ABSTRACT
BACKGROUND: The ability of the nitric oxide (NO) synthesis inhibitor NG-nitro-L-arginine methyl ester (L-NAME) to induce preterm parturition in the mouse has been previously documented. The present study tested the ability of progestational agents to prevent preterm birth induced by L-NAME. MATERIALS AND METHODS: L-NAME was administered subcutaneously at 90 mg/kg on gestation day 16. Progesterone, medroxyprogesterone acetate and hydroxyprogesterone caproate were administered subcutaneously at 0 (vehicle), 5 or 10 mg/kg on gestation day 16 one hour before L-NAME and on day 17. Parturition was considered preterm if occurring before gestation day 18. RESULTS: Following treatment with L-NAME alone, 56.5% of the pregnant animals delivered before term. Treatment with progesterone, medroxyprogesterone acetate or hydroxyprogesterone caproate at 5 mg/kg or 10 mg/kg significantly and comparably reduced the rate of preterm birth caused by L-NAME. CONCLUSION: Progestational agents are able to reduce preterm births induced by nitric oxide synthase (NOS) inhibition.
Subject(s)
Enzyme Inhibitors/pharmacology , NG-Nitroarginine Methyl Ester/pharmacology , Nitric Oxide/metabolism , Progestins/pharmacology , 17 alpha-Hydroxyprogesterone Caproate , Animals , Female , Hydroxyprogesterones/pharmacology , Medroxyprogesterone Acetate/pharmacology , Mice , Mice, Inbred ICR , Nitric Oxide Synthase/antagonists & inhibitors , Pregnancy , Pregnancy, Animal , Premature Birth/prevention & control , Progesterone/pharmacologyABSTRACT
The main aim of the study was to identify the critical periods of susceptibility for itraconazole-mediated teratogenesis in the mouse. Pregnant ICR (CD-1) mice received a single oral administration of itraconazole at 50 mg/kg b.w., 150 mg/kg b.w. or 250 mg/kg b.w. on gestation day 8, 9, 10, 11 or 12. Control animals were administered with vehicle on gestation days 8-12. The gestational outcome was evaluated near term, on gestation day 18. Treatment-related morphological findings, as they can be evaluated by external, visceral and skeletal examination, mainly included cleft palate, limb defects and axial skeletal malformations. Cleft palate and limb defects resulted after single exposures between gestation days 9 and 11, with a tendency toward maximal response on gestation day 10. Significant incidences of axial skeletal defects were seen exclusively on gestation days 8 and 9. Exposure on gestation day 12 did not yield significant teratogenic responses. Cleft palate was the most sensitive teratogenic response, being the only developmental lesion associated to exposure to itraconazole at 150 mg/kg b.w.
