Loss of skeletal integrity in rat fetuses from dams treated with histamine H1 antagonists
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Pregnant Lister Hooded rats were dosed orally with chlorocyclizine (60 mg/kg), promethazine (5 and 10 mg/kg) or doxylamine (500 and 750 mg/kg) (histamine H1 antagonists prescribed for nausea of pregnancy) over the period of organogenesis (days 7–13). Fetuses were removed by caesarian section on day 21 and stained with Alizarin Res S and Alcian Blue for calcified bone and cartilage respectively. There were no significant differences in fetal size with any of the treatments; however, all 3 antagonists caused dose-dependent loss of skeletal integrity and marked fragility compared to the controls. By dosing dams on selected days, skeletal fragility was seen in all fetuses; the most marked effects occurring after dosing on days 10–12. Prolonging the gestation period with progesterone (10 mg/dam orally) resulted in normal sekeletal calcification but fetuses were still very fragile. Therefore, histamine H1 antagonists may interfere with the development of rat fetal joints.
KeywordsProgesterone Alizarin Alcian Blue Promethazine Gestation Period
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