ИСТИНА

There are not so many approaches for treatment of acute kidney injury (AKI) which is a high-mortality disease affecting approximately a third of intensive care units patients. We investigated the nephroprotective possibility of two different methods, namely ischemic preconditioning (IPC) and dietary restriction (DR), and evaluated the role of autophagy and mitophagy in mechanisms of damage and protection of ischemic kidney. While the majority of patient with AKI are elderly, all parts of the research were performed in young and old animals. IPC consisted of 4 cycles, including 15 seconds of ischemia and 15 seconds of reperfusion, immediately before the 40 minutes ischemia. DR was performed for 4 weeks by limiting the amount of food to 65% of the daily intake. Both methods, IPC and DR, attenuated AKI induced by ischemia/reperfusion (I/R), but only in young rats. In old animals, those approaches were unable to decrease the levels of serum creatinine and blood urea nitrogen. To unravel mechanisms underlying those effects, we evaluated the activation of the autophagic-lysosomal system in kidney tissue. We have shown that in young rats with IPC, fluorescence intensity of LysoTracker Green was not as increased as in the group with I/R alone. However, in old rats we observed the increase only in the group with IPC. Similarly, DR significantly increased LysoTracker Green fluorescence intensity and LC3II/LC3I ratio in young rats, but there were no such alterations in old rats. Impaired mitochondrial quality control was demonstrated by analysis of mitochondrial transmembrane potential by flow cytometry. A fraction of low-potential mitochondria was found in old kidneys and this de-energized population was even increasing after IPC in old, but not in young rats. Ineffectiveness of mitophagy was also suggested by the evaluation of the PINK-1 level in mitochondria.