Eryptosis is a type of regulated cell death of mature erythrocytes characterized by excessive Ca2+ accumulation followed by phosphatidylserine externalization. Eryptosis facilitates erythrophagocytosis resulting in eradication of damaged erythrocytes, which maintains the population of healthy erythrocytes in blood. Over recent years, a wide array of diseases has been reported to be linked to accelerated eryptosis, which leads to anemia. A growing number of studies furnish evidence that eryptosis is implicated in the pathogenesis of liver diseases. Herein, we summarize the current knowledge of eryptosis signaling, its physiological role, and the impact of eryptosis on anemia and hypercoagulation. In this article, upon systemically analyzing the PubMed-indexed publications, we also provide a comprehensive overview of the role of eryptosis in the spectrum of hepatic diseases, its contribution to the development of complications in liver pathology, metabolites (bilirubin, bile acids, etc.) that might trigger eryptosis in liver diseases, and eryptosis-inducing liver disease medications. Eryptosis in liver diseases contributes to anemia, hypercoagulation, and endothelial damage (via ferroptosis of endothelial cells). Treatment-associated anemia in liver diseases might be at least partly attributed to drug-induced eryptosis. Ultimately, we analyze the concept of inhibiting eryptosis pharmaceutically to prevent eryptosis-associated anemia and thrombosis in liver diseases.

• Keywords
• bile acids, bilirubin, chronic liver disease, eryptosis, non-alcoholic fatty liver disease, regulated cell death,
• MeSH
• Anemia * pathology   etiology   MeSH
• Eryptosis * physiology   MeSH
• Erythrocytes pathology   metabolism   MeSH
• Humans MeSH
• Liver Diseases * complications   pathology   blood   MeSH
• Thrombophilia * etiology   pathology   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

Accumulating evidence suggests that manganese oxide nanoparticles (NPs) show multiple enzyme-mimicking antioxidant activities, which supports their potential in redox-targeting therapeutic strategies for diseases with impaired redox signaling. However, the systemic administration of any NP requires thorough hemocompatibility testing. In this study, we assessed the hemocompatibility of synthesized Mn3O4 NPs, identifying their ability to induce spontaneous hemolysis and eryptosis or impair osmotic fragility. Concentrations of up to 20 mg/L were found to be safe for erythrocytes. Eryptosis assays were shown to be more sensitive than hemolysis and osmotic fragility as markers of hemocompatibility for Mn3O4 NP testing. Flow cytometry- and confocal microscopy-based studies revealed that eryptosis induced by Mn3O4 NPs was accompanied by Ca2+ overload, altered redox homeostasis verified by enhanced intracellular reactive oxygen species (ROS) and reactive nitrogen species (RNS), and a decrease in the lipid order of cell membranes. Furthermore, Mn3O4 NP-induced eryptosis was calpain- and caspase-dependent.

• Keywords
• calcium signaling, cytotoxicity, eryptosis, nanoparticles, oxidative stress, regulated cell death,
• MeSH
• Cell Membrane * metabolism   drug effects   MeSH
• Eryptosis * drug effects   MeSH
• Erythrocytes drug effects   metabolism   MeSH
• Hemolysis drug effects   MeSH
• Calpain * metabolism   MeSH
• Caspases * metabolism   MeSH
• Humans MeSH
• Nanoparticles * chemistry   MeSH
• Oxides * pharmacology   chemistry   MeSH
• Reactive Nitrogen Species * metabolism   MeSH
• Reactive Oxygen Species * metabolism   MeSH
• Manganese Compounds * pharmacology   chemistry   MeSH
• Calcium * metabolism   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Calpain * MeSH
• Caspases * MeSH
• manganese oxide MeSH Browser
• Oxides * MeSH
• Reactive Nitrogen Species * MeSH
• Reactive Oxygen Species * MeSH
• Manganese Compounds * MeSH
• Calcium * MeSH