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Short-term toxicity study of ST-20 (NSC-741804) by oral gavage in Sprague-Dawley rats.
Terse, Pramod S; Johnson, Jerry D; Hawk, Michael A; Ritchie, Glenn D; Ryan, Michael J; Vasconcelos, Daphne Y; Contos, Denise A; Perrine, Susan P; Peggins, James O; Tomaszewski, Joseph E.
Afiliação
  • Terse PS; Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Rockville, MD 20852, USA. tersep@mail.nih.gov
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.
Assuntos

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

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