Genotoxic and mutagenic effects of vigabatrin, a γ-aminobutyric acid transaminase inhibitor, in Wistar rats submitted to rotarod task
| Autor: | VR Coelho, Priscila Guedes Pereira, LP de Souza, Jaqueline Nascimento Picada, Rva Schunck, Dkm Papke, Karen Sousa, Mirna Bainy Leal, Thienne Rocha Pires, CG Vieira |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Male Time Factors Health Toxicology and Mutagenesis Central nervous system Pharmacology Motor Activity Toxicology medicine.disease_cause Hippocampus Vigabatrin Transaminase 03 medical and health sciences GABA transaminase 0302 clinical medicine medicine Hippocampus (mythology) Animals Rats Wistar Micronuclei Chromosome-Defective Cerebral Cortex Micronucleus Tests Dose-Response Relationship Drug business.industry General Medicine Comet assay 030104 developmental biology medicine.anatomical_structure Liver Organ Specificity 4-Aminobutyrate Transaminase Rotarod Performance Test Micronucleus test Anticonvulsants Comet Assay business 030217 neurology & neurosurgery Genotoxicity medicine.drug DNA Damage |
| Zdroj: | Humanexperimental toxicology. 35(9) |
| ISSN: | 1477-0903 |
| Popis: | Vigabatrin (VGB) is an antiepileptic drug thatincreases brain γ-aminobutyric acid (GABA) levels through irreversible inhibition of GABA transaminase. The aim of this study was to evaluate neurotoxicological effects of VGB measuring motor activity and genotoxic and mutagenic effects after a single and repeated administration. Male Wistar rats received saline, VGB 50, 100, or 250 mg/kg by gavage for acute and subchronic (14 days) treatments and evaluated in the rotarod task. Genotoxicity was evaluated using the alkaline version of the comet assay in samples of blood, liver, hippocampus, and brain cortex after both treatments. Mutagenicity was evaluated using the micronucleus test in bone marrow of the same animals that received subchronic treatment. The groups treated with VGB showed similar performance in rotarod compared with the saline group. Regarding the acute treatment, it was observed that only higher VGB doses induced DNA damage in blood and hippocampus. After the subchronic treatment, VGB did not show genotoxic or mutagenic effects. In brief, VGB did not impair motor activities in rats after acute and subchronic treatments. It showed a repairable genotoxic potential in the central nervous system since genotoxicity was observed in the acute treatment group. |
| Databáze: | OpenAIRE |
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