A STUDY OF THE EFFECTS OF DIFFERENT DOSES OF SILYMARIN ON ROTENONE-INDUCED RAT MODEL OF PARKINSONISM

Aim of the work: This work was performed to study the effect of different doses of silymarin on rotenone-induced Parkinsonism in rats. Methods:60 rats divided into 3 groups, I- control group (10 rats) received no treatment, II- Positive control group (10 rats) received intraperitoneal injection of silymarin (SM) at a dose of 200 mg/kg daily for 2 weeks, III- Rotenone-treated (RT) group (40 rats) received subcutaneous injection of rotenone at a dose of 1.5 mg/kg/48h for 12 days, then subjected to preliminary behavioral tests. Rats with parkinsonian features were divided into 4 groups (10 rats each), (IIIa- RT group), (IIIb- 100 mg/Kg SM-RT), (IIIc- 200 mg/Kg SM-RT) and (IIId- 300 mg/Kg SM-RT) which received 100, 200, 300 mg/kg intraperitonealsilymarin daily for 2 weeks. Results: Rotenone injection caused significant increase of descent latency time in bar test, brain tissue homogenate levels of malondialdehyde, nitrite/nitrate, tumor necrosis factor-alpha, caspase-3 and serum 8-hydroxy-2'-deoxyguanosine and significant decrease of forepaw stride length, brain tissue homogenate levels of catalase, brain-derived neurotrophic factor and dopamine when compared to control groups. Silymarin treatment reversed rotenone effect significantly in a dose-dependent manner. Conclusion: Silymarin can be used as a promising adjuvant therapy in treatment of Parkinsonism. Its neuroprotective effect is mediated by silymarin?s antioxidant, anti-inflammatory and anti-apoptotic effect which eventually enhanced dopamine level and the characteristic motor deficits of PD in a dose-dependent manner. Further clinical trials are required with special reference to the dose.