Evaluation of the Effects of Dimenhydrinate at Different Dose Levels on Fetal Bone Development in Pregnant Rats: A Morphometric and Ultrastructural Study
摘要
The present study aimed to determine the potential teratogenic effects of dimenhydrinate (DMH) used during pregnancy on fetal bone development in rats at different concentrations.
MethodTwenty Wistar-Albino rats (150–200 g) were randomly divided into four groups (for each group n = 5): control, DMH-30 mg/kg/day, DMH-60 mg/kg/day and DMH-75 mg/kg/day. Ossification length (mm) and ossification areas (mm2) of the long bones were measured with double skeletal staining method. Tartrate-Resistant Acid Phosphatase (TRAP) and Alkaline Phosphatase (ALP) immunohistochemical (IHC) analyses were conducted. Scanning electron microscopy (SEM) was used to evaluate the micro structure of fetal femurs and to determine the density of minerals involved in the ossification.
ResultsIn the experimental groups, fetal weight and morphometric parameters decreased in a dose-dependent manner compared to the control group (p < 0.001). Double skeletal staining showed statistically significant differences in ossified areas between the control group and DMH 60 and 75 mg/kg/day groups (p < 0.001). While histological evaluation showed similar cell density in ossification areas between the control and 30 mg/kg/day groups, a decrease was found in bone density in 60 and 75 mg/kg/day groups. IHC results showed significant differences in ALP density between the control group and 30 and 75 mg/kg DMH groups (p < 0.001). TRAP density was found to be the lowest in 75 mg/kg DMH group. SEM analysis showed a significant and dose-dependent increase in bone loss accompanied by a decrease in calcium concentration in DMH groups (p < 0.05).
ConclusionIntrauterine exposure to DMH adversely affects bone metabolism.