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Microsomal membrane peroxidation by an Fe3+/paraquat system. Consequences of phenobarbital induction
Y Fernandez1, I Subirade, F Anglade
1Laboratoire des Xénobiotiques, INRA, Toulouse, France.
Abstract:
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.
Insights
Paraquat (P2+) effects on liver microsomes are unclear. This study found paraquat potentiates iron-induced lipid peroxidation but reduces it in phenobarbital-induced animals, suggesting complex interactions.
Area of Science:
- Biochemistry
- Toxicology
- Cell Biology
Background:
- The effects of paraquat (P2+) on liver microsomal peroxidation are inconsistent in scientific literature.
- Investigating factors like ferric iron (Fe3+) and mixed-function oxidase activity is crucial for understanding these discrepancies.
Purpose of the Study:
- To elucidate the divergent effects of paraquat (P2+) on liver microsomal peroxidation.
- To examine the roles of ferric iron (Fe3+) and the mixed-function oxidase system in paraquat-induced lipid peroxidation.
Main Methods:
- Incubation of liver microsomes with varying concentrations of paraquat (P2+) and ferric iron (Fe3+).
- Measurement of malondialdehyde (MDA) production as an indicator of lipid peroxidation.
- Comparison of results in control animals versus those induced with phenobarbital (Ph).
Main Results:
- Paraquat (P2+) at 100 microM potentiated MDA production induced by low concentrations of Fe3+ (< or = 15 microM).
- Paraquat's one-step reduction product (P+.) may reduce Fe3+, initiating peroxidation under specific conditions.
- In phenobarbital-induced animals, paraquat (P2+) with FeCl3 resulted in weaker MDA production compared to controls, possibly due to altered Fe3+/Fe2+ equilibrium.
Conclusions:
- Paraquat's impact on lipid peroxidation is complex and context-dependent, influenced by iron levels and the activity of the mixed-function oxidase system.
- The observed discrepancies in paraquat's pro-oxidant or anti-oxidant effects are likely related to the interplay between paraquat metabolism, iron redox cycling, and the microsomal enzyme system.