Dexamethasone inhibits inorganic phosphate stimulated Ca(2+)-dependent damage of isolated rat liver and renal cortex mitochondria.
The prevention of Ca(2+)-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 (Pi), or 20 nmol Ca2+/mg protein with 1 mM Pi, 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 microM 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 Ca(2+)-dependent 'non-specific pore' in the inner membranes of mitochondria from various sources.
Campbell
P I
PI
Department of Biochemistry, College of Science, King Saud University, Riyadh, Saudia Arabia.
al-Nasser
I A
IA
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002118:Calcium / Q000037:antagonists & inhibitors* / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D066298:In Vitro Techniques; D007672:Kidney Cortex / Q000187:drug effects* / Q000473:pathology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects*; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000473:pathology; D010710:Phosphates / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000893:Anti-Inflammatory Agents; D010710:Phosphates; D003907:Dexamethasone; D002118:Calcium