Metabolic and genetic basis of liver damage in mechanical jaundice of non-tumor genesis in obstractive cholangitis or biliary pancreatitis

Aim. Establishment of versatile mechanisms behind liver damage in mechanical jaundice of non-tumor genesis combined with acute obstructive cholangitis or acute biliary pancreatitis.

Materials and methods. In total, 64 cases of mechanical jaundice developed against the background of cholelithiasis were studied. Group 1 included 30 patients with mechanical jaundice combined with cholangitis; group 2 included 34 patients with acute biliary pancreatitis. Bile duct reconstruction was performed by an open method followed by standardized treatment. The intensity of membrane lipid peroxidation was determined by the level of diene conjugates, malonic dialdehyde, superoxide dismutase activity, and the activity of phospholipase A2. The severity of endotoxemia was estimated; a molecular-genetic test of the polymorphism of antioxidant system genes was performed.

Results. The significance of the gene polymorphism of antioxidant enzymes in the formation of systemic alterative phenomena and severity of liver damage in mechanical jaundice complicated by cholangitis or acute pancreatitis was determined by allocation of patient subgroups depending on the presence of mutant allele T in the gene of superoxide dismutase SOD2 (C1147T). The groups of patients with the presence of such polymorphism, regardless of the combined diseases, demonstrated more pronounced and prolonged liver functional disorders and homeostasis disorders after restoration of biliary tract patency.

Conclusion. The presence of mutant alleles of the SOD2 gene (C47T) in patients with non-tumor mechanical jaundice combined with acute cholangitis or pancreatitis is associated with an increase in the intensity of damage mechanisms at the systemic level, primarily with membrane lipid peroxidation, which correlates with the severity of liver damage (r = 0.834–0.967; p < 0.05).

1. Dibirov M.D., Elderkhanov M.M., Magomedaliev A.M. Results of implementing Fast Track principles in surgery for obstructive jaundice in high-risk individuals // Infections in surgery. 2020; 18 (3-4): 44–48. (In Russian)

2. Rybachkov V.V., Mayorov M.M., Dryazhenkov I.G., Dubrovina D.E.On the degree of effectiveness of surgical treatment for obstructive jaundice //Patient-oriented medicine and pharmacy. 2023; 1 (2): 8-14. (In Russian)

3. Vlasov A.P., Sheiranov N.S., Markin O.V., Shukshin A.N., Afonkin A.A., Myshkina N.A. Optimization of treatment of patients with obstructive jaundice// News of higher educational institutions. Volga region. Medical Sciences. 2022. No. 2 (62). pp. 74-82. (In Russian)

4. Mikhailichenko V.Yu., Kislyakov V.V., Reznichenko A.M., Samarin S.A. Modern aspects of surgical treatment of obstructive jaundice syndrome // Modern problems of science and education. 2019; 3. URL: http://www.science-education.ru/ru/article/view?id=28755. (In Russian)

5. Ruziboyzoda K.R., Gulov M.K., Safarzoda A.M., Safarov B.I., Khalimov J.S., Gulomov L.A., Nurov Z.Kh. Optimization of treatment of liver failure in patients with obstructive jaundice // Bulletin of the National Medical and Surgical Center named after. N.I. Piro-gova. 2023. 18 (1): 69-73. (In Russian)

6. Vinnik Yu.S., Achkasov E.E., Kochetova L.V., Pakhomova R.A. Atomic force microscopy of hepatocytes with varying degrees of bilirubinemia //Medical Bulletin of the North Caucasus. 2022; 17 (3): 291-294. (In Russian)

7. Gulov M.K., Ruziboyzoda K.R., Abdullozoda S.M., Safarov B.I. The role of endothelial dysfunction in the pathogenesis of liver failure in obstructive jaundice // Avicenna Bulletin. 2022; 24 (2): 218-228. (In Russian)

8. Fedorov V.E., Kharitonov B.S., Aslanov A.D., Logvina O.E., Naryzhnaya M.S. Changes in the blood coagulation system that determine postoperative complications in patients with non-tumor obstructive jaundice // Bulletin of Surgery named after. I.I. Grekova. 2021; 180(2):12–20. (In Russian)

9. Koshevsky P.P., Alekseev S.A., Bovtyuk N.Ya., Olesyuk D.V. Dynamics of cytokine status, level of endogenous intoxication, state of the antioxidant defense system and humoral immunity factors in patients with obstructive jaundice of non-tumor origin // Medical Journal. 2016; 55 (1): 123-127.(In Russian)

10. Shevchenko Yu.L., Vetshev P.S., Stoiko Yu.M. Levchuk A.L., Bardakov V.G., Stepanyuk I.V. Diagnosis and surgical tactics for obstructive jaundice syndrome // Surgical Annals. hepatology. 2008; 13 (4):.96-107. (In Russian)

11. Fomin A.M. The influence of selective plasma sorption on endotoxicosis and cytokinemia in obstructive jaundice // Bulletin of anesthesiology and resuscitation. 2021; 18 (5): 40–46. (In Russian)

12. Takada T., Toshihiko Т., Mayumi Т. Accuracy of the Tokyo Guidelines for the diagnosis of acute cholangitis and cholecystitis taking into consideration the clinical practice pattern in Japan// J. Hepatobiliary Pancreat. Sci. 2018; 18 (2): 250– 257.

13. Galperin E.I. Classification of the severity of obstructive jaundice // Annals of surgical hepatology. 2012; 2: 26-34. (In Russian)

14. Egorov D.Ju., Kozlov A.V. The nature of lipid peroxidation products, determined in blood serum by reaction with 2-thiobarbituric acid. M. 1988. P. 3-13. (In Russian)

15. Trofimov V.A., Vlasov A.P., Ashirov R.Z. Biochemical methods for the study of lipids in the clinic. Saransk, 2001. 80 p. (In Russian)

16. Dobrecov G.E. Serum albumin in clinical medicine. Moskva. GEOTAR_MED, 1998. 440 p. (In Russian)

17. Savchenko O.A., Pavlinova E.B., Polyanskaya N.A., Kirshina I.A., Kurmasheva E.I., Gubich A.A. The role of polymorphisms of antioxidant activity genes in the formation of disabling pathology of the central nervous system in premature newborns // Russian Bulletin of Perinatology and Pediatrics. 2020; 65 (5): 42-46. https://doi.org/10.21508/1027-4065-2020-65-5-42-46 (In Russian)

18.