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β-asarone and levodopa co-administration increase striatal dopamine level in 6-hydroxydopamine induced rats by modulating P-glycoprotein and tight junction proteins at the blood-brain barrier and promoting levodopa into the brain.
- Source :
-
Clinical & Experimental Pharmacology & Physiology . Jun2016, Vol. 43 Issue 6, p634-643. 10p. - Publication Year :
- 2016
-
Abstract
- Levodopa (L-dopa) is widely considered as one of the most effective drug constituents in the treatment of Parkinson's disease ( PD), but the blood-brain barrier ( BBB) permeability of L-dopa is <5%, which causes low efficacy. Neuroprotective effects of β-asarone on 6-hydroxydopamine (6- OHDA)-induced PD rats were demonstrated by our previous studies. Co-administration of β-asarone and L-dopa has not been explored until being investigated on PD rats in this study. PD rats were divided into four groups: untreated, L-dopa-treated, β-asarone-treated and co-administered-treated groups. All of the treatments were administered to the rats twice per day for 30 days. The L-dopa, dopamine ( DA), 3,4-dihydroxyphenylacetic acid ( DOPAC) and homovanillic acid ( HVA), S100 β and neuron-specific enolase ( NSE) levels were subsequently determined. The P-glycoprotein (P-gp), zonula occludens-1 ( ZO-1), claudin-5, occludin and actin expression was also assessed in cortex. Changes in BBB ultrastructure were observed using transmission electron microscopy. Our results showed that the co-administered treatment increased levels of L-dopa, DA, DOPAC and HVA in striatum, and S100 β in plasma, but down-regulated NSE, P-gp, ZO-1, occludin, actin and claudin-5 in cortex. Crevices were observed between capillary endothelial cells at intercellular tight junction of the striatum in co-administered-treated group, while the endothelial cells in untreated group were tightly jointing each other. In addition, the correlations of L-dopa or DA and P-gp or tight junction proteins respectively were significantly negative in co-administered- and β-asarone-treated groups. These findings suggest that co-administered treatment may enhance the L-dopa BBB permeability and attenuate brain injury, which may be beneficial to PD treatment. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 03051870
- Volume :
- 43
- Issue :
- 6
- Database :
- Academic Search Index
- Journal :
- Clinical & Experimental Pharmacology & Physiology
- Publication Type :
- Academic Journal
- Accession number :
- 115131681
- Full Text :
- https://doi.org/10.1111/1440-1681.12570