Cyclooxygenase inhibitors affect bone mineralization in rat fetuses.
Intrauterine growth retardation, increased incidence of developmental variations, lack of cartilage and joint developmental side effects were previously reported for nonselective (ibuprofen, piroxicam, tolmetin) and selective (DFU) cyclooxygenase (COX)-2 inhibitors, also known as nonsteroidal anti-inflammatory drugs. The aim of the present study was to evaluate the lumbar vertebra mineralization in fetuses prenatally exposed to COX inhibitors. All the tested compounds were administered intragastrically to pregnant rats from gestational days 8 to 21. Fetuses were delivered on gestational day 21, and after digital radiological examination were double-stained with alcian blue and alizarin. Decrease of alizarin staining, as a qualitative sign of mineralization, was significantly greater in groups exposed to the highest doses of the nonselective COX inhibitors. Decrease of vertebra mineralization in drug-exposed groups was also revealed using quantitative radiological analysis. However, significant differences were noted only for the fifth and sixth lumbar vertebrae in the group exposed to the highest dose of tolmetin. Strong influence of the total protein level in maternal sera on the fetal bone optic density was found. It should be stressed that unlike DFU, the examined nonselective COX inhibitors decreased fetal bone mineralization when administered in high maternal toxic doses. Moreover, maternal health status determined fetal bone mineralization.
Burdan
Franciszek
F
Experimental Teratology Unit, Human Anatomy Department, Medical University of Lublin, Lublin, Poland. fb3@wp.pl
Rozylo-Kalinowska
Ingrid
I
Szumilo
Justyna
J
Dudka
Jaroslaw
J
Klepacz
Robert
R
D000818:Animals; D002113:Calcification, Physiologic / Q000187:drug effects*; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D008159:Lumbar Vertebrae / Q000196:embryology* / Q000201:enzymology / Q000473:pathology; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects; D008431:Maternal-Fetal Exchange / Q000187:drug effects; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017208:Rats, Wistar
D052246:Cyclooxygenase 2 Inhibitors