The effect of free radical stress correction on corticoid signaling in the kidney of rat with different resistance to hypoxia after systemic circulation arrest

Abstract

Aim. To assess the influence of the pathogenetic action of the succinate-containing drug on corticosteroid regulation in the kidney of rats with different resistance to hypoxia during recovery after systemic circulation arrest. Methods. The object of the study was male non-inbred white rats weighing 200–220 g. A week after testing for resistance to hypoxia, a 5-minute systemic circulation arrest was simulated by intrathoracic clamping of the vascular bundle of the heart, followed by resuscitation. In the postresuscitation period, the experimental rats were once daily injected with a solution containing inosine + nicotinamide + riboflavin + succinic acid, and the control rats — 0.9% Sodium Chloride solution. The observation period was 35 days. We studied the content of corticosterone, aldosterone in blood plasma, gluco- and mineralocorticoid receptors, carbonylated proteins, dityrosine, and products that react with thiobarbituric acid in homogenates of the kidneys. Statistical data were presented as mean and standard deviation M±σ. Nonparametric Kruskal–Wallis (N) and Mann–Whitney (U) tests followed by Dunn test, Spearman correlation analysis were used. Differences were considered statistically significant at p ≤0.05. Results. The use of succinate-containing preparation reduced the intensity of free radical processes in both groups of animals. Against this background, in low-resistance rats, on the 1st day, the concentration of glucocorticoid receptors statistically significantly increased to 117% (p <0.05), and then was comparable to the control; the greatest statistically significant changes in the level of mineralocorticoid receptors occurred on the 1st day (increase by 25%, p <0.001) and at 21–35th days (decrease by 22–30%, p <0.001). In highly resistant rats, the correction led to a shift in the maximum content of glucocorticoid receptors from the last day (134% of the control level, p <0.01 without therapy) to the 1st (123%, p <0.05 with succinate-containing therapy) and maintaining the receptors level comparable to the initial, in the future. The level of mineralocorticoid receptors in highly resistant rats was lower than in low resistant rats, both in the group without correction and with correction. Conclusion. Correction of the course of the postresuscitation period with a succinate-containing drug in animals with a low resistance to hypoxia against the background of a decrease in the intensity of carbonyl stress and restoration of feedback mechanisms causes stabilization of glucocorticoid receptors level and a decrease in mineralocorticoid receptors to control values by the end of the experiment; in organisms highly resistant to hypoxia, against the background of correction, the activity of lipid peroxidation decreases and the level of both types of receptors are restored.