Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: KEGG:D04166 (FeCl3)
 1,389 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bleomycin was aerobically incubated with FeCl3, NADPH, isolated rat-liver microsomal cytochrome P-450 reductase and methional. The conversion of methional to ethene, which indicates oxy radicals, was determined. Ethene formation depended on oxygen, NADPH, FeCl3 and the enzyme. About equimolar concentrations of bleomycin and FeCl3 resulted in optimal ethene formation. Dimethyl sulfoxide, mannitol, glycerol, glutathione and glutathione disulfide inhibited ethene formation. These results indicate that oxy radicals are formed after reduction of the bleomycin-Fe-complex by NADPH-cytochrome P-450 reductase.
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PMID:Oxy radical formation during redox cycling of the bleomycin-iron (III) complex by NADPH-cytochrome P-450 reductase. 241 62

Aerobic incubations of bleomycin, FeCl3, DNA, NADPH, and isolated liver microsomal NADPH-cytochrome P-450 reductase resulted in NADPH and oxygen consumption and malondialdehyde formation, indicating that the deoxyribose moiety of DNA was split. All parameters measured depended on the active enzyme, bleomycin and FeCl3. In the absence of oxygen malondialdehyde formation was very low. When bleomycin, FeCl3 and the reductase were incubated with methional ethene (ethylene) was formed, suggesting that during the enzyme-catalyzed redox cycle of bleomycin-Fe(III/II) hydroxyl radicals were formed. Ethene formation also depended on oxygen, NADPH, the enzyme, bleomycin, and FeCl3. During aerobic incubations of bleomycin, FeCl3, NADPH, and isolated liver nuclei oxygen and NADPH were consumed and malondialdehyde was formed. Oxygen and NADPH consumption and malondialdehyde formation depended on bleomycin and FeCl3. In the absence of oxygen malondialdehyde was not formed. These results indicate that nuclear NADPH-cytochrome P-450 reductase redox cycles the bleomycin-Fe(III/II) complex and that the reduced complex activates oxygen, whereby hydroxyl radicals are formed which damage the deoxyribose of nuclear DNA.
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PMID:Oxygen radical formation and DNA damage due to enzymatic reduction of bleomycin-Fe(III). 244 82

When NADPH-cytochrome P-450 reductase isolated from rat liver microsomes was aerobically incubated with bleomycin, FeCl3, NADPH and DNA parallel NADPH and oxygen were consumed and malondialdehyde was formed. A similar parallelism of NADPH- and oxygen-consumption and malondialdehyde formation was observed when cell nuclei isolated from rat liver were incubated under the same conditions. The formation of malondialdehyde which was identified by HPLC and which was most likely released from oxidative cleavage of deoxyribose of nuclear DNA required oxygen, bleomycin, FeCl3 and NADPH. This indicates that a nuclear NADPH-enzyme, presumably NADPH-cytochrome P-450 reductase, is able to redox cycle a bleomycin-iron-complex which in the reduced form can activate oxygen to a DNA-damaging reactive species. The data suggest that the activity of this enzyme in the cell nucleus could play an important role in the cytotoxicity of bleomycin in tumor cells.
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PMID:Liver nuclear NADPH-cytochrome P-450 reductase may be involved in redox cycling of bleomycin-Fe(III), oxy radical formation and DNA damage. 246 31

Fe(III) complexes of EDTA and diethylenetriamine pentaacetic acid (DETAPAC) at low concentrations (between 1 and 100 microM) produced up to a 20-fold increase in anaerobic microsomal NADPH- and NADH-dependent reduction of indicine N-oxide. Under aerobic conditions microsomal indicine N-oxide reduction was stimulated to half the levels seen under anaerobic conditions. EDTA alone was much less effective at stimulating indicine N-oxide reduction, while FeCl3 alone had no effect on reduction. Other complexes of Fe(III) had little or no effect in stimulating microsomal indicine N-oxide reduction. Fe(III)-EDTA stimulated indicine N-oxide reduction by purified NADPH-cytochrome P-450 reductase and NADPH. It is probable that iron serves to transfer electrons between microsomal flavoprotein reductases and indicine N-oxide. The redox potential and the presence of an exchangeable ligand, such as water, in the inner ligand sphere of the iron complex are suggested to be important factors in determining which iron complexes will stimulate indicine N-oxide reduction. EDTA complexes of other transition metal ions do not stimulate indicine N-oxide reduction. Hydroxyl radicals, detected as the spin adduct of 5,5-dimethyl-1-pyroline-N-oxide, appear to be formed during Fe(II)-EDTA-dependent reduction of indicine N-oxide under anaerobic conditions. Fe(III)-EDTA at concentrations between 50 and 250 microM stimulated indicine N-oxide reduction by rat isolated hepatocytes up to 5-fold under anaerobic conditions and to half these values under aerobic conditions. By themselves, EDTA and FeCl3 at similar concentrations produced a small stimulation of indicine N-oxide reduction by hepatocytes under anaerobic conditions. Fe(III)-EDTA stimulated indicine N-oxide reduction by murine leukemia P-388 cells under aerobic conditions and by rat caecal flora under anaerobic but not aerobic conditions. Fe(III)-EDTA, EDTA or FeCl3 administered to rats produced a 3-fold increase in the 24-hr urinary excretion of indicine following an i.p. dose of indicine N-oxide.
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PMID:Iron-EDTA stimulated reduction of indicine N-oxide by the hepatic microsomal fraction, isolated hepatocytes, and the intact rat. 628 Jul 24

The ESR spin-trapping technique was employed to investigate the reaction of rabbit cytochrome P-450 1A2 (P450) with linoleic acid hydroperoxide. This system was compared with chemical systems where FeSO4 or FeCl3 was used in place of P450. The spin trap 5, 5'-dimethyl-1-pyrroline N-oxide (DMPO) was employed to detect and identify radical species. The DMPO adducts of hydroxyl, O2-., peroxyl, methyl and acyl radicals were detected in the P450 system. The reaction did not require NADPH-cytochrome P-450 reductase or NADPH. The same DMPO-radical adducts were detected in the FeSO4 system. Only DMPO-.OH radical adduct and carbon-centred radical adducts were detected in the FeCl3 system. Peroxyl radical production was completely O2-dependent. We propose that polyunsaturated fatty acids are initially reduced to form alkoxyl radicals, which then undergo intramolecular rearrangement to form epoxyalkyl radicals. Each epoxyalkyl radical reacts with O2, forming a peroxyl radical. Subsequent unimolecular decomposition of this peroxyl radical eliminates O2-. radical.
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PMID:Detection of free radicals produced from the reaction of cytochrome P-450 with linoleic acid hydroperoxide. 937 16