Antioxidants ameliorate oxidative stress in alcoholic liver injury by modulating lipid metabolism and phospholipid homeostasis.

Alcoholic liver disease (ALD) is a significant risk factor in the global disease burden. The antioxidants vitamin C (Vc) and N-acetyl cysteine (NAC) have shown hepatoprotective effects in preventing and treating ALD. However, the correlation between the improved effect of antioxidants and lipid metabolism is still unclear. In this study, AML12 cells and C57BL/6 mice stimulated with alcohol were used to investigate the protective effects and potential mechanisms of two antioxidants (Vc and NAC) on alcoholic liver injury. Results showed that Vc and NAC attenuated intracellular lipid accumulation and oxidative damage induced by excessive alcohol exposure in hepatic AML12 cells. The in vivo results indicated that antioxidants ameliorated alcohol-induced changes in histopathology, reducing the levels of alcohol metabolizing factors and aspartate aminotransferase (AST), alanine aminotransferase (ALT), triglyceride (TG), and total cholesterol (TC) contents, which demonstrated that antioxidants effectively mitigated liver injury in ALD mice. Further studies showed that antioxidants reversed the disruption of fatty acid (FA) synthesis and lipid transport induced by alcohol exposure, and restored phospholipid levels. Especially, Vc and NAC increased the endogenous antioxidant plasmenyl phosphatidylethanolamine (PlsEtn). Additionally, antioxidants ameliorated the alcohol-impaired mitochondrial function and inhibited excessive oxidative stress. In conclusion, antioxidants can regulate lipid metabolism and phospholipid homeostasis, which in turn inhibit oxidative stress and thereby exert protective effects against ALD.

Hepatoprotective effects of sea cucumber ether-phospholipids against alcohol-induced lipid metabolic dysregulation and oxidative stress in mice.

Sea cucumber is widely consumed as food and folk medicine in Asia, and its phospholipids are rich sources of dietary eicosapentaenoic acid enriched ether-phospholipids (ether-PLs). Emerging evidence suggests that ether-PLs are associated with neurodegenerative disease and steatohepatitis. However, the function and mechanism of ether-PLs in alcoholic liver disease (ALD) are not well understood. To this end, the present study sought to investigate the hepatoprotective effects of sea cucumber ether-PLs, including plasmenyl phosphatidylethanolamine (PlsEtn) and plasmanyl phosphatidylcholine (PlsCho), and their underlying mechanisms. Our results showed that compared with EtOH-induced mice, ether-PL treated mice showed improved liver histology, decreased serum ALT and AST levels, and reduced alcohol metabolic enzyme (ALDH2 and ADH1) expressions. Mechanistic studies showed that ether-PLs attenuated "first-hit" hepatic steatosis and lipid accumulation evoked by alcohol administration. Moreover, PlsEtn more effectively restored endogenous plasmalogen levels than PlsCho, thereby enhancing hepatic antioxidation against "second-hit" reactive oxygen species (ROS) due to the damaged mitochondria and abnormal ethanol metabolism. Taken together, sea cucumber ether-PLs show great potential to become a natural functional food against chronic alcohol-induced hepatic steatosis and lipid metabolic dysregulation.

Sea urchin gangliosides exhibit neuritogenic effects in neuronal PC12 cells via TrkA- and TrkB-related pathways.

Gangliosides (GLSs) are ubiquitously distributed in all tissues but highly enriched in nervous system. Currently, it is unclear how exogenous GLSs regulate neuritogenesis, although neural functions of endogenous GLSs are widely studied. Herein, we evaluated the neuritogenic activities and mechanism of sea urchin gangliosides (SU-GLSs) in vitro. These different glycosylated SU-GLSs, including GM4(1S), GD4(1S), GD4(2A), and GD4(2G), promoted differentiation of NGF-induced PC12 cells in a dose-dependent and structure-selective manner. Sulfate-type and disialo-type GLSs exhibited stronger neuritogenic effects than monosialoganglioside GM1. Furthermore, SU-GLSs might act as neurotrophic factors possessing neuritogenic effects, via targeting tyrosine-kinase receptors (TrkA and TrkB) and activating MEK1/2-ERK1/2-CREB and PI3K-Akt-CREB pathways. This activation resulted in increased expression and secretion of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF). These pathways were verified by specific inhibitors. Our results confirmed the neuritogenic functions of SU-GLS in vitro and indicated their potential roles as natural nutrition for neuritogenesis.

Co-oxidation of Antarctic krill oil with whey protein and myofibrillar protein in oil-in-water emulsions.

Antarctic krill oil (AKO) is usually encapsulated by the protein materials, enhancing its oxidative stability. Proteins exhibit immense effect on lipid oxidation and induce protein-lipid co-oxidation. This study aimed at elucidating the co-oxidation mechanism of AKO and whey protein (WP) or myofibrillar protein (MP) in oil-in-water emulsions. The estimations of malondialdehyde (MDA) content, phospholipid molecular species, and pyrrole content resulted in increased and decreased oxidation rate of AKO (especially phosphatidylethanolamine) by WP and MP, respectively. Meanwhile, protein concentration, sulfhydryl content, the loss of tryptophan fluorescence intensity, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis results demonstrated that AKO promoted WP oxidation but inhibited MP oxidation. Further, the antioxidative abilities of seven common antioxidants were evaluated. Ascorbyl palmitate showed the most substantial antioxidative effect for both AKO and proteins (about 70% decrease of MDA content and 30% decrease of the decrease ratio of tryptophan fluorescence intensity). This finding supported that different proteins could exhibit different pro/anti-oxidative effects on lipid oxidation, especially for marine lipids abundant in phospholipids and polyunsaturated fatty acids. Besides, MP could also act as antioxidant in MP AKO emulsions, further extending its application from traditional surfactants. PRACTICAL APPLICATION: AKO is usually encapsulated by the protein materials, enhancing its oxidative stability. The results demonstrated MP could inhibit AKO oxidation, and vice versa, especially when ascorbyl palmitate was added at the same time. As a result, this finding explored a new potential wall material with antioxidative ability for the encapsulated products of AKO.

The oxidation mechanism of phospholipids in Antarctic krill oil promoted by metal ions.

Antarctic krill oil (AKO) is an emerging dietary supplement containing metal ions that influence oil oxidation. Thus, this study focuses on the effect and mechanism of metal ions on phospholipid oxidation in AKO. Firstly, AKO containing Mg2+, Mn2+, Cu2+, Fe2+ and Fe3+ (200 µmol/kg) were prepared separately and incubated at 60 °C for 6 days. Peroxide value (POV) and malondialdehyde (MDA) content showed that Fe3+ exhibited the most effective prooxidative activity, with the prooxidative activity of Fe2(SO4)3 (water-soluble) being stronger than that of ferric oleate (FeOl, fat-soluble). In addition, phosphatidylethanolamine (PE) oxidation degree (more than 90%) was considerably greater than phosphatidylcholine (PC) oxidation degree (about 15%) in AKO. Differences in the structure of head group hindered chelation of PC with metal ions than PE due to electrostatic repulsion and steric hindrance. Therefore, PC significantly inhibited, while PE promoted, the oxidation of polyunsaturated triacylglycerol (TAG), like fish oil (p < 0.01).