FUNCTIONAL AND METABOLIC KIDNEY DISORDERS UNDER CONDITIONS OF SKELETAL TRAUMA COMPLICATED BY ACUTE BLOOD LOSS OF VARIOUS SEVERITY DEGREES AND EFFECTIVENESS OF 2-ETHYL-6-METHYL-3-HYDRO­XYPYRIDINE SUCCINATE IN THE CORRECTION OF IDENTIFIED DISORDERS

Abstract

Introduction. Trauma is one of the main causes of massive blood loss. According to the concept of "traumatic disease", trauma-induced violations of important functions and parameters of homeostasis have a prolonged nature and often become the main cause of death of the body due to the development of multiple organ failure syndrome. All this forces us to search for additional means of protecting tissues from hypoxic influence and oxidative stress - the key pathogenic factors in trauma and acute blood loss. Recently, 2-ethyl-6-methyl-3-hydroxypyridine succinate has been widely used among complex anti-oxidant and anti-hypoxant agents. However, its protective effect on the kidneys under conditions of trauma and acute blood loss has not been investigated.

The aim of the study – to find out the effect of 2-ethyl-6-methyl-3- hydroxypyridine succinate on functional and metabolic kidney disorders under conditions of skeletal trauma complicated by acute blood loss.

Research Methods. Experiments were performed on 114 white, sexually mature white male rats of the Wistar line. Skeletal trauma was simulated in anesthetized rats of the first experimental group. Rats of the second experimental group were additionally induced with acute blood loss in the volume of 1 % of body weight, in the third experimental group, in addition to skeletal trauma, acute blood loss was simulated in the volume of 2 % of body weight. In the fourth experimental group, animals with a similar injury were injected daily intraperitoneally with 2-ethyl-6-methyl-3- hydroxypyridine succinate at a dose of 100 mg·kg-1 for the correction purpose. Examined rats were only injected with thiopental sodium anesthesia. From the experiments, rats of experimental groups 1, 2, and 3 were taken out after 1, 3, and 7 days of the post-traumatic period, rats of experimental group 4 – after 7 days. Kidney function of all rats was first assessed by the water stress method, then they were taken out of the experiment and the creatinine content was determined in blood serum and urine, the glomerular filtration rate (GFR) was calculated, and the content of reagents to thiobarbituric acid (TBA-active LP products-active LP products) was determined in the cortical and medullary layers of the kidney.

Results and Discussion. Under the influence of skeletal trauma during the acute period and the period of early manifestations of the traumatic disease, the content of TBA-active LP products in the cortical and medullary layers of the kidney significantly increases and GFR decreases. Even greater violations occur after additional simulation of acute blood loss, which increased with an increase in its volume. According to the content of TBA-active LP products in the cortical layer of the kidney and the value of GFR after 1 day of post-traumatic period, the disturbances compared to the control were almost the same in groups of rats that were simulated only skeletal trauma, and additionally caused acute blood loss in the volume of 1 % of the rat's body weight. The use of 2-ethyl-6-methyl-3- hydroxypyridine succinate in the case of skeletal trauma complicated by acute blood loss in a volume of 2 % of body weight has a pronounced sanogenic effect on the body. Under the influence of the medication, after 7 days of the experiment, a significant decrease in the content of TBA-active LP products in the cortical and medullary layers of the kidney was noted. Against this background, the GFR increases significantly. Despite the fact that under the influence of the medication, the studied indicators did not reach the level of the control group, it can be of significant interest for complex intensive therapy of the severe trauma consequences already in the acute period of the traumatic disease. 

Conclusion. Complication of skeletal trauma by acute blood loss in the volume of 1 and 2 % of body weight compared to isolated skeletal trauma is accompanied by greater activation of lipid peroxidation processes in the cortical and medullary layers of the kidney and a decrease in GFR. Violation of indicators increase from 1 to 7 days of the post-traumatic period and intensify with an increase in the volume of blood loss. The application of 2-ethyl-6-methyl-3- hydroxypyridine succinate succinate under conditions of skeletal injury complicated by acute blood loss in the volume of 2 % of body weight, after 7 days of the experiment, is accompanied by significantly smaller violations of the content in the cortical and medullary layers of the kidney TBA-active LP products and higher GFR, compared to rats with a similar injury, which were not corrected.