ANTI-PARKINSON’S ACTIVITY OF SORAFENIB IN 6-OHDA INDUCED RAT MODEL

Objective: Studies have shown that sorafenib an anti-cancer agent has a neuroprotective effect. This study evaluated the neuroprotective activity of sorafenib in 6-OHDA induced rat model of Parkinson’s disease. Methods: 6-OHDA was injected into the forebrain bundle through the stereotaxic apparatus to induce fast and severe degeneration in dopaminergic neurons of substantianigra. The animals were divided into four groups. Group I- vehicle control, Group II- 6-OHDA induced, Group III- 6- OHDA + Levodopa (6 mg/kg), Group IV- 6-OHDA + sorafenib (10 mg/kg s.c). Treatment was given for 21 days after induction of 6-OHDA. The animals were subjected to behavioral parameters such as apomorphine-induced rotations, grip strength, catatonia and biochemical parameters such as total protein estimation, reduced glutathione, lipid peroxidase, calcium concentration in the brain. Results: Sorafenib significantly decreased the apomorphine-induced rotations as well as catatonia and significantly increased (p<0.001) the grip strength when compared to 6-OHDA. In biochemical estimation total protein and glutathione is increased (p<0.001). Both lipid peroxidase and calcium level have been decreased significantly (p<0.001) when compared to 6_­- OHDA. Conclusion: In the present study, antiparkinson’s effect of an LRRK2 inhibitor, sorafenib was evaluated in the 6-OHDA lesioned rat model. Behavioral and biochemical parameters were carried out. The parameters revealed that the LRRK2 inhibitor, sorafenib has shown significant antiparkinson’s activity. The estimated parameters altered the normal behavior of the animal and the drug treatment protected the diseased brain of rat.