RESUMEN
OBJECTIVE: To test the impact of subchronically administered Bismerthlazol on the thyroid morphosis of rats. METHODS: One hundred SD rats were randomly divided into one negative control group and four experimental groups with 7.0, 27.9, 111.7, and 447.0 mg/kg daily doses of Bismerthlazol, respectively. The Bismerthlazol was administered by gavage for 90 d. At the end of the experiment, the thyroids of the rats were harvested and weighted. The pathological changes of the thyroids were observed under light microscopes. The positive expression of PCNA in the thyroid glands were examined by histochemistry methods. RESULTS: Increased coefficients of thyroid gland weight were found in the experimental groups (P < 0.01). The thyroid glands showed different hyperplasia of follicular cells. Increased positive cells of PCNA were observed in the experimental groups (P < 0.05 or P < 0.01) except for the 7.0 mg/kg dose group. CONCLUSION: Long-time administered Bismerthlazol causes thyroids hyperplasia in rats. Further study on the mechanisms is warranted.
Asunto(s)
Tiadiazoles/toxicidad , Glándula Tiroides/efectos de los fármacos , Animales , Peso Corporal/efectos de los fármacos , Femenino , Fungicidas Industriales/administración & dosificación , Fungicidas Industriales/toxicidad , Hiperplasia , Inmunohistoquímica , Masculino , Antígeno Nuclear de Célula en Proliferación/análisis , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Tiadiazoles/administración & dosificación , Glándula Tiroides/metabolismo , Glándula Tiroides/patologíaRESUMEN
OBJECTIVE: To detect adverse effects on the pregnant/lactating dams and on the development of the offspring following exposure to sibutramine hydrochloride of the dams from the closure of the hard palate through weaning. METHODS: Studies on the effects of this new drug on pre- and postnatal development, including maternal function of mice were conducted. The pregnant mice were randomly divided into four groups. The dose levels were 32 mg/(kg.d) (1/5 LD50), 2.83 mg/(kg.d), 0.25 mg/(kg.d) for three groups respectively, and the fourth group was for negative control. Females were administered sibutramine hydrochloride in drink water from the closure of the hard palate (pregnant 15 d) to the end of lactation. Adverse effects on pregnant mice, pre- and postnatal deaths of offspring, altered growth and development, functional deficits in offspring were assessed. Terminal examinations included: necropsy (macroscopic examination) of all adults, abnormalities, live offspring at birth, body weight at birth, pre- and postweaning survival and growth/body weight, maturation, physical development, sensory functions and reflexes and behavior. RESULTS: The increase of death (above 10%) of pregnant and lactating mice was observed in the group of 32 mg/(kg.d). No other adverse effects on the maternal animals and offspring were observed. CONCLUSION: The data of these studies on mice showed no evidence for the reproductive toxicity to pregnant mice and the developmental toxicity to offspring induced by sibutramine hydrochloride.