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Introduction. The development of oxidative stress and nonspecific inflammation is one of the leading factors in the development of benign prostatic hyperplasia (BPH) and associated urination disorders in metabolic syndrome (MS). However, the specific mechanisms of these processes are not entirely clear. The purpose of the study. To study the activity of reactive oxygen species production and the functional state of mitochondria in the prostate and bladder and their role in the dysfunction of these organs using an experimental model of MS induction in rats. Material and methods. In 10 adult mongrel male rats MS was induced by keeping them on a high-calorie diet with an increased content of carbohydrates and fats for 3 months. 10 rats kept on a standard vivarium diet served as controls. The development of MS was confirmed by characteristic changes in the biochemical analysis of blood (hyperglycemia, hyperuricemia, dyslipidemia, hyperinsulinemia). In both series of rats, sections of the native prostate and bladder were examined by laser confocal microscopy and stained with fluorescent probes that characterize the activity of the production of reactive oxygen species (dichlorofluorescein-DCF) and the functional state of the mitochondria (tetramethylrodamine ether – TMRE). The activity of a number of intracellular enzymes (AST, ALT. Alkaline phosphatase, LDH) was investigated in the tissues and urine. Results. In rats with MS, the development of BPH and hypertrophy of the bladder were revealed, confirmed histologically. The study of sections of both organs by confocal microscopy revealed a significant increase in the production of reactive oxygen species by their cells and a decrease in the functional activity of mitochondria, which indicated the development of oxidant stress and tissue hypoxia. In the prostate, this was accompanied by a decrease in the secretory activity of the prostate glands, and in the bladder – the release of cytoplasmic enzymes from damaged cells into the urine, indicating cell damage. Conclusion. The causes of the development of a non-specific inflammatory process in the prostate and bladder, leading to dysfunction of these organs in MS, are increased production of reactive oxygen species and the development of tissue hypoxia.

Male infertility represents a severe social and medical challenge. In recent years the progress in regenerative medicine promoted the development of novel options to overcome this medical condition. We are elaborating a promising approach to restore spermatogenesis using mesenchymal stromal cell (MSC) secretome components as a novel class of cell-free cell therapy medicinal products for regenerative medicine. However, the choice of the representative in vivo model of spermatogenesis failure to evaluate the effectiveness of regenerative drugs remains challenging. Using the rat model of bilateral abdominal cryptorchidism, we studied the contribution of MSC conditioned medium contained bioactive cell secreted products to the spermatogenesis recovery. The feasibility of this model to evaluate the drug-driven regenerative effects on spermatogenesis restoration after the injury was demonstrated. We revealed significant correlations between the extent of spermatogonial stem cell niche recovery, spermatozoa count and serum concentration of androgens as an indicator of Leydig cell function. The obtained results can be applied in preclinical studies to choose the proper criteria to appraise the specific activity of novel regenerative drugs developed for the treatment of non-obstructive spermatogenesis disorders.

The study revealed the regenerative effects of MSC and MSC secretome in a model of abdominal cryptorchidism in rats.

Background Injury of stem cell niches may disturb tissue homeostasis and regeneration coordinated by specific niche components. Yet, the mechanisms of stem cell niche restoration remain poorly understood. Herein, we examined the role of mesenchymal stromal cells (MSCs) as pivotal regulators of stem cell niche recovery focusing on the effects of their secretome. Methods The spermatogonial stem cell (SSC) niche was selected as a model. SSC niches were injured by inducing abdominal cryptorchidism in rats. Briefly, testes of anesthetized rats were elevated into the abdominal cavity through the inguinal canal for 14 days. After descent of testes, MSC or MSC secretome treatment was applied to the animals by local subtunical injections. Results Local administration of MSC or MSC secretome was sufficient to recover spermatogenesis and production of functional germ cells. The effects of MSC and their secreted components were comparable, leading to restoration of Sertoli cell pools and recovery of Leydig cell secretory functions. Conclusion Our data suggest that MSCs mimic the functions of lost supportive cells within the stem cell niche, transiently providing paracrine stimuli for target cells and triggering tissue regenerative processes after damage.

Acute urine retention is a frequent complication in patients with benign hyperplasia of the prostate gland. According to studies made on experimental animals and people, it is accompanied by the deterioration of the bladder blood supply. This study attempts to explore the relationship of intramural blood flow, production of reactive oxygen species, and functional state of the bladder detrusor in modeling of acute urine retention in rats, as well as the impact of mitochondria-targeted antioxidants (which are supposed to alleviate the effects of oxidative stress induced by experimental ischemia) on these parameters. The study showed beneficial effects of mitochondria-targeted antioxidant SkQR1 in preventing damage of the bladder caused by acute urinary retention, which suggests the therapeutic use of this type of compounds for the treatment of ischemic abnormalities of the urinary bladder.

Vitamin E was quantified in renal cell carcinomas (RCC) and in 'intact' renal cortex, obtained from 31 patients subjected either to unilateral nephrectomy or to partial resection of the only kidney. Histologically, 14 tumors consisted predominantly of clear cells (group 1) and 17 of other cell types (group 2). In both groups, a significant increase in vitamin E concentration, as compared to the 'intact' cortex, was observed: 167.8 +/- 27.9 and 68.2 +/- 15.2 micrograms/g wet tissue weight (mean +/- SEM) for groups 1 and 2, respectively, versus 10.1 +/- 0.53 micrograms/g wet tissue weight for the cortex. Although the total lipid content was also increased in tumors (especially in group 1), the vitamin E concentration in tumor tissue, calculated per milligram of total lipids, proved to be much higher in both groups than in 'intact' cortex. A significant positive correlation was observed between vitamin E and total lipid content in group 1 and 2 carcinomas. It was also found that vitamin E accumulation in RCC is unlikely to be attributed to an enhanced lipid deposit in the tumor cells. Thus, in 8 tumors of group 2 the vitamin E levels were markedly enhanced although these tumors did not differ from the cortex in total lipid concentrations. Vitamin A content determined in 17 carcinomas, when calculated per milligram of total lipids, was the same as in 'intact' cortex.

Pharmacological preconditioning with insulin and lithium ions prevented the death of renal cells under conditions of ischemia/reperfusion. Preincubation of cells with insulin or lithium ions decreased production of reactive oxygen species after ischemia/reoxygenation. These agents also prevented the development of mitochondrial dysfunction in renal cells induced by ischemia/reoxygenation. It was hypothesized that the protective effects of these agents are related to inhibition of glycogen synthase kinase-3(. This enzyme is inactivated upon phosphorylation of serine residue in position 9. We found that in vivo administration of lithium ions to animals before renal ischemia prevents the development of kidney failure.

Effects of 10-(6'-plastoquinonyl) decyltriphenylphosphonium (SkQ1) and 10-(6'-plastoquinonyl) decylrhodamine 19 (SkQR1) on rat models of H2O2- and ischemia-induced heart arrhythmia, heart infarction, kidney ischemia, and stroke have been studied ex vivo and in vivo. In all the models listed, SkQ1 and/or SkQR1 showed pronounced protective effect. Supplementation of food with extremely low SkQ1 amount (down to 0.02 nmol SkQ1/kg per day for 3 weeks) was found to abolish the steady heart arrhythmia caused by perfusion of isolated rat heart with H2O2 or by ischemia/reperfusion. Higher SkQ1 (125-250 nmol/kg per day for 2-3 weeks) was found to decrease the heart infarction region induced by an in vivo ischemia/reperfusion and lowered the blood levels of lactate dehydrogenase and creatine kinase increasing as a result of ischemia/reperfusion. In single-kidney rats, ischemia/reperfusion of the kidney was shown to kill the majority of the animals in 2-4 days, whereas one injection of SkQ1 or SkQR1 (1 micromol/kg a day before ischemia) saved lives of almost all treated rats. Effect of SkQR1 was accompanied by decrease in ROS (reactive oxygen species) level in kidney cells as well as by partial or complete normalization of blood creatinine and of some other kidney-controlled parameters. On the other hand, this amount of SkQ1 (a SkQ derivative of lower membrane-penetrating ability than SkQR1) saved the life but failed to normalize ROS and creatinine levels. Such an effect indicates that death under conditions of partial kidney dysfunction is mediated by an organ of vital importance other than kidney, the organ in question being an SkQ1 target. In a model of compression brain ischemia/reperfusion, a single intraperitoneal injection of SkQR1 to a rat (1 micromol/kg a day before operation) effectively decreased the damaged brain area. SkQ1 was ineffective, most probably due to lower permeability of the blood-brain barrier to this compound.

Efficiency of bioimpedance measurements were assessed and used to evaluate the passage of urine, as well as motility and structure of the upper and lower urinary tracts. The rheographs “RPKA2-01”, “ITU-6”, and bioimpedance analyzer "ABC-01" produced by Medass (Russia) were used with a probe equipped with 9 individual electrodes. During measurements the probe was introduced endoscopically into various regions of urinary tract in patients with the urologic diseases. Three diagnostic approaches were assessed: 1. The multichannel impedance ureterography (MIUG) was developed to quantitatively and qualitatively estimate the ureteral peristalsis. 2. The impedance ureteromety yielding impedance ratio (Zlow/Zhigh) detected the region of ureteral stricture if this ratio surpassed the critical level. 3. The urethral wide-band impedance measurements made at the frequency range 5–500 kHz revealed the intrinsic individual peculiarities of male and female urethra that could be helpful in diagnostics of urination disorders. The examined bioimpedance methods could serve as efficient diagnostic tools characterized by portable equipment, pick-and-go application, lack of radiation, and the reliable quantitative output.

Ureteral endoprostheses are used for dilatation of strictures in order to maintain upper urinary tract (UUT) function for a longer period.Three kinds of short (3-4-cm) endoprostheses were inserted into the ureter of mongrel dogs with intact UUT or experimental ureter strictures. The UUT function was evaluated by means of radiographic examinations and in terms of following measures of contractility: intraluminal pressure, electroureterography (EUG), and multichannel impedance ureterography (MIUG). Studies were performed 1, 3 to 6 months, and 1 to 3 years after prostheses implantation.Similar urodynamic changes were registered in prosthetically treated ureters of dogs with initially intact UUTs and those with ureteral strictures. These disorders consisted of increased UUT intraluminal pressure and different functioning of the upper and lower regions of the ureter. The bioelectric and contractile activity of the upper UUT regions was reinforced, accelerated, and dysrhythmic, while peristaltic ureter wall function below the endoprosthesis was rare and weak.The changes observed are typical for ureteral prosthetics. The UUT urodynamic alterations could be attributable entirely to the excluding of the ureteral segment from active contraction and were the result of the local absence of the ureteral wall closing mechanism. One must keep in mind that UUT endoprostheses produce a high load on the ureter wall. The transition from UUT hyperfunction to contractile function decompensation may depend on the intrinsic compensatory reserves of the ureter.

Reoxygenation following ischemia causes tissue oxidative stress. We studied the role of oxidative stress caused by kidney ischemia/reperfusion (I/R) on the mitochondria of renal tissue slices. I/R caused the mitochondria to be swollen, fragmented, and have lower membrane potential. The mitochondria generated more reactive oxygen species (ROS) and nitric oxide (NO) in situ as measu red by fluorescence of ROS- and NO-sensitive probes. Infusion of lithium ion, an inhibitor of glycogen kinase synthase-3, caused phosphorylation of its Ser-9 and restored the membrane potential and decreased ROS production of the mitochondrial fraction. Ischemic kidney and hypoxic rat preconditioning improved mitochondrial membrane potential and lowered ROS production caused by subsequent I/R similar to lithium ion infusion. Preconditioning normalized NO production in mitochondria as well. The drop in the mitochondrial membrane potential was prevented by NO synthase inhibition, demonstrating a strong contribution of NO to changes in mitochondrial energy metabolism during the I/R transition. Mitochondria in the I/R-stressed kidney contained less cytochrome c and more pro-apoptotic Bax, consistent with apoptotic degradation.