MECHANISMS OF THE REALIZATION OF PROTECTIVE INFLUENCE OF SOME OLIGOPEPTIDES IN ISCHEMIA-REPERFUSION INJURY OF KIDNEYS

The aim of research was to study the nephroprotective activity of oligopeptides AED and EDL, synthesized in the St.-Peterburg Institute of Bioregulation and Gerontology (RF) on a model of ischemia-reperfusion (I/R) kidney injury in rats.

Methods. Animals were randomly divided into 4 groups: I — sham-operated animals, II — modeling of ischemic acute kidney failure (AKF) by clamping of both kidney pedicles for 60 min and 24 h of reperfusion, animals of III and IV grous three days before operation received tripeptides EDL and AED in dose 3 mg/kg.

Results. I/R resulted in development of AKF characterized by a fall in diuresis by 48.8%, 2-fold decrease of creatinine clearance (Clcr) and severe tubular injury which confirmed by a significant proteinuria, and an increase of fractional excretion of sodium (FENa) up to 2.16%. Pretreatment with tripeptides decreased the severity of ischemic injury realized in increase of diuresis 1.9 times in case of EDL use and 1.3 times in case of AED treatment, and decrease of protein excretion by 2.4 and  1.7 times, respectively (р<0.01). EDL also significantly decreased Clcr 2.4 times and FENa to 0.55%. Development of AKF was accompanied with activation of peroxidation processes in kidney tissue: MDA content increased by 47%, OMP — by 49% along with 2-fold inhibition of GPx activity and CAT activity — by 42%. Pretreatment with EDL increased GPx activity 1.6 times, CAT — 1.5 times, decreased MDA content by 1.3 times and OMP — by 1.2 times (р<0.01). AED pretreatment has shown less significant effect. EDL administration caused an increase in succinate dehydrogenase activity 5.4 times, AED — 3.3 times comparing to untreated animals.

Conclusions. Pretreatment with oligopeptides decreases I/R-caused injury of nephrons, normalizing their functional state and pro-antioxidant balance in kidney tissue with more significant effect of peptide EDL.