71 research outputs found
Modulation of apoptotic signaling pathways in brain cells of adult male rats after chronic dexamethasone treatment
Deksametazon, jak sintetski glukokortikoid, se dugi niz godina koristi kao lek u tretmanu razliÄitih bolesti poput psorijaze, adrenalne insuficijencije, bakterijalnog meningitisa, moždanih trauma, Å”loga, alergija, spazma bronhija, reumatidnog artritisa, itd; ali i kao pomoÄni lek u hemo- i radioterapiji. Brojne studije ukazuju da deksametazon može regulisati sinaptiÄku plastiÄnost, poveÄati vijabilnost Äelija i njihovu proliferaciju u in vivo i in vitro uslovima. MeÄutim, uprkos Å”irokoj primeni u terapijske svrhe primeÄeno je da deksametazon ispoljava i niz negativnih efekata u mozgu, na primer apoptozu u granularnom sloju dentatnog girusa hipokampusa kod mladih i starih pacova, kao i smanjenje kognitivnih funkcija i motornog razvoja. Usled neusklaÄenosti rezultata mnogih studija, prouÄavanje sistemskih efekata, kao i efekata deksametazona u mozgu predstavljaju interesantno polje istraživanja prvenstveno jer se efekti niskih doza ovog sintetskog glukokortikoida ne mogu ispitivati centralno usled blokiranja njegovog ulaska dejstvom MDR p-glikoproteina i/ili nekim drugim mehanizmom. Stoga, za potrebe eksperimenta, odrasli mužjaci pacova Wistar soja su podeljeni u dve grupeā kontrolne jedinke i životinje tretirane deksametazonom (100 g/kg/dan) tokom 7 uzastopnih dana. 28 h nakon zavrÅ”etka hroniÄnog tretmana životinje su žrtvovane. Sistemski efekat deksametazona je praÄen promenom biometrijskih parametara (telesna masa, masa timusa i nadbubrežnih žlezdi), kao i koncentracije kortikosterona u serumu i moždanom tkivu. Kako bi se utvrdilo da li male doze deksametazona dovode do apoptoze u hipofizi, hipotalamusu, hipokampusu i preÄeonoj kori koriÅ”Äen je DNK fragmentacioni esej, dok se metodama histoloÅ”kog bojenja hipokampusa i preÄeone kore (fluoro-jade B i krezil ljubiÄastim) istraživao obim neuralne smrti i morfoloÅ”ke promene. Western blot i RT-PCR analizama su ispitivane promene u ekspresiji proteina i iRNK markera procesa smrti odnosno preživljavanja Äelija.
Rezultati ove studije su pokazali da hroniÄan tretman malim dozama deksametazona uzrokuje hipoaktivnost hipotalamo-hipofizno-adrenalne ose, koja se ogleda u smanjenju telesne mase, mase timusa i nadbubrežnih žlezdi, kao i kortikosterona u serumu...For many years, dexamethasone, a potent synthetic glucocorticoid, has been used as a medication in the treatment of psoriasis, adrenal insufficiency, bacterial meningitis, brain trauma, stroke, allergies, bronchial spasm, rheumatoid arthritis, etc., and as a co-medicament in chemo- and radiotherapy. Numerous studies suggest that dexamethasone is able to regulate synaptic plasticity, enhance cell viability and proliferation in vivo and in vitro. However, dexamethasone exerts a number of adverse reactions in the brain, such as apoptosis in the hippocampal granular layer of dentate gyrus in young and old rats, as well as reduced cognitive and motor development. The dexamethasone-induced systemic effects and dexamethasone-provoked effects in the brain are an interesting field of research, mainly because the effects of low-dose dexamethasone treatment could not be tested directly in brain tissue due to the central blocking action of MDR p-glycoprotein and/or some other mechanism. Therefore, for the purposes of the experiment, adult male Wistar rats were divided into two groups ā controls and animals treated with dexamethasone (100 g/kg/day) per 7 days. 28 h upon chronic treatment, rats from both groups were sacrificed. Late systemic effects of dexamethasone were monitored by alterations of biometric parameters (body weight, thymus and adrenal glands mass) and level of corticosterone in serum and brain tissue. Further, using DNA fragmentation assay, present study aimed to determine whether low dose dexamethasone treatment is able to cause apoptosis in the pituitary gland, hypothalamus, hippocampus and prefrontal cortex, while histological staining methods (fluoro-jade B and cresyl violet staining) were applied to investigated the extent of neuronal death and morphological changes in hippocampus and prefrontal cortex. Changes in protein and mRNA expression of cell death and cell survival markers were examined by Western blot and RT-PCR analyzes.
The results obtained in this thesis revealed that chronic low dose dexamethasone treatment caused hypoactivity of hypothalamus-pituitary-adrenal axis, reflected in the reduction of body weight, thymus and adrenal glands masses, as well as levels of corticosterone in serum...
Early effects of ionizing ir-radiation on the ecto- 5'nucleotidase activity in rat brain during postnatal development
In the present study, early effects of low (50 cGy) and therapeutic dose (2 Gy) of ionizing Ī³-irradiation on ecto-5ānucleotidase activity in rat brain neuronal cells during postnatal development were studied. Ecto-5ā-nucleotidase is the major enzyme that hydrolyzes extracellular AMP and is responsible for the formation of the P1 receptor agonist-adenosine. It was shown that the levels of AMP hydrolyses by the enzyme were not affected by irradiation in the rats during first 4 postnatal weeks. A both low- and therapeutic dose significantly decreased hydrolyses of extracellular AMP in pubertal and adult rats by 10-14%. These findings indicate that low dose exerts the same effects on ecto-5'nucleotidase activity as therapeutic one in first hour after irradiation. Another findings is that in early postnatal development, brain ecto-5'nucleotidase was resistant to irradiation damage.Physical chemistry 2008 : 9th international conference on fundamental and applied aspects of physical chemistry; Belgrade (Serbia); 24-28 September 200
Ionizing irradiation affect extracellular nucleotide hydrolysis in brain of rats in different stages of development: i 15-day-old rats
Ionizing radiation affects plasma membrane functions mediated through transmembrane proteins including enzymes. Plasma membrane surface-located enzyme chain of ecto-nucleotide triphospho diphosphohydrolases (NTPDases) are involved in termination of cell purinergic signalization by hydrolysing extracellular adenosine tri- and di-phosphate (ATP and ADP). In the present study, effects of low (50 cGy) and therapeutic (2 Gy) dose of ionizing Ī³-irradiation on NTPDase activity in early postnatal rat brain neuronal cells were studied. Both low- and therapeutic doses significantly decreased hydrolyze of extracellular ATP (by 11% and 30%) and ADP (18% and 46%) in postnatal rats. These findings indicate that gammaradiation inhibits the enzyme activity in dose-dependent manner. This decreasing NTPDase activity 24h after whole body irradiation may lead to neuronal cell function disturbance, even cell death.Physical chemistry 2008 : 9th international conference on fundamental and applied aspects of physical chemistry; Belgrade (Serbia); 24-28 September 200
Ionizing irradiation affect extracellular nucleotide hydrolysis in brain of rats in different stages of development: ii 30-day-old rats
The effect of acute gamma irradiation (IR) on enzyme activity of rat brain Ecto-Nucleotide Diphosphohydrolase (E-NTPDase), in presence of adenosine triand diphophashates (ATP and ADP) and divalent cations (Ca2+ and Mg2+), has been investigated. The aim of research was to study the influence of low (50 cGy) and therapeutic (2Gy) doses of whole-body irradiation on rat brain E-NTPDase enzyme activity 24h after treatment in prepubertal and adult rats. Our results suggest that whole-body irradiation could induce modulation of neural activity in rat brain, especially in young rats.Physical chemistry 2008 : 9th international conference on fundamental and applied aspects of physical chemistry; Belgrade (Serbia); 24-28 September 200
Time-dependent expression of Bcl-2 and Bax proteins in cortical brain area of adult wistar rats after permanent bilateral occlusions
Model of permanent bilateral occlusion of common carotid arteries (2VO) is generally
used to investigate mechanisms of chronic cerebral hypoperfusion that occurs in aging
and other neurodegenerative processes. The aim of this study was to determine timedependent modulation of mitochondrial apoptotic signaling in cortical brain area
following chronic cerebral hypoperfusion. Using Western blot technique we monitored
the changes in the expression of proteins of Bcl-2 family (Bcl-2, Bax) 3, 7 and 90 days
following the insult. According to our results the greatest impact of chronic cerebral
hipoperfusion occurred on 7th day.Physical chemistry 2012 : 11th international conference on fundamental and applied aspects of physical chemistry; Belgrade (Serbia); 24-28 September 201
L-cysteine modulates the ecto-atpase activity inhibition in presence of cadmium (ii) and mercury (ii) ions
L-cysteine is used as effective oral chelating agent due to property of its sulfhydryl
group to bind heavy metal ions. The aim of this study was to investigate ability of
L-cysteine to prevent mercury (II) and cadmium (II) induced ecto-ATPase activity
inhibition of rat uterus plasma membranes. Results show that 10 mmol/l L-cysteine
have protective effect on enzyme activity in the presence of cadmium and mercury
ions
Kinetic properties of ntpdases in rat brain synaptic plasma membranes
Kinetic properties of ecto-nucleoside triphosphate diphosphohydrolase (NTPDases)
in synaptic terminals from whole rat brain were characterised. Three different
NTPDases are present in nervous system and hydrolysing ATP and ADP with
different affinities. ATP and ADP hydrolysis exhibited kinetic properties typical
for all members of the NTPDase, low substrate specificity for tri- and
diphosphonucleosides, divalent cation dependency and insensitivity towards iontransporting
ATPase inhibitors. Kinetic properties of ATPase and ADPase
component of NTPDases depend on postnatal developmental stages of rats, and
indicated different NTPDase family members present in various ontogeny stages.
Lowering in the NTPDases activities could result in a decreased production of
adenosine and change in extracellular ATP/adenosine ratio
Time-Related Sex Diffrences in Cerebral Hypoperfusion-Induced Brain Injury
Although the model of cerebral hypoperfusion in rats has been a matter of many investigations over the years, the exact intracellular and biochemical mechanisms that lead to neuron loss and memory decline have not been clearly identified. In the current study, we examined whether cerebral hypoperfusion causes changes in hippocampal protein expression of apoptotic markers in the synaptosomal fraction and neurodegeneration in a time-dependent and sex-specific manner. Adult male and female Wistar rats were divided into two main groups, controls that underwent sham operation, and animals subjected to permanent bilateral occlusion of common carotid arteries. Both male and female rats were killed 3, 7 or 90 days following the insult. The obtained results indicate that the peak of processes that lead to apoptosis occured on postoperative day 7 and that they were more prominent in males, indicating that neuroprotective effects of certain substances (planned for future experiments), should be tested at this time point
Toxicity assessment of Gentiana lutea L. root extract and its monoterpene compounds
Root of Gentiana lutea commercially available as gentian root, a natural antidote for different types of poisons, possess antioxidative, immunomodulatory, cytoprotective and anti-inflammatory, and adverse, genotoxic and mutagenic effects. It has monoterpenes loganic acid, swertiamarin, gentiopicroside and sweroside as most abundant constituents. In this study, we assessed the toxicity of monoterpenesā reactive molecular fragments using in silico prediction by VEGA-QSAR platform. Further, we compared the data obtained with in vitro geno- and cyto- toxicity testing of the above monoterpenes and the G. lutea root extract (GE), on human primary unstimulated and mitogen-stimulated peripheral blood mononuclear cells (PBMCs). Viability was assessed by TB and XTT tests after 48 h treatment. DNA damage was evaluated by alkaline comet assay on unstimulated cells, whereas cytokinesis-block micronucleus assay was employed on mitogen-stimulated PBMCs. Stability of compounds throughout treatment was monitored by UPLC. The observed in vitro results had highest compliance with in silico IRFMN/ISSCAN-CGX prediction model. Compounds showed high stability during experiment while treatment with single compounds reduced number of viable cells and increased DNA damage. GE treatment had toxic impact on unstimulated PBMCs but no significant genotoxic influence on mitogen-stimulated PBMCs. In summary, the mild GE effect suggests that the complexity of crude GE extract chemical composition may attenuate the toxicity of the tested monoterpenes loganic acid, swertiamarin, gentiopicroside and sweroside
Theoretical and experimental evaluation of K2Br+ and K3Br+ clusters' ionization energies
In current study, a non-stoichiometric bromine-doped potassium K2Br+and K3Br+clusters are generated by combining a Knudsen effusion cell as a chemical reactor with thermal or surface ionization,and selected by a magnetic sector mass spectrometer. Furthermore, their ionization energies (IEs) are calculated for the first time using B3LYP/9-ve PP(K),cc-pVTZ-PP(Br) level of theory. Herein, presented results indicate that experimentally obtained IEs by Ionov equation, 4.10 Ā± 0.20 eV for K2Br+, and 4.03 Ā± 0.20 eV for K3Br+, are in consistence with their theoretically determined IEs.Physical chemistry 2016 : 13th international conference on fundamental and applied aspects of physical chemistry; Belgrade (Serbia); 26-30 September 2016
- ā¦