ИСТИНА

In our study, in vitro and in vivo models of experimental pyelonephritis were employed to define the role of mitochondria in this pathology and to find a way to alleviate the kidney damage. We showed that pyelonephritis was associated with the oxidative stress and renal cells death. In the in vivo model of acute pyelonephritis, blood leukocytes concentration 3 days after infection was increased 2-fold compared to the intact animals. Leukocytosis correlated with neutrophilia and monocytosis while lymphocyte content did not change. The treatment with mitochondria-targeted antioxidant SkQR1 prevented an elevation of total leukocytes and subpopulations. We observed the reduced content of mitochondrial Bcl-2 and significantly increased TNFalpha level in pyelonephritic kidney. All these changes were diminished after SkQR1 treatment. It was revealed that although bacterial lysate induces a robust TNFalpha production by leukocytes in culture, such a production was even higher after co-cultivation of leukocytes with renal tubular cells which points to the important role of direct interaction between renal cell and leukocytes in the induction of inflammation. Importantly, renal cell death and animal mortality were both alleviated by mitochondria-targeted antioxidant SkQR1. These findings suggest that pyelonephritis can be treated by reducing mitochondrial reactive oxygen species and thus by protecting mitochondrial integrity and lowering kidney damage.