Protective effect of candesartan cilexetil on rotenone-induced Parkinson's disease in rats

Abstract

Objective To investigate the effect of candesartan cilexetil on rotenone-induced Parkinson's disease (PD) in rats.Methods Forty 10-week-old male Lewis rats were chosen in our study and equally randomized into control group,rotenone group,rotenone+candesartan cilexetil group and candesartan cilexetil group (n=10); rotenone (2.5-3.0 mg/[kg· d]) was given for 4 weeks to the rats of rotenone group and rotenone+candesartan cilexetil group by subcutaneous osmotic minipumps implantation under the back; rats in the rotenone+candesartan cilexetil group and candesartan cilexetil group were orally administered candesartan cilexetil.Neurological behavioral measurements were performed to evaluate the motor features; tyrosine hydroxylase (TH) and α-synuclein immunoreactivities in the substantia nigra pars compacta (SNc) were observed.Protein level of α-synuclein was determined by Westem blotting.Results The weight of rats in the rotenone group reduced to (297.3±12.2) g,with significant difference as compared with that of the other three groups (P＜0.05); decreased TH immunoreactivity (377.0±41.6) cells/mm2) and increased α-synuclein immunoreactivity (0.75±0.02) in the SNc of rats in the rotenone group was noted,enjoying significant differences as compared with the other three groups (P＜0.05); these values in the rotenone+candesartan cilexetil group were (337.2±26.3) g,(639.7±46.0) cells/mm2 and 0.57±0.01,respectively (P＜0.05).Western blotting confirmed that rotenone up-regulated the expression ofα-synuclein in the SNc,and candesartan ceilexetil markedly attenuated the increase (P＜0.05).Conclusion Candesartan cilexetil can protect rotenone-induced PD in rats through decreasing TH-positive cell apoptosis and α-synuclein deposition. Key words: Parkinson's disease; Rotenone; Candesartan cilexetil