Comparative analysis of the nephroprotective action of ademetioninee and glutathione in ischemia-reperfusion acute kidney injury

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