RESUMEN
The pro-oxidant activity of uranium (U) was assessed in kidney and testes of male rats, tissues in which toxic effects of this metal are well established. Eight groups of Sprague-Dawley rats received uranyl acetate dihydrate (UAD) in the drinking water at 0, 10, 20, and 40 mg/kgday for 3 months. Rats in four groups were concurrently subjected to restraint during 2 h/day throughout the study. Histopathological examination of the kidneys revealed an angiomatose transformation in U-treated animals. In kidney, thiobarbituric acid-reactive substances (TBARS) levels and oxidized glutathione (GSSG) activity were correlated with U exposure. The superoxide dismutase (SOD) activity was significantly enhanced in both kidney and testis. Oral UAD administration induced a decrease of glutathione reductase (GR) and reduced glutathione (GSH) in the male reproductive tract. The results of this study suggest that graded doses of U elicit depletion of the antioxidant defence system of the rat and induce oxidative stress in testes and kidneys. Although at the current U doses, restraint stress scarcely showed additional adverse effects, its potential influence should not be underrated.
Asunto(s)
Riñón/efectos de los fármacos , Estrés Oxidativo , Especies Reactivas de Oxígeno/metabolismo , Testículo/efectos de los fármacos , Uranio/toxicidad , Animales , Antioxidantes/metabolismo , Riñón/metabolismo , Riñón/patología , Masculino , Ratas , Ratas Sprague-Dawley , Superóxido Dismutasa/metabolismo , Testículo/metabolismo , Uranio/farmacocinéticaRESUMEN
The influence of restraint stress on uranium (U)-induced behavioral effects was assessed in adult male rats. Eight groups of animals received uranyl acetate dihydrate (UAD) in the drinking water at doses of 0, 10, 20 and 40 mg/kg/day during 3 months. Rats in four groups were concurrently subjected to restraint during 2 h per day throughout the study. At the end of the period of uranium exposure, the following behavioral tests were carried out: open-field activity, passive avoidance and Morris water maze. Uranium concentrations in brain were also determined. At 10 and 20 mg/kg/day of UAD restraint significantly affected the total distance traveled in the open-field during the first and third periods tested, respectively, while no significant differences between groups were observed on the passive avoidance test. In the Morris water maze test, the influence of restraint was only significant on the latency time measured on Day 3 in rats exposed at 10 mg/kg/day. Restraint stress did not affect significantly the uranium levels in brain of rats. Although the results of the present study scarcely show uranium-induced behavioral effects at the oral doses of UAD here administered, these effects, as well as the slight influence of restraint stress noted in some tests should not be underrated.
Asunto(s)
Conducta Animal/efectos de los fármacos , Estrés Psicológico/psicología , Uranio/toxicidad , Animales , Reacción de Prevención/efectos de los fármacos , Encéfalo/metabolismo , Relación Dosis-Respuesta a Droga , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Compuestos Organometálicos/toxicidad , Ratas , Ratas Sprague-Dawley , Restricción Física , Uranio/farmacocinéticaRESUMEN
The influence of stress on postnatal development and behavior was assessed in the offspring of male rats exposed to uranium (U). Eight groups of adult animals received uranyl acetate dihydrate (UAD) in the drinking water at doses of 0, 10, 20 and 40 mg/kg/day during 3 months. One half of rats in each group were concurrently subjected to restraint stress during 2 h per day throughout the study. At the end of the experimental period, male rats were mated with untreated females (1:2). On gestation day 14, one half of pregnant rats were euthanized in order to evaluate maternal toxicity and gestational parameters. The remaining dams were allowed to deliver and wean their offspring. Pups were evaluated for physical development, neuromotor maturation, as well as for behavioral effects. Restraint significantly increased the gravid uterine weight at 40 mg/kg/day. However, no significant interactions between restraint and U could be established in the remaining parameters of maternal toxicity. In the offspring, no remarkable effects of U, restraint or their combination were noted on developmental landmarks, or in the passive avoidance and water maze test. It is concluded that at the current U doses, restraint stress did not enhance the few uranium-induced physical, neuromotor and behavioral changes in the offspring of UAD-exposed male rats.
Asunto(s)
Conducta Animal/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Compuestos Organometálicos/toxicidad , Exposición Paterna/efectos adversos , Estrés Psicológico/fisiopatología , Animales , Femenino , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Memoria/efectos de los fármacos , Actividad Motora/efectos de los fármacos , Embarazo , Resultado del Embarazo , Ratas , Ratas Sprague-Dawley , Restricción FísicaRESUMEN
The effects of stress on the potential reproductive toxicity of long-term exposure to uranyl acetate dihydrate (UAD) were assessed in adult male rats. Six groups of animals were given UAD at 10, 20, and 40 mg/kg/day in the drinking water during 3 months. Animals in three of these groups were also subjected to restraint for 2 h/day during the same period. Control groups included restrained and unrestrained male rats not exposed to UAD. To evaluate the fertility, male rats were mated with untreated females for 2 weeks. Although body weight was not affected by uranium at any dose, there was a significant (not dose-related) decrease in the pregnancy rate. Moreover, spermatid number/testis was significantly decreased by uranium administration. Histopathological examination of the testes in rats killed after 3 months of treatment revealed few differences in the tubule and interstitial alterations (focal atrophy, binucleated cells) between control and uranium-exposed animals. The results of this investigation show that at the current UAD doses, restraint stress did not enhance the uranium-induced adverse effects on reproduction in male rats.
Asunto(s)
Reproducción/efectos de los fármacos , Estrés Psicológico/fisiopatología , Testículo/efectos de los fármacos , Uranio/toxicidad , Animales , Peso Corporal/efectos de los fármacos , Femenino , Masculino , Tamaño de los Órganos/efectos de los fármacos , Compuestos Organometálicos/toxicidad , Ratas , Ratas Sprague-Dawley , Espermatozoides/efectos de los fármacos , Testículo/metabolismo , Testículo/patología , Uranio/farmacocinéticaRESUMEN
It has been demonstrated that uranium is an embryo/fetal toxicant when given orally or subcutaneously to pregnant mice. On the other hand, maternal stress has been shown to enhance the developmental toxicity of a number of metals. In this study, maternal toxicity and developmental effects of a concurrent exposure to uranyl acetate dihydrate (UAD) and restraint stress were evaluated in rats. Four groups of pregnant animals were given subcutaneous injections of UAD at 0.415 and 0.830 mg/kg/day on Days 6 to 15 of gestation. Animals in two of these groups were also subjected to restraint for 2 hr/day during the same gestational days. Control groups included restrained and unrestrained pregnant rats not exposed to UAD. Cesarean sections were performed on gestation Day 20, and the fetuses were weighed and examined for malformations and variations. Maternal toxicity and embryotoxicity were noted at 0.830 mg/kg/day of UAD, while fetotoxicity was evidenced at 0.415 and 0.830 mg/kg/day of UAD by significant reductions in fetal body weight and increases in the total number of skeletally affected fetuses. No teratogenic effects were noted in any group. Maternal restraint enhanced uranium-induced embryo/fetal toxicity only at 0.830 mg/kg/day, a dose that was also significantly toxic to the dams. As in previous studies with other metals, maternal stress enhances uranium-induced developmental toxicity at uranium doses that are highly toxic to the dams; however, at doses that are less acutely toxic the role of maternal stress would not be significant.
Asunto(s)
Exposición Materna , Uranio/toxicidad , Anomalías Inducidas por Medicamentos , Animales , Relación Dosis-Respuesta a Droga , Femenino , Masculino , Ratas , Ratas Sprague-Dawley , Restricción Física , Factores de TiempoRESUMEN
The maternal and developmental toxicity of combined exposure to restraint stress and caffeine was assessed in mice. On gestational Days 0-18, three groups of plug-positive females (n = 13-15) were given by gavage caffeine at 30, 60, and 120 mg/kg/day. Three additional groups received the same caffeine doses and were restrained for 2 hr/day. Control groups included restrained and unrestrained plug-positive mice not exposed to caffeine. All animals in the group concurrently exposed to 120 mg/kg/day of caffeine and restraint died during the experimental period. In the remaining groups, cesarean sections were performed on Day 18 of gestation, and the fetuses were weighed and examined for external, internal, and skeletal malformations and variations. Although maternal and embryo/fetal toxicity were observed at all caffeine doses, the adverse maternal and developmental effects were significantly enhanced in the groups concurrently exposed to caffeine and restraint. It was especially remarkable at 60 and 120 mg/kg/day. The results of this study suggest that maternal and developmental toxic effects might occur if high amounts of caffeine were consumed by women under a notable stress during pregnancy.