Literature data support that green tea and its major component epigallocatechin gallate (EGCG) have powerful antioxidant effects. Contrary, hepatotoxicity can be induced by high-dose EGCG. The timing of exposure to green tea in relation to administration of hepatotoxic agent plays an import role too. The aim of our work was a verification of antioxidative effect of EGCG on D-galactosamine-induced injury in primary culture of rat hepatocytes. Hepatocytes were incubated with EGCG at concentrations of 1.25-10 μM and toxic D-galactosamine (GalN) for 24 hrs. Alternatively, hepatocytes were pretreated with EGCG for 24 hrs, and then incubated with EGCG and GalN for further 24 hrs. Cytotoxicity was analysed by lactate dehydrogenase activity, functional capacity by albumin production. Oxidative stress was evaluated from a production of malondialdehyde and glutathione content in the cells. EGCG protected hepatocytes against GalN-induced cytotoxicity but preventive treatment of intact hepatocytes with EGCG was required to diminish the development of hepatocyte injury. Oxidative stress induced in our study seems to overcome the ability of hepatocytes to improve GSH depletion and albumin production. Prolongation of the pretreatment with EGCG could be a promising strategy leading to amelioration of its hepatoprotective effect. and Alena Moravcová, Zuzana Červinková, Otto Kučera, Vojtěch Mezera, Halka Lotková
Activated hepatic stellate cells (HSC) are a major source offibrous proteins in cirrhotic liver. Inducing or accelerating their apoptosis is a potential way of liver fibrosis treatment. Extracellular matrix (ECM) surrounding cells in tissue affects their differentiation, migration, proliferation and function. Type I collagen is the main ECM component in fibrotic liver. We have examined how this protein modifies apoptosis of normal rat HSC induced by gliotoxin, cycloheximide and cytochalasin D in vitro and spontaneous apoptosis of HSC isolated from CCl4-damaged liver. We have found that type I collagen gel enhances HSC apoptosis regardless of the agent triggering this process. and L. Bittnerová, A. Jiroutová, E. Rudolf, M. Rezácová, J. Kanta
Užití mezenchymálních kmenových buněk (MSC) je jedním z experimentálních terapeutických přístupů k léčbě poranění míchy. MSC lze získat z kostní dřeně, tukové tkáně i z jiných periferních tkání dospělých jedinců. Výhodou je, v porovnání s jinými kmenovými buňkami, jejich dobrá dostupnost, snadná expanze a možnost autologního použití. MSC byly v posledních 15 letech studovány v experimentálním míšním poranění zejména u hlodavců se slibnými výsledky. Existuje několik mechanizmů, jakými působí MSC na míšní lézi. Především to je remyelinizace demyelinizovaných vláken, podpora pučení axonů (sprouting), angiogeneze, imunosupresivní efekt či sekrece neurotrofních faktorů, které mohou vést k funkčnímu zlepšení. Tyto slibné výsledky urychlily zahájení klinických studií u pacientů s poraněním míchy. Klinické studie fáze I/II ukázaly, že se jedná o bezpečnou metodu, avšak funkční průkaz vyžaduje další klinické studie. Ukazuje se, že MSC bude třeba kombinovat s jinými metodami, jako je přemostění léze, enzymatické štěpení jizvy a blokátory inhibičních faktorů. Tato práce přináší přehledný souhrn o aplikaci MSC u míšního poranění v experimentu i klinice., The use of mesenchymal stem cells (MSC) represents an experimental therapeutic modality in the treatment of spinal cord injury. MSC can be harvested from the bone marrow, fat tissue and other peripheral tissues from adult individuals. Compared to other types of stem cells, MSC are easy to access and expand and they can be used in autologous settings. Over the last 15 years, MSC have been widely studied in experimental spinal cord injury, especially in rodents, with promising results. MSC support remyelination of demyelinated axons, axonal sprouting, angiogenesis, have immunosuppressive effect and secrete neurotrophic factors that may led to functional improvement. These promising results led to launching of clinical studies in patients with spinal cord injury. Phase I/II clinical studies showed that the use of MSC represent a safe method. However, functional effect needs to be proved in further clinical studies. Data suggest that MSC will need to be combined with other methods, such as lesion bridging, scar tissue breakdown and blocking of inhibitory molecules. This paper provides an overview of the use of MSC in experimental and clinical SCI., and A. Hejčl, P. Jendelová, M. Sameš, E. Syková
Carnosine is a dipeptide formed of the amino acids β-alanine and histidine. Only a limited number of studies have examined the effects of carnosine on sympathetic nerve activation and anxiety. The present study was undertaken to determine the dose-related effects of carnosine on anxiety in the elevated T-maze test (ETM) with electrodermal activity (EDA). Carnosine was injected in three groups of rats with doses of 10 (low dose), 100 (medium dose) and 1000 (high dose) mg/kg i.p. Physiological saline was injected in the sham group. The anxiety scores of the rats were measured with ETM 20 minutes after injection. Then, SCL was measured. The decreased number of entries into the open arm (NEOA), the percentage of time spent in the open arm (% TSOA) and higher EDA [shown by skin conductance level (SCL)] indicate higher anxiety. The NEOA and % TSOA were lower in the high-dose group than in the other groups. SCL was lower in the medium-dose carnosine group than in the high-dose carnosine and sham groups. SCL was higher in the high-dose group than in the medium-dose and sham groups. Our results suggest that high-dose carnosine produced anxiety-like effects as assessed in the SCL and ETM. Medium-dose carnosine acted as an anxiolytic. The anxiety-related responses of carnosine depend on its dose-related effect. and N. Dolu, H. Acer, A. Y. Kara
BACKGROUND: The method of continual determination of the rat blood cholinesterase activity was developed to study the changes of the blood cholinesterases following different intervetions. AIMS: The aim of this study is registration of cholinesterase activity in the rat blood and its changes to demonstrate detoxification capacity of rats to inactivate sarin or VX in vivo. METHODS: The groups of female rats were premedicated (ketamine and xylazine) and cannulated to a. femoralis. Continual blood sampling (0.02 ml/min) and monitoring of the circulating blood cholinesterase activity were performed. Normal activity was monitored 1-2 min and then the nerve agent was administered i.m. (2×LD50). Using different time intervals of the leg compression and relaxation following the agent injection, cholinesterase activity was monitored and according to the inhibition obtained, detoxification capacity was assessed. RESULTS: Administration of sarin to the leg, then 1 and 5 min compression and 20 min later relaxation showed that further inhibition in the blood was not observed. On the other hand, VX was able to inhibit blood cholinesterases after this intervention. CONCLUSIONS: The results demonstrated that sarin can be naturally detoxified on the contrary to VX. Described method can be used as model for other studies dealing with changes of cholinesterases in the blood following different factors. and J. Bajgar, J. Cabal, J. Kassa, M. Pavlík
AIM/BACKGROUND: Pistacia terebinthus is used as a coffee substitute in the East and Southern Anatolia regions of Turkey. It contains unsaturated fatty acids, tocopherols, polyphenols and carotenoids. P. terebinthus has anti-inflammatory and potential antioxidant activity. In this study we evaluated the protective effects of P. terebinthus coffee (PTC) on thioacetamide (TAA)-induced liver injury in rats. MATERIALS AND METHODS: Twenty-eight male Sprague-Dawley rats were equally randomized into four groups. Chronic liver injury was induced with TAA (100 mg/kg i.p. three times weekly). The first group of rats served as control and received only tap water (G1), and the remaining groups of rats received PTC, p.o (G2); TAA (G3); TAA plus PTC, p.o (G4), respectively. RESULTS: After 8 weeks, PTC intake significantly reduced fibrosis/inflammation scores (p PTC intake reduced transforming growth factor beta (TGF-β) concentrations in the liver (p PTC intake. DISCUSSION AND CONCLUSION: PTC intake provided beneficial effects against TAA-induced liver injury in rats. PTC probably suppresses the proinflammatory cytokines through NF-κB signaling pathway. and I. H. Bahcecioglu, M. Ispiroglu, M. Tuzcu, C. Orhan, M. Ulas, U. Demirel, M. Yalniz, I. H. Özercan, N. Ilhan, K. Sahin
This study aimed to investigate alterations in hemorheology induced by L-carnosine, an anti- oxidant dipeptide, and to determine their relationship to oxidative stress in density-separated erythrocytes of aged and young rats. 28 male Sprague Dawley rats were divided into 4 groups as aged (Aca), young (Yca) L-carnosine groups (250 mg/kg L-carnosine, i.p.) and aged (As), young (Ys) control groups (saline, i.p.). Density separation was further performed to these groups in order to separate erythrocytes according to their age. Blood samples were used for the determination of erythrocyte deformability, aggregation; and oxidative stress parameters. Erythrocyte deformability of Yca group measured at 0.53 Pa was lower than Aca group. Similarly, deformability of least-dense (young) erythrocytes of Yca group was decreased compared to least-dense erythrocytes of Aca groups. Total antioxidant capacity (TAC) of Aca group was higher and oxidative stress index (OSI) lower than As group. Although L-carnosine resulted in an enhancement in TAC of aged rats, this favorable effect was not observed in erythrocyte deformability and aggregation in the dose applied in this study. and G. Erken, M. Bor-Kucukatay, E. KilicToprak, B. Akdag, V. Kucukatay
AIM: The ability of two newly developed oximes (K727, K733) to reduce tabun-induced acute neurotoxic signs and symptoms was evaluated and compared with currently available trimedoxime in rats. METHODS: The neuroprotective effects of the oximes studied combined with atropine on Wistar rats poisoned with tabun at a lethal dose (380 µg/kg i.m.; 90% of LD50 value) were evaluated. Tabun-induced neurotoxicity was monitored by the functional observational battery consisting of 38 measurements of sensory, motor and autonomic nervous functions at 2 hours following tabun challenge. RESULTS: All tested oximes combined with atropine enable tabun-poisoned rats to survive till the end of experiment. Both newly developed oximes (K727, K733) combined with atropine were able to decrease tabun-induced neurotoxicity in the case of lethal poisoning although they did not eliminate all tabun-induced acute neurotoxic signs and symptoms. CONCLUSION: The ability of both novel bispyridinium oximes to decrease tabun-induced acute neurotoxicity was slightly lower than that of trimedoxime. Therefore, the newly developed oximes are not suitable for the replacement of commonly used oximes such as trimedoxime in the treatment of acute tabun poisonings. and J. Kassa, J. Hatlapatková, J. Žďárová Karasová