Fluoride promotes the secretion of inflammatory factors in microglia through NLRP3/Caspase-1/GSDMD pathway.

It is widespread of endemic fluorosis in China, and the exposure of excessive fluoride will cause nervous system disease and activate microglia. However, the mechanism of the damage is not clear. It is well-known that NLRP3/Caspase-1/GSDMD pathway, a classic pyroptosis pathway, is widely involved in the occurrence and development of nervous system-related diseases, infectious diseases, and atherosclerotic diseases. This research aimed to explore the molecular mechanism of sodium fluoride on inflammation and pyroptosis in BV2 microglia based on the NLRP3/Caspase-1/GSDMD signaling pathway. BV2 microglia was treated with sodium fluoride at the dose of 0.25, 1, and 2 mmol/L for 24, 48, and 72 h, respectively. Cell viability, cell morphology, lactate dehydrogenase content, and related proteins and genes were examined to investigate if sodium fluoride caused damage to BV2 microglia through the pyroptosis pathway. Dithiolam (5 µmol/L), a pyroptosis inhibitor, was added for further verification. NaF could induced BV2 cells injury in a dose-dependent fashion through disrupting the integrity of cell membranes and increasing IL-1ß via upregulating NLRP3, Caspase-1, and its downstream protein GSDMD. Disulfiram could improve these changes caused by NaF. In conclusion, our results suggested that NLRP3/Caspase-1/GSDMD-mediated classical pyroptosis pathway was involved in fluoride-induced BV2 microglia damage.

Polygalasaponin F inhibits neuronal apoptosis induced by oxygen-glucose deprivation and reoxygenation through the PI3K/Akt pathway.

Cerebral ischaemia is a common cerebrovascular disease and often induces neuronal apoptosis, leading to brain damage. Polygalasaponin F (PGSF) is one of the components in Polygala japonica Houtt, and it is a triterpenoid saponin monomer. This research focused on anti-apoptotic effect of PGSF during oxygen-glucose deprivation and reoxygenation (OGD/R) injury in rat adrenal pheochromocytoma cells (PC12) and primary rat cortical neurons. OGD/R treatment reduced viability of PC12 cells and primary neurons. This reduced viability was prevented by PGSF, as shown by MTT assay. OGD/R insult decreased expression of Bcl-2/Bax both in PC12 cells and primary neurons but elevated levels of caspase-3 in primary neurons. However, PGSF may up-regulate expression of Bcl-2/Bax and down-regulate caspase-3 in these particular cells. Furthermore, Bcl-2/Bax and the ratio between phosphorylated Akt and total Akt were decreased in PC12 cells treated with OGD/R, and both were increased by PGSF. Moreover, increase in the ratios of Bcl-2/Bax and phosphorylated Akt/total Akt in PC12 cells was suppressed by phosphatidylinositol 3-kinase (PI3K) inhibitor. Data suggest PGSF might prevent OGD/R-induced injury via activation of PI3K/Akt signalling. The ability of PGSF to block the effects of OGD/R appears to involve regulation of Bcl-2, Bax and caspase-3, which are related to apoptosis.

Aluminum-induced oxidative stress and changes in antioxidant defenses in the roots of rice varieties differing in Al tolerance.

The effects of aluminum (Al) on root elongation, lipid peroxidation, hydrogen peroxide (H(2)O(2)) accumulation, antioxidant levels, antioxidant enzymatic activity, and lignin content in the roots of the Al-tolerant rice variety azucena and the Al-sensitive variety IR64 were investigated. Treatment with Al induced a greater decrease in root elongation and a greater increase in H(2)O(2) and lipid peroxidation as determined by the total thiobarbituric acid-reactive substance (TBARS) level in IR64 than in azucena. Azucena had significantly higher levels of superoxide dismutase, ascorbate peroxidase, glutathione reductase, and glutathione peroxidase GSH POD activity compared with IR64. The concentrations of reduced glutathione (GSH) and ascorbic acid, and the GSH/GSSG ratio (reduced vs. oxidized glutathione) were also higher in azucena than in IR64 in the presence of Al. The addition of 1 mg/L GSH improved root elongation in both varieties and decreased H(2)O(2) production under Al stress. By contrast, treatment with buthionine sulfoximine, a specific inhibitor of GSH synthesis, decreased root elongation in azucena and stimulated H(2)O(2) production in both varieties. Moreover, Al treatment significantly increased the cytoplasmic activity of peroxidase (POD) as well as the levels of POD bound ionically and covalently to cell walls in the Al-sensitive variety. The lignin content was also increased. Treatment with exogenous H(2)O(2) also increased the lignin content and decreased root elongation in IR64. These results suggest that Al induces lignification in the roots of Al-sensitive rice varieties, probably through an increase in H(2)O(2) accumulation.