Short-term toxicity study of ST-20 (NSC-741804) by oral gavage in Sprague-Dawley rats.
Toxicol Pathol
; 39(4): 614-22, 2011 Jun.
Article
em En
| MEDLINE
| ID: mdl-21558467
ABSTRACT
ST-20 (sodium 2,2-dimethylbutyrate) is a potential therapeutic agent for treatment of ß-thalassemia and sickle cell disease. A subchronic oral toxicity study was conducted in Sprague-Dawley rats (10/sex/dose) at gavage dosages of 0 (vehicle control), 200, 600, or 1,000 mg/kg, once daily for up to 15 days followed by a 14-day recovery. Ataxia (females), rough coat/thin appearance (males), and decreased body weights were observed at 1,000 mg/kg. Functional observational battery (FOB) deficits were observed more frequently in females and included decreased body tone, rectal temperature, emotional reactivity, neuromotor-neuromuscular activity (as exhibited by a deficit in visual/tactile placing accuracy, ataxia, hind limb dragging, and decreased grip strength), and rearing. ST-20 caused a decrease in WBC/RBC counts and RBC parameters; increase in reticulocytes and red cell inclusion bodies; decrease in total protein, globulin, and glucose; and increase in AG ratio. Micronucleated polychromatic erythrocytes of the bone marrow increased significantly in males at 1,000 mg/kg. Mean liver and kidney weights increased, and hepatocellular hypertrophy was observed in males at 1,000 mg/kg. Toxicologic findings were fully recovered during the 14-day recovery period. In conclusion, the no-observed adverse effect level for FOB and general toxicity was 200 mg/kg following gavage administration of ST-20 for up to 15 consecutive days.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Tamanho do Órgão
/
Reticulócitos
/
Butiratos
/
Testes de Toxicidade Aguda
/
Rim
/
Fígado
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Toxicol Pathol
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Estados Unidos