Long-term administration of Silymarin augments proinflammatory mediators in the hippocampus of rats: evidence for antioxidant and pro-oxidant effects.

Silymarin (SMN) is used as an antioxidant complex to attenuate the pro-oxidant effects of toxic agents. This study was designed to investigate the impact of a long-term administration of SMN on proinflammatory mediators, oxidative stress biomarkers and on the levels of interleukin-1β (IL-1β) transcript in the hippocampus. A total of 40 adult male Wistar rats were assigned into control and test groups. Animals in the test group were subdivided into four subgroups according to the following treatment profile: carbon tetrachloride (CCl(4), 0.5 ml/kg), SMN 25, SMN 50 and SMN 100 (mg/kg). The animals received the compounds by gastric gavage. Following the 8-week treatment period, animals in the CCl(4) group showed body weight loss, while the test groups except SMN 100 revealed a significant (p < 0.05) positive body weight gain. The levels of nitric oxide (NO) and malondialdehyde (MDA) as pro-oxidant and lipid peroxidation index, respectively, increased in CCl(4)- and SMN 100-treated groups, while SMN at lower dose levels did not alter the NO and MDA content. The concentration of total thiol molecules increased in the SMN 50 group and showed a remarkable decrease in CCl(4) and SMN 100 groups. Animals treated with CCl(4) or SMN 100 showed an upregulation of IL-1β, while animals in SMN 25 and SMN 50 groups showed a slight downregulation of expression of IL-1β at the messenger RNA level. These findings suggest that SMN at higher dosage level might exert pro-oxidant effect as an increase in the level of MDA and proinflammatory mediators such as NO, and upregulation of IL-1β in the hippocampus were shown.