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

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 -D...

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Published in	Archives of pharmacal research Vol. 36; no. 6; pp. 759 - 767
Main Authors	Shin, Keon Sung, Choi, Hyun Sook, Zhao, Ting Ting, Suh, Kwang Hoon, Kwon, Ik Hyun, Choi, Soon Ok, Lee, Myung Koo
Format	Journal Article
Language	English
Published	Heidelberg Pharmaceutical Society of Korea 01.06.2013 대한약학회
Subjects	animal models Animals Antiparkinson Agents - administration & dosage Antiparkinson Agents - pharmacology Antiparkinson Agents - toxicity berberine Berberine - administration & dosage Berberine - pharmacology Berberine - toxicity cell death dopamine Dopamine - metabolism Dose-Response Relationship, Drug Drug Therapy, Combination homovanillic acid L-dopa Levodopa - administration & dosage Levodopa - pharmacology Male Medicine monitoring neurons Neurons - drug effects Neurons - pathology neurotoxicity Neurotoxicity Syndromes - etiology Neurotoxicity Syndromes - pathology norepinephrine Oxidopamine - toxicity Parkinson disease Parkinsonian Disorders - drug therapy Parkinsonian Disorders - physiopathology Pharmacology/Toxicology Pharmacy Rats Rats, Sprague-Dawley Research Article Substantia Nigra - drug effects Substantia Nigra - pathology therapeutics Time Factors 약학 Berberine Tyrosine hydroxylase Dopamine DOPA 6-Hydroxydopamine-lesioned rats Parkinson’s disease
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ISSN	0253-6269 1976-3786 1976-3786
DOI	10.1007/s12272-013-0051-4

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Abstract	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.
AbstractList	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. The effects of berberine on long-term administration of L-DOPAin 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 groupswas 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. KCI Citation Count: 35 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. 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.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.
Author	Zhao, Ting Ting Kwon, Ik Hyun Lee, Myung Koo Shin, Keon Sung Suh, Kwang Hoon Choi, Soon Ok Choi, Hyun Sook
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Snippet	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.... 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.... 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.... The effects of berberine on long-term administration of L-DOPAin 6-hydroxydopamine (6-OHDA)-lesioned rat model of Parkinson’s disease (PD) were investigated....
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SubjectTerms	animal models Animals Antiparkinson Agents - administration & dosage Antiparkinson Agents - pharmacology Antiparkinson Agents - toxicity berberine Berberine - administration & dosage Berberine - pharmacology Berberine - toxicity cell death dopamine Dopamine - metabolism Dose-Response Relationship, Drug Drug Therapy, Combination homovanillic acid L-dopa Levodopa - administration & dosage Levodopa - pharmacology Male Medicine monitoring neurons Neurons - drug effects Neurons - pathology neurotoxicity Neurotoxicity Syndromes - etiology Neurotoxicity Syndromes - pathology norepinephrine Oxidopamine - toxicity Parkinson disease Parkinsonian Disorders - drug therapy Parkinsonian Disorders - physiopathology Pharmacology/Toxicology Pharmacy Rats Rats, Sprague-Dawley Research Article Substantia Nigra - drug effects Substantia Nigra - pathology therapeutics Time Factors 약학
Title	Neurotoxic effects of berberine on long-term l-DOPA administration in 6-hydroxydopamine-lesioned rat model of Parkinson’s disease
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ispartofPNX	Archives of Pharmacal Research, 2013, 36(6), , pp.759-767
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