DEXAMETHASONE INHIBITS INORGANIC-PHOSPHATE STIMULATED CA2+-DEPENDENT DAMAGE OF ISOLATED RAT-LIVER AND RENAL-CORTEX MITOCHONDRIA

The prevention of Ca2+-induced permeabilization of rat liver and kidney cortex mitochondria by dexamethasone, a common anti-inflammatory glucocorticoid, was the subject of this study, A non-specific release of matrix Ca2+ and membrane depolarization was observed in respiring mitochondrial suspensions subjected to a 30 nmol Ca2+/mg protein load in the presence of 2 mM inorganic phosphate (P-i), or 20 nmol Ca2+/mg protein with 1 mM P-i, for Liver and renal cortex mitochondria (RCM), respectively, Additions of dexamethasone prior to Ca2+ in mitochondrial suspensions from liver or kidney cortex (80 and 200 mu M final concentrations, respectively) led to 75-80% protection from these permeabilization-associated alterations of functional integrity, In conclusion, dexamethasone appears to show great promise in blocking the opening of a Ca2+-dependent 'non-specific pore' in the inner membranes of mitochondria from various sources.