RESUMEN
Piper amalago L. (Piperaceae) is traditionally used due to its anti-inflammatory, analgesic, diuretic, and antiparasitic properties. However, few studies have focused on its adverse effects, compromising its safe use. This study evaluated the toxicological safety of ethanolic extract from Piper amalago leaves (EEPA), through subacute toxicity and genotoxicity assays in rodents. In subacute toxicity, 100, 200 or 300 mg/kg of EEPA were tested in female Wistar rats, by gavage, for 28 days. For genotoxicity test, female Swiss mice were orally treated with 17.5, 175 or 1750 mg/kg of EEPA and the comet, micronucleus, and splenic phagocytic assays were evaluated. In subacute toxicity, the extract induced an increase in the food and water intakes, as well as in the liver absolute weight, and in the heart and kidney relative weights. EEPA also provoked alterations in histopathological analysis of liver and in hemato-biochemical parameters, evidenced by a decrease in hematocrit levels and albumin levels, and an increase in the number of platelets and in alkaline phosphatase and cholesterol levels. However, EEPA did not presented genotoxic nor mutagenic properties. EEPA showed hemato-biochemical toxicity profile in rats and should be used with caution, especially when for prolonged period.
Asunto(s)
Piper , Extractos Vegetales/farmacología , Animales , Sangre/efectos de los fármacos , Análisis Químico de la Sangre , Daño del ADN/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Femenino , Hígado/efectos de los fármacos , Ratones , Pruebas de Mutagenicidad , Hojas de la Planta , Distribución Aleatoria , Ratas , Ratas Wistar , Pruebas de Toxicidad SubagudaRESUMEN
Tamoxifen, a selective non-steroidal estrogen receptor modulator, is the standard adjuvant endocrine treatment for breast cancer. Since information on the risk of using tamoxifen during pregnancy is still scarce, this study evaluated whether the in utero and lactational treatment with this drug could compromise reproductive and behavioural parameters in male offspring. Pregnant Wistar rats were exposed to three doses of tamoxifen (0.12; 0.6; 3 µg/kg), by gavage, from gestational day 15 to lactational day 20. Tamoxifen exposure did not alter the anogenital distance in the male offspring; however, there was a significant increase in the body weight in the 0.12 µg/kg dose and a decrease in the 0.6 µg/kg dose. The male offspring treated with the highest dose exhibited a delay in the onset of puberty, evidenced by an increase in the age of preputial separation. Regarding sperm parameters, there was an increase in the sperm count in the cauda epididymis in the intermediate and highest dose groups, in addition to an increase in the number of static sperm and a decrease in the progressive sperm in the same groups. Moreover, an increase in the number of hyperplasia of the epithelial clear cells was observed in the epididymis. In conclusion, the present study demonstrated that maternal exposure to tamoxifen compromised the installation of puberty of the male offspring and the maturation of the epididymis, affecting sperm storage and motility in the adult life.
Asunto(s)
Conducta Animal/efectos de los fármacos , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Moduladores Selectivos de los Receptores de Estrógeno/toxicidad , Espermatozoides/efectos de los fármacos , Tamoxifeno/toxicidad , Animales , Epidídimo/efectos de los fármacos , Epidídimo/crecimiento & desarrollo , Femenino , Hipotálamo/citología , Lactancia , Masculino , Intercambio Materno-Fetal , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Embarazo , Ratas Wistar , Receptores Androgénicos/metabolismo , Maduración Sexual/efectos de los fármacos , Recuento de Espermatozoides , Motilidad Espermática/efectos de los fármacos , Espermatozoides/fisiologíaRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Serjania marginata Casar. (Sapindaceae) is a species traditionally known to be used for the treatment of gastric pain and inflammatory symptoms. AIM OF THIS STUDY: Due to the therapeutic importance of this species, this study investigated the toxicological effects of S. marginata leaves (AESM), after a single and a repeated exposure in rats. MATERIALS AND METHODS: For the acute toxicity test, 2000â¯mg/kg of AESM was administered to male and female rats by gavage, whereas for subacute toxicity test, 30, 150, or 750â¯mg/kg of AESM were used. RESULTS: No evidence of toxicity was observed in the animals acutely exposed to the extract, indicating that the LD50 is higher than 2000â¯mg/kg. After the repeated administration of AESM the hematological and biochemical parameters were unaltered, except the erythrocytes number and albumin levels in the exposed animals. Moreover, daily administration of this extract caused alteration on kidney histology. AESM also induced an increase of abnormal sperm, however the other reproductive parameters analyzed, in both sexes, were not altered by the treatment. CONCLUSION: Although AESM was not toxic after a single exposure, its use after prolonged periods affected some analyzed parameters, indicating that precautions should be taken when it is given over longer periods.