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2018, vol. 57, iss. 3, pp. 66-74
Nitrates and nitrites significance in the development of alcoholic liver disease
aKliničko-bolnički centar Gračanica, Laplje selo
bUniversity of Priština - Kosovska Mitrovica, Faculty of Medicine, Serbia
Alcoholism is one of the most common addictions affecting health and the immune system in people worldwide. Chronic alcohol consumption over a prolonged period of time causes metabolic liver injury, along with arginine metabolism and nitric oxide (NO) synthase disorders. Ethanol intoxication under cumulative nitrooxidative and nitrosative stress conditions, as well as in inflammation, stimulates the production of NO anion (NO-) and superoxide anion (O2-), i.e. peroxynitrite formation in hepatocytes and endothelium. Mitochondrial dysfunction and disorders of adenosine triphosphate (ATP) molecules synthesis in hepatocytes cause disorders of intra - and extracellular antioxidants synthesis (glutathione and superoxide dismutase) and neutralization of toxic nitrates and nitrites. Peroxynitrites damage cell membranes lipoproteins, as well as the membrane enzyme systems and the mitochondrial matrix. They also damage the enzymes of ethanol and arginine metabolism in cytosol, and nucleic acid repair enzymes in hepatocytes. In the development of alcoholic liver disease (ALD), peroxynitrites cause reversible injuries of the structure and function of hepatocytes that proceed irreversibly, and vascular sinus endothelial damage, mediated by the mechanisms of apoptosis and necrosis. Considering the fact that 3.3 million people die of ALD and its complications annually, the measures should be taken and aimed at reducing the onset, development, and progression of ALD. The priority is timely ALD diagnosis, as well as the severity of alcoholic liver damage. The studies have shown that the values of peroxynitrite elevation correlate with the severity of liver injury. It can be concluded that timely determination of peroxynitrite values followed by suitable antioxidant therapies may slow down the processes of hepatocyte apoptosis and necrosis, as well as the course of ALD.
Alam, I., Bass, N.M., Bacchetti, P., Gee, L., Rockey, D.C. (2000) Hepatic tissue endothelin-1 levels in chronic liver disease correlate with disease severity and ascites. American Journal of Gastroenterology, 95(1): 199-203
Ali, E.M., Soha, M., Tarek, M. (2012) Nitric Oxide Synthase and Oxidative Stress: Regulation of Nitric Oxide Synthase. in: Lushchak, Volodymyr [ed.] Oxidative Stress - Molecular Mechanisms and Biological Effects, Rijeka: IntechOpen
Ambade, A., Mandrekar, P. (2012) Oxidative Stress and Inflammation: Essential Partners in Alcoholic Liver Disease. International Journal of Hepatology, 2012: 1-9
Armstrong, J.S. (2006) Mitochondrial membrane permeabilization: the sine qua non for cell death. BioEssays, 28(3): 253-260
Beier, J.I., McClain, C.J. (2010) Mechanisms and cell signaling in alcoholic liver disease. Biological Chemistry, 391(11):
Bhandari, S., Agarwal, M., Dwivedi, S., Banerjee, B. (2008) Monitoring oxidative stress across worsening child pugh class of cirrhosis. Indian Journal of Medical Sciences, 62(11): 444
Bonfoco, E., Krainc, D., Ankarcrona, M., Nicotera, P., Lipton, S.A. (1995) Apoptosis and necrosis: two distinct events induced, respectively, by mild and intense insults with N-methyl-D-aspartate or nitric oxide/superoxide in cortical cell cultures. Proceedings of the National Academy of Sciences, 92(16): 7162-7166
Brookes, P.S., Darley-Usmar, V.M. (2004) Role of calcium and superoxide dismutase in sensitizing mitochondria to peroxynitrite-induced permeability transition. American Journal of Physiology-Heart and Circulatory Physiology, 286(1): H39-H46
Cassina, A.M., Hodara, R., Souza, J.M., Thomson, L., Castro, L., Ischiropoulos, H., Freeman, B.A., Radi, R. (2000) Cytochrome c Nitration by Peroxynitrite. Journal of Biological Chemistry, 275(28): 21409-21415
Cederbaum, A.I., Lu, Y., Wu, D. (2009) Role of oxidative stress in alcohol-induced liver injury. Archives of Toxicology, 83(6): 519-548
Chacko, K.R., Reinus, J. (2016) Spectrum of Alcoholic Liver Disease. Clinics in Liver Disease, 20(3): 419-427
Cui, H., Kong, Y., Zhang, H. (2012) Oxidative Stress, Mitochondrial Dysfunction, and Aging. Journal of Signal Transduction, 2012: 1-13
Forstermann, U., Sessa, W.C. (2012) Nitric oxide synthases: regulation and function. European Heart Journal, 33(7): 829-837
Gracia-Sancho, J., Laviña, B., Rodríguez-Vilarrupla, A., García-Calderó, H., Fernández, M., Bosch, J., García-Pagán, J. (2007) Increased oxidative stress in cirrhotic rat livers: A potential mechanism contributing to reduced nitric oxide bioavailability. Hepatology, 47(4): 1248-1256
Ha, H.C., Snyder, S.H. (1999) Poly(ADP-ribose) polymerase is a mediator of necrotic cell death by ATP depletion. Proceedings of the National Academy of Sciences, 96(24): 13978-13982
Han, D., Canali, R., Garcia, J., Aguilera, R., Gallaher, T.K., Cadenas, E. (2005) Sites and Mechanisms of Aconitase Inactivation by Peroxynitrite:  Modulation by Citrate and Glutathione †. Biochemistry, 44(36): 11986-11996
Hannah, E. (2010) The effect of acute alcohol exposure on hepatic oxidative stress and function: Revention by micronutrients. University of Westminster
Haynes, V., Elfering, S., Traaseth, N., Giulivi, C. (2004) Mitochondrial Nitric-Oxide Synthase: Enzyme Expression, Characterization, and Regulation. Journal of Bioenergetics and Biomembranes, 36(4): 341-346
Heck, D., Kagan, V., Shvedova, A., Laskin, J. (2005) An epigrammatic (abridged) recounting of the myriad tales of astonishing deeds and dire consequences pertaining to nitric oxide and reactive oxygen species in mitochondria with an ancillary missive concerning the origins of apoptosis. Toxicology, 208(2): 259-271
Herceg, Z., Wang, Z. (2001) Functions of poly(ADP-ribose) polymerase (PARP) in DNA repair, genomic integrity and cell death. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 477(1-2): 97-110
Iwakiri, Y., Kim, M.Y. (2015) Nitric oxide in liver diseases. Trends in Pharmacological Sciences, 36(8): 524-536
Kanwar, J., Kanwar, R., Burrow, H., Baratchi, S. (2009) Recent Advances on the Roles of NO in Cancer and Chronic Inflammatory Disorders. Current Medicinal Chemistry, 16(19): 2373-2394
Li, S., Tan, H., Wang, N., Zhang, Z., Lao, L., Wong, C., Feng, Y. (2015) The Role of Oxidative Stress and Antioxidants in Liver Diseases. International Journal of Molecular Sciences, 16(11): 26087-26124
Louvet, A., Mathurin, P. (2015) Alcoholic liver disease: mechanisms of injury and targeted treatment. Nature Reviews Gastroenterology & Hepatology, 12(4): 231-242
Manzo-Avalos, S., Saavedra-Molina, A. (2010) Cellular and Mitochondrial Effects of Alcohol Consumption. International Journal of Environmental Research and Public Health, 7(12): 4281-4304
Martindale, J.L., Holbrook, N.J. (2002) Cellular response to oxidative stress: Signaling for suicide and survival. Journal of Cellular Physiology, 192(1): 1-15
Newmeyer, D.D., Ferguson-Miller, S. (2003) Mitochondria. Cell, 112(4): 481-490
Nickovic, V., Kocic, G., Bjelakovic, G., Pavlovic, R., Stojanovic, I., Katanic, R., Stojanovic, S., Djindjic, B. (2013) Diagnostic Significance of Nitrates and Nitrites and L-Arginine, in Development of Hepatorenal Syndrome in Patients with End Stage Alcoholic Liver Cirrhosis. Renal Failure, 35(5): 633-639
Ničković, V., Nikolić, J., Kocić, G., Ilić, M., Đinđić, B. (2011) Complications of alcoholic liver disease and diagnostic markers. Acta medica Medianae, vol. 50, br. 4, str. 55-61
Nikolić, J., Ničković, V., Aćimović, D. (2012) Contemporary aspects of the diagnostics of alcoholic liver disease. Vojnosanitetski pregled, vol. 69, br. 10, str. 874-879
Pavlović, D. (2006) Biološka oksidacija. in: Koračević D.; Bjelaković G.; Đorđević V.; Nikolić J.; Pavlović D.; Kocić G. [ed.] Biohemija, Beograd: Savremena administracija, p. 678-705
Pearce, L.L., Kanai, A.J., Epperly, M.W., Peterson, J. (2005) Nitrosative stress results in irreversible inhibition of purified mitochondrial complexes I and III without modification of cofactors. Nitric Oxide, 13(4): 254-263
Pearce, L.L., Kanai, A.J., Birder, L.A., Pitt, B.R., Peterson, J. (2002) The Catabolic Fate of Nitric Oxide. Journal of Biological Chemistry, 277(16): 13556-13562
Rouach, H., Fataccioli, V., Gentil, M., French, S.W., Morimoto, M., Nordmann, R. (1997) Effect of chronic ethanol feeding on lipid peroxidation and protein oxidation in relation to liver pathology. Hepatology, 25(2): 351-355
Shah, V., Haddad, F.G., Garcia-Cardena, G., Frangos, J.A., Mennone, A., Groszmann, R.J., Sessa, W.C. (1997) Liver sinusoidal endothelial cells are responsible for nitric oxide modulation of resistance in the hepatic sinusoids. Journal of Clinical Investigation, 100(11): 2923-2930
Stachowiak, O., Dolder, M., Wallimann, T., Richter, C. (1998) Mitochondrial Creatine Kinase Is a Prime Target of Peroxynitrite-induced Modification and Inactivation. Journal of Biological Chemistry, 273(27): 16694-16699
Szabo, C., Zingarelli, B., Connor, O.M., Salzman, A.L. (1996) DNA strand breakage, activation of poly (ADP-ribose) synthetase, and cellular energy depletion are involved in the cytotoxicity of macrophages and smooth muscle cells exposed to peroxynitrite. Proc Natl Acad Sci USA, 93(5): 1753-8
Vairappan, B. (2015) Endothelial dysfunction in cirrhosis: Role of inflammation and oxidative stress. World Journal of Hepatology, 7(3): 443
Vieira, H.L., Belzacq, A., Haouzi, D., Bernassola, F., Cohen, I., Jacotot, E., Ferri, K.F., el Hamel, C., Bartle, L.M., Melino, G., Brenner, C., Goldmacher, V., Kroemer, G. (2001) The adenine nucleotide translocator: a target of nitric oxide, peroxynitrite and 4-hydroxynonenal. Oncogene, 20(32): 4305-4316
Wray, G.M., Millar, C.G., Hinds, C.J., Thiemermann, C. (1998) Selective inhibition of the activity of inducible nitric oxide synthase prevents the circulatory failure, but not the organ injury/dysfunction, caused by endotoxin. Shock, 9(5): 329-335
Zhou, L., Zhu, D. (2009) Neuronal nitric oxide synthase: Structure, subcellular localization, regulation, and clinical implications. Nitric Oxide, 20(4): 223-230
Zhu, H., Jia, Z., Misra, H., Li, Y.R. (2012) Oxidative stress and redox signaling mechanisms of alcoholic liver disease: Updated experimental and clinical evidence. Journal of Digestive Diseases, 13(3): 133-142


article language: English
document type: Review Paper
DOI: 10.5633/amm.2018.0309
published in SCIndeks: 10/01/2019
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