“The role of endothelial dysfunction and polymorphism of NOS genes in the mechanism of liver lesions of various genesis”

  • Grant registration: SSV-F-038
  • Grant location: Tashkent city, Tashkent Medical Academy.
  • Grant funding: 270.59 million sums
  • Financial organization: The Ministry of Innovation of the Republic of Uzbekistan
  • Grant type: Fundamental.
  • Grant period: 2017-2020 г.

Principle investigator:

  • Okhunov O. Alisher
  • Doctor of Medical Sciences, Professor
  • Place of work: Head of the Department of General and Pediatric Surgery TMA.
  • Еmail:
  • Contact phone: +998 (90) 947-45-68


In the pathogenesis of hepatitis, impaired intrahepatic hemodynamics are due to the damage of the sinusoids endothelial lining and endothelial dysfunction is of great importance. The pathogenetic role of the endothelial dysfunction has been proven in a number of the most common diseases and pathological conditions. In recent decades, paracrine – non-adrenergic, non-cholinergic regulation involving nitric oxide (NO) has occupied an important place in this aspect. NO mediates the vasodilating effect of many other mediators including kinins, acetylcholine, serotonin and catecholamines, polypeptide hormones of apudocytic origin; regulates the function of metabolic and immune systems, cytokine, endocrine, nervous, participates in carbohydrate, protein and lipid metabolism, the process of apoptosis.

The main source of vasoactive nitrogen in the intact bloodstream is the vascular endothelium, where it is produced by the activity of endothelial synthase nitric oxide (NOS). Its gene is localized on chromosome 7g35-36, has 26 exons and 25 introns. There is a polymorphism of the gene encoding NOS3, which is associated with the change in the concentration of NO in the plasma. The substitution of guanine with thymine at the 894 positions in exon 7 (894G> T polymorphism), associated with the decrease in basal NO production. However, a polymorphism in the promoter (786T> C polymorphism) leads to a significant reduction in the number of eNOS.

In recent decades, the role of NOS genes in the formation of susceptibility to multifactorial human diseases has been actively studied in the world. The association of polymorphic loci of candidate genes with the risk of development liver diseases remains studied inadequately. Therefore, the study of endothelium dysfunction and its genetic characteristics in liver pathologies seems to be an urgent task of pathophysiology and gastroenterology.

In the planned study, the role of endothelial dysfunction and polymorphism of NOS genes in the mechanism of liver lesions of various genesis will be clarified.

Publications on the project: 10 works were published during the reporting period

Articles (far abroad) –2:

  1. Sayfullaeva S.A. Functional and metabolic relationship of nitrergic and monooxygenase systems in hepatocyte microsomes during experimental liver ischemia // Medical News. -Minsk. -2019. – No. 5. – S. 82-86.
  2. Sayfullaeva S., Okhunov A., Jumanova N. Activity of Monooxygenase and Nitrogenous Systems in Liver Microsomes Under the Influence of Inducers and Inhibitors of Medicinal Metabolism on the Organism in Conditions of Liver Pathology // International Journal of Psychosocial Rehabilitation, Vol. 24, Issue 02, 2020.
  3. Sayfullaeva S. A., Zhumanova N. A., Adilkhanova N. A. Influence of the inducer of drug metabolism of benzonal on the activity of monooxygenase and nitrergic systems in experimental animals / Conf. young “Actual issues of medicine” .- Baku .- 2017.- Page 66.
  4. Sayfullaeva SA, Zhumanova NA, Makhkamova DB. The activity of the nitrergic system in microsomes under the action of inducers and inhibitors of monooxygenases in the ischemic liver / Conf. young “Actual issues of medicine” .- Baku .- 2017.- Page 29.

Abstracts (local) – 1:

Sayfullaeva S.A., Zhumanova N.A. Metabolic activity of the nitrergic system in animals with acute toxic hepatitis … / Collection of scientific. tr. scientific and practical. conf. with the participation of international experts “Modern methods of diagnosis, prevention and treatment of HIV infection.” – April 13-14, 2018. – Andijan. – P. 122-123.

Monograph (international) – 2:

  1. Okhunov A.O., Sayfullaeva S.A. The role of nitric oxide in the regulation of gastric functions / – LAP: Latvia. -2018.- 109s.
  2. Okhunov A.O., Sayfullaeva S.A., Zhumanova N.A. Activity of the nitrergic system in acute toxic hepatitis / – LAP: Latvia. -2018.- 69s.

Patent (international) – 2:

  1. S.A. Sayfullaeva, A.O. Okhunov, N.A. Zhumanova, I.O. Marupov “A method for assessing the activity of antioxidant and nitrergic systems in acute toxic hepatitis”. Electronic Depository “Interoco” (International online copyright offiice), 2018
  2. Sayfullaeva S.A., Okhunov A.O., Zhumanova N.A., Marupov I.O. A new theory on the mechanism of the relationship between nitrergic and monooxygenase systems in the implementation of pro-apoptotic processes in the liver // Interoco Electronic Depository (International online copyright offiice), – 2018. – No. EC-01-001985.

Guidelines (local) – 1:

Sayfullaeva S.A. Zhumanova N.A., Okhunov A.O. Activity of antioxidant and nitrergic systems in acute toxic hepatitis / Guidelines. -Tashkent. 2019. -60s.

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