title: Neurotoxic effects of berberine on long-term L-DOPA administration in 6-hydroxydopamine-lesioned rat model of Parkinson's disease.
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.
authors.affiliation: College of Pharmacy and Research Center for Bioresource and Health, Chungbuk National University, 52, Naesudong-ro, Heungduk-gu, Cheongju 361-763, Republic of Korea.
authors.forename: Keon Sung
authors.initials: KS
authors.lastname: Shin
authors.forename: Hyun Sook
authors.initials: HS
authors.lastname: Choi
authors.forename: Ting Ting
authors.initials: TT
authors.lastname: Zhao
authors.forename: Kwang Hoon
authors.initials: KH
authors.lastname: Suh
authors.forename: Ik Hyun
authors.initials: IH
authors.lastname: Kwon
authors.forename: Soon Ok
authors.initials: SO
authors.lastname: Choi
authors.forename: Myung Koo
authors.initials: MK
authors.lastname: Lee
mesh_terms: D000818:Animals; D000978:Antiparkinson Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D001599:Berberine / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D007980:Levodopa / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D020258:Neurotoxicity Syndromes / Q000209:etiology / Q000473:pathology; D016627:Oxidopamine / Q000633:toxicity; D020734:Parkinsonian Disorders / Q000188:drug therapy* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000187:drug effects / Q000473:pathology; D013997:Time Factors
chemical_list: D000978:Antiparkinson Agents; D001599:Berberine; D007980:Levodopa; D016627:Oxidopamine; D004298:Dopamine