Genotoxic and mutagenic effects of vigabatrin, a γ-aminobutyric acid transaminase inhibitor, in Wistar rats submitted to rotarod task.
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.
Laboratory of Neuropharmacology and Preclinical Toxicology, Department of Pharmacology, Institute of Basic Health Sciences, Federal University of Rio Grande doSul, Porto Alegre, Brazil.
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Coelho
Laboratory of Genetic Toxicology, Lutheran University of Brazil, Canoas, Brazil.
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Sousa
Laboratory of Genetic Toxicology, Lutheran University of Brazil, Canoas, Brazil.
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Pires
Laboratory of Genetic Toxicology, Lutheran University of Brazil, Canoas, Brazil.
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Papke
Laboratory of Neuropharmacology and Preclinical Toxicology, Department of Pharmacology, Institute of Basic Health Sciences, Federal University of Rio Grande doSul, Porto Alegre, Brazil.
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Vieira
Laboratory of Neuropharmacology and Preclinical Toxicology, Department of Pharmacology, Institute of Basic Health Sciences, Federal University of Rio Grande doSul, Porto Alegre, Brazil.
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de Souza
Laboratory of Pharmacology and Toxicology of Natural Products, Department of Pharmacology, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.
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Leal
Laboratory of Pharmacology and Toxicology of Natural Products, Department of Pharmacology, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.
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Schunck
Laboratory of Genetic Toxicology, Lutheran University of Brazil, Canoas, Brazil.
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Picada
Laboratory of Neuropharmacology and Preclinical Toxicology, Department of Pharmacology, Institute of Basic Health Sciences, Federal University of Rio Grande doSul, Porto Alegre, Brazil patipere@yahoo.com.br.
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Pereira
D000612:4-Aminobutyrate Transaminase / Q000037:antagonists & inhibitors*; D000818:Animals; D000927:Anticonvulsants / Q000633:toxicity*; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D020552:Comet Assay; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008297:Male; D048629:Micronuclei, Chromosome-Defective / Q000139:chemically induced*; D015162:Micronucleus Tests; D009043:Motor Activity / Q000187:drug effects; D009928:Organ Specificity; D017208:Rats, Wistar; D045442:Rotarod Performance Test; D013997:Time Factors; D020888:Vigabatrin / Q000633:toxicity*
D000927:Anticonvulsants; D000612:4-Aminobutyrate Transaminase; D020888:Vigabatrin
Comet assay; GABA; GABA transaminase; genotoxicity; rotarod; vigabatrin.