Abstract
Despite significant advances in drug therapy and improvements in renal replacement therapy, mortality rate of acute kidney injury (AKI) continuously increases and is about 25-70 %. Ischemia-reperfusion AKI is not an exception with its multifactorial pathogenesis and rapid progressive development, usually resulting from trauma, sepsis, kidney transplantation, or an influence of toxic substances. For this reason, drugs with potent cytoprotective and antioxidant activity – ademetionine and glutathione have drawn our attention as remedies for the pathogenetic correction of ischemia-reperfusion AKI.Aim. To compare the influence of ademetionine and glutathione on the functional state and antioxidant balance in kidneys of rats with ischemia-reperfusion AKI.Methods. Research was conducted on 28 mature non-linear white rats weighting 130-180 g, randomly divided into 4 groups (n = 7): I group – control (pseudo-operated animals), II group – modeling of ischemia-reperfusion kidney injury (I/R), III group –administration of ademetionine (Heptral, “Abbott SpA”, Italy) at a dose of 20 mg/kg prior to I/R modeling, animals of IV group were daily injected with glutathione (TAD 600, “Biomedica Foscama”, Italy) at a dose of 30 mg/kg. Functional state and histological changes in kidneys was estimated after 24 hours of reperfusion by the indices of diuresis, GFR, urine protein excretion, excretion of sodium and potassium ions with urine. Peroxidation processes in kidneys were evaluated by the malone dialdehyde and oxidative modification of proteins levels, antioxidant defense – by catalase and glutathione peroxidase activity. Histological examination was conducted by hematoxylin and eosin staining of kidney tissue sections.Results. It was established the use of studied drugs in I/R AKI ameliorated excretory kidney function of rats, which was realized in an increase in GFR and diuresis with simultaneous decrease in azotemia and proteinuria. It was accompanied by a restoration of ion-regulatory kidney function, confirmed by an increase in sodium reabsorption with recovery of proximal and distal tubular transport. Analysis of antioxidant system shows an inhibition of lipid peroxidation processes on the background of antioxidant system activation with significantly better effect of glutathione, which was confirmed by the histological study.Conclusion. As it is shown, both ademetionine and glutathione exhibit nephroprotective effect in rats with ischemia-reperfusion acute kidney injury. At the same time, effect of glutathione administration significantly exceeds that of ademetionine by the restoration of the functional state of nephrons as well as the effect on the prooxidant - antioxidant balance in renal tissue, which is confirmed by the histological study. Obtained results give a background for the further research of nephroprotective potential of the ademetionine and glutathione in conditions of AKI of different etiology
Highlights
Today, due to significant advances in drug treatment and the improvement of renal substitution therapy, the mortality rate from acute kidney injury (AKI) remains high and is about 25–70 % [1]
The ischemic injury primarily affects the structure and function of the tubular epithelium cells, which is accompanied by dysfunction of the microcirculation, the development of hypoxia, oxidative stress and inflammatory reactions, which further leads to necrosis and apoptosis of the nephrocytes
Animals were divided into 4 groups (n=7): group I – control, group II – Ischemia/Reperfusion modeling (I/P), group III animals received intramuscular injection of ademetionine 20 mg/kg (Heptral, “Abbott SpA”, Italy) intradermally during the three days prior to I/P simulation, animals of the IV group received glutathione 30 mg/kg (TAD 600, “Biomedica Foscama”, Italy)
Summary
Due to significant advances in drug treatment and the improvement of renal substitution therapy, the mortality rate from acute kidney injury (AKI) remains high and is about 25–70 % [1]. AMP is metabolized in two ways: 1) the formation of nucleotides, the loss of which leads to a decrease in the formation of ATP and an increase in the intracellular level of calcium ions, which in turn activates proteinases and phospholipases – enzymes that violate cell cytoskeleton; 2) by the formation of hypoxanthine, the accumulation of which promotes the generation of active forms of oxygen, and its subsequent biotransformation leads to the formation of hydrogen peroxide and superoxide, which, along with free iron ions and nitric oxide, which is formed in parallel with renal tubules by means of NO synthase, contribute to the formation peroxinitrate, which in turn leads to cellular damage through nitrosylation of cellular proteins, activation of peroxide lipid oxidation, damage to the DNA of nephrocytes and induction of apoptosis [5]. Analysis of recent studies and publications in which a solution of the problem are described and to which the author refers
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