Resumen de Effects of pyrazinamide on pregnant albino rats
Marisa Pascale Quintino, Manuel de Jesus Simões, Mary Uchiyama Nakamura, Ricardo Martins Oliveira-Filho, Silvia Espiridião, Luiz Kulay Júnior
- español
La pyrazinamida es un fármaco muy utilizado para el tratamiento de la tuberculosis, pero no hay datos en la literatura respecto a sus potenciales riesgos para la preñez. Debido a esto, en este trabajo tratamos ratas preñadas durante toda la gestación (desde el día 0 hasta el día 20) con 3 dosis de pyrazinamida (35, 105 o 315 mg/kg, una vez al día) para una primera observación sobre los efectos de la pyrazinamida durante la preñez. Las ratas control recibieron el vehículo de la droga (agua destilada). Los resultados mostraron que no hubo alteraciones significativas en cuanto a la evolución del peso corporal de las ratsa madres, al peso de los fetos, al número de implantaciones y reabsorciones, ni tampoco en cuanto a los pesos de placentas y fetos. Además, no se observaron malformaciones fetales mayores, muertes intrauterinas o aumento de la mortalidad materna. El único efecto significativo observado con la dosis de 315 mg/kg de pyrazinamida, fue una reducción del peso uterino
- English
Although being used for years in the treatment of tuberculosis, no data are available in the literature on the safety of pyrazinamide during pregnancy. Accordingly, we aimed to make a first approach to this problem by evaluating the effects of this drug administered during the entire pregnancy of albino rats. Fourty female, EPM-1 Wistar albino rats of about 250 g b.w. were used. Upon conception (day zero of pregnancy) the animals were randomly divided in 4 groups of 10 rats each and labeled as follows. Controls (C), animals treated with the drug vehicle (destilled water); experimental groups (E1, E2 and E3), animals treated with 35, 105 or 315 mg/kg b.w. pyrazinamide by gavage (oral route) once daily up to the term (20th day of pregnancy). Drug or vehicle volume was always 0.5 ml. Body weight gain was followed up every week. At term, upon sacrifice (in excess of anesthesia) and histerectomy, the following parameters have been studied: number of implantations and reabsorptions; intrauterine deaths; number of living foetuses and of placentae; weights of concepts and of placentae; major foetal malformations; maternal mortality index. No significant effects of pyrazinamide on rat pregnancy have been observed regarding the maternal body weight gain, the weights of concepts, the number of implantations and reabsorptions and the weights of placentae and foetuses. Also, no deleterious effects have been noticed regarding major foetal malformations, intrauterine deaths or maternal mortality. With the highest pyrazinamide dosis employed (315 mg/kg b.w.), however, a significant lowered uterine weight was recorded. Although otherwise safe, a high-dose regimen of pyrazinamide during rat pregnancy can induce a slight yet significant reduction of uterine weight.
