DHA-enriched phosphatidylserine alleviates bisphenol A-induced liver injury through regulating glycerophospholipid metabolism and the SIRT1-AMPK pathway.

To investigate the alleviating effect and mechanism of the docosahexaenoic acid-enriched phosphatidylserine (DHA-PS) on bisphenol A (BPA)-induced liver injury in mice, the murine liver injury model was established by gavage of BPA (5 mg/kg) or co-administration of BPA and DHA-PS (50 mg/kg or 100 mg/kg) for 6 weeks. The results showed that after administration of 100 mg/kg DHA-PS, the liver index, serum levels of AST, ALT, TC, TG, NEFA, and LDL-C in mice were significantly decreased, while HDL-C was significantly increased. The LPS, IL-6, IL-1ß, TNF-α, and MDA levels in liver tissues were effectively down-regulated, and IL-10, SOD, GSH-Px, and CAT levels were effectively up-regulated. The H&E and Oil Red O staining results showed that liver damage was notably repaired and lipid deposition was notably reduced after DHA-PS administration. Furthermore, metabolomics and immunohistochemical studies revealed that DHA-PS mainly regulates glycerophospholipid metabolism and the SIRT1-AMPK pathway to improve metabolic disorders of the liver caused by BPA. Therefore, DHA-PS could potentially alleviate BPA-induced murine liver injury through suppressing inflammation and oxidative stress, and modulating lipid metabolism disorders.

Investigation of the potential ameliorative effects of DHA-enriched phosphatidylserine on bisphenol A-induced murine nephrotoxicity.

In order to investigate the amelioration of docosahexaenoic acid-enriched phosphatidylserine (DHA-PS) on bisphenol A (BPA)-induced nephrotoxicity, the murine nephrotoxicity model was established by intragastric administration of BPA (5 mg/kg/B.W.) for 6 weeks. The biochemical indices, hematoxylin-eosin (H&E) staining, kidney metabolomics, and related protein expression levels of SIRT1-AMPK pathway were then determined. Our results indicated that DHA-PS (100 mg/kg/B.W.) ameliorated the BPA-induced nephrotoxicity after 6 weeks of intragastric administration, primarily by decreasing the serum creatinine (CRE) and blood urea nitrogen (BUN), renal inflammatory cytokines and lipid levels, and increasing the antioxidant enzyme activities. In addition, the untargeted metabolomics of the kidney indicated that BPA perturbed the tryptophan metabolism, pyridine metabolism, and valine, leucine, and isoleucine biosynthesis, while DHA-PS administration significantly affected the glycerophospholipid metabolism, valine, leucine, and isoleucine biosynthesis to ameliorate the BPA-induced metabolic disorder. Moreover, DHA-PS administration could ameliorate the BPA-induced lipid disturbance by upregulating the expressions of AMPKα1, SIRT1, and PPARα while downregulating the expression of SREBP-1c through the SIRT1-AMPK pathway. This is the first time that the amelioration effects of DHA-PS on BPA-induced nephrotoxicity have been investigated from multiple perspectives, suggesting that DHA-PS might be a potential dietary supplement for reducing BPA-induced nephrotoxicity.

Investigation of nephrotoxicity on mice exposed to polystyrene nanoplastics and the potential amelioration effects of DHA-enriched phosphatidylserine.

Nanoplastics (NPs) induce nephrotoxicity in mammals, but an understanding of the potential mechanism or amelioration strategies is lacking. Herein, we established the polystyrene nanoplastics (PS-NPs, 100 nm)-induced nephrotoxicity murine model, and investigated the potential molecular mechanism of docosahexaenoic acid-enriched phosphatidylserine (DHA-PS) alleviating effects. Based on the biochemical indices, H&E staining and kidney metabolomics, we found that PS-NPs did cause murine nephrotoxicity, mainly due to inflammation, oxidative stress, and lipid disturbance. DHA-PS administration alleviated these effects, mainly by decreasing renal levels of IL-6, IL-1ß, TNF-α and MDA, increasing the level of IL-10, increasing the activities of SOD, GSH-Px, CAT, and alleviating lipid disturbance, mainly by modulating kidney glycerophospholipid metabolism, linoleic acid metabolism and the SIRT1-AMPK pathway. This is the first time that the amelioration effects of DHA-PS on PS-NPs-induced nephrotoxicity have been investigated from multiple perspectives, providing a potential mechanism of nephrotoxicity caused by PS-NPs.

Effects of Fucoidan Isolated From Laminaria japonica on Immune Response and Gut Microbiota in Cyclophosphamide-Treated Mice.

The effects of Laminaria japonica fucoidan (LF) on immune regulation and intestinal microflora in cyclophosphamide (CTX)-treated mice were investigated in this work. Results indicated that LF significantly enhanced the spleen and thymus indices, promoted spleen lymphocyte and peritoneal macrophages proliferation, and increased the immune-related cytokines production in serum. Moreover, LF could regulate intestinal flora composition, increasing the abundance of Lactobacillaceae and Alistipes, and inhibiting Erysipelotrichia, Turicibacter, Romboutsia, Peptostreptococcaceae, and Faecalibaculum. These results were positively correlated with immune characteristics. Overall, LF could be useful as a new potential strategy to mitigate CTX immunosuppression and intestinal microbiota disorders.