

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AnimalsAzathioprineCalciumCyclosporineImmunosuppressive AgentsKidneyMaleMitochondriaMitochondrial SwellingOxidative PhosphorylationOxygen ConsumptionPrednisoloneRatsRats, WistarSuccinatesSuccinic AcidJournal ArticleResearch Support, Non-U.S. Gov't

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N Simon, R Zini, C Morin, F Bree, J P Tillement. 1997. Prednisolone and azathioprine worsen the cyclosporine A-induced oxidative phosphorylation decrease of kidney mitochondria.. https://doi.org/10.1016/s0024-3205(97)00442-6

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