Mitochondrial dysfunction in kidney cortex and medulla of subtotally nephrectomized rats.

Five-sixths nephrectomy is a widely used experimental model of chronic kidney disease (CKD) that is associated with severe mitochondrial dysfunction of the remnant tissue. In this study, we assessed the effect of CKD on mitochondrial respiration separately in the rat kidney cortex and medulla 10 weeks after induction of CKD by subtotal 5/6 nephrectomy (SNX). Mitochondrial oxygen consumption was evaluated on mechanically permeabilized samples of kidney cortex and medulla using high-resolution respirometry and expressed per mg of tissue wet weight or IU citrate synthase (CS) activity. Mitochondrial respiration in the renal cortex of SNX rats was significantly reduced in all measured respiratory states if expressed per unit wet weight and remained lower if recalculated per IU citrate synthase activity, i.e. per mitochondrial mass. In contrast, the profound decrease in the activity of CS in SNX medulla resulted in significantly elevated respiratory states expressing the OXPHOS capacity when Complexes I and II or II only are provided with electrons, LEAK respiration after oligomycin injection, and Complex IV-linked oxygen consumption per unit CS activity suggesting compensatory hypermetabolic state in remaining functional mitochondria that is not sufficient to fully compensate for respiratory deficit expressed per tissue mass. The results document that CKD induced by 5/6 nephrectomy in the rat is likely to cause not only mitochondrial respiratory dysfunction (in the kidney cortex), but also adaptive changes in the medulla that tend to at least partially compensate for mitochondria loss.

Impact of aging on mitochondrial respiration in various organs.

Mitochondria are considered central regulator of the aging process; however, majority of studies dealing with the impact of age on mitochondrial oxygen consumption focused on skeletal muscle concluding (although not uniformly) a general declining trend with advancing age. In addition, gender related differences in mitochondrial respiration have not been satisfactorily described yet. The aim of the present study was to evaluate mitochondrial oxygen consumption in various organs of aging male and female Fischer 344 rats at the ages of 6, 12 and 24 months. Mitochondrial respiration of homogenized (skeletal muscle, left and right heart ventricle, hippocampus, cerebellum, kidney cortex), gently mechanically permeabilized (liver) tissue or intact cells (platelets) was determined using high-resolution respirometry (oxygraphs O2k, Oroboros, Austria). The pattern of age-related changes differed in each tissue: in the skeletal muscle and kidney cortex of both sexes and in female heart, parameters of mitochondrial respiration significantly declined with age. Resting respiration of intact platelets displayed an increasing trend and it did not correlate with skeletal muscle respiratory states. In the heart of male rats and brain tissues of both sexes, respiratory states remained relatively stable over analyzed age categories with few exceptions of lower mitochondrial oxygen consumption at the age of 24 months. In the liver, OXPHOS capacity was higher in females than in males with either no difference between the ages of 6 and 24 months or even significant increase at the age of 24 months in the male rats. In conclusion, the results of our study indicate that the concept of general pattern of age-dependent decline in mitochondrial oxygen consumption across different organs and tissues could be misleading. Also, the statement of higher mitochondrial respiration in females seems to be conflicting, since the gender-related differences may vary with the tissue studied, combination of substrates used and might be better detectable at younger ages than in old animals.

Hyperbaric oxygen enhances collagen III formation in wound of ZDF rat.

Diabetic foot ulcer (DFU) is a serious complication of diabetes and hyperbaric oxygen therapy (HBOT) is also considered in comprehensive treatment. The evidence supporting the use of HBOT in DFU treatment is controversial. The aim of this work was to introduce a DFU model in ZDF rat by creating a wound on the back of an animal and to investigate the effect of HBOT on the defect by macroscopic evaluation, quantitative histological evaluation of collagen (types I and III), evaluation of angiogenesis and determination of interleukin 6 (IL6) levels in the plasma. The study included 10 rats in the control group (CONT) and 10 in the HBOT group, who underwent HBOT in standard clinical regimen. Histological evaluation was performed on the 18th day after induction of defect. The results show that HBOT did not affect the macroscopic size of the defect nor IL6 plasma levels. A volume fraction of type I collagen was slightly increased by HBOT without reaching statistical significance (1.35+/-0.49 and 1.94+/-0.67 %, CONT and HBOT, respectively). In contrast, the collagen type III volume fraction was ~120 % higher in HBOT wounds (1.41+/-0.81 %) than in CONT ones (0.63+/-0.37 %; p=0.046). In addition, the ratio of the volume fraction of both collagens in the wound ((I+III)w) to the volume fraction of both collagens in the adjacent healthy skin ((I+III)h) was ~65 % higher in rats subjected to HBOT (8.9+/-3.07 vs. 5.38+/-1.86 %, HBOT and CONT, respectively; p=0.028). Vessels density (number per 1 mm2) was found to be higher in CONT vs. HBOT (206.5+/-41.8 and 124+/-28.2, respectively, p<0.001). Our study suggests that HBOT promotes collagen III formation and decreases the number of newly formed vessels at the early phases of healing.

Hyperbaric oxygen influences chronic wound healing - a cellular level review.

Chronic wound is a serious medical issue due to its high prevalence and complications; hyperbaric oxygen therapy (HBOT) is also considered in comprehensive treatment. Clinical trials, including large meta-analyses bring inconsistent results about HBOT efficacy. This review is summarizing the possible effect of HBOT on the healing of chronic wound models at the cellular level. HBOT undoubtedly escalates the production of reactive oxygen and nitrogen radicals (ROS and RNS), which underlie both the therapeutic and toxic effects of HBOT on certain tissues. HBOT paradoxically elevates the concentration of Hypoxia inducible factor (HIF) 1 by diverting the HIF-1 degradation to pathways that are independent of the oxygen concentration. Elevated HIF-1 stimulates the production of different growth factors, boosting the healing process. HBOT supports synthesis of Heat shock proteins (HSP), which are serving as chaperones of HIF-1. HBOT has antimicrobial effect, increases the effectiveness of some antibiotics, stimulates fibroblasts growth, collagen synthesis and suppresses the activity of proteolytic enzymes like matrix metalloproteinases. All effects of HBOT were investigated on cell cultures and animal models, the limitation of their translation is discussed at the end of this review.

Mitochondrial respiration of human platelets in young adult and advanced age - Seahorse or O2k?

The objective of the present study was to evaluate platelet mitochondrial oxygen consumption using high-resolution respirometry (HRR) and metabolic flux analysis (MFA) and to verify the effect of advanced age on these parameters. HRR was used to analyze permeabilized and intact platelets, MFA to measure oxygen consumption rates (OCR), extracellular acidification rates (ECAR) and ATP production rate in intact fixed platelets. Two groups of healthy volunteers were included in the study: YOUNG (20-42 years, n=44) and older adults (OLD; 70-89 years; n=15). Compared to YOUNG donors, platelets from group OLD participants displayed significantly lower values of oxygen consumption in the Complex II-linked phosphorylating and uncoupled states and the Complex IV activity in HRR protocols for permeabilized cells and significantly lower resting and uncoupled respirations in intact cells when analyzed by both methods. In addition, mitochondrial ATP production rate was also significantly lower in platelets isolated from older adults. Variables measured by both methods from the same bloods correlated significantly, nevertheless those acquired by MFA were higher than those measured using HRR. In conclusion, the study verifies compromised mitochondrial respiration and oxidative ATP production in the platelets of aged persons and documents good compatibility of the two most widely used methods for determining the global performance of the electron-transporting system, i.e. HRR and MFA.

Norepinephrine turnover in the left ventricle of subtotally nephrectomized rats.

Increased activity of the sympathetic nervous system (SNS) has been proposed as a risk factor for increased cardiovascular mortality in patients with chronic kidney disease (CKD). Information on the activity of cardiac sympathetic innervation is non-homogeneous and incomplete. The aim of our study was to evaluate the tonic effect of SNS on heart rate, norepinephrine turnover and direct and indirect effects of norepinephrine in left ventricles of subtotally nephrectomized rats (SNX) in comparison with sham-operated animals (SHAM). Renal failure was verified by measuring serum creatinine and urea levels. SNX rats developed increased heart rates and blood pressure (BP). The increase in heart rate was not caused by sympathetic overactivity as the negative chronotropic effect of metipranolol did not differ between the SNX and SHAM animals. The positive inotropic effects of norepinephrine and tyramine on papillary muscle were not significantly different. Norepinephrine turnover was measured after the administration of tyrosine hydroxylase inhibitor, pargyline, tyramine, desipramine, and KCl induced depolarization. The absolute amount of released norepinephrine was comparable in both groups despite a significantly decreased norepinephrine concentration in the cardiac tissue of the SNX rats. We conclude that CKD associated with renal denervation in rats led to adaptive changes characterized by an increased reuptake and intracellular norepinephrine turnover which maintained normal reactivity of the heart to sympathetic stimulation.

Mitochondrial respiration of adipocytes differentiating from human mesenchymal stem cells derived from adipose tissue.

Burden of obesity is increasing in the contemporary world. Although multifactorial in origin, appropriate mitochondrial function of adipocytes emerges as a factor essential for healthy adipocyte differentiation and adipose tissue function. Our study aimed to evaluate mitochondrial functions of human adipose-derived mesenchymal stem cells committed to adipogenesis. On days 0, 4, 10, and 21 of adipogenesis, we have characterized adipocyte proliferation and viability, quantified lipid accumulation in maturing cells, performed qualitative and quantitative analysis of mitochondria, determined mitochondrial respiration of cells using high-resolution respirometry, and evaluated mitochondrial membrane potential. In the course of adipogenesis, mitochondrial oxygen consumption progressively increased in states ROUTINE and E (capacity of the electron transfer system). State LEAK remained constant during first days of adipogenesis and then increased probably reflecting uncoupling ability of maturing adipocytes. Citrate synthase activity and volume of mitochondrial networks increased during differentiation, particularly between days 10 and 21. In addition, lipid accumulation remained low until day 10 and then significantly increased. In conclusion, during first days of adipogenesis, increased mitochondrial respiration is needed for transition of differentiating cells from glycolytic to oxidative metabolism and clonal expansion of preadipocytes and then more energy is needed to acquire typical metabolic phenotype of mature adipocyte.

Variability of mitochondrial respiration in relation to sepsis-induced multiple organ dysfunction.

Ample experimental evidence suggests that sepsis could interfere with any mitochondrial function; however, the true role of mitochondrial dysfunction in the pathogenesis of sepsis-induced multiple organ dysfunction is still a matter of controversy. This review is primarily focused on mitochondrial oxygen consumption in various animal models of sepsis in relation to human disease and potential sources of variability in experimental results documenting decrease, increase or no change in mitochondrial respiration in various organs and species. To date, at least three possible explanations of sepsis-associated dysfunction of the mitochondrial respiratory system and consequently impaired energy production have been suggested: 1. Mitochondrial dysfunction is secondary to tissue hypoxia. 2. Mitochondria are challenged by various toxins or mediators of inflammation that impair oxygen utilization (cytopathic hypoxia). 3. Compromised mitochondrial respiration could be an active measure of survival strategy resembling stunning or hibernation. To reveal the true role of mitochondria in sepsis, sources of variability of experimental results based on animal species, models of sepsis, organs studied, or analytical approaches should be identified and minimized by the use of appropriate experimental models resembling human sepsis, wider use of larger animal species in preclinical studies, more detailed mapping of interspecies differences and organ-specific features of oxygen utilization in addition to use of complex and standardized protocols evaluating mitochondrial respiration.

Beneficial effects of mesenchymal stem cells on adult porcine cardiomyocytes in non-contact co-culture.

Mesenchymal stem cells (MSCs) have been reported to improve survival of cardiomyocytes (CMCs) and overall regeneration of cardiac tissue. Despite promising preclinical results, interactions of MSCs and CMCs, both direct and indirect, remain unclear. In this study, porcine bone marrow MSCs and freshly isolated porcine primary adult CMCs were used for non-contact co-culture experiments. Morphology, viability and functional parameters of CMCs were measured over time and compared between CMCs cultured alone and CMCs co-cultured with MSCs. In non-contact co-culture, MSCs improved survival of CMCs. CMCs co-cultured with MSCs maintained CMCs morphology and viability in significantly higher percentage than CMCs cultured alone. In viable CMCs, mitochondrial respiration was preserved in both CMCs cultured alone and in CMCs co-cultured with MSCs. Comparison of cellular contractility and calcium handling, measured in single CMCs, revealed no significant differences between viable CMCs from co-culture and CMCs cultured alone. In conclusion, non-contact co-culture of porcine MSCs and CMCs improved survival of CMCs with a sufficient preservation of functional and mitochondrial parameters.

Repeated exposure to hyperbaric hyperoxia affects mitochondrial functions of the lung fibroblasts.

Hyperbaric oxygen (HBO) therapy, i.e. breathing pure oxygen under increased environmental pressures serves as a treatment for diverse medical conditions. However, elevated oxygen concentration can be detrimental to central nervous system or lungs. Our study aimed to evaluate the effects of repeated exposure to HBO on mitochondrial respiration assessed by high-resolution respirometry (HRR), cell viability estimated by PrestoBlue® reaction, morphology analyzed by routine phase contrast and fluorescent microscopy, and superoxide dismutase (SOD) and citrate synthase (CS) activities using human lung fibroblasts. The cells were exposed to HBO for 2 h per day for 5 consecutive days. One day after the last exposure, HBO cells displayed significantly smaller area and perimeter, compromised viability and elevated SOD activity. No changes were detected in CS activity or quality of mitochondrial network. HRR revealed impaired mitochondrial oxygen consumption manifested by increased leak respiration, decreased activity of complex II and compromised ATP-related oxygen consumption when fatty acids were oxidized. Our findings document that in conditions mimicking chronic intermittent exposure to HBO, lung fibroblasts suffer from compromised mitochondrial respiration linked to complex II and impaired cellular growth in spite of increased antioxidant defense. Underlying mechanism of this HBO-induced mitochondrial dysfunction should be further explored.

Polychlorinated biphenyl 153 in lipid medium modulates differentiation of human adipocytes.

Emerging evidence indicates that polychlorinated biphenyls (PCBs) are involved in the development of diabetes mellitus in the obese. The purpose of this study was to determine mechanisms by which PCB 153 (2,2´,4,4´,5,5´-hexachloro-biphenyl) could influence diet-induced obesity and insulin resistance during adipogenesis. Lineage of h-ADMSCs was differentiated either as control (differentiation medium only), or with lipid vehicle modeling high fat nutrition (NuTRIflex) or lipid free vehicle (dimethylsulfoxide) for 28 days with or without PCB 153 daily co-exposure (in three concentrations 0.1, 1, and 10 microM). Gene expression analyses were performed using RT-qPCR at days 4, 10, 21, 24, 28; protein levels Akt and phosphorylated Akt (Phospho-Akt) by Western blot at days 4, and 21. PCB 153 treatment of h-ADMSCs only in lipid vehicle was associated with down regulation of key master genes of adipogenesis: PPARgamma, SREBP-1, PPARGC1B, and PLIN2 during the whole process of differentiation; and with increased Akt and decreased Phospho-Akt protein level at day 21. We have shown that PCB 153, in concentration 0.1 microM, has a potential in lipid rich environment to modulate differentiation of adipocytes. Because European and U.S. adults have been exposed to PCB 153, this particular nutrient-toxicant interaction potentially impacts human obesity and insulin sensitivity.

Multiple roles of mitochondria in aging processes.

Aging is a multifactorial process influenced by genetic factors, nutrition, and lifestyle. According to mitochondrial theory of aging, mitochondrial dysfunction is widely considered a major contributor to age-related processes. Mitochondria are both the main source and targets of detrimental reactions initiated in association with age-dependent deterioration of the cellular functions. Reactions leading to increased reactive oxygen species generation, mtDNA mutations, and oxidation of mitochondrial proteins result in subsequent induction of apoptotic events, impaired oxidative phosphorylation capacity, mitochondrial dynamics, biogenesis and autophagy. This review summarizes the major changes of mitochondria related to aging, with emphasis on mitochondrial DNA mutations, the role of the reactive oxygen species, and structural and functional changes of mitochondria.

Propofol-induced mitochondrial and contractile dysfunction of the rat ventricular myocardium.

Propofol is a short-acting hypnotic agent used in human medicine for sedation and general anesthesia. Its administration can be associated with serious cardiovascular side-effects that include decrease in arterial blood pressure and cardiac output. The aim of the present study was to evaluate propofol effects on mitochondrial respiration, myocardial contractility and electrophysiology in the same samples isolated from the heart ventricles of adult rats. Mitochondrial oxygen consumption was measured in permeabilized samples dissected from free walls of both ventricles using high-resolution respirometry. State LEAK was determined with malate and glutamate. Active respiration was induced by ADP (state PI) and further by succinate, a Complex II substrate (PI+II). Rotenone was injected to measure state PII. Antimycin A, a Complex III inhibitor was used to determine residual oxygen consumption (ROX). N,N,N',N'-tetramethyl-p-phenylenediamine dihydrochloride and ascorbate were injected simultaneously for respirometric assay of cytochrome c oxidase activity (CIV). Isometric contractions and membrane potentials were determined on multicellular preparations isolated from right and left ventricles. Propofol concentrations used ranged from 0.005 to 0.5 mmol/l. All respiratory parameters were significantly higher in the left control ventricles compared to the right ones. Propofol significantly decreased Complex I activity at concentration 0.025 mmol/l and papillary muscle contraction force at 0.1 mmol/l. Propofol did not affect action potential duration at any concentration studied. Our study suggests that mechanisms contributing to the impaired myocardial contraction during propofol anesthesia might include also mitochondrial dysfunction manifested by compromised activity of the respiratory Complex I.

Neonatal capsaicin administration impairs postnatal development of the cardiac chronotropy and inotropy in rats.

The present study evaluated the impact of neonatal administration of capsaicin (neurotoxin from red hot pepper used for sensory denervation) on postnatal development of the heart rate and ventricular contractility. In the rats subjected to capsaicin administration (100 mg/kg) on postnatal days 2 and 3 and their vehicle-treated controls at the ages of 10 to 90 days, function of the sympathetic innervation of the developing heart was characterized by evaluation of chronotropic responses to metipranolol and atropine, norepinephrine concentrations in the heart, and norepinephrine release from the heart atria. Sensory denervation was verified by determination of calcitonin gene-related peptide levels in the heart. Direct cytotoxic effects of capsaicin were assessed on cultured neonatal cardiomyocytes. Capsaicin-treated rats displayed higher resting heart rates, lower atropine effect, but no difference in the effect of metipranolol. Norepinephrine tissue levels and release did not differ from controls. Contraction force of the right ventricular papillary muscle was lower till the age of 60 days. Significantly reduced viability of neonatal cardiomyocytes was demonstrated at capsaicin concentration 100 micromol/l. Our study suggests that neonatal capsaicin treatment leads to impaired maturation of the developing cardiomyocytes. This effect cannot be attributed exclusively to sensory denervation of the rat heart since capsaicin acts also directly on the cardiac cells.

[Contractile functions of myocardium and their regulation]. / Kontraktilní funkce myokardu a jejich regulace.

Myocardial contractility is the ability of the cardiac muscle to contract, thereby generating force. Contractile functions of the myocardium are influenced by a number of intrinsic and extrinsic factors. The intrinsic factors, including the initial length of the muscle fibers, stimulation frequency and cardiac rhythm are modulated by neurohumoral mechanisms and extrinsic factors (ions and energy balance, temperature, pH, drugs, etc.). The mechanism of the cardiac contraction, intrinsic and neurohumonal regulation of the cardiac activity and changes in contractile functions of the myocardium and their regulation under pathological conditions are described in this article.

[Sperm mitochondrial function in men with normozoospermia and asthenozoospermia]. / Funkce mitochondrií ve spermii u muzu s normozoospermií a astenozoospermií

OBJECTIVE: One of causes of male infertility is reduced sperm motility. It turns out that the reduced efficiency of the mitochondrial respiratory activity may play a role in the development of this disorder. The aim of our study was to comprehensively determine mitochondrial respiratory activity of sperm with normal and reduced motility. DESIGN: Prospective study. SETTING: Department of Histology and Embryology, Faculty of Medicine in Pilsen, Charles University in Prague; Department of Physiology, Faculty of Medicine in Pilsen, Charles University in Prague; Institute of Reproductive Medicine and Endocrinology, IVF Centers Prof. Zech, Plzen. METHODS: Ejaculates of 14 men were obtained from IVF Center Prof. Zech, Pilsen. According to the World Health Organization classification, samples were divided into normozoospermatic (n = 7) and asthenozoospermatic(n = 7) groups. Respiratory activity of sperm was measured on two-chamber oxygraph Oroboros. RESULTS: In asthenozoospermatic samples, significantly reduced activity of complex I (p = 0.007) and increased respiration after application of ATP-synthase inhibitor oligomycin (showing increased uncoupled oxidation and phosphorylation, p = 0.046) were found. Inhibition of complex I by rotenone showed that complex I contribution to the total capacity of oxidative phosphorylation of healthy sperm was relatively lower than it is typical for somatic cells. CONCLUSION: In our study, we measured mitochondrial respiratory activity of human sperm, permeabilized by digitonin, by high-resolution oxygraphy, which allows the determination of oxygen consumption from the smallest possible number of germ cells. The study results confirm reduced activity of complex I in asthenozoospermatics and suggest that increased leakage of protons from the mitochondrial matrix, which leads to reduced efficiency of phosphorylating process, could participate in the reduced sperm motility. Better characterization of male germ cells, either completely healthy or with affected motility, will help us to understand better the physiological process of fertilization and also to choose the most viable sperm for infertility treatment by methods of assisted reproduction.

The contribution of vascular smooth muscle, elastin and collagen on the passive mechanics of porcine carotid arteries.

The main components responsible for the mechanical behavior of the arterial wall are collagen, elastin, and smooth muscle cells (SMCs) in the medial layer. We determined the structural and mechanical changes in porcine carotid arteries after administration of Triton® X-100, elastase, and collagenase using the inflation-deflation test. The arteries were intraluminarly pressurized from 0 to 200 mmHg, and the outer diameter of the artery was measured. The pressure-strain elastic modulus was determined based on the pressure/diameter ratio. The intima-media thickness, wall thickness, thickness of the tunica adventitia layer, and the area fractions of SMCs, elastin, and collagen within the arterial wall (A(A)(SMC/elastin/collagen, wall)) were measured using stereological methods. The relative changes in the relevant components of the treated samples were as follows: the decrease in A(A)(SMC, wall) after administration of Triton® X-100 was 11% ± 7%, the decrease in A(A)(elastin, wall) after administration of elastase was 40% ± 22%, and the decrease in A(A)(collagen, wall) after the application of collagenase was 51% ± 22%. The Triton® X-100 treatment led to a decrease in the SMC content that was associated with enlargement of the arterial wall (outer diameter) for pressures up to 120 mmHg, and with mechanical stiffening of the arterial wall at higher pressures. Elastase led to a decrease in the elastin content that was associated with enlargement of the arterial wall, but not with stiffening or softening. Collagenase led to a decrease in collagen content that was associated with a change in the stiffness of the arterial wall, although the exact contribution of mechanical loading and the duration of treatment (enlargement) could not be quantified.

Tissue concentrations of vasoactive intestinal peptide are affected by peritonitis-induced sepsis and hemofiltration in pigs.

Vasoactive intestinal peptide (VIP) is a neuropeptide released from the autonomic nerves exerting multiple antiinflammatory effects. The aim of the present study was to investigate the impact of severe sepsis and hemofiltration in two settings on plasma and tissue concentrations of VIP in a porcine model of sepsis. Thirty-two pigs were divided into 5 groups: 1) control group; 2) control group with conventional hemofiltration; 3) septic group; 4) septic group with conventional hemofiltration; 5) septic group with high-volume hemofiltration. Sepsis induced by faecal peritonitis continued for 22 hours. Hemofiltration was applied for the last 10 hours. Hemodynamic, inflammatory and oxidative stress parameters (heart rate, mean arterial pressure, cardiac output, systemic vascular resistance, plasma concentrations of tumor necrosis factor-alpha, interleukin-6, thiobarbituric acid reactive species, nitrate + nitrite, asymmetric dimethylarginine) and the systemic VIP concentrations were measured before faeces inoculation and at 12 and 22 hours of peritonitis. VIP tissue levels were determined in the left ventricle, mesenteric and coronary arteries. Sepsis induced significant increases in VIP concentrations in the plasma and mesenteric artery, but it decreased peptide levels in the coronary artery. Hemofiltration in both settings reduced concentrations of VIP in the mesenteric artery. In severe sepsis, VIP seems to be rapidly depleted from the coronary artery and, on the other hand, upregulated in the mesenteric artery. Hemofiltration in both settings has a tendency to drain away these upregulated tissue stores which could result in the limited secretory capacity of the peptide.

Cardiovascular parameters in rat model of chronic renal failure induced by subtotal nephrectomy.

Chronic renal failure (CRF) is associated with high incidence of cardiovascular complications. To clarify pathogenesis of CRF numerous animal models have been developed. The aim of our work was to describe methodology of subtotal surgical renal ablation in rat and to characterize some biochemical and cardiovascular parameters of this animal model. Male rats underwent 5/6 surgical nephrectomy or sham operations in two steps. The following parameters were measured on day 10 and in week 10 after the surgery: plasma concentrations of creatinine and urea, blood pressure, resting heart rate, chronotropic response to atropine and metipranol, heart ventricles weight, contraction parameters and action potential duration in the left ventricle. Increased serum concentrations of creatinine and urea, decreased creatinine clearance, polyuria and alteration of the remnant kidney tissue were found in CRF rats. Changes in cardiovascular parameters identified after subtotal nephrectomy resembled alterations of cardiovascular system in uremic patients and included hypertension, elevated resting heart rate, diminished parasympathetic cardiac tone, hypertrophy of the left ventricle associated with weakened force of contraction, prolonged contraction and relaxation and shortening of action potential duration. These data suggest that the present model can be a useful tool in the study of CRF and its cardiovascular complications.

Serum resistin levels in benign prostate hyperplasia and non-metastatic prostate cancer: possible role in cancer progression.

Resistin is a member of adipokine family involved in the regulation of inflammatory reactions and insulin sensitivity. In presented study its possible role in the development of benign prostate hyperplasia and prostate cancer was evaluated. Blood samples and prostate specimens were collected from 26 patients with benign prostate hyperplasia (BPH) and from 42 patients with prostate cancer (PCa) stage pT2 (n=18) and pT3 (n=24). Selected metabolic and biochemical parameters and serum resistin levels were measured and anthropometric measurements were performed as well as tissue immunohistochemistry for resistin. Serum resistin levels did not differ significantly between benign hyperplasia and prostate cancer but in cancer patients there was a trend towards decrease with higher cancer stage. Moreover, serum resistin levels were significantly lower in patients with seminal vesicle invasion in comparison to those without invasion. While in BPH serum resistin levels correlated with insulin resistance, inflammatory status and cortisol, in PCa positive correlation with F/T PSA ratio and cortisol was observed. Tissue immunohistochemistry did not show any differences in staining pattern between benign and neoplastic prostate tissue. We conclude that serum resistin levels do not significantly differ between patients with benign prostate hyperplasia and prostate cancer, but there is a trend towards decrease in resistin serum levels in advanced cancer cases.