title: Scavenging of reactive oxygen species by silibinin dihemisuccinate.
abstract: Silibinin dihemisuccinate (SDH) is a flavonoid of plant origin with hepatoprotective effects which have been partially attributed to its ability to scavenge oxygen free radicals. In the present paper the antioxidant properties of SDH were evaluated by studying the ability of this drug to react with relevant biological oxidants such as superoxide anion radical (O2-), hydrogen peroxide (H2O2), hydroxyl radical (HO.) and hypochlorous acid (HOCl). In addition, its effect on lipid peroxidation was investigated. SDH is not a good scavenger of O2- and no reaction with H2O2 was detected within the sensitivity limit of our assay. However, it reacts rapidly with HO. radicals in free solution at approximately diffusion-controlled rate (K = (1.0-1.2) x 10(10)/M/sec) and appears to be a weak iron ion chelator. SDH at concentrations in the micromolar range protected alpha 1-antiproteinase against inactivation by HOCl, showing that it is a potent scavenger of this oxidizing species. Luminol-dependent chemiluminescence induced by HOCl was also inhibited by SDH. The reaction of SDH with HOCl was monitored by the modification of the UV-visible spectrum of SDH. The studies on rat liver microsome lipid peroxidation induced by Fe(III)/ascorbate showed that SDH has an inhibitory effect, which is dependent on its concentration and the magnitude of lipid peroxidation. This work supports the reactive oxygen species scavenger action ascribed to SDH.
authors.affiliation: Instituto de Química Fisiológica, Faculdade de Medicina de Lisboa, Portugal.
authors.forename: L
authors.initials: L
authors.lastname: Mira
authors.forename: M
authors.initials: M
authors.lastname: Silva
authors.forename: C F
authors.initials: CF
authors.lastname: Manso
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology; D005290:Ferric Compounds / Q000494:pharmacology; D016166:Free Radical Scavengers; D006997:Hypochlorous Acid / Q000737:chemistry; D019272:Leukocyte Elastase; D015227:Lipid Peroxidation / Q000187:drug effects; D008163:Luminescent Measurements; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects; D010196:Pancreatic Elastase / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000737:chemistry*; D012838:Silymarin / Q000494:pharmacology*; D000515:alpha 1-Antitrypsin / Q000737:chemistry
chemical_list: D000975:Antioxidants; D005290:Ferric Compounds; D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D012838:Silymarin; D000515:alpha 1-Antitrypsin; C037741:alpha 1-antitrypsin-leukocyte elastase complex; D006997:Hypochlorous Acid; C061126:iron(III)-ascorbic acid complex; D010196:Pancreatic Elastase; D019272:Leukocyte Elastase; D001205:Ascorbic Acid