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Prednisolone and azathioprine worsen the cyclosporine A-induced oxidative phosphorylation decrease of kidney
1Département de Pharmacologie, Faculté de Médecine de Paris XII, Créteil, France.
Life Sciences
|January 1, 1997
Summary
Cyclosporine A, prednisolone, and azathioprine impair rat kidney mitochondrial function. Azathioprine and prednisolone may worsen cyclosporine A-induced mitochondrial damage, affecting oxidative phosphorylation.
Area of Science:
- Mitochondrial toxicology
- Pharmacology
- Nephrology
Background:
- Cyclosporine A, prednisolone, and azathioprine are commonly used immunosuppressants.
- Their effects on kidney mitochondrial function are not fully understood.
- Mitochondrial dysfunction is implicated in various kidney diseases.
Purpose of the Study:
- To investigate the impact of cyclosporine A, prednisolone, and azathioprine on rat kidney mitochondria.
- To determine the effects on respiration, Ca2+-induced swelling, and Ca2+ fluxes.
- To elucidate the mechanisms of action and potential drug interactions.
Main Methods:
- Isolated rat kidney mitochondria were used.
- Respiration rates, Ca2+-induced swelling, and Ca2+ fluxes were measured.
- Concentration-dependent effects and EC50 values were determined for each drug.
Main Results:
- All three drugs decreased succinate-induced respiration rates in a concentration-dependent manner.
- Prednisolone showed the highest inhibition of the respiratory control ratio, followed by azathioprine and cyclosporine A.
- Drug combinations showed synergistic but not additive effects on respiratory control; swelling and Ca2+ fluxes were similar to cyclosporine A alone.
Conclusions:
- Azathioprine and prednisolone may exacerbate cyclosporine A-induced mitochondrial alterations in kidney oxidative phosphorylation.
- Cyclosporine A and prednisolone's mechanisms are Ca2+-dependent, while azathioprine's is Ca2+-independent.
- These findings highlight potential nephrotoxic interactions between these immunosuppressants.