ИСТИНА

In experimental pyelonephritic model we observed a number of signs of inflammation and kidney tissue damage including leukocyte infiltration of the kidney, elevated level of peroxidative products, degeneration of the tissue and high mortality of the animals. Pre-treatment the rat with mitochondrial-targeted antioxidant SkQR1 resulted in improvement of the kidney structure and functions and much lower mortality. Pre-treatment with SkQR1 reduced the kidney tissue concentration of TNFalpha which plays an essential role in inflammatory response. In pyelonephritic leukocytes we observed all signs of oxidative stress and depletion in the pro-survival phosphorylated form of GSK-3beta (P-GSK-3beta), which was partially abolished by SKQR1 pretreatment of the rat. The level of anti-apoptotic protein Bcl-2 in the pyelonephritic kidney is diminished which was partially restored by administration of SkQR1. The content of Bcl-2 in the mitochondria isolated from kidneys of pyelonephritic animals was lower than in control mitochondria. We present a model of the pathological events occurring in pyelonephritic kidney with ROS playing a key role. In many pathological steps, pro-death and pro-survival signaling is related to mitochondrial function. We conclude that mitochondrial antioxidants may be effective anti-pyelonephritic drugs.