[Molecular mechanisms of ischemic-reperfusion syndrome and its personalized therapy].

Cardiovascular pathologies are the major causes of morbidity and mortality in the world. Cessation of the blood flow in large vessels, supplying tissues with oxygen and substrates, leads to ischemic conditions accompanied by unwanted shifts of oxidative metabolism and rise of the reactive oxygen species (ROS) generation. Small amounts of ROS are essential elements of the cell metabolism, however pathological elevation of ROS jeopardizes the survival of cells, organs and even organisms. Paradoxically, blood flow restoration during prolonged ischemia leads to oxidative stress that is often fatal for a live system. Oxygen paradox appears to be a limiting factor in clinical practice that intuitively seeks for immediate and complete restoration of a damaged blood flow. Mitochondrion is a major ROS source and a key element of pro-apoptotic signaling, however it is clear, that mitochondria are the main target for anti-ischemic treatment. In the present review we consider two ways of such anti-ischemic strategy, bringing ischemic tolerance to the organ through mitochondrial involvement, such as intrinsic, biological, or artificial, pharmacological adaptive systems (preconditioning). The latter is aimed to simulate elements and high efficiency of intrinsic protective system. The role of antioxidants in anti-ischemic therapy and their effects on preconditioning signaling are discussed in the review.

[Mechanism of action and efficacy of litium chloride in thermal ischemia of the kidney].

A protective effect of lithium chloride (LC) in thermal ischemia of the kidney of different duration was studied in rats. LC efficacy was estimated by functional activity of ischemic kidney in early and late reperfusion period, by damage to mitochondria of tubular epithelial cells and production of active oxygen forms (AOF) and nitric oxide (NO). LC has a marked anti-ischemic effect. In thermal renal ischemia for 40 and 60 min LC provides functional safety of the ischemic organ. In longer ischemia, 50% of the animals died. The mechanism of the protective action of LC is related to reduction of APK production, support of a high transmembrane potential of mitochondria and NO synthesis redistribution in the cells of tubular epithelium cells.

[Regeneration of testicular tissue and restoration of rat fertility in xenotransplantation of enriched fetal cell cultures in bilateral abdominal cryptorchism].

The study of cell cultures enriched with stem and progenitor cells in the treatment of experimental hypergonadotropic hypogonadism was made on 30 white non-inbred rats with experimental cryptorchism who have undergone xenotransplantation of human fetal enriched cell cultures. Spermatogenic epithelium on histological sections was studied on day 14 and 28 after xenotransplantation with calculation of the spermatogenesis index. The fertility index was estimated for each of the groups. Transplantation of enriched cell cultures enhances efficacy of restoration of adequate germinogenic and spermatogenic testicular function, accelerates recovery of spermatogenesis and fertility with high indices of spermatogenesis and fertility but effect of the above recovery after treatment with enriched cell cultures can be seen not earlier than 72 days after transplantation.

[Application of cell technologies for therapy of chronic renal insufficiency (experimental study)].

The experiments on 29 white non-inbred rats with chronic renal failure (CRF) induced by right-side nephrectomy and coagulation of 1/2-2/3 of parenchyma of the left kidney were made to study the trend in renal function after injection (into renal cortex or intravenously) of cultured stem or progenitor cells from human fetuses (total culture of fetal kidney or mesenchymal stem cells of the bone marrow). In control tests with salt solution functional indices reflected persistence of CRF. On day 4 after introduction of the fetal cells into renal parenchyma renal function improved and normalized in 2 weeks. After intravenous injection of fetal cells CRF reduced slowly, especially after injection of medullary mesenchymal cells with normalization in 1 month. 2.5-3.5 months after the injection test parameters in some rats deteriorated but remained close to normal values. Glomerular filtration after injection of stem and progenitor cells recovered better while canalicular sodium reabsorption underwent normalization but was followed by deterioration.

[The role of the mitochondria generating reactive oxygen species and nitric oxide in postischemic functional disturbance of the kidney].

Experiments on 10 rats and 10 rabbits were made to investigate metabolic aftereffects of 40-minute heat ischemia and subsequent reperfusion. It was found that mitochondrial function deteriorated significantly in an early postischemic period. The disorder manifested with a relative prevalence of cell ATP consumption over its synthesis. This is accompanied with intensive production by mitochondria of nitric oxide and oxygen free radicals. Fluorescent probes and confocal microscopy of vital renal sections showed that mitochondria are responsible for excessive generation of nitric oxide and oxygen radicals in the kidney in an early reperfusion period. The discussion concerns the role of nitric oxide in reperfusion renal damage and participation of mitochondria in formation of its anti-ischemic resistance.