Microsomal membrane peroxidation by an Fe3+/paraquat system. Consequences of phenobarbital induction.
Descriptions of the effects of paraquat (P2+) on the peroxidation of liver microsomes are very divergent. Therefore, the presence of ferric iron in the medium and the activity of microsomal mixed-function oxidase system are two factors that we have taken into consideration to explain the discrepancies. The results showed that 100 microM P2+ potentializes the slight production of MDA induced by low concentrations of Fe3+ (< or = 15 microM). In these conditions, P+., arising from the one-step reduction of P2+ by NADPH-cytochrome C reductase, could reduce Fe3+ and cause the formation of species that initiate peroxidation. However, unlike the results obtained with CBrCl3, for animals induced by phenobarbital (Ph), the production of MDA in the presence of FeCl3 and of P2+ was weaker than for the controls. The establishment of a new Fe3+/Fe2+ equilibrium owing to increased production of P+. could be responsible.
Fernandez
Y
Y
Laboratoire des Xénobiotiques, INRA, Toulouse, France.
Subirade
I
I
Anglade
F
F
Periquet
A
A
Mitjavila
S
S
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D007425:Intracellular Membranes / Q000187:drug effects / Q000378:metabolism; D007501:Iron / Q000494:pharmacology*; D007700:Kinetics; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008563:Membrane Lipids / Q000378:metabolism; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D006899:Mixed Function Oxygenases / Q000096:biosynthesis*; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D010269:Paraquat / Q000494:pharmacology*; D010634:Phenobarbital / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D008563:Membrane Lipids; D008315:Malondialdehyde; D003577:Cytochrome P-450 Enzyme System; D007501:Iron; D006899:Mixed Function Oxygenases; D009251:NADPH-Ferrihemoprotein Reductase; D010269:Paraquat; D010634:Phenobarbital