Substituent effects in the free radical reactions of silybin: radiation-induced oxidation of the flavonoid at neutral pH.
Silybin dihemisuccinate sodium salt, a flavonoid used in human therapy of liver dysfunction, has an inhibitory effect in vivo on radiation-induced deactivation of enzymes and peroxidation of membrane lipids in rat liver microsomes. The reactivity of silybin and its phenolic OH groups towards free radicals (OH, N3., (SCN)2.-, Cl3CO2.) in aqueous solution was studied by pulse radiolysis. Absorption spectra for the phenoxyl-type radicals were assigned using structurally similar models. The one-electron reduction potential for silybin at pH 7 (E07 = 0.76 V), determined using the p-methoxy-phenoxyl/phenolate redox couple as reference standard (E07 = 0.72 V, Lind et al. 1990), is related to the 3'-methoxy-4'-OH structure, the exclusive target for one-electron oxidation at pH 7, while the 7-OH and 5-OH groups are prevented from oxidation by 4-keto substitution and intramolecular H-bonding, respectively. The free radical reactivity of silybin compares favourably with poly-OH-substituted flavonoids; however, the latter compounds have been reported to generate potentially toxic oxygen species at a biologically relevant pH.
György
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I
Institute of Isotopes of the Hungarian Academy of Sciences, Budapest.
Antus
S
S
Blázovics
A
A
Földiák
G
G
D000818:Animals; D005609:Free Radicals; D006878:Hydroxides; D017665:Hydroxyl Radical; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology / Q000528:radiation effects; D010084:Oxidation-Reduction; D011675:Pulse Radiolysis; D051381:Rats; D011919:Rats, Inbred Strains; D012838:Silymarin / Q000494:pharmacology
D005609:Free Radicals; D006878:Hydroxides; D012838:Silymarin; D017665:Hydroxyl Radical