Pre-treatment with silymarin reduces brain myeloperoxidase activity and inflammatory cytokines in 6-OHDA hemi-parkinsonian rats

Abstract

Most chronic neurodegenerative diseases such as Parkinson's disease (PD) are accompanied by neuroinflammation which is associated with glial cells activation and production of different inflammatory cytokines. In the present study we evaluated the anti-cataleptic effect of silymarin pre-treatment in 6-hydroxydopamine (6-OHDA)-lesioned rats, striatum myeloperoxidase (MPO) activity and cerebrospinal fluid (CSF) levels of inflammatory cytokines. Male Wistar rats were pre-treated with intraperitoneal (i.p.) injections of silymarin (100, 200 and 300mg/kg) for 5 consecutive days. Then, catalepsy was induced by unilateral infusion of 6-OHDA (8μg/2μl/rat) into the central region of the SNc. The anti-cataleptic effect of silymarin was assessed by the bar test 3-weeks after neurotoxin injection. Striatal myeloperoxidase activity and CSF levels of TNF-α and IL-6 were assessed at the end of behavioral experiments. Our data demonstrated that silymarin pre-treatment decreased catalepsy. The most anti-cataleptic effect was observed at the dose of 300mg/kg of silymarin (p<0.001). There was a significant (p<0.001) increase in MPO activity of 6-OHDA-lesioned rats whereas; in silymarin (in all 3 doses, i.p. for 5 days) pre-treated hemi-parkinsonian rats’ MPO activity was decreased markedly (p<0.001). Furthermore the CSF levels of TNF-α and IL-6 were decreased (p<0.001) in silymarin (100, 200 and 300mg/kg) pre-treated rats up to the range of normal non-parkinsonian animals. From these results, it may be concluded that pre-treatment with silymarin attenuates 6-OHDA-induced catalepsy by decreasing striatal MPO activity and restores CSF concentration of inflammatory cytokines, TNF-α and IL-6 to the levels of normal non-parkinsonian rats.