Phytomedicine 14 (2007) 129–135 Protective effect of silymarin on oxidative stress in rat brain C. Nencini, G. Giorgi, L. Micheli à Department of Pharmacology ‘‘Giorgio Segre’’, University of Siena, Italy Abstract Brain is susceptible to oxidative stress and it is associated with age-related brain dysfunction. Previously, we have pointed out a dramatic decrease of glutathione levels in the rat brain after acetaminophen (APAP) oral administration overdose. Silymarin (SM) is a mixture of bioactive flavonolignans isolated from Silybum marianum (L.) Gaertn., employed usually in the treatment of alcoholic liver disease and as anti-hepatotoxic agent in humans. In this study, we have evaluated the effect of SM on enzymatic and non enzymatic antioxidant defensive systems in rat brain after APAP-induced damage. Male albino Wistar rats were treated with SM (200 mg/kg/die orally) for three days, or with APAP single oral administration (3 g/kg) or with SM (200 mg/kg/die orally) for 3 days and APAP single oral administration (3 g/kg) at third day. Successively the following parameters were measured: reduced and oxidized glutathione (GSH and GSSG), ascorbic acid (AA), enzymatic activity variations of superoxide dismutase (SOD) and malondialdehyde levels (MDA). Our results showed a significant decrease of GSH levels, AA levels and SOD activity and an increase of MDA and GSSG levels after APAP administration. After SM administration GSH and AA significantly increase and SOD activity was significantly enhanced. In the SM+APAP group, GSH values significantly increase and the others parameters remained unchanged respect to control values. These results suggest that SM may to protect the SNC by oxidative damage for its ability to prevent lipid peroxidation and replenishing the GSH levels. r 2006 Elsevier GmbH. All rights reserved. Keywords: Oxidative stress; Glutathione; Micromethod; Silymarin; APAP; Brain Introduction Silybum marianum (L.) Gaertn., known as milk thistle, is one of the most popular herbal remedies for liver disease. It is a member of the Asteraceae family (Compositae) native to a narrow area of the Mediterra- nean, but grown for centuries throughout Europe and naturalized on that continent and also in the North and South America (Morazzoni and Bombardelli, 1995; Flora et al., 1998). Silymarin (SM), the active complex in milk thistle, is a lipophilic fruit extract and is composed of several isomer flavonolignans: silybin (also spelled silybinin or silibinin), isosilybin, silychristin, silydianin, and dehydrosilibinin (Valenzuela and Guer- ra, 1985; Ding et al., 2001). Silybin is the main component and is often considered to be the substance responsible for SM biological activity, however the other flavonolignans could also play roles in its final effect. For over 30 years, SM has been used clinically in ARTICLE IN PRESS www.elsevier.de/phymed 0944-7113/$ - see front matter r 2006 Elsevier GmbH. All rights reserved. doi:10.1016/j.phymed.2006.02.005 Abbreviations: AA, ascorbic acid; APAP, acetaminophen; GSH, reduced glutathione; GSSG, oxidized glutathione; LP, lipid peroxida- tion; MDA, malondialdehyde; ROS, reactive oxygen species; SOD, superoxide dismutase; SM, silymarin à Corresponding author. Tel.: +39 0577233251; fax: +39 0577233102. E-mail address: michelil@unisi.it (L. Micheli).