Formation of the knee joint after prenatal propyphenazone (isopropylantipyrine) administration

Cyclooxygenase (COX) inhibitors could produce cartilage toxicity as well as delayed skeleton formation when administrated during pregnancy. The purpose of this experiment was to determine the effect of a nonselective COX inhibitor, propyphenazone (isopropylantipyrine), on the development of the knee joint in rats. The drug was administered orally in Tween 80 water suspension once a day on days 8-14 of gestation in three doses: R1: 2.1 mg/kg, R2: 21.0 mg/kg and R3: 210.0 mg/kg. Two control groups were formed: untreated control (K) and Tween 80-treated (T) animals. Fetuses were delivered by cesarean section on day 21 of gestation and examined macroscopically for external malformations. The knee joints of two fetuses of each litter were sectioned in situ or paraffin-em bedded. The slides were examined microscopically. The remaining fetuses were stained using the Alcian blue and red S alizarin skeleton double-staining method. Reduced alizarin staining in bones from the knee joint, and wider epiphysial cartilage was seen in 2 of 53 examined fetuses (3.77%) exposed prenatally to the highest dose of propyphenazone. The extra sesamoid cartilage, located close to the lateral epicondyle of the femur, was absent in 10 cases in group T (15.87%), 9 cases in group K (15.00%), 8 cases in group R1 (12.50%), 9 cases in group R2 (14.75%) and 9 cases in group R3 (14.28%). Similarly sesamoid cartilage close to the middle epicondyle was seen in one fetus from group K (1.66%) and in one fetus from group R2 (1-63%). No histological changes were observed. Based on obtained results, it could be concluded that propyphenazone did not delay the formation of the knee joint.