ABSTRACT
Increasing widespread use of St. John's Wort (SJW, Hypericum perforatum) has led to concerns about its use in pregnant women. Behavioral and physiological alterations resulting from developmental treatment were investigated in Sprague-Dawley rats exposed to diets containing 0, 180, 900, 1800 or 4500ppm SJW beginning on gestational day 3 and ending at offspring weaning on postnatal day (PND) 21. These dietary doses span 1-25 times the recommended human dose. Post-weaning behavioral assessments of male and female offspring included: open field activity, acoustic startle, performance of complex and Morris water mazes, and activity in an elevated plus-maze. There were no SJW effects on maternal weight gain or duration of gestation; offspring body weights were similar to controls from PND 2 through PND 56 after which, some treated groups weighed significantly less than the controls. There were no SJW-related behavioral alterations on any measure. Whole and regional brain weights of offspring at adulthood indicated no significant effects of SJW. These results indicate that there are few neurobehavioral alterations resulting from developmental SJW treatment in rats.
Subject(s)
Hypericum , Plant Preparations/pharmacology , Prenatal Exposure Delayed Effects , Animals , Body Weight , Brain/anatomy & histology , Brain/drug effects , Dose-Response Relationship, Drug , Female , Humans , Male , Maze Learning/drug effects , Models, Animal , Motor Activity/drug effects , Organ Size , Pregnancy , Rats , Rats, Sprague-Dawley , Reflex, Startle/drug effects , WeaningABSTRACT
The developmental toxicity of purified fumonisin B1 (FB1), a mycotoxin from the common corn fungus Fusarium moniliforme, was examined in Charles River rats. Pregnant rats were dosed orally on gestation days 3-16 at 0, 6.25, 12.5, 25 or 50 mg FB1/kg body weight/day. FB1 was not teratogenic at the doses tested. At 50 mg/kg, maternal toxicity (inappetence, emaciation, lethargy, death, resorption of entire litters) and foetal toxicity (increased number of late deaths, decreased foetal body weight, decreased crown rump length, increased incidence of hydrocephalus, increased incidence of skeletal anomalies) were seen. The foetal toxicity observed at 50 mg/kg may be related to maternal toxicity. Histopathological evaluation of tissues from dams of control and all treated groups revealed dose-related toxic changes in kidney and liver tissues. Acute toxic tubular nephrosis was seen in kidneys from all treated groups. Hepatocellular cytoplasmic alteration and individual cellular necrosis of the liver was seen in the two high-dose groups. Sphinganine (Sa) and sphingosine (So) were measured in day-17 adult and foetal tissues. Dose related increases in Sa/So ratios were seen in maternal liver, kidney, serum and brain, but there was no effect on foetal liver, kidney and brain. These data suggest that FB1 does not cross the placenta and further suggest that the observed foetal toxicity is a secondary response to maternal toxicity.
Subject(s)
Carboxylic Acids/toxicity , Fumonisins , Mycotoxins/toxicity , Pregnancy, Animal/drug effects , Teratogens/toxicity , Animals , Eating/drug effects , Embryonic and Fetal Development/drug effects , Female , Fetus/pathology , Kidney/embryology , Kidney/pathology , Liver/embryology , Liver/pathology , Male , Organ Size/drug effects , Pregnancy , Rats , Rats, Inbred Strains , Reproduction/drug effects , Sphingolipids/metabolism , Weight Gain/drug effectsABSTRACT
Glucocorticoids cause stunting and cleft palate in rodents. The aim of this study is to identify fetal organs and developmental periods sensitive to stunting induced by maternal exposure to dexamethasone (DEX). DEX (0.2 or 0.4 mg/kg) or saline was given sc to pregnant CD albino rats on Gestation Days (GD) 9-14 or 14-19. On GD 20 dams were euthanized. Fetuses were weighed and examined for cleft palate. Eight fetuses/litter were randomly selected, and weights were obtained. Fetal skeletons were examined for abnormalities, and long bone measurements were taken. A dose-related decrease in maternal and fetal body weights occurred at both exposure periods. Developmental stage-specific malformations were noted in the high-dose group on GD 9-14 (cleft palate) and on GD 14-19 (wavy ribs). A dose-response in stunting occurred in all organs except cerebellum in at least one exposure period. Across both exposure periods the brain, heart, testes, and long bones were relatively resistant to DEX. Sensitive organs included thymus, spleen, adrenals, lungs, liver, and kidneys. DEX substantially reduced maternal food intake and increased water intake in some dams. Pair-feeding experiments suggested that the hypophagic effect of DEX was not responsible for the noted malformations and had little impact on growth stunting. The present findings have identified fetal organs, skeletal regions, and developmental periods sensitive to DEX exposure.