Neurotoxic effects of berberine on long-term l-DOPA administration in 6-hydroxydopamine-lesioned rat model of Parkinson's disease

被引:44
作者
Shin, Keon Sung [1 ,2 ]
Choi, Hyun Sook [1 ,2 ]
Zhao, Ting Ting [1 ,2 ]
Suh, Kwang Hoon [1 ,2 ]
Kwon, Ik Hyun [1 ,2 ]
Choi, Soon Ok [1 ,2 ]
Lee, Myung Koo [1 ,2 ]
机构
[1] Chungbuk Natl Univ, Coll Pharm, Cheongju 361763, South Korea
[2] Chungbuk Natl Univ, Res Ctr Bioresource & Hlth, Cheongju 361763, South Korea
关键词
Berberine; L-DOPA; 6-Hydroxydopamine-lesioned rats; Tyrosine hydroxylase; Dopamine; Parkinson's disease; PC12; CELLS; PROTOBERBERINE ALKALOIDS; TYROSINE-HYDROXYLASE; INDUCED CYTOTOXICITY; STRIATAL DOPAMINE; BIOSYNTHESIS; INHIBITION; BRAIN; METABOLISM; APOPTOSIS;
D O I
10.1007/s12272-013-0051-4
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
The effects of berberine on long-term administration of l-DOPA in 6-hydroxydopamine (6-OHDA)-lesioned rat model of Parkinson's disease (PD) were investigated. Rat models of PD were prepared by 6-OHDA lesions in the ipsilateral sides, and then were treated with berberine (5 and 15 mg/kg) and/or l-DOPA (10 mg/kg) once daily for 21 days. Treatments with either concentration of berberine (5 and 15 mg/kg) in 6-OHDA-lesioned groups decreased the numbers of tyrosine hydroxylase (TH)-immunopositive neurons in the substantia nigra and the levels of dopamine, norepinephrine, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the striatum as compared to 6-OHDA-lesioned groups. In addition, dopaminergic neuronal cell death of the ipsilateral sides in 6-OHDA-lesioned groups was attenuated by l-DOPA administration. However, both concentrations of berberine in 6-OHDA-lesioned groups treated with l-DOPA aggravated the numbers of TH-immunopositive neurons in the substantia nigra and the levels of dopamine, norepinephrine, DOPAC and HVA in the striatum as compared to rats not treated with berberine. These results suggest that berberine leads to the degeneration of dopaminergic neuronal cells in the substantia nigra in the rat model of PD with chronic l-DOPA administration. Long-term l-DOPA therapy that may involve possibly neurotoxic isoquinoline agents including berberine should involve monitoring for adverse symptoms.
引用
收藏
页码:759 / 767
页数:9
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