Low glucocorticoid concentrations decrease oxidative phosphorylation of isolated rat brain mitochondria: an additional effect of dexamethasone

The effects of hydrocortisone. triamcinolone, prednisolone and dexamethason e have been investigated in vitro using mitochondria isolated from rat brai n. Respiratory control ratio (RCR), oxygen consumption, ATP synthesis, enzy matic activities of involved complexes and superoxide anion generation have been measured to assess the effects of these drugs. Our data showed that t he decrease of RCR induced by glucocorticoids was due to a common inhibitio n of oxidative phosphorylation (State 3) and of complex V activity and a mo dification of the proton-fluxes through the mitochondrial inner membrane. T hese effects were quantitatively limited, since they occurred at concentrat ions lower than 2 nM. Dexamethasone was the only one able to induce a speci fic inhibition of complex I activity and to decrease the superoxide anion r adical generation. Inhibition of complex V and partial reversion of uncoupl ing seem to be common properties of glucocorticoids. The theoretical conseq uence of these inhibitions could be the modulation of the mitochondrial fun ction. oxygen consumption rate, ATP synthase activity and superoxide anion radical production involved in many patho-physiological phenomena. (C) 2000 Editions scientifiques et medicales Elsevier SAS.