Selenium Exerts Protective Effects Against Fluoride-Induced Apoptosis and Oxidative Stress and Altered the Expression of Bcl-2/Caspase Family.

Fluoride is widely distributed in nature, and at high concentrations, it targets the kidney and especially proximal tubule epithelial cells. Selenium is a typical trace element beneficial to humans, and the role of selenium in the prevention and treatment of fluoride-induced organ damage is an important research topic. The purpose of this study was to investigate the possible protective effects of selenium against fluoride-induced oxidative stress and apoptosis in rat renal tubular epithelial cells. We showed that the activity of antioxidant enzymes (superoxide dismutase and glutathione peroxidase) and total antioxidant capacity were significantly reduced in NaF-treated normal rat kidney cells (NRK-52E), whereas the levels of nitrogen monoxide (NO) and malondialdehyde (MDA) were significantly increased. Moreover, the number of apoptotic cells, mRNA expression of Bax, Bad, caspase-3, caspase-8, and caspase-9, and protein expression of Bax were elevated, while mitochondrial membrane potential and the protein expression of Bcl-2 were reduced. Compared with the NaF group, pretreatment with selenium enhanced the activity of antioxidant enzymes, mitochondrial membrane potential, and protein expression of Bcl-2, while the levels of NO and MDA, number of apoptotic cells, mRNA expression of Bax, Bad, caspase-3, caspase-8, and caspase-9, and protein expression of Bax were decreased. In conclusion, selenium exerted remarkable protective effect against NaF-induced oxidative stress and apoptosis and altered the expression of Bcl-2/caspase family.

Green tea polyphenols protect PC12 cells against H2O2-induced damages by upregulating lncRNA MALAT1.

It is of significance to alleviate oxidative damages for the treatment of spinal cord injury (SCI). Studies have ascertained that green tea polyphenols (GTPs) exert protective activities against oxidative damages. In this study, we aimed to investigate the protective effects of GTP against H2O2-caused injuries in PC12 cells as well as the molecular underpinnings associated with long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1). PC12 cells were preincubated with GTP prior to H2O2 stimulation. Furthermore, MALAT1-deficient PC12 cells were constructed by transfection and identified by quantitative real-time polymerase chain reaction (qRT-PCR) assay. Next, viability and apoptosis were detected by cell counting kit-8 and flow cytometry, respectively. Meanwhile, Western blot assay was carried out to monitor the expression alteration of proteins associated with apoptosis (Bcl-2, Bax, pro-Caspase-3/9, and cleaved Caspase-3/9) and autophagy (microtubule-associated protein 1 light chain 3 (LC3)-II, LC3-I, Beclin-1, and p62). Moreover, we examined the expression of ß-catenin and dissected the phosphorylation of phosphatidylinositol 3'-kinase (PI3K) and protein kinase B (AKT). We found that H2O2 decreased the viability of PC12 cells while initiated apoptosis and autophagy processes. GTP-preincubated PC12 cells maintained the viability and resisted the apoptosis and autophagy induced by H2O2. Pointedly, GTP-pretreated PC12 cells showed an increase in MALAT1 after H2O2 stimulation. Of note, the protective effects of GTP were buffered in MALAT1-deficient cells in response to H2O2. The expression of ß-catenin and phosphorylation of PI3K and AKT were upregulated by GTP, while MALAT1 knockdown led to opposite results. To sum up, GTP protected PC12 cells from H2O2-induced damages by the upregulation of MALAT1. This process might be through activating Wnt/ß-catenin and PI3K/AKT signal pathways.

Selenium attenuates apoptosis and p-AMPK expressions in fluoride-induced NRK-52E cells.

Fluoride is widely distributed in the environment, and excessive fluoride intake can induce cytotoxicity, DNA damage, and cell cycle changes in many tissues and organs, including the kidney. Accumulating evidence demonstrates that selenium (Se) administration ameliorates sodium fluoride (NaF)-induced kidney damage. However, the potentially beneficial effects of Se against NaF-induced cytotoxicity of the kidney and the underlying molecular mechanisms of this protection are not fully understood. At present, in this study, the normal rat kidney cell (NRK-52E) was used to investigate the potentially protective mechanism of Se against NaF-induced apoptosis, by using the methods of pathology, colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometry, and Western blot. The experiment was designed with a control group, two NaF-treated groups (NaF, 5, 20 mg/L), two sodium selenite-treated groups (Na2SeO3, 17.1, 34.2 µg/L), and four Se + NaF-treated groups (Na2SeO3, 17.1, 34.2 µg/L; NaF, 5, 20 mg/L). The results indicate that selenium can attenuate apoptosis and AMPK phosphorylation in the NRK-52E cell induced with fluoride. These results imply that selenium is capable to modulate fluoride-induced NRK-52E cell apoptosis via regulating the expression levels of the proteins involved in mitochondrial pathway and changes in p-AMPK expressions may also be a key process in preventing fluorosis.

Cigarette smoke exposure impairs reverse cholesterol transport which can be minimized by treatment of hydrogen-saturated saline.

BACKGROUND: Cigarette smoke (CS) exposure impaired plasma lipid profiles by modification of apolipoproteins. Hydrogen (H2) has been proved effective on reducing oxidative stress or improving HDL functionalities in animal models or metabolic syndrome volunteers. This study was undertaken to explore the effects of CS exposure on reverse cholesterol transport (RCT) and the antioxidative effects of H2 treatment against CS exposure in mice transgenic for human cholesteryl ester transfer protein (CETP). METHODS: [(3)H]-cholesterol-laden macrophages were injected intraperitoneally into mice, and the samples of blood, bile, liver, and feces were collected for radioactivity determination to evaluate RCT. [(3)H]-cholesterol-laden macrophages were incubated with HDL isolated from different groups of mice, and the samples of cell medium supernatants were collected for evaluating the HDL functionality to elicit cholesterol efflux. RESULTS: CS exposure significantly decreased plasma HDL cholesterol level (HDL-C) by 22% and increased LDL cholesterol level (LDL-C) by 21% compared with the control group (p < 0.05, p < 0.01), while H2 treatment significantly improved the CS-impaired levels of TC, LDL-C and HDL-C by 10, 27 and 31%, respectively, compared with the CS group (p < 0.05, p < 0.01 and p < 0.05). Besides, CS exposure significantly decreased [(3)H] tracer concentrations in liver, bile and feces by 17, 35 and 48%, respectively, compared with the control group (p < 0.05 for liver and feces), while H2 treatment significantly improved them by 21, 72% and 89%, respectively, compared with the CS group (all p < 0.05). Furthermore, CS exposure significantly decreased the HDL functionality to elicit cholesterol efflux by 26% (p < 0.05), while H2 treatment also improved it by 32% (p < 0.05). We did not find any significant alterations in protein expressions of RCT involved genes. CONCLUSIONS: These findings provided direct evidence supporting the notion that CS exposure in vivo impairs plasma lipid profiles, HDL functionalities and macrophage-to-feces RCT pathway in CETP transgenic mice, all of which can be minimized by treatment of H2-saturated saline.

Celastrus orbiculatus Thunb. decreases athero-susceptibility in lipoproteins and the aorta of guinea pigs fed high fat diet.

Celastrus orbiculatus Thunb. (COT), a traditional Chinese herb, has anti-inflammatory and anti-oxidative properties. In this study, we examined the protective effect of COT on the initiation of atherosclerosis induced by high fat diet and explored the underlying mechanisms. We established guinea pig models of hyperlipidemia and treated them with three dosages of COT or 20 mg/kg/d simvastatin (a positive control drug) for 8 weeks. Plasma lipid analysis indicated that COT decreased total cholesterol (TC), non-high-density lipoprotein cholesterol (non-HDL-C), triglyceride (TG), apolipoprotein B100 (apoB100) and apolipoprotein E (apoE) levels and increased high density lipoprotein cholesterol (HDL-C) level. The analysis of the hepatic gene involving cholesterol metabolism by quantitative real-time PCR revealed that COT upregulated the mRNA abundance of LDL receptor (LDL-R), scavenger receptor class B type 1 (SR-B1), cholesterol 7α-hydroxylase A1 (CYP7A1) and the 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGCR). Oil red O staining showed COT significantly reduced lipid deposition in the arterial wall. Moreover, ELISA assay revealed COT lowered the levels of C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in plasma. Meanwhile, the level of Nitric oxide (NO) in plasma was increased by COT. Immunohistochemistry and Western blot analysis showed the expression of CD68 and active NF-kB p65 proteins in the arterial wall was decreased by COT. The content of Malondialdehyde (MDA) and activity of Superoxide dismutase (SOD) in plasma were determined and the data indicated COT suppressed oxidative stress reaction. These results reveal that administration of COT decreases athero-susceptibility through lowering plasma lipid, attenuating inflammation, and suppressing oxidative stress in guinea pig fed high fat diet.