Desferrioxamine dehydrogenates bilirubin in two stages, leading to a 1:1 red-coloured adduct. Characterization of the products by high-performance liquid chromatography/electrospray ionization mass spectrometry.
We have used open-chain tetrapyrroles, such as bilirubin, as molecular probes to investigate the pro-oxidant activity of desferrioxamine (DES) and its modulation by Trolox. On exposure to Fe-EDTA/H2O2, bilirubin and mesobilirubin underwent bleaching. When DES was present, bleaching was prevented and both rubins were converted into green-coloured derivatives and then into red pigments. Trolox added with DES inhibited the colour changes induced by DES. The oxidative products were resolved from their parent compounds by high-performance liquid chromatography (HPLC) and studied by electrospray ionization mass spectrometry and by UV/visible spectroscopy. The green products were identified as biliverdin or mesobiliverdin; the red pigments as the 1:1 molar adduct of DES with biliverdin or mesobiliverdin, less two hydrogens in both cases. It is concluded that DES exercises its oxidative activity through nitroxyl oxidizing radicals capable of efficient hydrogen abstraction, dehydrogenating either rubin to the corresponding verdin. A diradical derivative of DES (bearing two nitroxyl radicals in the same molecule) may be involved in the oxidation of verdins to red pigments, through concerted dehydrogenation and adduct formation. These results shed further light on the redox properties of bilirubin, DES and Trolox, and their interactions. They provide further evidence of the pro-oxidant activity of DES and suggest a more general biological significance, as rapid removal of bilirubin by bleaching or dehydrogenation may have pharmacological/toxicological implications in severe jaundice.
De Matteis
Francesco
F
MRC Bioanalytical Science Group, School of Biological and Chemical Sciences, Birkbeck, University of London, Malet Street, London WC1 7HX, UK. fandjdem@waitrose.com
Lord
Gwyn A
GA
D000975:Antioxidants / Q000737:chemistry; D001663:Bilirubin / Q000737:chemistry*; D001664:Biliverdine / Q000737:chemistry; D002839:Chromans / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D003676:Deferoxamine / Q000737:chemistry*; D016877:Oxidants / Q000737:chemistry*; D010084:Oxidation-Reduction; D011166:Porphyrins / Q000737:chemistry; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
D000975:Antioxidants; D002839:Chromans; D016877:Oxidants; D011166:Porphyrins; C054069:verdin; D003676:Deferoxamine; D001664:Biliverdine; D001663:Bilirubin; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid