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.

• Klíčová slova
• bile acids, bilirubin, chronic liver disease, eryptosis, non-alcoholic fatty liver disease, regulated cell death,
• MeSH
• anemie * patologie   etiologie   MeSH
• eryptóza * fyziologie   MeSH
• erytrocyty patologie   metabolismus   MeSH
• lidé MeSH
• nemoci jater * komplikace   patologie   krev   MeSH
• trombofilie * etiologie   patologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

The pathogenesis of non-alcoholic fatty liver disease (NAFLD) is associated with abnormalities of liver lipid metabolism. On the contrary, a diet enriched with n-3 polyunsaturated fatty acids (n-3-PUFAs) has been reported to ameliorate the progression of NAFLD. The aim of our study was to investigate the impact of dietary n-3-PUFA enrichment on the development of NAFLD and liver lipidome. Mice were fed for 6 weeks either a high-fat methionine choline-deficient diet (MCD) or standard chow with or without n-3-PUFAs. Liver histology, serum biochemistry, detailed plasma and liver lipidomic analyses, and genome-wide transcriptome analysis were performed. Mice fed an MCD developed histopathological changes characteristic of NAFLD, and these changes were ameliorated with n-3-PUFAs. Simultaneously, n-3-PUFAs decreased serum triacylglycerol and cholesterol concentrations as well as ALT and AST activities. N-3-PUFAs decreased serum concentrations of saturated and monounsaturated free fatty acids (FAs), while increasing serum concentrations of long-chain PUFAs. Furthermore, in the liver, the MCD significantly increased the hepatic triacylglycerol content, while the administration of n-3-PUFAs eliminated this effect. Administration of n-3-PUFAs led to significant beneficial differences in gene expression within biosynthetic pathways of cholesterol, FAs, and pro-inflammatory cytokines (IL-1 and TNF-α). To conclude, n-3-PUFA supplementation appears to represent a promising nutraceutical approach for the restoration of abnormalities in liver lipid metabolism and the prevention and treatment of NAFLD.

• Klíčová slova
• lipidome, lipids, n-3 fatty acids, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis,
• MeSH
• cholesterol metabolismus   MeSH
• cholin metabolismus   MeSH
• dieta s vysokým obsahem tuků škodlivé účinky   MeSH
• játra metabolismus   MeSH
• kyseliny mastné neesterifikované metabolismus   MeSH
• methionin metabolismus   MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• nealkoholová steatóza jater * etiologie   genetika   MeSH
• nenasycené mastné kyseliny metabolismus   MeSH
• omega-3 mastné kyseliny * farmakologie   terapeutické užití   metabolismus   MeSH
• Racemethionin metabolismus   farmakologie   MeSH
• triglyceridy metabolismus   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• cholesterol MeSH
• cholin MeSH
• kyseliny mastné neesterifikované MeSH
• methionin MeSH
• nenasycené mastné kyseliny MeSH
• omega-3 mastné kyseliny * MeSH
• Racemethionin MeSH
• triglyceridy MeSH

The temporal relationship of hepatic steatosis and changes in liver oxidative stress and fatty acid (FA) composition to the development of non-alcoholic steatohepatitis (NASH) remain to be clearly defined. Recently, we developed an experimental model of hepatic steatosis and NASH, the transgenic spontaneously hypertensive rat (SHR) that overexpresses a dominant positive form of the human SREBP-1a isoform in the liver. These rats are genetically predisposed to hepatic steatosis at a young age that ultimately progresses to NASH in older animals. Young transgenic SHR versus SHR controls exhibited simple hepatic steatosis which was associated with significantly increased hepatic levels of oxidative stress markers, conjugated dienes, and TBARS, with decreased levels of antioxidative enzymes and glutathione and lower concentrations of plasma alpha- and gamma-tocopherol. Transgenic rats exhibited increased plasma levels of saturated FA, decreased levels of n-3 and n-6 polyunsaturated FA (PUFA), and increased n-6/n-3 PUFA ratios. These results are consistent with the hypothesis that excess fat accumulation in the liver in association with increased oxidative stress and disturbances in the metabolism of saturated and unsaturated fatty acids may precede and contribute to the primary pathogenesis of NASH.

• MeSH
• genetická predispozice k nemoci MeSH
• játra metabolismus   patologie   MeSH
• krysa rodu Rattus MeSH
• lidé MeSH
• nenasycené mastné kyseliny metabolismus   MeSH
• oxidační stres * MeSH
• potkani inbrední SHR MeSH
• potkani transgenní MeSH
• protein SREBP1 genetika   metabolismus   MeSH
• ztučnělá játra genetika   metabolismus   patologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• nenasycené mastné kyseliny MeSH
• protein SREBP1 MeSH
• SREBF1 protein, human MeSH Prohlížeč