Oxidative Distress in Pathogenesis of Alcoholic Liver and Its Correction

The aim of the study was to evaluate the effect of the succinatecontaining antioxidants Reamberin and Cytoflavin on (1) free radical oxidation of lipids and functioning of the antioxidant system in patient with alcoholic liver disease and hepatic encephalopathy and (2) severity of hepatocellular dysfunction.

Material and methods. Prospective study involved 150 patients with alcoholic liver disease divided into three groups: Group 1 (n=50), Group 2 (n=50) and the control group (n=50). Patients of two main experimental groups (Group 1 and Group 2) received antioxidants in addition to conventional basic therapy: patients of Group 1 were administered with Reamberin, whereas in Group 2 Cytoflavin was administered. Intensive care for the patients of the control group did not include any antioxidants. The study involved assessment of the clinical course of hepat ic encephalopathy, biochemical markers of hepatic cell dysfunction, and indicators of lipid oxidation and antioxi dant defense system of the body. Nonparametric statistic methods were used for evaluation of the results.

Results. All examined patients had an increased intensity of free radical oxidation of lipids and low general antioxidant activity demonstrating oxidative distress. Patients from groups 1and 2 exhibited significant improve ment in cognitive and motor functions, positive dynamics of the clinical course of the disease and hepatocellular dysfunction. There was also a trend towards normalization of free radical oxidation of lipids antioxidant para metrs of blood.

Conclusion. Administration of succinatecontaining drugs in alcoholic liver disease resulted in reduction of the period of patients' stay at the Intensive Care Unit and improved longterm effects manifested as prolonged periods of clinical remission of hepatic encephalopathy.

1. Paukov V.S., Erokhin Ya.A. Patologicheskaya anatomiya pyanstva i alkogolizma. [Pathologic anatomy of hard drinking and alcoholism]. Arkhiv Patologii. 2004; 66 (4): 3—9. PMID: 15449679. [In Russ.]

2. Antonyan A.A., Kashkina E.I., Lyakisheva R.V. Sovremennye predstavleniya ob alkogolnoi bolezni pecheni. [New data on alcoholic liver disease]. Saratovsky NauchnoMeditsinsky Zhurnal. 2010; 6 (2): 317—322. [In Russ.]

3. Khoroshilov S.E., Polovnikov S.G., Astashev V.L., Skvortsov S.V., Kudryashov S.K., Khazanov A.I. Ostraya (molnienosnaya) i ostraya/khronicheskaya pechenochnaya nedostatochnost: vozmozhnosti korrektsii albuminovym dializom na apparate MARS. [Acute (fulminant) and acute/chronic hepatic failure: potential for correction by albumin dialysis with MARS device]. Rossiisky Zhurnal Gastroenterologii, Gepatologii, Koloproktologii. 2007; 17 (2): 57—62. [In Russ.]

4. Bueverov A.O. Oksidativnyi stress i ego rol v povrezhdenii pecheni. [Oxidative stress and its role in liver injury]. Rossiisky Zhurnal Gastroenterologii, Gepatologii, Koloproktologii. 2002; 12 (4): 21—25. [In Russ.]

5. Moroz V.V. Strategiya i taktika primeneniya antigipoksantov pri kriticheskikh sostoyaniyakh. V kn.: Moroz V.V. (red.). Fundamentalnye problemy reanimatologii. t.5. Istoricheskie aspekty i obshchie problemy reanimatologii. [Strategy and tactics of antihypoxants administration in critical states. In.: Moroz V.V. (ed.). Fundamental problems of reanimatology. v. 5. Historical aspects and general problems of reanimatology]. Moscow: FGBNU NIIOR; 2014: 56—62. [In Russ.]

6. Panchenko L.F., Davydov B.V., Terebilina N.N., Baronets V.Yu., Zhuravleva A.S. Okislitelnyi stress pri alkogolnoi bolezni pecheni. [Oxidative stress in alcoholic liver disease]. Biomeditsinskaya Khimiya. 2013; 59 (4): 452—458. PMID: 24502143. [In Russ.]

7. Shabanov P.D., Zarubina I.V., Novikov V.E., Tsygan V.N. Metabolicheskie korrektory gipoksii. [Metabolic correctors of hypoxia]. SanktPeterburg: Inform – Navigator; 2010: 916. [In Russ.]

8. Ha H.L., Shin H.J., Feitelson M.A., Yu D.Y. Oxidative stress and antioxidants in hepatic pathogenesis. World J. Gastroenterol. 2010; 16 (48): 6035—6043. http://dx.doi.org/10.3748/wjg.v16.i48.6035. PMID: 21182217

9. Shinde A., Ganu J., Naik P., Sawant A. Oxidative stress and antioxidative status in patients with alcoholic liver disease. Biomedical Research. 2012; 23 (1): 105—108.

10. Golubev A.M., Sundukov D.V., Bashirova A.R., Golubev M.A. Morfologicheskie izmeneniya golovnogo mozga pri ostrykh kombinirovannykh otravleniyakh azaleptinom i etilovym alkogolem. Obshchaya Reanimatologiya. [Brain morphological changes in acute combined intoxication with asaleptin and ethyl alcohol. General Reanimatology]. 2012; 8 (6): 31—36. http://dx.doi.org/10.15360/181397792012631. [In Russ.]

11. Lemberg A., Fernández M.A. Hepatic encephalopathy, ammonia, glutamate, glutamine and oxidative stress. Ann. Hepatol. 2009; 8 (2): 95—102. PMID: 19502650

12. Seyan A.S., Hughes R.D., Shawcross D.L. Changing face of hepatic encephalopathy: role of inflammation and oxidative stress. World J. Gastroenterol. 2010; 26 (27): 3347—3357. http://dx.doi.org/10.3748/wjg.v16.i27.3347. PMID: 20632436

13. Bajaj J.S. Review article: the modern management of hepatic encephalopathy. Aliment. Pharmacol. Ther. 2010; 31 (5): 537—547. http://dx.doi.org/10.1111/j.13652036.2009.04211.x. PMID: 20002027

14. Butterworth R.F. Hepatic encephalopathy: a central neuroinflammatory disorder? Hepatology. 2011; 53 (4): 1372—1376. http://dx.doi.org/10.1002/ hep.24228. PMID: 21480337

15. Cordoba J. New assessment of hepatic encephalopathy. J. Hepatology. 2011; 54 (5): 1030—1040. http://dx.doi.org /10.1016/ j.jhep.2010. 11.015. PMID: 21145874

16. Bismuth M., Funakoshi N., Cadranel J.F., Blanc P. Hepatic encephalopathy: from pathophysiology to therapeutic management. Eur. J. Gastroenterol. Hepatol. 2011; 23 (1): 8—22. http://dx.doi.org/10.1097/MEG.0b013e3283417567. PMID: 21099434

17. Montagnese S., Biancardi A., Schiff S., Carraro P., Carlà V., Mannaioni G., Moroni F., Tono N., Angeli P., Gatta A., Amodio P. Diffirent biochemical correlates for diffirent neuropsychiatric abnormalities in patients with cirrhosis. Hepatology. 2011; 53 (2): 558—566. http://dx.doi.org/10.1002/ hep.24043. PMID: 21274876

18. Afanasyev V.V., Lukyanova I.Yu. Osobennosti primeneniya Tsitoflavina v sovremennoi klinicheskoi praktike. Metodicheskie rekomendatsii. [Guidelines on the use of Cytoflavin in modern clinical practice]. SanktPeterburg: Taktik – Studio; 2010: 80. [In Russ.]

19. Bueverov A.O. Patogeneticheskie osnovy pechenochnoi entsefalopatii: focus na ammiak. [Pathogenic bases of hepatic encephalopathy: focus on ammonia]. Klinicheskie Perspektivy Gastroenterologii, Gepatologii. 2012; 6: 3—10. [In Russ.]

20. Zakharov V.V. Neiropsikhologicheskie testy. Neobkhodimost i vozmozhnost primeneniya. [Neurophsycological tests. Necessity and possibilities of implementation]. Consilium Medicum. 2011; 13 (2): 98—106. [In Russ.]