Protective effects and mechanism of chemical- and plant-based selenocystine against cadmium-induced liver damage.

Although selenium (Se) and cadmium (Cd) often coexist naturally in the soil of China, the health risks to local residents consuming Se-Cd co-enriched foods are unknown. In the present study, we investigated the effects of chemical-based selenocystine (SeCys2) on cadmium chloride-induced human hepatocarcinoma (HepG2) cell injury and plant (Cardamine hupingshanensis)-derived SeCys2 against Cd-induced liver injury in mice. We found that chemical- and plant-based SeCys2 showed protective effects against Cd-induced HepG2 cell injury and liver damage in mice, respectively. Compared with Cd intervention group, co-treatment with chemical- or plant-based SeCys2 both alleviated liver toxicity and ferroptosis by decreasing ferrous iron, acyl-CoA synthetase long-chain (ACSL) family member 4, lysophosphatidylcholine acyltransferase 3, reactive oxygen species and lipid peroxide levels, and increasing ACSL3, peroxisome proliferator-activated receptor α, solute carrier family 7 member 11 (SLC7A11) and glutathione and glutathione peroxidase 4 (GPX4) levels. In conclusion, chemical- and plant-based SeCys2 alleviated Cd-induced hepatotoxicity and ferroptosis by regulating SLC7A11/GPX4 signaling and lipid peroxidation. Our findings indicate that potential Cd toxicity from consuming foods grown in Se- and Cd-rich soils should be re-evaluated. This study offers a new perspective for the development of SeCys2-enriched agricultural products.

Effects of selenium-cadmium co-enriched Cardamine hupingshanensis on bone damage in mice.

Selenium (Se) and cadmium (Cd) usually co-existed in soils, especially in areas with Se-rich soils in China. The potential health consequences for the local populations consuming foods rich in Se and Cd are unknown. Cardamine hupingshanensis (HUP) is Se and Cd hyperaccumulator plant that could be an ideal natural product to assess the protective effects of endogenous Se against endogenous Cd-caused bone damage. Male C57BL/6 mice were fed 5.22 mg/kg cadmium chloride (CdCl2) (Cd 3.2 mg/kg body weight (BW)), or HUP solutions containing Cd 3.2 mg/kg BW and Se 0.15, 0.29 or 0.50 mg/kg BW (corresponding to the HUP0, HUP1 and HUP2 groups) interventions. Se-enriched HUP1 and HUP2 significantly decreased Cd-induced femur microstructure damage and regulated serum bone osteoclastic marker levels and osteogenesis-related genes. In addition, endogenous Se significantly decreased kidney fibroblast growth factor 23 (FGF23) protein expression and serum parathyroid hormone (PTH) levels, and raised serum calcitriol (1,25(OH)2D3). Furthermore, Se also regulated gut microbiota involved in skeletal metabolism disorder. In conclusion, endogenous Se, especially with higher doses (the HUP2 group), positively affects bone formation and resorption by mitigating the damaging effects of endogenous Cd via the modulation of renal FGF23 expression, circulating 1,25(OH)2D3 and PTH and gut microbiota composition.

Protective effects of epigallocatechin-3-o-gallate combined with organic selenium against transforming growth factor-beta 1-induced fibrosis in LX-2 cells.

In this study, we investigated the protective effects and possible mechanism of epigallocatechin-3-o-gallate (EGCG) combined with organic selenium in transforming growth factor (TGF)-ß1-activated LX-2 cells. After 12 h of starvation, LX-2 cells were treated with 10 ng/ml of recombinant TGF-ß1 and different concentrations of EGCG, L-selenomethionine (L-SeMet), or L-selenomethylcysteine (L-SeMC) for 24 h. We found that 100 and 200 µM EGCG combined with 1 mM L-SeMet or L-SeMC showed a synergistic effect in decreasing the survival rate of activated LX-2 cells. In addition, the combination of 100 mM EGCG and 1 mM L-SeMet or L-SeMC promoted the apoptosis of activated LX-2 cells. Compared with the EGCG treatment group, the combination intervention group had significantly suppressed levels of hepatic stellate cell activation markers including alpha-smooth muscle actin, collagen type I alpha 1, collagen type III alpha 1, 5-hydroxytryptophan (5-HT), and 5-HT receptors 2A and 2B. Moreover, interleukin-10 levels were decreased, while TGF-ß1 levels were increased after TGF-ß1 activation in LX-2 culture medium, whereas the combin1ation intervention reversed this phenomenon. The combination treatment had a more pronounced effect than any single treatment at the same dose. These results demonstrated that the combination of EGCG and organic selenium synergistically improves the TGF-ß1-induced fibrosis of LX-2 cells to some extent by promoting apoptosis and inhibiting cell activation. PRACTICAL APPLICATIONS: Here, we found that the effects of epigallocatechin-3-o-gallate (EGCG) + L-selenomethionine or L-selenomethylcysteine were more pronounced than those of EGCG alone. Future studies should investigate the protective effects of green tea and selenium-enriched green tea against hepatic fibrosis and explore the differences in their molecular mechanisms. The results of this study will be helpful for the development and utilization of selenium-enriched tea for food processing and health supplement production.

Lactoferrin improves hepatic insulin resistance and pancreatic dysfunction in high-fat diet and streptozotocin-induced diabetic mice.

Lactoferrin (Lf) is an iron-binding glycoprotein with potentially beneficial biological functions. However, the interaction between Lf and type 2 diabetes mellitus (T2DM) remains unclear. We hypothesized that Lf would improve hepatic insulin resistance and pancreatic dysfunction in diabetic mice. Male C57BL/6J mice were fed a high-fat diet for 15 weeks and injected with streptozotocin (STZ) for 5 consecutive days to establish a T2DM model. One week after STZ injection, mice with ≥11.1 mmol/L fasting blood glucose concentration were considered T2DM mice. These mice received 0.5% or 2% Lf solution for another 12 weeks. Biochemical parameters were measured, and histopathological examination of the pancreas and liver was performed. Hepatic protein expression related to the insulin signalling pathway was also assessed. Diabetic mice showed insulin resistance and abnormal glucolipid metabolism. Lf decreased serum concentrations of glycated serum protein, fasting insulin, cholesterol, and triglyceride and increased liver insulin sensitivity. Hematoxylin-eosin staining showed that Lf reversed the abnormal pancreatic islets of diabetic mice. Lf improved pancreatic dysfunction by reducing oxidative stress and inflammation responses. Furthermore, Lf upregulated the protein expression of insulin receptor, insulin receptor substrate-1, glucose transporter 4, phosphor phosphatidylinositol 3-kinase/phosphatidylinositol 3-kinase (PI3K), and phosphor protein kinase B/protein kinase B (AKT) in the liver. This study indicated that Lf supplementation improved hepatic insulin resistance and pancreatic dysfunction, possibly by regulating the PI3K/AKT signaling pathway in T2DM mice.

The Protective Effects of Zornia diphylla (L.) Pers. Against Acute Liver Injury Induced by Carbon Tetrachloride in Mice.

Background: Zornia diphylla (L.) Pers. (ZDP) is a traditional Chinese herbal medicine that has been used for several decades to treat patients with liver diseases. Whether ZDP is best administered as a single agent or adjunctive therapy has yet to be determined as does the mechanism whereby it exerts its effects on antagonizing acute liver injury (ALI). Aim of the study: To investigate the protective effects of ZDP on ALI induced by carbon tetrachloride (CCl4) and the potential underlying mechanisms. Materials and Methods: Sixty adult mice were randomized into six study groups (n = 10/group). Three groups were treated with different concentrations of ZDP (2.5, 1.25, 0.625 g/kg), one with bifendate (0.0075 g/kg) alone (positive control) and one with physiologic saline (normal, negative control). All groups were treated for 14 days. Two hours after the last administration, the normal group received an intraperitoneal injection of peanut oil, and the other five groups received an intraperitoneal injection of an equal dose of CCl4 peanut oil solution. At 24 h, the liver index, histology and serum or tissue levels and/or protein expression of aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (TBIL), alkaline phosphatase (ALP), superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT), glutathione (GSH), Akt, phosphorylated Akt (p-Akt), nuclear factor kappa B p65 (NF-κB p65), inhibitor of NF-κB α (IκB-α), interleukin-1 ß (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), E-cadherin and vimentin were determined. Results: Compared to the model controls, the degree of inflammatory cell infiltration and hepatocyte injury of liver tissue was relieved in the bifendate and three ZDP groups; liver index in the ZDP (2.5, 1.25 g/kg) groups and serum liver function indices in the ZDP (2.5, 1.25 and 0.625 g/kg) groups were decreased; antioxidants SOD, CAT and GSH in liver tissue were increased but the lipid peroxidation index MDA was decreased; protein expression of inflammatory cytokines Akt, p-Akt, NF-κB p65, IκB-α, IL-1ß, IL-6 and TNF-α in the liver was ameliorated, and E-cadherin expression was increased. The results of liver histopathology also showed that ZDP had a significant effect on ALI. Conclusion: ZDP has obvious protective effects on CCl4-induced ALI as a single therapy and appears to act by inhibiting oxidation, reducing the release of inflammatory factors and promoting hepatocyte repair.