The kinetics of urea in the body in chronic inflammatory liver disease

Abstract

The participation of the endogenous antioxidant, urea, in the regulation of many physiological processes and biochemical reactions explains the scientific and practical interest in studying its kinetics during illness, especially when the urea-producing function of the liver is disturbed. The aim of this work was to study the kinetics of urea in chronic inflammatory liver damage. Methods. Experiments were performed on 96 white female rats weighing 180-220 g. Chronic inflammatory liver disease was induced by subcutaneous administration of a 50% CCl₄ solution in olive oil, 0.1 ml/100 g body weight, every other day, for 65 days with two two-week breaks between the 6^th and 7^th, 13^th and 14^th injections to reduce mortality. The material was collected for study on the 65^th day (the last day) of CCl₄ administration and on the 3^rd, 7^th, and 14^th days after stopping CCl₄. The following materials were studied: tissues of visceral organs (thyroid gland, lungs, heart, liver, stomach, duodenum, colon, spleen, kidneys); biological fluids: blood (aorta and femoral, hepatic, portal, and renal veins), bile, and urine. The urea content was determined by the diacetyl monoxime method. The activity of arginase in the homogenate and the cytosolic fraction of the liver were evaluated by the urea formation rate. Results. In chronic CCl₄ hepatitis, the formation of urea by hepatocytes was disrupted as a result of a decrease in their arginase activity, which did not recover by the 14^th day after stopping CCl₄ withdrawal. This was accompanied by a decrease in the concentration of urea in the affected liver and an increase in its content in the blood flowing through the liver. This was due to the activation of portal, pulmonary, renal, and visceral mechanisms aimed at increasing the concentration of urea in arterial blood and in portal and renal venous blood. As a result, the urea content in the arterial blood of rats with chronic CCl₄ hepatitis was elevated, despite the disruption of the urea-synthetic function of hepatocytes. At the same time, the kinetics of urea changed in both the whole body and in individual organs. Conclusion. The ability of the body to prevent a decrease in the concentration of blood urea during disruption of the urea-producing function of the liver, as caused by the prolonged action of CCl₄, indicates the important role of urea in sanogenic reactions that are triggered during chronic CCl₄-hepatitis.