Treatment with 1,25(OH)2D3induced HDAC2 expression and reduced NF-κB p65 expression in a rat model of OVA-induced asthma

Recent evidence indicates that a deficiency of 1,25-dihydroxyvitamin D3 (1,25[OH]2D3) may influence asthma pathogenesis; however, its roles in regulating specific molecular transcription mechanisms remain unclear. We aimed to investigate the effect of 1,25(OH)2D3 on the expression and enzyme activity of histone deacetylase 2 (HDAC2) and its synergistic effects with dexamethasone (Dx) in the inhibition of inflammatory cytokine secretion in a rat asthma model. Healthy Wistar rats were randomly divided into 6 groups: control, asthma, 1,25(OH)2D3 pretreatment, 1,25(OH)2D3 treatment, Dx treatment, and Dx and 1,25(OH)2D3 treatment. Pulmonary inflammation was induced by ovalbumin (OVA) sensitization and challenge (OVA/OVA). Inflammatory cells and cytokines in the bronchoalveolar lavage (BAL) fluid and histological changes in lung tissue were examined. Nuclear factor kappa B (NF-κB) p65 and HDAC2 expression levels were assessed with Western blot analyses and quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR). Enzyme activity measurements and immunohistochemical detection of HDAC2 were also performed. Our data demonstrated that 1,25(OH)2D3 reduced the airway inflammatory response and the level of inflammatory cytokines in BAL. Although NF-κB p65 expression was attenuated in the pretreatment and treatment groups, the expression and enzyme activity of HDAC2 were increased. In addition, 1,25(OH)2D3 and Dx had synergistic effects on the suppression of total cell infusion, cytokine release, and NF-κB p65 expression, and they also increased HDAC2 expression and activity in OVA/OVA rats. Collectively, our results indicated that 1,25(OH)2D3might be useful as a novel HDAC2 activator in the treatment of asthma.

Rat visceral yolk sac cells: viability and expression of cell markers during maternal diabetes

The function of the visceral yolk sac (VYS) is critical for embryo organogenesis until final fetal development in rats, and can be affected by conditions such as diabetes. In view of the importance of diabetes during pregnancy for maternal and neonatal health, the objective of this study was to assess fetal weight, VYS cell markers, and viability in female Wistar rats (200-250 g) with induced diabetes (alloxan, 37 mg/kg) on the 8th gestational day (gd 8). At gd 15, rats from control (n=5) and diabetic (n=5) groups were anesthetized and laparotomized to remove the uterine horns for weighing of fetuses and collecting the VYS. Flow cytometry was used for characterizing VYS cells, and for determining mitochondrial activity, cell proliferation, DNA ploidy, cell cycle phases, and caspase-3 activity. Fetal weight was reduced in the diabetic group. Expression of the cell markers CD34, VEGFR1, CD115, CD117, CD14, CCR2, CD90, CD44, STRO-1, OCT3/4, and Nanog was detected in VYS cells in both groups. In the diabetic group, significantly decreased expression of CD34 (P<0.05), CCR2 (P<0.001), and OCT3/4 (P<0.01), and significantly increased expression of CD90 (P<0.05), CD117 (P<0.01), and CD14 (P<0.05) were observed. VYS cells with inactive mitochondria, activated caspase-3, and low proliferation were present in the rats with diabetes. Severe hyperglycemia caused by maternal diabetes had negative effects on pregnancy, VYS cell viability, and the expression of cell markers.

Essential oil of Lippia alba and its main constituent citral block the excitability of rat sciatic nerves

Lippia alba is empirically used for infusions, teas, macerates, and hydroalcoholic extracts because of its antispasmodic, analgesic, sedative, and anxiolytic effects. Citral is a mixture of trans-geranial and cis-neral and is the main constituent of L. alba essential oil and possesses analgesic, anxiolytic, anticonvulsant, and sedative effects. The present study evaluated the effects of the essential oil of L. alba (EOLa) and citral on compound action potentials (CAPs) in Wistar rat sciatic nerves. Both drugs inhibited CAP in a concentration-dependent manner. The calculated half-maximal inhibitory concentrations (IC50) of peak-to-peak amplitude were 53.2 µg/mL and 35.00 µg/mL (or 230 µM) for EOLa and citral, respectively. Peak-to-peak amplitude of the CAP was significantly reduced by 30 µg/mL EOLa and 10 µg/mL citral. EOLa and citral (at 60 and 30 µg/mL, values close to their respective IC50 for CAP blockade) significantly increased chronaxy and rheobase. The conduction velocity of the first and second CAP components was statistically reduced to ∼86% of control with 10 µg/mL EOLa and ∼90% of control with 3 µg/mL citral. This study showed that EOLa inhibited nerve excitability and this effect can be explained by the presence of citral in its composition. Both EOLa and citral showed inhibitory actions at lower concentrations compared with other essential oils and constituents with local anesthetic activity. In conclusion, these data demonstrate that EOLa and citral are promising agents in the development of new drugs with local anesthetic activity.