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Biomedical subjects

M Fontecave

Publications and source records attributed to M Fontecave.

95 records · Page 6Linked to original sources
PubMed1987

The stimulatory effects of asbestos on NADPH-dependent lipid peroxidation in rat liver microsomes.

Lipid peroxidation in rat liver microsomes induced by asbestos fibres, crocidolite and chrysotile, is greatly increased in the presence of NADPH, leading to malondialdehyde levels comparable with those induced by CCl4, a very strong inducer of lipid peroxidation. This synergic effect only occurs during the first minutes and could be explained by an increase or a regeneration of the ferrous active sites of asbestos by NADPH, which in turn could rapidly be prevented by the adsorption of microsomal proteins on the surface of the fibres. It is not inhibited by superoxide dismutase, catalase and mannitol, indicating that oxygen radicals are not involved in the reaction. It is also not inhibited by desferrioxamine, indicating that it is not due to a release of free iron ions in solution from the fibres. Lipid peroxidation in NADPH-supplemented microsomes is also greatly increased upon addition of magnetite. This could be linked to the presence of ferrous ions in this solid iron oxide, since the ferric oxides haematite and goethite are completely inactive.

Animals↗
PubMed1984

Oxidation of monosubstituted olefins by cytochromes P-450 and heme models: evidence for the formation of aldehydes in addition to epoxides and allylic alcohols.

Aldehydes RCH2CHO are formed in addition to epoxides and allylic alcohols upon oxidation of the monosubstituted olefins RCH=CH2, styrene and 6-phenoxy-hex-1-ene, either by liver microsomal systems in the presence of NADPH and O2 or C6H5IO, or by iron-porphyrin- C6H5IO model systems. These aldehydes do not derive from rearrangement of the corresponding epoxides suggesting that they are formed by an hydrogen migration within an interdiate formed by reaction of the olefin with the active oxygen-iron complex. Heme model studies show that the competition between the three possible routes of oxidation of these olefins is greatly dependent upon the environment of the iron.

1-Propanol↗
PubMed1983

Reduction of benzyl halides by liver microsomes. Formation of 478 NM-absorbing sigma-alkyl-ferric cytochrome P-450 complexes.

The benzyl halides benzyl bromide and 4-nitrobenzyl chloride are reduced anaerobically by NADPH and rat liver microsomes to yield toluene and 4-nitrotoluene, respectively. These reductions and cytochrome P-450-dependent since they are inhibited by CO and metyrapone, and are increased after pretreatment of rats by phenobarbital and 3-methylcholanthrene. During benzyl halide reduction, cytochrome P-450 complexes, which are very unstable to O2 and characterized by a Soret peak at 478 nm, are formed in steady-state concentrations. These concentrations are very dependent on pretreatment of rats and on the nature of the reducing agent (NADPH or dithionite) and the benzyl halide:4-methylbenzyl bromide and benzyl bromide lead to 478 nm absorbing complexes in the presence of NADPH whereas 4-nitrobenzyl chloride and benzyl chloride lead to such completes only in the presence of dithionite. Microsomal reductions of 4-nitrobenzyl chloride and benzyl bromide in D2O lead to partially deuterated 4-nitrotoluene and toluene. From these results, we propose a mechanism for anaerobic microsomal reduction of benzyl halides involving the intermediate formation of sigma-alkyl cytochrome P-450-Fe(III)-CH2Ar complexes which exhibit red-shifted Soret peaks around 478 nm. Toluenes, ArCH3, are formed either by protonation of the sigma-alkyl complexes or by hydrogen abstraction by the intermediate free radical ArCH2.

Animals↗