The anti-oxidant ebselen antagonizes the release of the apoptogenic factor cytochrome c induced by Fe2+/citrate in rat liver mitochondria.
We studied the effects of ebselen (a seleno-organic anti-oxidant), on the release of the apoptogenic factor, cytochrome c, in two different experimental situations damaging mitochondria: (1) Fe(2+)/citrate, known to induce lipid peroxidation consecutively to an oxidative stress; and (2) atractyloside, a ligand of the adenine nucleotide translocator. The effects of ebselen were compared to those of butylated hydroxytoluene (BHT, an inhibitor of lipid peroxidation), and cyclosporine A (CsA, a classical pore antagonist). Ebselen, like BHT, inhibited Fe(2+)/citrate-induced release of cytochrome c, whereas CsA was inactive. On the contrary, neither ebselen nor BHT inhibited atractyloside-induced release of cytochrome c, whereas CsA was potently active. The antioxidant properties of ebselen may protect mitochondria from the consequences of the release of cytochrome c. Thus, it is suggested that the neuroprotective effect of ebselen previously demonstrated in humans and in animals may be due, at least in part, to a mitochondrial protection.
Boireau
A
A
Département Biologie, Aventis Pharma S.A., Centre de Recherche de Vitry-Alfortville, 13 quai Jules Guesde, 94403, Vitry-sur-Seine Cedex, France. alain.boireau@aventis.com
Maréchal
P M
PM
Meunier
M
M
Dubédat
P
P
Moussaoui
S
S
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001278:Atractyloside / Q000494:pharmacology; D001393:Azoles / Q000494:pharmacology*; D002951:Citrates / Q000494:pharmacology*; D003574:Cytochrome c Group / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005296:Ferrous Compounds / Q000494:pharmacology*; D007425:Intracellular Membranes / Q000187:drug effects / Q000201:enzymology / Q000502:physiology; D054833:Isoindoles; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D016566:Organoselenium Compounds / Q000494:pharmacology*; D010539:Permeability / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013053:Spectrophotometry
D000975:Antioxidants; D001393:Azoles; D002951:Citrates; D003574:Cytochrome c Group; D005296:Ferrous Compounds; D054833:Isoindoles; D016566:Organoselenium Compounds; D001278:Atractyloside; C042986:ebselen