Is superoxide an initiator of microsomal lipid peroxidation?
The effects of "pro-oxidant" quinones, doxorubicin, Fe(3+)-ADP-doxorubicin complex, and menadione, as well as of free radical scavengers possessing superoxide-dismuting activities, Fe(3+)-rutin and Cu(2+)-rutin, on superoxide production and lipid peroxidation in rat liver microsomes have been studied. All quinone compounds efficiently suppressed lucigenin-dependent chemiluminescence produced in NADPH-dependent microsomal lipid peroxidation, but exhibited different effects on cytochrome c reduction: doxorubicin and Fe(3+)-ADP-doxorubicin weakly inhibited and menadione enhanced it. In accord with previous findings, menadione inhibited malondialdehyde (MDA) formation in microsomes, while Fe3-ADP-doxorubicin enhanced it. Efficiency of inhibition of MDA formation by the Fe(3+)-rutin and Cu(2+)-rutin complexes correlated well with their superoxide-dismuting activities in contrast to the findings obtained in nonenzymatic liposomal peroxidation, where the formation of superoxide ion is not expected. On these grounds, we propose that superoxide ion is an obligatory initiation species in microsomal lipid peroxidation; the effects of pro-oxidant quinones on lipid peroxidation depends on their ability to chelate iron ions and not on their redox-cycling activities.
Afanas'ev
I B
IB
Vitamin Research Institute, Moscow, Russia.
Dorozhko
A I
AI
Polozova
N I
NI
Kuprianova
N S
NS
Brodskii
A V
AV
Ostrachovitch
E A
EA
Korkina
L G
LG
D000166:Acridines / Q000494:pharmacology; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D002417:Cattle; D003300:Copper / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology; D005290:Ferric Compounds / Q000494:pharmacology; D016166:Free Radical Scavengers; D015227:Lipid Peroxidation / Q000187:drug effects*; D008163:Luminescent Measurements; D008315:Malondialdehyde / Q000378:metabolism; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D009249:NADP / Q000494:pharmacology; D011809:Quinones / Q000494:pharmacology; D051381:Rats; D012431:Rutin / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism / Q000494:pharmacology*; D014812:Vitamin K / Q000494:pharmacology
D000166:Acridines; D005290:Ferric Compounds; D016166:Free Radical Scavengers; D011809:Quinones; D013481:Superoxides; D014812:Vitamin K; C033472:10,10'-dimethyl-9,9'-biacridinium; D008315:Malondialdehyde; D009249:NADP; D012431:Rutin; D000244:Adenosine Diphosphate; D003300:Copper; D004317:Doxorubicin