The hydroxy-analogue of selenomethionine alleviated lipopolysaccharide-induced inflammatory responses is associated with recover expression of several selenoprotein encoding genes in the spleens of Kunming mice.

This study aimed to determine whether hydroxy-analogue of selenomethionine (HMSeBA) supplementation could alleviate LPS-induced immunological stress in mice. A total of 90 Kunming mice were randomly assigned into 5 groups. The CON-LPS and CON+LPS groups were fed basal diet (BD), the others were fed BD with different levels of HMSeBA (0.15, 0.30 and 0.45 mg Se per kg) for 4 weeks. Mice were injected with LPS (3 mg per kg BW) or the corresponding physiological saline at 14 d and 28 d. Plasma and spleens were collected at 28 d. The results showed that: (1) LPS injection decreased ADG of mice at the 3rd week, and increased the concentration of IL-6 and TNF-α in plasma and the spleen index; (2) LPS injection induced immunological stress, up-regulated 8 inflammation-related genes and 3 selenoprotein encoding genes, and down-regulated 16 selenoprotein encoding genes in spleens; (3) compared with the CON+LPS group, HMSeBA supplementation increased ADG of mice at 3 weeks and GSH-Px activity in plasma and spleens, decreased spleen index and plasma IL-6 and TNF-α levels, down-regulated mRNA levels of COX-2, ICAM-1, TNF-α, IL-6, and MCP-1, and up-regulated IL-10 and iNOS in spleens. 0.30 mg Se per kg of HMSeBA exhibited the optimal protective effect; (4) HMSeBA supplementation modestly recovered the expression of 8 selenoprotein encoding genes in the spleens of the stressed mice. The results indicated that HMSeBA supplementation alleviated LPS-induced immunological stress accompanied up-regulation of a subset of selenoprotein encoding genes in spleens of mice.

Protective Effect of Selenoprotein X Against Oxidative Stress-Induced Cell Apoptosis in Human Hepatocyte (LO2) Cells via the p38 Pathway.

Oxidative stress, as mediated by ROS (reactive oxygen species), is a significant factor in initiating the cells damaged by affecting cellular macromolecules and impairing their biological functions; SelX, a selenoprotein also known as MsrB1 belonging to the methionine sulfoxide reductase (Msr) family, is the redox repairing enzyme and involved in redox-related functions. In order to more precisely analyze the relationship between oxidative stress, cell oxidative damage, and SelX, we stably overexpressed porcine Selx full-length cDNA in human normal hepatocyte (LO2) cells. Cell viability, cell apoptosis rate, intracellular ROS, and the expression levels of mRNA or protein of apoptosis-related genes under H2O2-induced oxidative stress were detected. We found that overexpression of SelX can prevent the oxidative damage caused by H2O2 and propose that the main mechanism underlying the protective effects of SelX is the inhibition of LO2 cell apoptosis. The results revealed that overexpressed SelX reduced the H2O2-induced intracellular ROS generation, inhibited the H2O2-induced upregulation of Bax and downregulation of Bcl-2, and increased the mRNA and protein ratio of Bcl-2/Bax. Furthermore, it inhibited H2O2-induced p38 MAPK phosphorylation. Taken together, our findings suggested that SelX played important roles in protecting LO2 cells against oxidative damage and that its protective effect is partly via the p38 pathway by acting as a ROS scavenger.

The prolonged effect of glucagon-like peptide 2 pretreatment on growth performance and intestinal development of weaned piglets.

BACKGROUND: Glucagon-like peptide 2 (GLP-2) is a potent epithelium-specific intestinal growth factor. The aim of this study was to demonstrate the prolonged effect of GLP-2 on the growth performance of weaned piglets. Forty piglets weaned at the age of 28 d with an average BW of 6.8 ± 0.4 kg were assigned to four treatments: (i) non-challenged control; (ii) LPS-challenged control; (iii) LPS + low GLP-2; and (iv) LPS + high GLP-2. Piglets in groups (i), (ii), and (iv) were s.c. injected with PBS supplemented with human [Gly2]GLP-21-34 at doses of 0, 2 and 10 nmol/kg BW per day for seven consecutive days. BW, gain:feed ratio (G:F), and plasma GLP-2 levels were determined on d 0, 7, and 14 after weaning. Piglets were challenged with i.p. administration of Escherichia coli lipopolysaccharide (LPS) at a dose of 100 µg/kg on d 14 to induce intestinal damage. Twenty-four hours later, intestinal tract samples were collected to assess intestinal morphology and quantify enzyme activity. RESULTS: Plasma GLP-2 levels decreased after weaning, but in the high GLP-2 group, plasma GLP-2 was maintained on d 7 and even increased to a level higher than the preweaning level on d 14 (P < 0.05). High GLP-2 treatment significantly increased the duodenal, jejunal and ileal weight, as well as the gross weight of the small intestine (SI), and the SI weight index (P < 0.05). LPS caused villous atrophy and disrupted intestinal morphology in the duodenum, jejunum and ileum. GLP-2 also significantly increased the villus height and the villus height/crypt depth ratio (VCR) of the duodenum, jejunum, and ileum (P < 0.05). Histological examination revealed that in GLP-2-treated groups, the integrity of the villus was maintained, and the villus was protected against LPS-induced damage. GLP-2 significantly increased the activity of alkaline phosphatase (AKP), γ-glutamyltranspeptidase (γ-GT), and pancreatic lipase in the duodenum and jejunum (P < 0.05). GLP-2 treatment also significantly increased the average daily gain (ADG) and G:F of piglets at 0 to 7, 7 to 14, as well as 0 to14 d (P < 0.05), resulting in a significant increase of final BW in high GLP-2 pigs (P = 0.016). CONCLUSIONS: Exogenous GLP-2 improved the growth of weaned piglets and protected them against LPS-induced intestinal damage. These effects may be due to the ability of GLP-2 to promote the secretion of endogenous GLP-2 to stimulate the small intestinal development.