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Sci Rep ; 8(1): 2308, 2018 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-29396538

RESUMO

The cyanobacterial toxins ß-methylamino-L-alanine (L-BMAA) and microcystin-LR (MC-LR; a potent liver toxin) are suspected to cause neurological disorders. Adult male C57BL/6JOlaHsd mice aged approximately 11 months were subcutaneously injected for five consecutive days with L-BMAA and microcystin-LR alone, or as a mixture. A dose-range study determined a tolerable daily dose to be ~31 µg MC-LR/kg BW/day based on survival, serum liver status enzymes, and relative liver and kidney weight. Mice tolerating the first one-two doses also tolerated the subsequent three-four doses indicating adaptation. The LD50 was 43-50 µg MC-LR/kg BW. Long-term effects (up to 10 weeks) on spatial learning and memory performance was investigated using a Barnes maze, were mice were given 30 µg MC-LR/kg BW and/or 30 mg L-BMAA/kg BW either alone or in mixture for five consecutive days. Anxiety, general locomotor activity, willingness to explore, hippocampal and peri-postrhinal cortex dependent memory was investigated after eight weeks using Open field combined with Novel location/Novel object recognition tests. Toxin exposed animals did not perform worse than controls, and MC-LR exposed animals performed somewhat better during the first Barnes maze re-test session. MC-LR exposed mice rapidly lost up to ~5% body weight, but regained weight from day eight.


Assuntos
Diamino Aminoácidos/toxicidade , Cognição/efeitos dos fármacos , Inibidores Enzimáticos/toxicidade , Agonistas de Aminoácidos Excitatórios/toxicidade , Microcistinas/toxicidade , Diamino Aminoácidos/administração & dosagem , Animais , Toxinas de Cianobactérias , Inibidores Enzimáticos/administração & dosagem , Agonistas de Aminoácidos Excitatórios/administração & dosagem , Injeções Subcutâneas , Rim/patologia , Dose Letal Mediana , Fígado/patologia , Testes de Função Hepática , Masculino , Toxinas Marinhas , Memória/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Microcistinas/administração & dosagem , Aprendizagem Espacial/efeitos dos fármacos , Análise de Sobrevida
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