Abstract

Glucocorticoids, such as Deflazacort (DFC), are widely used in clinical practice, yet their direct effects on fundamental cellular processes, particularly mitochondrial function, remain a critical area of investigation. This study aimed to elucidate the direct impact of DFC on the bioenergetic status and membrane integrity of isolated rat liver mitochondria. Using high-resolution respirometry, we assessed the effects of DFC on oxygen consumption rates in various respiratory states, fueled by different substrates. Furthermore, we employed calcium retention capacity assays to monitor the drug's influence on the calcium-dependent mitochondrial permeability transition pore (MPTP), a key regulator of cell fate. Our findings indicate that DFC, at therapeutically relevant concentrations, does not significantly alter the basal or maximal respiration rates, nor does it affect the efficiency of oxidative phosphorylation in rat liver mitochondria. Crucially, DFC was also found to have no direct effect on the calcium-induced opening of the MPTP. These results suggest that the beneficial clinical effects of DFC, particularly in conditions like Duchenne muscular dystrophy, are likely mediated through indirect, systemic pathways rather than a direct, acute modulation of mitochondrial bioenergetics or membrane permeability in non-target tissues like the liver.