Emprego da citotoxicidade basal in vitro na redução do número de animais em ensaios de avaliação da toxicidade oral aguda: a grandisina e seu metabólito majoritário como protótipos
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Data
2009-04-14
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Universidade Federal de Goiás
Resumo
The animal replacement in expirements has been very encouraged by government and
other institutions. However, in drugs development the animal replacement is not yet a reality, like
at oral acute systemic tests. The validation of in vitro protocols is necessary for data generation
with reproducibility, repetability and accuracy. In this study was validated at the Laboratório de
Farmacologia e Toxicologia Celular- Faculdade de Farmácia/Universidade Federal de Goiás the
protocol already validated by three laboratories (two in the USA and one at United Kingdom) and
coordinated by ICCVAM: In Vitro Cytotoxicity Methods for Estimating Starting Doses for Acute
Systemic Toxicity Tests, using the neutral red uptake in BAL/c 3T3-A31 cell line. It was used the
grandisine, a lignan, and its major metabolite taken by fungi biodegradation. Our research group
has identified a potential anti-tumoral action of grandisine, data not yet published. After in house
validation we estimated the LD50 of grandisin and 4-O-demethylgrandisin: 617.72 mg/kg and
429.95 mg/kg, respectively. Both were classified under the GSH category 4.
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Citação
VIEIRA, Marcelo de Sousa. Use of basal cytotoxicity in vitro in reducing the number of animals
tests in the evaluation of acute oral toxicity: a grandisin and its
major metabolite as prototypes. 2009. 66 f. Dissertação (Mestrado em Ciências da Saúde - Medicina) - Universidade Federal de Goiás, Goiânia, 2009.