Radiotherapy is an important therapeutic approach against cervical cancer but associated with adverse effects including vaginal fibrosis and dyspareunia. We here assessed the immunological and oxidative responses to cervical irradiation in an animal model for radiation-induced cervicitis. Rats were sedated and either exposed to 20 Gy of ionising radiation given by a linear accelerator or only sedated (controls) and euthanized 1-14 days later. The expressions of toll-like receptors (TLRs) and coupled intracellular pathways in the cervix were assessed with immunohistofluorescence and western blot. Expression of cytokines were analysed with the Bio-Plex Suspension Array System (Bio-Rad). We showed that TLRs 2-9 were expressed in the rat cervix and cervical irradiation induced up-regulation of TLR5, TRIF and NF-κB. In the irradiated cervical epithelium, TLR5 and TRIF were increased in concert with an up-regulation of oxidative stress (8-OHdG) and antioxidant enzymes (SOD-1 and catalase). G-CSF, M-CSF, IL-10, IL- 17A, IL-18 and RANTES expressions in the cervix decreased two weeks after cervical irradiation. In conclusion, the rat uterine cervix expresses the TLRs 2-9. Cervical irradiation induces immunological changes and oxidative stress, which could have importance in the development of adverse effects to radiotherapy.
- MeSH
- adaptorové proteiny vezikulární transportní imunologie MeSH
- cervix uteri imunologie patologie MeSH
- cytokiny imunologie MeSH
- experimentální radiační poranění imunologie patologie MeSH
- krysa rodu rattus MeSH
- NF-kappa B imunologie MeSH
- oxidační stres imunologie účinky záření MeSH
- potkani Sprague-Dawley MeSH
- regulace genové exprese imunologie účinky záření MeSH
- toll-like receptory imunologie MeSH
- zánět děložního hrdla imunologie patologie MeSH
- záření gama škodlivé účinky MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
PURPOSE: We examined the effect of epidermal growth factor (EGF) and bone marrow transplantation (BMT) on gastrointestinal damage after high-dose irradiation of mice. MATERIAL AND METHODS: C57Black/6 mice were used. Two survival experiments were performed (12 and 13 Gy; (60)Co, 0.59-0.57 Gy/min). To evaluate BMT and EGF action, five groups were established - 0 Gy, 13 Gy, 13 Gy + EGF (at 2 mg/kg, first dose 24 h after irradiation and then every 48 h), 13 Gy + BMT (5 × 10(6) cells from green fluorescent protein [GFP] syngenic mice, 4 h after irradiation), and 13 Gy + BMT + EGF. Survival data, blood cell counts, gastrointestine and liver parameters and GFP positive cell migration were measured. RESULTS: BMT and EGF (three doses, at 2 mg/kg, administered 1, 3 and 5 days after irradiation) significantly increased survival (13 Gy). In blood, progressive cytopenia was observed with BMT, EGF or their combination having no improving effect early after irradiation. In gastrointestinal system, BMT, EGF and their combination attenuated radiation-induced atrophy and increased regeneration during first week after irradiation with the combination being most effective. Signs of systemic inflammatory reaction were observed 30 days after irradiation. CONCLUSIONS: Our data indicate that BMT together with EGF is a promising strategy in the treatment of high-dose whole-body irradiation damage.
- MeSH
- apoptóza účinky léků účinky záření MeSH
- celotělové ozáření škodlivé účinky MeSH
- epidermální růstový faktor aplikace a dávkování terapeutické užití MeSH
- experimentální radiační poranění farmakoterapie patologie terapie MeSH
- gastrointestinální trakt zranění patologie účinky záření MeSH
- kombinovaná terapie MeSH
- lithostatin účinky léků MeSH
- mitóza účinky léků účinky záření MeSH
- myši inbrední C57BL MeSH
- myši transgenní MeSH
- myši MeSH
- transplantace kostní dřeně * MeSH
- zánět patologie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- centrální nervový systém * účinky záření MeSH
- elektromagnetická pole škodlivé účinky MeSH
- experimentální radiační poranění * patologie psychologie MeSH
- modely nemocí na zvířatech MeSH
- myši - mutanty neurologické MeSH
- myši MeSH
- neurodegenerativní nemoci MeSH
- vztah dávky záření a odpovědi * MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- práce podpořená grantem MeSH
The UVB-irradiated cornea is damaged by oxidative stress. Toxic oxygen products induced by UVB radiation in the cornea are insufficiently removed by antioxidants, whose numbers decrease with increasing UVB irradiation. In addition, the UVB-irradiated cornea suffers from hypoxic conditions because damaged corneal cells cannot utilize oxygen normally, although the supply of oxygen to the cornea is unchanged (normal). This contributes to attenuated re-epithelialization, corneal neovascularization and apoptotic cell death. Our previous publications reported that trehalose applied on the corneal surface during irradiation significantly suppressed UVB-induced corneal oxidative damage. The results of this study provide for the first time important evidence that trehalose applied on the surface of corneas for two weeks following repeated UVB irradiation (312 nm, daily dose 0.5 J/cm2) accelerated corneal healing, restored corneal transparency and suppressed corneal neovascularization. Compared to buffered saline treatment, following which caspase-3, nitrotyrosine, malondialdehyde and urokinase-type plasminogen activator were still strongly expressed in the corneal epithelium two weeks after irradiation and corneal neovascularization was evident, apoptotic cell death was already significantly reduced after one week of trehalose application. The expression of other markers of injury returned to normal levels during two weeks of trehalose treatment. In conclusion, our results show that trehalose accelerated healing of the UVB irradiated cornea, very probably via suppression of hypoxia-response injury. In addition, immunohistochemical results on corneal cryostat sections corresponded with those obtained using corneal impression cytologies, thus confirming that corneal impression cytologies are useful for diagnostic purposes.
- MeSH
- aktivátor plasminogenu urokinasového typu metabolismus MeSH
- apoptóza účinky léků MeSH
- biologické markery metabolismus MeSH
- cytodiagnostika metody MeSH
- experimentální radiační poranění farmakoterapie metabolismus patologie MeSH
- hojení ran účinky léků MeSH
- imunohistochemie metody MeSH
- injekce nitrooční MeSH
- kaspasa 3 metabolismus MeSH
- králíci MeSH
- malondialdehyd metabolismus MeSH
- nemoci rohovky farmakoterapie metabolismus patologie MeSH
- oxidační stres MeSH
- patologická angiogeneze farmakoterapie MeSH
- rohovkový epitel účinky záření MeSH
- trehalosa aplikace a dávkování terapeutické užití MeSH
- tyrosin analogy a deriváty metabolismus MeSH
- ultrafialové záření MeSH
- zmrazené řezy metody MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Mouse hematopoiesis, suppressed by a sublethal dose of ionizing radiation, was the target for combined therapy with a cyclooxygenase-2 (COX-2) inhibitor meloxicam and an adenosine A₃ receptor agonist IB-MECA. The drugs were administered in an early postirradiation treatment regimen: meloxicam was given in a single dose 1hour after irradiation, IB-MECA in two doses 24 and 48hours after irradiation. Treatment-induced changes in several compartments of hematopoietic progenitor and precursor cells of the bone marrow were evaluated on day 3 after irradiation. Values of hematopoietic progenitor cells for granulocytes/macrophages and erythrocytes (GM-CFC and BFU-E, respectively), as well as those of proliferative granulocytic cells were found to be significantly higher in the mice treated with the drug combination in comparison to irradiated controls and attained the highest increase factors of 1.6, 1.6, and 2.6, respectively. The study emphasizes the significance of the combined treatment of suppressed hematopoiesis with more agents. Mechanisms of the action of the individual compounds of the studied drug combination and of their joint operation are discussed.
- MeSH
- adenosin aplikace a dávkování analogy a deriváty terapeutické užití MeSH
- agonisté adenosinového receptoru A3 aplikace a dávkování terapeutické užití MeSH
- celotělové ozáření MeSH
- erytroidní prekurzorové buňky účinky léků účinky záření MeSH
- experimentální radiační poranění krev farmakoterapie patologie MeSH
- faktor stimulující kolonie granulocytů krev MeSH
- hematinika aplikace a dávkování terapeutické užití MeSH
- hematopoetické kmenové buňky účinky léků účinky záření MeSH
- hematopoéza účinky léků účinky záření MeSH
- inhibitory cyklooxygenasy 2 aplikace a dávkování terapeutické užití MeSH
- kombinovaná farmakoterapie MeSH
- křížení genetické MeSH
- myši inbrední CBA MeSH
- myši MeSH
- počet buněk MeSH
- prekurzorové buňky granulocytů účinky léků účinky záření MeSH
- thiaziny aplikace a dávkování terapeutické užití MeSH
- thiazoly aplikace a dávkování terapeutické užití MeSH
- záření gama škodlivé účinky MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Ozone depletion leads to an increase in UV rays of solar radiation reaching the surface of the Earth which is harmful to biological systems. Of the eye, the cornea is directly open to increased amount of UV rays of which mainly UVB rays are capable to induce reactive oxygen species damaging the cells. Previous studies showed that the irradiation of the cornea with UVB rays leads to morphological as well as metabolic disturbances of the cornea. Also, corneal hydration and corneal light absorption are increased after UVB rays. These changes were observed after five days of repeated irradiation of the cornea with UVB rays. The aim of the present paper was to examine how early the changes of corneal hydration and light absorption occur after UVB irradiation. The rabbit corneas were irradiated with UVB rays for one, two, three or four days. Corneal light absorption was examined spectrophotometrically and corneal hydration measured by pachymeter (as corneal thickness). Results show that changes of corneal hydration and light absorption appear early after UVB irradiation and increase along with the number of irradiations. In conclusion, irradiation of the rabbit cornea with UVB rays leads to harmful changes of its optical properties.
- MeSH
- absorpce MeSH
- časové faktory MeSH
- experimentální radiační poranění etiologie metabolismus patologie MeSH
- financování organizované MeSH
- králíci MeSH
- modely nemocí na zvířatech MeSH
- rohovka metabolismus patologie účinky záření MeSH
- spektrofotometrie MeSH
- světlo MeSH
- tělesná voda metabolismus MeSH
- ultrafialové záření škodlivé účinky MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- zvířata MeSH
The local temporary ischaemia effect on radiation-induced lipid peroxidation, superoxide dismutase isoenzyme activities, and intestinal crypt number was estimated in male WAG-strain rats in vivo. The animals were irradiated in the abdomen area with doses of 2 Gy for ten consecutive days using a Philips 60Co source. The calculated dose rate was 0.595 Gy/min. Local temporary ischaemia was induced by clamping the tail base before each irradiation. The parameters evaluated were: TBA-RS level and enzymatic activities of CuZnSOD, MnSOD in serum and jejunum. The number of jejunum crypts was assigned as a histopathologic parameter. The results showed a clear protection by ischaemic preconditioning for crypt survival. The difference in the number of crypts in irradiated animals with and without local temporary ischaemia was statistically significant (Student's t-test P < 0.05). Also, significant enhancement of TBA-RS was observed in the serum of irradiated animals. Local temporary ischaemia application diminished the concentration of radiation- induced TBA-RS. The differences in the levels of TBA-RS in the serum were statistically significant (ANOVA P < 0.002). In contrast, there was no evident effect on the level of TBA-RS in tissue homogenates in any investigated groups. Some fluctuation of CuZnSOD isoenzyme activity in intestinal tissue was noted; however, the differences were not significant. Local temporary ischaemia had no influence on Mn- SOD activity in serum, and in both irradiated groups the behaviour of this isoenzyme was similar. Also, there were no differences in MnSOD activity measured in tissue homogenates. These findings support results of our previous in vivo studies, suggesting that local temporary ischaemia can prevent oxidative effects of fractionated radiotherapy.
- MeSH
- experimentální radiační poranění metabolismus patologie MeSH
- ischemie metabolismus patologie MeSH
- jejunum MeSH
- krysa rodu rattus MeSH
- látky reagující s kyselinou thiobarbiturovou metabolismus MeSH
- přivykání k ischémii MeSH
- superoxiddismutasa krev MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
Gastrointestinal form is the second stage of the Acute Radiation Syndrome (ARS) with a threshold dose of 8 Gy. It represents an absolutely lethal clinical-pathological unit, enteritis necro-hemorrhagica (duodenitis, jejunitis, ileitis, respectively) with unknown causal therapy. The purpose of our study has been to evaluate the morphological changes in a model of radiation-induced enteritis in rats and estimate the significance of changes in biodosimetry. Wistar rats were randomly divided into 21 groups, 10 animals per group. Samples of the jejunum were taken 24, 48, 72, and 96 h after the whole-body gamma-irradiation with the doses of 1, 5, 10, 15, and 20 Gy, and routinely stained with hematoxylin and eosin. Five morphometric markers--intercryptal distance, enterocytal height on the top and base of villus, length of basal lamina of 10 enterocytes and enterocytal width--in irradiated rat jejunum were examined. The results were compared with sham-irradiated control group. After lethal doses of irradiation, all morphometric parameters of jejunum significantly changed. With the exception of intercryptal distance, they might be considered as suitable biodosimetric markers under these experimental conditions. Our morphometry results in radiation-induced jejunitis are in accordance with those in other studies. We were the first who quantified morphological post-irradiation changes in animal jejunum. Some of them might be used under experimental conditions. This experimental study is a predecessor of the clinical assessment of a specific marker. Under clinical practice, the sensitive biodosimetric parameter could serve as one of the guidance for evaluation of the absorbed dose in irradiated troops as well as rescue workers. This is in accordance with tasks and Standardization Agreement of the North Atlantic Treaty Organization.
- MeSH
- bazální membrána patologie účinky záření MeSH
- časové faktory MeSH
- celotělové ozáření MeSH
- enteritida etiologie patologie MeSH
- enterocyty patologie účinky záření MeSH
- experimentální radiační poranění patologie MeSH
- hodnocení rizik MeSH
- jejunum patologie účinky záření MeSH
- krysa rodu rattus MeSH
- nemoci jejuna etiologie patologie MeSH
- potkani Wistar MeSH
- radiometrie MeSH
- vztah dávky záření a odpovědi MeSH
- záření gama MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
Transforming growth factor beta 1 (TGF-beta1) plays an important role in the development of radiation- and drug-induced organ diseases. Proteinases-activated receptor 1 (PAR-1) is involved in many pathophysiologic processes after its activation by serine proteases. The aim of the present study was to determine messenger RNA (mRNA) production of TGF-beta1 and PAR-1 in the lungs after local irradiation. Mice of C57BL/6 and C3H/J strains with different susceptibility to fibrosis development were exposed to a of 15Gy. Non-irradiated mice of both strains were used as negative controls. Control (irradiated) and irradiated angiotensin-converting enzyme (ACE) inhibitor-treated animals were examined simultaneously. The ACE inhibitor group was given butylaminiperindopril for 9 days after irradiation (15Gy) at a daily dose of 0.1 or 0.2mg/kg per rectum. On day 9, all mice were sacrificed, and the production of mRNA TGF-beta1 and PAR-1 in lung tissue was determined semiquantitatively using reverse transcriptase polymerase chain reaction, and immunohistochemical analysis of PAR-1 expression in pulmonary tissue was performed. In the fibrosing murine strain C57Bl/6, there was an increase in the mRNA TGF-beta1 and PAR-1 levels in lungs 9 days after irradiation as compared with non-irradiated controls and non-fibrosing murine strain C3H/J. In butylaminiperindopril-treated mice, a decrease in transcript of TGF-beta1 and PAR-1 was observed. Thus, PAR-1 is involved in radiation-induced lung fibrosis in correlation with TGF-beta1 production. Administration of ACEI influences PAR-1 and TGF-beta1 expression.
- MeSH
- experimentální radiační poranění farmakoterapie metabolismus patologie MeSH
- financování organizované MeSH
- imunoenzymatické techniky MeSH
- inhibitory ACE terapeutické užití MeSH
- messenger RNA metabolismus MeSH
- myši inbrední C3H MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- perindopril terapeutické užití MeSH
- plíce metabolismus patologie účinky záření MeSH
- plicní fibróza farmakoterapie metabolismus patologie MeSH
- polymerázová řetězová reakce s reverzní transkripcí MeSH
- radioprotektivní látky terapeutické užití MeSH
- receptor PAR-1 genetika metabolismus MeSH
- transformující růstový faktor beta genetika metabolismus MeSH
- záření gama škodlivé účinky MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Klíčová slova
- simulované sluneční záření,
- MeSH
- dávka záření MeSH
- experimentální radiační poranění * patologie MeSH
- klinická studie jako téma MeSH
- kožní testy metody MeSH
- lidé MeSH
- poruchy fotosenzitivity * etiologie patologie MeSH
- sluneční záření škodlivé účinky MeSH
- statistika jako téma MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- pozorovací studie MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Spojené království MeSH
