Morphological changes in developing rats exposed to valproic acid

Valproic Acid [VPA] is a broad spectrum antiepileptic drug. Its use during pregnancy has been associated with congenital anomalies and hepatotoxicity. This study was designed to assess the effects of VPA on the morphology of the fetuses of albino rats exposed to the drug during various trimesters of pregnancy. Experimental study. In this study pregnant rats were divided into four groups A,B,C and D. Group A [n=10] received VPA in a dose of 500mg/kg/day intraperitonealy [I/p] on days 3, 4 and 5 of gestation. Group B [n=10] received the drug in a dose of 500mg/kg/day I/P on days 8,9 and 10 of gestation. Group C [n=10] received VPA in a dose of 500mg/kg/day I/P on days 16, 17 and 18 of gestation. Group D [n=10] received no treatment and was kept as a control group. On day 21, the rats were euthanized by cervical dislocation. The fetuses were examined for any gross congenital malformation, Congenital malformations were noted in 20% of the fetuses exposed to VPA during second week of gestation i.e. group B. The anomalies included spina bifida [occulta and aperta], exophthalmia, digital abnormalities, cleft lip etc. The other experimental groups showed no such anomalies but high rate of underdevelopment was noted in group A, Moreover, there was significant reduction in body weight and crown rump length [CRL] of the fetuses in group B and C, VPA use during various gestational periods produces deleterious effects in developing rats. So, the use of this drug during pregnancy should be carefully decided

Developmental Toxicity by Exposure to Bisphenol A Diglycidyl Ether during Gestation and Lactation Period in Sprague-dawley Male Rats / 예방의학회지

OBJECTIVES: Bisphenol A diglycidyl ether (BADGE) is the major component in commercial liquid epoxy resins, which are manufactured by co-reacting bisphenol A with epichlorohydrin. This study was performed to show the developmental effects of prenatal and postnatal exposures to BADGE in male rat offspring. METHODS: Mated female rats were divided into four groups, each containing 12 rats. The dosing solutions were prepared by thoroughly mixing BADGE in corn oil at the 0, 375, 1500 and 3000 mg/kg/day concentrations. Mated females were dosed once daily by oral gavage on gestation day (GD) 6 - 20 and postnatal day (PND) 0 - 21. Pregnant female dams were observed general symptoms and body weight. Also, male pups were observed the general symptoms, body weight, developmental parameters (e.g. anogenital distance, pina detachment, incisor eruption, nipple retention, eye opening, testis descent), organ pathologic changes and hormone levels of plasma. RESULTS: Pregnant rats treated with BADGE died at a rate of about 70% in the 1500 mg/kg/day group and all rats treated with 3000 mg/kg/day died. Body weight, for male pups treated with doses of 375 mg/kg/day, was significantly lower than in the control group at PND 42, 56, and 63 (p<0.05). Evaluation of body characteristics including; separation of auricle, eruption of incisor, separation of eyelid, nipple retention, descent of testis, and separation of the prepuce in the BADGE treated group showed no difference in comparisons with the control group. AGD and adjusted AGD (mm/kg) for general developmental items in BADGE 375 mg/kg/day treated pups tended to be longer than in controls, however, these differences were not statistically significant. Relative weights of adrenal gland, lung (p<0.05), brain, epididymis, prostate, and testis (p<0.01) were heavier than in control in measures at PND 9 weeks. There were no significant changes in comparisons of histological findings of these organs. Loss of spermatids was observed in the seminiferous tubule at PND 9 weeks, but no weight changes were observed. The plasma estrogen levels were similar in the control and treatment groups at PND 3, 6 and 9 weeks. The plasma testosterone levels in the control group tended to increase with age. However, in the BADGE 375 mg/kg/day treated male pups it did not tend to increase. CONCLUSIONS: These findings suggest that BADGE is a chemical that has developmental effects consistent with it being an endocrine disruptor.

Metabolismo de peróxidos en músculos respiratorios: efecto del crecimiento, desarrollo y envejecimiento / Glutathione peroxidase and catalase activity in rat respiratory muscles: effect of growth, maturation and aging

Background: Glutathione peroxidase (GSHPx) and catalase are two important cellular antioxidant enzymes involved in H2O2 and lipid-peroxide metabolism. Aim: To study the effects of growth, maturation and aging on the activity of these enzymes. Material and methods: GSHPx and catalase specific activities were measured in samples of diaphragm and intercostal muscle of male Sprague-Dawley rats of different ages (21, 50, 70, 180 and 365 days), anesthetised with chloral hydrate (45 mg/100 g ip). Results: The diaphragm and intercostal muscles did not differ in GSHPx activity at 21 days. After that, GSHPx activity increased progressively with age, but following a different pattern, in each muscle, suggesting an increase in enzyme substrates with age. In one year old animals, GSHPx activity was 5 times higher for the diaphragm and 3 times higher for the intercostal muscles, when compared with values observed at 21 days of age. Catalase activity also increased with age in the diaphragm but not in the intercostal muscles. Conclusions: GSHPx activity increases progressively with age in rat respiratory muscles, with a time course that is specific of each muscle. Catalase activity increases with age only in the diaphragm. These results support the hypothesis that antioxidants in respiratory muscles undergo specific regulatory changes with age

Intoxicación con ion cobre en ratas preñadas y su efecto en formación de centros primarios de osificación en fetos / Cooper ion intoxication in pregnant rats and their effects on the primary ossification center in fetus

La actividad socioeconómica de la II Región de Chile es la minería del cobre, generándose subproductos que son eliminados al medio. Se ha informado en centros industrializados, que los metales pesados se transfieren de las madres a los fetos, vía placenta. Se propone conocer la bioacumulación de cobre en órganos y fluidos en ratas gestantes y su efecto en la formación de centros primarios de osificación (CPO). Hembras de tres meses Sprague Dowley, se ciclan y se cruzan en estro. Al octavo día de gestación, se inyectan i.p. con 1 ml de CuSO en concentraciones 1024, 512, 256, 128 y 64 ppm y suero fisiológico, el grupo control. A los 18 días, se sacrifican y se evalúan los fetos, procesándose por técnicas de tinción, diafanización e histológica. Secciones de 5 um se tiñen con azul de Alcian /Azul de Toluidina. Se recupera sangre materna, membranas amniocoriónica, líquido amniótico y placenta, entre grupos tratados y controles. Una diferencia significativa en la formación de los CPO en vértebras y dorsales, se encontró con el tratamiento de 256 ppm, en comparación con el control (p<0.05). No se observaron anomalías externas. Se infiere que ión cobre se transfiere a los fetos vía placenta, bioacumulándose en el hígado e induciendo alteraciones o retardo en la formación de CPO, especialmente a nivel de vértebras cervicales y dorsales; observándose microscópicamente en dichas zonas, ausencias de tejido cartilaginoso característico