title: In vivo protective effect of Uridine, a pyrimidine nucleoside, on genotoxicity induced by Levodopa/Carbidopa in mice.
abstract: Parkinson's disease (PD) is a common neurodegenerative disorder that affects millions of people all over the world. Motor symptoms of PD are most commonly controlled by L-3,4-dihydroxyphenylalanine (Levodopa, L-DOPA), a precursor of dopamine, plus a peripherally-acting aromatic-L-amino-acid decarboxylase (dopa decarboxylase) inhibitor, such as carbidopa. However, chronic treatment with a combination of Levodopa plus carbidopa has been demonstrated to cause a major complication, namely abnormal involuntary movements. On the other hand, the effect of this treatment on bone marrow cells is unknown. Therefore, in this study, we aimed to investigate possible genotoxic effects of Levodopa and Carbidopa using male Balb/C mice. Our results showed that Levodopa alone or in combination with carbidopa caused genotoxicity in in vivo micronucleus test (mouse bone marrow) and Comet assay (blood cells). Furthermore, we showed that simultaneous administration of uridine, a pyrimidine nucleoside, reversed the genotoxic effect of Levodopa and Carbidopa in both assays. Our data show for the first time that Levodopa plus carbidopa combination causes genotoxicity which is reversed by uridine treatment. These findings might enhance our understanding for the complications of a common Parkinson's treatment and confer benefit in terms of reducing a possible genotoxic effect of this treatment.
authors.affiliation: Department of Biology, Faculty of Arts and Sciences, Adnan Menderes University, Aydin, Turkey.
authors.forename: Esra
authors.initials: E
authors.lastname: Orenlili Yaylagul
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Uludag University, Bursa, Turkey.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Cansev
authors.affiliation: Department of Biology, Faculty of Arts and Sciences, Uludag University, Bursa, Turkey. Electronic address: scelikler@uludag.edu.tr.
authors.forename: Serap
authors.initials: S
authors.lastname: Celikler Kasimogullari
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects; D002230:Carbidopa / Q000633:toxicity*; D020552:Comet Assay; D015259:Dopamine Agents / Q000633:toxicity; D007980:Levodopa / Q000633:toxicity*; D008297:Male; D008807:Mice, Inbred BALB C; D015162:Micronucleus Tests; D020011:Protective Agents / Q000494:pharmacology; D014529:Uridine / Q000494:pharmacology*
chemical_list: D015259:Dopamine Agents; D020011:Protective Agents; D007980:Levodopa; D002230:Carbidopa; D014529:Uridine
keywords: Carbidopa; Comet; Genotoxicity; Levodopa; Micronuclei; Uridine