ИСТИНА

Myoglobine (Mb) is believed to be the major nephrotoxic effector under rhabdomyolysis. Recent data pointed to oxidative stress as a principal mechanism of acute kidney injury (AKI) after myoglobinuria, and the excessive reactive oxygen species (ROS) generation is a result of redox transformations of heme in Mb. ROS-mediated lipid peroxidation leads to nephron damage and renal failure.The development of oxidative stress was estimated by the increased level of lipid peroxides product – malonic dialdehyde (MDA) in kidney tissue or isolated mitochondria under rhabdomyolysis.Oxidative stress was followed by renal failure, as measured by serum creatinine and BUN elevation.We observed increased activity of enzymes, involved in Mb degradation in renal cells. Particularly, the rise of hemoxygenase-1 was revealed in kidney tissues 24 h after rhabdomyolysis induction. The same hemoxygenase-1 accumulation occurred in rat kidney after i/v injection of Mb. Interestingly, such Mb injection didn't caused AKI development, as creatinine and BUN concentration were 60 uM and 9 mM, respectively. However, preliminary Mb injection before rhabdomyolysis reduced the severity of AKI, lowering serum creatinine and BUN levels.The treatment of animals with experimental rhabdomyolysis with proteases inhibitor aprotinin led to higher MDA level in kidney and deterioration of kidney function (increased creatinine and BUN). The same effects were observed in experiments with Mb cytotoxicity on renal tubular cells culture, as incubation with proteases inhibitors induced aggravation of cells death after Mb treatment.Obviously, Mb proteolysis and following heme degradation are essential steps for Mb elimination from tubules and lowering of its nephrotoxic effects. Activation of enzymes, involved in Mb degradation, could alleviate renal damage.