DYNAMICS OF ANTIOXIDANT-PROOXIDANT BALANCE OF RENAL CORTEX AND MEDULLA AFTER ACUTE BLOOD LOSS COMPLICATED BY ISCHEMIA-REPERFUSION OF THE EXTREMITY, AND ITS CORRECTION WITH CARBACETAM
DOI:
https://doi.org/10.11603/1811-2471.2019.v.i4.10815Keywords:
blood loss, limb ischemia-reperfusion, anioxidant-prooxidant balanceAbstract
The aim of the study – to find out the effect of acute blood loss, complicated by two-hour limb ischemia and its reperfusion, on the antioxidant-prooxidant balance in the renal cortex and medulla.
Material and Methods. The experiments were performed on 108 non-linear male rats weighing 160–180 g. All animals were divided into four groups: control and four research (6 rats per group). The first experimental group included animals that simulated limb ischemia-reperfusion. Under thiopental sodium anesthesia, animals were proximally placed on the left foot for 120 min with a 10 mm SWAT-T tourniquet (USA), which completely stopped the blood flow. In the second experimental group, in conditions of animal anesthesia, acute blood loss was simulated in the amount of 20–22 % of the circulating blood volume by crossing the femoral vein. In the third experimental group, these injuries were combined. In the fourth experimental group, animals with acute hemorrhage complicated by limb ischemia-reperfusion were administered Carbacetam at a dose of 5 mg per kilogram of the animal’s weight with the aim of correction. Animals were withdrawn from the experiment under thiopental sodium anesthesia after 3 and 4 hours, as well as 1, 7 and 14 days after reperfusion, acute blood loss and their combination, after preliminary determination of the functional state of the kidneys by stimulated diuresis. In the control group, animals were injected anesthesia using an equivalent dose of thiopental sodium, a tourniquet was applied without stopping blood flow for 2 hours, then after 1 hour the functional state of the kidneys was determined by the method of stimulated diuresis, and then animals were removed from the experiment using thiopental sodium anesthesia by a similar method. In the removed kidney, the content of reagents in thiobarbituric acid and the activity of catalase were determined in the homogenates of the cortical and brain layers. Based on these data, the antioxidant-prooxidant index (API) was calculated.
Results. Modeling of limb ischemia-reperfusion in the studied functional layers of the kidney during the experiment led to a significant increase in the API value with a maximum after 1 day, which indicated the dominance of antioxidant mechanisms in the kidney tissues. Under the influence of acute blood loss, the IPA value in the cortical and brain layers of the kidney decreased sharply, reaching a minimum after 1 day and did not return to the control level after 14 days. We first established that the modeling of acute blood loss and limb ischemia-reperfusion led to an even greater decrease in the API value in the functional layers of the kidney. If in the cortical layer under these conditions the indicator became significantly lower compared with the group with acute blood loss after 3 and 4 hours, and 14 days of observation, then in the cerebral layer additional ischemia-reperfusion was accompanied by a significant decrease in the API value during all periods of the reperfusion period.
The use of Carbacetam at a dose of 5 mg per kilogram of mass for 14 days in the reperfusion period in animals with acute blood loss complicated by limb ischemia-reperfusion compared with animals without correction was accompanied with a significant increase in API, starting from 7 days in the renal cortex, and after 14 days – both in the renal cortex and medulla. The obtained result indicates the future outlook of Carbacetam as a means of systemic correction in conditions of acute blood loss complicated by limb ischemia-reperfusion, and is the theoretical basis for its use in the clinic.
Conclusions. Due to two-hour ischemia and reperfusion of the limb in the studied functional layers of the kidney, the API increases significantly with a maximum after 1 day of the reperfusion period, which decreases to 14 days, but does not reach the level of the control group. Under the influence of acute blood loss, the IPA value in the kidney tissues decreases sharply, which indicates a significant dominance of prooxidant mechanisms and is due to a decrease in kidney perfusion. Complications of acute hemorrhage by ischemia-reperfusion of the limb cause a statistically significantly greater decrease in the API value in the cortical layer of the kidney compared with the group with acute blood loss after 3, 2 hours, and 14 days of observation, in the medulla during all periods of the reperfusion period.
The use of Carbacetam during 14 days of the reperfusion period in animals with acute blood loss complicated by limb ischemia-reperfusion, compared with animals without correction, causes a significant increase in the magnitude of API, starting from 7 days in the renal medulla, and after 14 days, both in the medulla and in the cortex.
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