Content of Some Endothotelium-Dependent Vasoactive Substances in the Blood of Patients, Depending on the Liver Cirrhosis Severity and the Organism’s Redox System State

Abstract

Introduction. It is known that liver cirrhosis (LC) is a chronic diffuse liver disease, the severity of which is manifested by the restructuring of its parenchyma in the form of nodular transformation and fibrosis due to necrosis of hepatocytes, the appearance of shunts between the portal and central veins and liver failure. Oxidative stress is one of the primary pathogenetic links of the LC onset. The aim of study. To determine the content of some endothelium-dependent vasoactive substances in the blood of patients, depending on the liver cirrhosis severity and the organism’s redox system state. Materials and methods. 81 patients (26 females (32.1 %), 55 males (67.9 %) aged 27 to 73 years (mean age – 46.9 ± 10.8 years) were included in the randomized trial with the preliminary stratification by the presence of LC (experimental group – EG). All of them were hospitalized and treated at the Department of Internal Medicine N 1 at Danylo Halytsky Lviv National Medical University and the Gastroenterology Department of Lviv Regional Clinical Hospital – Lviv Regional Hepatology Center. We also examined 20 practically healthy persons (8 females (40.0 %), 12 males (60.0 %)) aged 19 to 70 years (mean age – 41.8 ± 4.2 years) from which a control group (CG) was formed. All patients underwent a comprehensive clinical laboratory and instrumental examination of all organs and systems in accordance with the requirements of the modern medicine. According to the results of the examinations, all the patients of the EG were divided into 3 groups, according to the LC severity by the criteria of C. H. Child – R. N. Pugh – in the first (class A) was 19, in the second (class B) – 29, in the third (class C) – 27 persons. To study the concentration of some endothelium-dependent vasoactive substances in blood of the cirrhotic patients, the content of endothelin-1, cyclic guanosine monophosphate (cGMP), renin, aldosterone, and also natriuretic peptide were determined using standard methods. The activity of catalase and content of thiobarbituric acid (TBA) products, including malondialdehyde (MDA), was studied to determine the redox system state. The actual material was handled on a personal computer in Exel 2010, Statistica 6.0, RStudio v. 1.1.442 and R Commander v.2.4-4 using descriptive statistics. The results obtained in the case of normal distribution were presented as M ± σ, n – the number of patients examined in the group, in case of abnormal distribution – Me [25,0 %; 75.0 %]. The difference was considered statistically significant if p < 0.05. Results. In accordance with the results of the study, it was found that the activity of catalase in the cirrhotic patients significantly (p < 0.001) decreased, and content of MDA content significantly (p < 0.001) increased with the LC severity increase according to the criteria of C. H. Child – R. N. Pugh. It testifies the reduction of antioxidant activity and enhancement of the reactive oxygen species activity with the formation of such toxic substances as MDA in the blood of this category of persons confirming the redox homeostasis disorders. It leads to the impaired functioning of the endothelial cells that are one of the most sensitive to the reactive oxygen species cells. As a result, NO-dependent vasodilatation, increased endothelin-1 synthesis, activation of the renin-aldosterone system, whose effect is negligible, since the decreased sensitivity of the vascular receptors to the influence of endogenous vasoconstrictors, increase of the content of natriuretic peptide, due to the inhibition of renin and aldosterone secretion, as well as a direct effect on the smooth muscle cells of the vascular wall. This is confirmed by the increase of the content of endothelin-1, cGMP, renin, aldosterone, natriuretic peptide in the blood of this category of patients with the LC increasing severity according to the criteria of C. H. Child – R. N. Pugh. Conclusions. The liver significantly influences the endothelium state due to the role of oxidative stress in the metabolisms of NO, endothelin-1, natriuretic peptide, renin-aldosterone system. The cirrhotic patients revealed the increase in malondialdehyde and the decrease in catalase activity with the disease severity increase according to the criteria of C. H. Child – R. N. Pugh. It evidences the significant abnormalities in the redox homeostasis of such patients, and subsequently leads to the endothelial dysfunction with impaired metabolism of vasoactive humoral-metabolic substances in the blood of patients. In particular, them become the prerequisite for the occurrence of extrahepatic comorbid syntropic lesions, that significantly complicate the underlying disease course.

Keywords

• endothelial dysfunction
• liver cirrhosis
• oxidative stress
• portal hypertension
• redox homeostasis