Deposition features of heterovalent iron (Fe2 + and Fe3 +) in the liver in alcoholic and nonalcoholic steatohepatitis
DOI:
https://doi.org/10.14739/2310-1237.2015.3.55589Keywords:
Fatty Liver, Alcoholic Steatohepatitis, Nonalcoholic Steatohepatitis, Ferrous (Fe2 ) Iron, Ferric (Fe3 ) Iron, Hepatocytes, Macrophages KupfferAbstract
Aim. The article describes morphological characteristics of the heterovalent iron compounds (ferric (Fe3 +) iron, ferrous (Fe2 +) iron) deposition in the acini of the liver.
Methods and results. Using histochemical methods, features of accumulation of ferrous (Fe2 +) and ferric (Fe3 +) iron in hepatic acinar zone were studied in the trephine biopsy and autopsy liver material of 35 patients suffering from alcoholic steatohepatitis (ASH) of different (S1, S2, S3) degree, and trephine liver biopsy of 15 patients suffering from moderate S2 non-alcoholic steatohepatitis (NASH). It was found that in the ASH Fe3 + deposition in liver macrophages and hepatocytes predominates over Fe2 +accumulation, and Fe3 + extracellular localization is defined primarily in the areas of liver steatonecrosis. The intensity of Fe3 + and Fe2 + deposition in the liver increases from G2 to G4 degree with increasing of severity of ASH from S1 to S3. In patients with NASH of moderate degree, accumulation of Fe3 + and Fe2 + is determined in liver macrophages and hepatocytes in mild G2 degree.
Conclusions. It is assumed that the deposition of Fe3 + and Fe2 + in liver cells and extracellular matrix most likely contributes to the ASH development.
References
Kurz, T., Eaton, J., & Brunk, U. (2011). The role of lysosomes in iron metabolism and recycling. The International Journal of Biochemistry & Cell Biology, 48(12), 1686-1697.
Ganz, T., & Nemeth, E. (2011). Hepcidin and Disorders of Iron Metabolism. Annu. Rev. Med., 62, 347-360. doi:10.1146/annurev-med-050109-142444.
Bogush, L. S., Bychkov, V. M., Rogov, Ju. I., Kleckij, S. K., Omel'janjuk N. N., & Burceva, O. V. (2008). Osobennosti gemosideroza u bol'nyh diffuznymi zabolevanijami pecheni [Features hemosiderosis in patients with diffuse liver diseases]. Recept, 4, 122–130.
Filimonov, V. I., Tihonovskaja, M. A., Bessarab, G. I., Suhomlinova, I. E., Pirtja, G. V., Burega, I. Ju., & Tihonovskij, A. V. (2012). Sovremennye aspekty metabolizma zheleza i ego reguljacii [Modern aspects of iron metabolism and its regulation]. Zaprozhskij medicinskij zhurnal, 4, 54–59. [in Ukrainian].
Levina, A. A., Kazjukova, T. V., Cvetaeva, N. V., Sergeeva, A. I., Mamukova, Ju. I., Romanova, E. A., & Cybul'skaja, M. M. (2008). Gepsidin kak reguljator gomeostaza zheleza [Hepcidin as a regulator of iron homeostasis]. Pediatrija, 87(1), 67-74. [in Russian].
Pigeon, C., Ilyin, G., Courselaud, B., Leroyer, P., Turlin, B., Brissot, P., & Loreal, O. (2001). A New Mouse Liver-specific Gene, Encoding a Protein Homologous to Human Antimicrobial Peptide Hepcidin, Is Overexpressed during Iron Overload. Journal of Biological Chemistry, 276(11), 7811-7819.
Deugnier, Y., Turlin, B. (2012). Section IV Disorders of Iron Homeostasis: Iron Overload and Related Conditions - The Pathology of Hepatic Iron Overload. In Iron Physiology and Pathophysiology in Humans. Springer: New York, Dordrecht Heidelberg London.
Aigner, E., Weiss, G., & Datz, C. (2015). Dysregulation of iron and copper homeostasis in nonalcoholic fatty liver. World J Hepatology,7(2), 177–188.
Valenti, L., Fracanzani, A. L., Dongiovanni, P., Rovida, S., Rametta, R., Fatta, E., Pulixi, E., Maggioni, M., & Fargion, S. (2014). A randomized trial of iron depletion in patients with nonalcoholic fatty liver disease and hyperferritinemia. World J Gastroenterol. 20(11), 3002–3010. doi: 10.3748/wjg.v20.i11.3002.
Sorrentino, P., D’Angelo, S., Ferbo, U., Micheli, P., Bracigliano, A., & Vecchione, R. (2010). Liver iron excess in patients with hepatocellular carcinoma developed on non-alcoholic steato-hepatitis. Journal of Hepatology, 50(2), 351-357. doi: 10.1016/j.jhep.2008.09.011.
Tiniakos D. G., Vos, M. B., & Brunt, E. M. (2010). Nonalcoholic fatty liver disease: pathology and pathogenesis. Annual Review of Patholog, 5, 145-171. doi: 10.1146/annurev-pathol-121808-102132.
Acton, R. T, Barton, J. C, Snively, B. M, McLaren, C. E, Adams, P. C., & Harris E. L. (2006). Hemochromatosis and Iron Overload Screening (HEIRS) Study Ethnicity and Disease, 16(4), 815–821.
Merryweather-Clarke, A. T, Pointon, J. J, Jouanolle, A. M., Rochette, J., & Robson, K. J. (2000). Geography of HFE C282Y and H63D mutations. J. Genetic Testing, 4(2), 183–198.
Bogush, L. S., Sivickaja, L. N, & Danilenko, N. G. (2009). Rol' C282Y i H63D mutacij HFE gena v formirovanii vtorichnoj peregruzki zhelezom [The role of the C282Y and H63D mutations in HFE gene in the formation of secondary iron overload]. Med. panorama. 7, 52-55. [in Russian].
Ningning, Z., An-Sheng Zhang, & Caroline, A. (2013). Enns: Iron regulation by hepcidin. J Clin Invest. 123(6), 2337–2343.
Penkova, M., Gulubova, M., Ananiev, J., Ivanova, R., & Mateva, L. (2012). Role of hepcidin in the regulation of iron metabolism in patients with chronic liver diseases. Inter. J. of Business Humanities and Technology, 2(7), 89–94.
Smirnov, O. A. (2001). Kliniko-morfologicheskaja harakteristika pervichnyh i vtorichnyh gipersiderozov [Clinical and morphological characteristics of primary and secondary gipersiderozov]. Avtoref. dis. na soisk. uchen. step. d.m.n. Spec. 14.00.15 [S.-Peterb. med. akad. poslediplom. obrazovanija]. SPb. [in Russian].
Kleiner, D. E., Brunt, E. M., Natta, van M., & Behling, C. (2005). Design and validation of a histological scoring system for nonalcoholic fatty liver disease. J. Hepatology, 41(6), 1313-1321.
Celujko, S. S., & Zinov'ev, S. V. (2013). Predpolagaemye mehanizmy gistohimicheskogo issledovanija kal'cija, zheleza, natrija, cinka i vitaminov v organizme [Proposed mechanisms histochemical studies of calcium, iron, sodium, zinc and vitamins in the body]. Blagoveshhensk. [in Russian].
Lilli R. (1969). Patogistologicheskaja tehnika i prakticheskaja gistohimija [Histopathological technique and practical histochemistry]. Moscow: Mir. [in Russian].
Torbenson, M. (2009). Classification of iron grading. Linda, F., Sanjay, K., David, E. (ed.). Book Liver Pathology. USA, Pennsylvania.
Pulixi, E. A., & Arosio, P. (2010). Relative contribution of iron genes, dysmetabolism and alcoholic steatohepatitis in the pathogenesis of altered iron regulation in chronic hepatitis. Heamatologica, 92(8), 1037-1042.
Kuznecova, A. V., Dubotolkina, E. V., & Lojfman, E. A. (2009). Pokazateli obmena zheleza pri alkogol'nom steatogepatite [Indicators iron metabolism in alcoholic steatohepatitis]. Rossijskij zhurnal Gastrojenterologii, Gepatologii, Koloproktologii. 19(5), 92. [in Russian].
Harrison-Findik D. D. (2010). Gender-related variations in iron metabolism and liver diseases. World J Hepatol, 2(8), 302–310.
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