[Show abstract][Hide abstract] ABSTRACT: This study examined the hypothesis that apoptotic inhibition via mitochondrial pathway was involved in hyperbaric oxygen preconditioning (HBO-PC)-induced neuroprotection on ischemia-reperfusion injury in rat brain. Male Sprague-Dawley rats (250 approximately 280 g, n=144) were divided into control, middle cerebral artery occlusion (MCAO) for 90 min, and HBO-PC plus MCAO groups. HBO-PC was conducted four times by giving 100% oxygen at 2.5 atm absolute (ATA), for 1 h at 12 h intervals for 2 days. At 24 h after the last HBO-PC, MCAO was performed and at 24 h after MCAO, neurological function, brain water content, infarct volume, and cell death were evaluated. Enzymatic activity of capase-3 and -9, and expression of cytochrome c, Bcl-2 and Bax proteins were performed in the samples from hippocampus, ischemic penumbra and core of the brain cortex, respectively. HBO-PC reduced brain edema, decreased infarction volume, and improved neurological recovery. HBO-PC reduced cytoplasm cytochrome c levels, decreased caspase enzyme activity, upregulated the ratio of Bcl-2 and Bax expression, and abated the apoptosis of ischemic tissue. HBO-PC protects brain tissues from ischemia-reperfusion injury by suppressing mitochondrial apoptotic pathways.
[Show abstract][Hide abstract] ABSTRACT: Glucocorticoids (GCs) are the most potent anti-inflammatory agents available for allergic diseases including asthma, which are routinely believed to need several hours to take effect through regulating gene expression. Our previous report had shown that GCs could inhibit allergic asthma within 10 min, which the classical mechanism could not explain.
To confirm the existence and verify the sites of GCs' rapid action, we investigated nongenomic effects of GCs on degranulation of mast cells in allergic asthma. Methods: The GCs' rapid action on airway mast cells deregulations was evaluated in the allergic asthma model of guinea pigs by the computer-assisted morphometry. Using whole-cell patch clamp and fluorometric assay, we examined GCs' nongenomic effect on IgE-mediated exocytosis and histamine release of rat basophilic leukaemia-2H3 mast cells. Employing the flash photolysis technique, we studied the role of Ca(2+) signal in the GCs' nongenomic effect.
Inhaled GCs significantly inhibited airway mast cells degranulation in the allergic asthma model of guinea pigs within 10 min. In vitro, GCs could rapidly inhibit IgE-mediated exocytosis and histamine release of mast cells, and neither GC nuclear receptor antagonist nor protein synthesis inhibitor could block the rapid action. We further demonstrated that GCs' nongenomic effect was not through direct action on secretory machinery, but was mediated by a reduction in the [Ca(2+)](i) elevation.
The study suggested for the first time that nongenomic pathway was involved in GCs' rapid inhibition on allergic asthma, and raised the possibility of new therapeutic strategies for allergic diseases including asthma.
[Show abstract][Hide abstract] ABSTRACT: Glucocorticoids are steroids endowed with powerful anti-inflammatory properties, which are routinely believed to require several hours to take effect through modulation of gene expression. Our recent report has shown that glucocorticoids could inhibit allergic reaction within 10 minutes, which the classical genomic mechanism could not explain. Histamine is thought to be one of major mediators in the allergic reaction, and IgE-mediated histamine release from mast cells plays a pivotal role in allergic diseases. Here, we have determined a rapid effect of corticosterone on histamine release from rat peritoneal mast cells, using fluorometric assay. The results showed that corticosterone could inhibit antigen-induced histamine release from rat peritoneal cells within 15 minutes (p<0.05), which could be mimicked by membrane-impermeable BSA conjugated corticosterone (p<0.05). Neither glucocorticoid nuclear receptor antagonist nor protein synthesis inhibitor could block the rapid action (p<0.05). The study provided evidence that nongenomic mechanism might be involved in rapid effect of glucocorticoids on mast cells in allergic disease.
Hormone and Metabolic Research 04/2007; 39(4):273-7. · 2.15 Impact Factor