ABSTRACT
Preeclampsia (PE) is a leading cause of maternal morbidity and mortality. Nicotinamide has beneficial effects on PE. In this study, we evaluated the effect of nicotinamide on placental development using a PE mouse model. To generate the PE model, a recombinant adenovirus to overproduce soluble fms-like tyrosine kinase 1 (sFlt-1) was administered to mice (Jcl:ICR) at 8.5 day post-coitum (dpc). Plasma and placenta samples were harvested at 12.5 dpc. Fetal and placental weight was significantly decreased at 12.5 dpc in PE mice. Plasma and placental acylcarnitine levels were significantly higher in PE mice than those in control mice. Glycolysis was accelerated and glucose metabolic flow was altered with hypoxia, leading to ATP shortage in the labyrinth of PE mice. In PE mice, ATP production was diminished, and fatty acid oxidation was accelerated in the placenta, consequently, blood carnitine and acylcarnitine levels were increased. The mitochondrial morphology in BeWo cells was impaired under hypoxia. Nicotinamide treatment reversed fetal growth restriction, placental development, and altered metabolic flow in the early stage in PE. In addition, nicotinamide normalized impaired mitochondrial morphology. Hence, targeting this metabolic alteration in the placenta using nicotinamide may serve as a potential therapeutic approach for PE treatment.
Subject(s)
Metabolomics , Pre-Eclampsia/genetics , Up-Regulation , Vascular Endothelial Growth Factor Receptor-1/genetics , Animals , Carnitine/analogs & derivatives , Carnitine/metabolism , Cell Line , Disease Models, Animal , Fatty Acids/metabolism , Female , Fetal Growth Retardation/etiology , Glycolysis , Humans , Mice , Mice, Inbred ICR , Placenta/metabolism , Placenta/pathology , Pre-Eclampsia/metabolism , Pre-Eclampsia/pathology , Pregnancy , Vascular Endothelial Growth Factor Receptor-1/metabolismABSTRACT
The present study aimed to evaluate the acute locally injurious property of hydroxyl radical generation system by photolysis of H(2)O(2), which is a new disinfection system for the treatment of periodontitis developed in our laboratory. Firstly, generation of the hydroxyl radical by a test device utilizing the photolysis of H(2)O(2) was confirmed by applying an electron spin resonance (ESR)-spin trapping technique. Secondly, the bactericidal effect of the device was examined under a simulant condition in which Staphylococcus aureus suspended in 1 M H(2)O(2) was irradiated with laser light emitted from the test device, resulting in substantial reduction of the colony forming unit of the bacteria within a short time as 2 min. Finally, acute topical effect of the disinfection system on rat oral mucosa and wounded skin was evaluated by histological examination. No abnormal findings were observed in the buccal mucosal region treated three times with 1 M H(2)O(2) and irradiation. Similarly, no abnormal findings were observed during the healing of skin treated with 1 M H(2)O(2) and irradiation immediately after wounding. Since topical treatment with the novel disinfection technique utilizing the photolysis of H(2)O(2) had no detrimental effect on the oral mucosa and the healing of full thickness skin wounds in rats, it is expected that the acute locally injurious property of the disinfection technique is low.
