Consumption of seafood containing toxin domoic acid (DA) causes an alteration of glutamatergic signaling pathways and could lead to various signs of neurotoxicity in animals and humans. Neonatal treatment with domoic acid was suggested as valuable model of schizophrenia and epilepsy. We tested how repeated early postnatal DA administration influences the spontaneous behavior of rats in adulthood. Rats were injected with 30 μg DA/kg from postnatal day (PND) 10 until PND 14. Their behavior was observed in the open field test for one hour (Laboras, Metris) at PND 35, PND 42 and PND 112. We did not find any difference between DA treated rats and animals injected with equivalent volume of saline in both test sessions at PND 35 and PND 42. DA rats at PND 112 exhibited significantly higher vertical and horizontal exploratory activity (tested parameters: locomotion, distance travelled, average speed reached during test, grooming and rearing) between the 30th-40th min of the test session and habituated over 10 min later. We conclude that at least in the given experimental design, neonatal DA treatment results in alteration of the spontaneous behavior of rats in adulthood., K. Jandová, P. Kozler, M. Langmeier, D. Marešová, J. Pokorný, V. Riljak., and Obsahuje bibliografii
Photothrombotic model of ischemia (PT) is based on free radical-mediated endothelial dysfunction followed by thrombosis. Free radicals are also involved in hypoxic preconditioning. We tested the sensitivity of PT to preconditioning with hypobaric hypoxia and to pretreatment with melatonin. In adult Wistar rats, after intravenous application of Rose Bengal, a stereo-tactically defined spot on the denuded skull was irradiated by a laser for 9 min. The first experimental group underwent hypobaric hypoxia three days before irradiation. In the second experimental group, melatonin was applied intraperitoneally one hour before irradiation. Three days after irradiation, animals were sacrificed, the brains perfused, and stained with TTC. Ischemic lesions were divided into grades (I, II, III). In the control group (where no manipulation preceded photothrombosis), most animals displayed deep damage involving the striatum (grade III). The group pre-exposed to hypoxia showed similar results. Only 28.57 % of the melatonin pretreated animals exhibited grade III lesions, and in 57.14 % no signs of lesions were detected. Pre-exposure to hypoxia was not protective in our model. Pretreatment with melatonin lead to a significant reduction of the number of large ischemic lesions. This result is probably caused by protection of endothelial cells by melatonin., I. Matějovská, K. Bernášková, D. Krýsl, J. Mareš., and Obsahuje bibliografii a bibliografické odkazy
High blood pressure (BP) of L-NAME hypertensive rats is maintained not only by the absence of nitric oxide (NO)-dependent vasodilatation but also by the enhancement of both sympathetic and angiotensin II-dependent vasoconstriction. The aim of the present study was to evaluate the role of inhibitory G (Gi) proteins, which are involv ed in tonic sympathetic vasoconstriction, in the pathogenesis of NO-deficient hypertension. We therefore studied BP response to chronic L-NAME administration (60 mg/kg/day for 4 weeks) in rats in which the in vivo inactivation of Gi proteins was induced by injection of pertussis toxin (PTX, 10 μg/kg i.v.). The impairment of sympathetic vasoconstriction due to PTX-induced Gi protein inactivation prevents the full development of NO-deficient hypertension because BP of PTX-treated rats subjected to chronic L-NAME administration did not reach hypertensive values. Nevertheless, chronic NO synthase inhibition per se is capable to increase moderately BP even in PTX-treated rats. Our data suggest that the sympathetic vasoconstriction is essential for the development of established NO-deficient hypertension., J. Zicha ... [et al.]., and Obsahuje seznam literatury
Mitochondria as an energy generating cell device are very sensitive to oxidative damage. Our previous findings obtained in hepatocytes demonstrated that Complex I of the respiratory chain is more sensitive to oxidative damage than other respiratory chain complexes. We present additional data on isolated mitochondria showing that palmityl carnitine oxidation is strongly depressed at a low (200 μM) tert-butyl hydroperoxide (tBHP) concentration, while oxidation of the flavoprotein-dependent substrate - succinate is not affected and neither is ATP synthesis inhibited by tBHP. In the presence of tBHP, the respiratory control index for palmityl carnitine oxidation is strongly depressed, but when succinate is oxidized the respiratory control index remains unaffected. Our findings thus indicate that flavoprotein-dependent substrates could be an important nutritional factor for the regeneration process in the necrotic liver damaged by oxidative stress., Z. Červinková, H. Rauchová, P. Křiváková, Z. Drahota., and Obsahuje bibliografii a bibliografické odkazy
The detailed mechanisms determining the course of congestive heart failure (CHF) and associated renal dysfunction remain unclear. In a volume overload model of CHF induced by creation of aorto- caval fistula (ACF) in Hannover Sprague -Dawley (HanSD) rats we explored the putative pathogenetic contribution of epoxyeicosatrienoic acids (EETs), active products of CYP -450 dependent epoxygenase pathway of arachidonic acid metabolism, and compared it with the role of the renin-angiotensin system (RAS). Chronic treatment with cis -4-[4-(3-adamantan -1-yl- ureido) cyclohexyloxy]benzoic acid (c-AUCB, 3 mg /l in drinking water), an inhibitor of soluble epoxide hydrolase (sEH) which normally degrades EETs, increased intrarenal and m yocardial EETs to levels observed in sham -operated HanSD rats, but did not improve the survival or renal function impairment. In contrast, chronic angiotensin -converting enzyme inhibition (ACEi, trandolapril, 6 mg /l in drinking water) increased renal blood flow, fractional sodium excretion and markedly improved survival, without affecting left ventricular structure and performance. Hence, renal dysfunction rather than cardiac remodeling determines long-term mortality in advanced stage of CHF due to volume o verload. Strong protective actions of ACEi were associated with suppression of the vasoconstrictor/sodium retaining axis and activation of vasodilatory/natriuretic axis of the renin -angiotensin system in the circulating blood and kidney tissue., L. Červenka, V. Melenovský, Z. Husková, A. Sporková, M. Bürgelová, P. Škaroupková, S. H. Hwang, B. D. Hammock, J. D. Imig, J. Sadowski., and Obsahuje bibliografii
In the horse, the inflammation response to various pathologies (intestinal strangulations, laminitis, etc.) involves an excessive stimulation of the polymorphonuclear neutrophils releasing reactive oxygen species (ROS) and myeloperoxidase (MPO). The aim of the present work was to study the effect of natural polyphenols, curcumin oids and tetrahydrocurcuminoids (THC) on isolated stimulated equine neutrophils and on the activity of purified MPO. The ROS production and the release of MPO by activated neutrophils were measured by chemiluminescence and ELISA techniques, respectively. The activity of purified MPO was measured by studying its nitration, chlorination or oxidation capacity and by using an original method called SIEFED allowing the study of drug interaction with the enzyme without interferences of the medium. Curcuminoids and THC had dose-dependent inhibitory effects on ROS production and MPO release by activated neutrophils and on purified MPO activity. We suggest that the higher efficacy of curcuminoids versus THC could be explained, at least partially, by its chemical structure: the conjugated double bounds and the plane structure of curcuminoids made easier the neutralization of the radical species generated by activated neutrophils and the interaction of the drug with the active site of MPO. These inhibitory effects of curcuminoids on the oxidant activity of equine neutrophils and on MPO activity open therapeutic perspectives in equine pathologies with excessive inflammatory reactions., T. Franck, S. Kohnen, S. Grulke, P. Neven, Y. Goutman, F. Peters, B. Pirotte, G. Deby-Dupont, D. Serteyn., and Obsahuje bibliografii a bibliografické odkazy
Metformin is widely used in the treatment of Type 2 diabetes, however, mechanisms of its antihyperglycemic effect were not yet fully elucidated. Complex I of mitochondrial respiration chain is considered as one of the possible targets of metformin action. In this paper, we present data indicating that the inhibitory effect of metformin can be tested also in liver homogenate. Contrary to previous findings on hepatocytes or mitochondria under our experimental conditions, lower metformin concentrations and shorter time of preincubation give significant inhibitory effects. These conditions enable to study the mechanism of the inhibitory effect of metformin in small samples of biological material (50-100 mg wet weight) and compare more experimental groups of animals because isolation of mitochonria is unnecessary., E. Páleníčková ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Vitamin D status and the relationship between serum 25(OH) vitamin D concentrations and the components of insulin resistance were examined in 120 patients with chronic kidney disease stage 2 and 3. Insulin sensitivity/resistance was calculated by the quantitative insulin sensitivity check index (QUICKI). In this analysis, the prevalence of insulin resistance was 42 %. Only 17 % of patients had serum 25(OH) vitamin D concentration in the recommended range ( ≥ 30 ng/ml), 42 % suffered from vitamin D insufficiency and 41 % had moderate vitamin D deficiency. Insulin resistance significantly correlated with serum 25(OH)D and 1,25(OH) 2 D concentrations, renal function and protein excretion rate. Our results support the increasing evidence that vitamin D deficiency may be one of the factors participating in the development of insulin resistance already in the early stages of chronic kidney disease. and K. Štefíková ... [et al.].
Numerous studies concerning the cardiovascular system in SHR often yield controversial data. The background of this diversity has various roots, ranging from different vascular segments or areas studied up to the different age of experimental animals. Our study aimed to follow the BP as an integrated response of vascular system. This approach was justified since stabilized cardiac output in SHR was proved till 1 year of age. The groups of male SHR (aged 3, 5, 9, 17 and 52 weeks) and age-matched Wistar rats were used. Significant basal BP difference between SHR and Wistar rats was found at 9 weeks of age and continued till the age of 52 weeks, reaching 189.6±11.9 mm Hg in SHR and 117.3±6.9 mm Hg in Wistar rats (P<0.01). The significant difference in BP increase to two doses of noradrenaline (0.1μg and 1 μg) between SHR and control rats was also found at the age of 9 weeks. At 52 weeks the BP increment to two doses of noradrenaline was in SHR 19.7±2.0 mm Hg and 60.5±3.9 mm Hg and in Wistar rats 7.4±1.9 mm Hg and 40.5±3.2 mm Hg (P<0.01). The hypotensive response to acetylcholine (0.1 μg, 1 μg and 10 μ) in SHR was enhanced at 17 weeks of age only and this amplification persisted till the age of 52 weeks. In 52-week-old SHR the hypotensive response to three doses was 69.9±10.2 mm Hg, 87.5±11.8 mm Hg and 103.4±10.6 mm Hg, while in Wistar rats it was 37.4 4.2 mm Hg P<0.0), 62.3±3.5 mm Hg (P<0.01) and 73.5±2.8 mm Hg (P<0.05). In conclusion, the efficiency of cardiovascular system of SHR to respond to noradrenaline was already enhanced from 9 weeks of age, whereas the response to acetylcholine was not augmented before the age of 17 weeks., M. Gerová, F. Kristek., and Obsahuje bibliografii a bibliografické údaje
The two i nferior colliculi (IC) are paired structures in the midbrain that are connected to each other by a bundle of commissural fibers. The fibers play an important role in coordinating sound signal processing between the two inferior colliculi. This study examined inter-collicular suppression on sound signal processing in amp litude domain of mice by measuring the rate-amplitude functions (RAFs) of neurons in one IC during the electrical stimulation of the opposite IC. Three types (monotonic, saturated and non-monotonic) RAFs of collicular neurons were measured before and durin g inter-collicular suppression. Inter-collicular suppression significantly increased the slope, decreased the dynamic range and narrowed down the responsive amplitude of all RAFs to high amplitude level but did not change the type of most (36/43, 84 % ) RAFs. As a result, all types of RAFs were compressed at a greater degree at low than at high sound amplitude during inter-collicular suppression. These data indicate that inter-collicular suppression improve sound processing in the high amplitude domain., Liang Cheng, Hui-Xian Mei, Yun Huang., and Obsahuje bibliografii