Substituent Effects in the Free Radical Reactions of Silybin: Radiation-induced Oxidation of the Flavonoid at Neutral pH

Abstract

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.

Metabolic Alterations of Toxic and Nonessential Elements by the Treatment of Sempervivum tectorum Extract in a Hyperlipidemic Rat Model

“…The antioxidant and membrane-protecting effects of Sylibum marianum, Raphanus sativus and S. tectorum extracts were proved within that time (Abram and Donko, 1999;Blázovics et al, 1992Blázovics et al, , 1993aBlázovics et al, , 1993bGyörgy et al, 1992;Hagymási et al, 2001;Kocsis et al, 2002;Szentmihályi et al, 2000aSzentmihályi et al, , 2000b. The dose of extract was calculated to be below the letal dose (2,276 mg/kg body weight for male rats after ip administration) (György et al, 1992). This study was approved by the Regional Committee of Science and Research Ethics Semmelweis University, Permission Number TUKEB 24/1996.…”

Differences in the Disposition of Silymarin between Patients with Nonalcoholic Fatty Liver Disease and Chronic Hepatitis C

“…Silymarin may be the most potent antioxidant in nature by virtue of its free radical scavenger reactivity and favorable membrane-lipid/ water partitioning (György et al, 1992). Oxidative stress is thought to play a central role in the etiology of nonalcoholic steatohepatitis (NASH), a specific subset of nonalcoholic fatty liver disease (NAFLD), and is hypothesized to represent a "second hit" triggering the necroinflammatory response characteristic of NASH (Day and James, 1998).…”

Free‐radical scavenging activities of silybin and its analogues: A pulse radiolysis study

“…As reported in the case of SLB dihemisuccinateNa salt [25], the azide radical can oxidize more than one phenolic site, resulting in the formation of a mixture of phenolic radicals, which on further transformation leads to the formation of a phenoxyl radical with lowest reduction potential. The rate constants are obtained by plotting the pseudo-first-order rates obtained from the build-up traces at 370 and 520 nm to be 8.2 × 10 8 M −1 s −1 at 370 nm and 2.0 × 10 9 M −1 s −1 at 520 nm, respectively.…”

“…Further when increasing the pH value to 11, the rate constants at 520 nm increases to 5.7 × 10 9 M −1 s −1 . This increase indicates the existence of an acid-base equilibrium [25].…”