3-nitropropionic acid (3-NP), a substance used for modelling Huntington's disease, was given to m... more 3-nitropropionic acid (3-NP), a substance used for modelling Huntington's disease, was given to male Wistar rats in a single 20 mg/kg b.w. dose, and the resulting behavioral alterations in spontaneous locomotor activity were measured after 30 minutes. To detect the involvement of neurotransmitter systems in this immediate effect, the NMDA antagonist MK-801 (0.8 mg/kg); as well as an agonist, quinpirole (QP, 5 mg/kg) and an antagonist, sulpiride (SP, 80 mg/kg) of the dopamine D2 receptors, were given before 3-NP to separate groups of rats. Controls were given saline. All substances were injected ip. 3-NP decreased the rats' locomotor, especially vertical, activity, whereas local activity was increased. Based on the further changes of 3-NP effects in the combination groups it could be concluded that dopaminergic rather than glutamatergic mechanisms were possibly involved in the acute behavioral effect of 3-NP.
In this study, the acute effect of 3-nitropropionic acid was investigated on open field and start... more In this study, the acute effect of 3-nitropropionic acid was investigated on open field and startle behavior of rats, and on their cortical electrical activity. Spontaneous locomotor activity, acoustic startle response, and pre-pulse inhibition of acoustic startle were measured in male Wistar rats (10 weeks old, 180200 g body weight) after a single dose of 10 or 20 mg/kg i.p. 3-nitropropionic acid. After the behavioral tests, the rats were anaesthetized, and spontaneous cortical electrical activity was recorded. The vertical, horizontal and local open field performance showed dose-dependent deterioration in the rats treated with 3-nitropropionic acid. The number of noise-positive startle responses showed non-significant changes, but the inhibition by pre-pulse was significantly reduced in the high dose animals. High dose also increased the proportion of low-frequencies in the cortical activity. 3-nitropropionic acid, known primarily to act in repeated doses (e.g., in animal models of Huntingtons disease) had also some clear-cut acute effects on behavioral and electrophysiological parameters of the treated rats.
ABSTRACT Heavy metals have been known and used by mankind for over 3000 years. The large amounts ... more ABSTRACT Heavy metals have been known and used by mankind for over 3000 years. The large amounts mined, smeltered, processed and finally discarded resulted in massive occupational and environmental exposure. Certain metal-induced diseases have been well-described but the knowledge on toxic, first of all neurotoxic mechanisms of the heavy metals is far from complete. In this work, an inorganic and an organic form of lead, mercury and manganese was orally administered to rats for 12 weeks. It was found that at comparable doses the effects of the same metal were of different strength and/or direction. Conclusion: The actual chemical form may be decisive in the neurotoxic damage induced by human exposure to heavy metals, and the most sensitive functional indicator may be different.
Environmental Toxicology and Pharmacology, May 1, 2005
Young adult male Wistar rats (24/group) were treated for 5 weeks with methyl mercury(II)chloride ... more Young adult male Wistar rats (24/group) were treated for 5 weeks with methyl mercury(II)chloride (corresponding to 0.5 and 2.0 mgHg • /kg b.w., control: distilled water) by gavage, followed by a 19 weeks post-treatment period. Spontaneous motility, psychomotor performance and sensorimotor gating was repeatedly tested, electrophysiological recordings done, in the rats throughout the whole experiment. Decreased horizontal open field activity, reduced number of "noise positive" startle responses, as well as increase of startle response onset latency and peak time, and decrease of peak amplitude, was seen in the treated animals. Most changes disappeared in the post-treatment period. In the spontaneous cortical and hippocampal activity, altered distribution of the frequency bands was seen after 5 weeks of treatment but not at the end of the post-treatment period. Hippocampal population spikes in the treated animals were depressed and showed less potentiation, which effect was still present 19 weeks after finishing the treatment. The duration of the sensory cortical evoked potentials was shorter than in the controls. In the treated rats, tyrosine hydroxylase-immunoreactive boutons in the substantia nigra pars reticulata were shrunk; blood and brain Hg levels were significantly higher and decreased only slowly. Considering the continuous presence of low levels of mercurials in the human environment, effects of this kind may be supposed as the background of some human neurobehavioral abnormalities.
Heavy metals, due to their numerous applications in industrial processes, agrochemicals and house... more Heavy metals, due to their numerous applications in industrial processes, agrochemicals and household articles, have caused a widespread pollution and can be found in different foods. One of their target organs is the central nervous system. The toxic effects of heavy metals can be modified by lifestyleoriginated factors such as consumption of alcohol. The aim of this study was to investigate the changes in spontaneous cortical activity (ECoG), cortical sensory evoked potentials (EPs) and peripheral nerve action potentials, recorded in rats pre-treated with alcohol and acutely treated with lead, mercury and manganese by intraperitoneal injection. In the ECoG, Hg2+ caused a massive shift to lower frequencies while the effect of Mn2+ and Pb2+ was slight, and alcohol pre-treatment altered the effect of the metals minimally. The amplitude of EPs increased upon the application of heavy metals, and the peak latency lengthened. The effect of Hg2+ was the strongest and that of Pb2+ the weak...
Heavy metals have been known and used by mankind for over 3000 years. The large amounts mined, sm... more Heavy metals have been known and used by mankind for over 3000 years. The large amounts mined, smeltered, processed and finally discarded resulted in massive occupational and environmental exposure. Certain metal-induced diseases have been well-described but the knowledge on toxic, first of all neurotoxic mechanisms of the heavy metals is far from complete. In this work, an inorganic and an organic form of lead, mercury and manganese was orally administered to rats for 12 weeks. It was found that at comparable doses the effects of the same metal were of different strength and/or direction. Conclusion: The actual chemical form may be decisive in the neurotoxic damage induced by human exposure to heavy metals, and the most sensitive functional indicator may be different.
Oral exposure of humans by excess amounts of arsenic and/or fluorine may cause disturbances of th... more Oral exposure of humans by excess amounts of arsenic and/or fluorine may cause disturbances of the nervous system. In the present experiment, such exposure was modelled in rats, with general and behavioral endpoints being examined. Seven weeks old adult male SPF Crl:WI BR Wistar rats (160±20 g, 4 groups of 12 rats each) were treated with sodium (meta)arsenite (10 mg/kg b.w.; As), sodium-fluoride (5 mg/kg b.w.; F) and their combinations (As+F) per os by gavage, 5 days a week once a day for 6 weeks. An untreated control group was also used (Control). General toxicological parameters (body weight gain, food and water consumption) were measured daily. Behavioral investigations (rota-rod and open field) were done in the 4th and 6th weeks of treatment.Weekly body weight gain was significantly reduced in the As (vs. F) and As+F (vs. Control and F) groups from the first week on. This difference was seen during the whole treatment period, and was more prominent from the second week on (As an...
I. Vezer, T., Schulz, H., Nagymajtenyi, L.: memory effects following subchronic organic and inorg... more I. Vezer, T., Schulz, H., Nagymajtenyi, L.: memory effects following subchronic organic and inorganic lead administration in rats. J. Physiol. (London) 526: 162P-163P (2000) Impact factor: 4,455 II. Vezer, T., Papp, A., Nagymajtenyi, L.: Behavioral and neurotoxicological alterations induced by subchronic inorganic lead and mercury treatment in rats. Neurobiology 9: 273 (2001) III. Vezer, T., Papp, A., Nagymajtenyi, L.: Behavioral alterations in male Wistar rats induced by subchronic treatment with organic lead and mercury compounds. Toxicol. Lett. 123 Suppl 1: 77 (2001) Impact factor: 1,587 IV. Papp, A., Vezer, T., Nagymajtenyi, L.: The effect of subacute mercury exposure on behavioural and neurophysiological parameters in rats. NeuroToxicol. 222: 543 (2001) Impact factor: 1,576 V. Vezer, T., Papp, A., Nagymajtenyi, L.: Subchronic exposure by methyl mercury in male Wistar rats: effects on neurobehavioral performance. Pflugers Arch. Eur. J. Physiol., 442 Suppl: 369 (2002) Impact fact...
Background: Non-spherical titanium dioxide (TiO 2) nanoparticles have been increasingly applied i... more Background: Non-spherical titanium dioxide (TiO 2) nanoparticles have been increasingly applied in various biomedical and technological fields. Their toxicological characterization is, however, less complete than that of roundish nanoparticles. Materials and Methods: Anatase form TiO 2 nanorods, ca. 15x65 nm in size, were applied to cultured astrocytes in vitro and to the airways of young adult Wistar rats in vivo in 5, 10, and 8 mg/kg BW dose for altogether 28 days. Presence of nanorods and cellular damage was investigated in the astrocytes and in rat lungs and kidneys. Functional damage of the nervous system was studied by electrophysiological methods. Results: The treated astrocytes showed loss of viability without detectable apoptosis. In rats, TiO 2 nanorods applied to the airways reached the blood and various organs including the lungs, kidneys, and the central nervous system. In lung and kidney samples, nanorods were observed within (partly damaged) phagolysosomes and attached to organelles, and apoptotic cell death was also detected. In cortical and peripheral electrophysiological activity, alterations corresponding to energy shortage (resulting possibly from mitochondrial damage) and astrocytic dysfunction were detected. Local titanium levels and relative weight of the investigated organs, apoptotic cell death in the lungs and kidneys, and changes in the central and peripheral nervous activity were mostly proportional to the applied doses, and viability loss of the cultured astrocytes was also dose-dependent, suggesting causal relationship of treatments and effects. Conclusion: Based on localization of the visualized nanorods, on neuro-functional changes, and on literature data, the toxic mechanism involved mitochondrial damage, oxidative stress, and apoptotic cell death. These indicate potential human toxicity and occupational risk in case of exposure to rod-shaped TiO 2 nanoparticles.
Introduction and aims-Nanoparticles of titanium dioxide are suspected neurotoxic agents and have ... more Introduction and aims-Nanoparticles of titanium dioxide are suspected neurotoxic agents and have numerous applications possibly resulting in human exposure by several ways including inhalation. In the present work, rats were exposed to spherical TiO 2 nanoparticles of two different sizes by the intratracheal route. It was investigated how the neuro-functional alterations, detected by electrophysiological and behavioral methods, were related to the concentration of Ti in the tissue samples and what the influence of the size of the NPs was. Materials and methods-Rats (young adult Wistar males, 10/group) were exposed to TiO 2 nanoparticles of ca. 10 and 100 nm diameter (suspension medium: neutral PBS with 1% hydroxyethyl cellulose) by intratracheal instillation in 5 and 18 mg/kg b.w. dose; 5 days per week for 6 weeks. Controls were instilled with saline, and vehicle controls, with the suspension medium. To see general toxicity, body weight was checked daily, and organ weights were measured at the end of experiment. Grip strength test, to assess motor function damage, was done before and after the 6-week treatment. Finally, the rats were anesthetized with urethane, spontaneous cortical activity and sensory evoked potentials were recorded, then the rats were dissected and tissue samples were taken for Ti level measurement. Results-Body weight gain indicated no general toxicity, and no significant change in the relative organ weights, except that of the lungs, was seen. However, change of time-to-fall in the grip strength test, and latency of cortical evoked potentials, were altered in the treated groups, indicating functional damage. Correlation of these alterations with the cortical Ti level was dissimilar for the two sizes of nanoparticles.
Bevezetés: Napjainkban a nanotechnológia intenzív terjedésével nő a munkahelyi és lakossági nanor... more Bevezetés: Napjainkban a nanotechnológia intenzív terjedésével nő a munkahelyi és lakossági nanorészecske-expozíció veszélye. Jelenleg azonban kevés tudományosan megalapozott, ellentmondásmentes ismeret áll rendelkezésre a nehézfém nanorészecskék toxicitásáról és potenciális egészségkárosító hatásairól. Célkitűzés: Szubakut, intratrachealisan instillált, pálcika alakú titán-dioxid (TiO 2)-nanorészecskék indukálta tüdőszövet-károsodás vizsgálata morfológiai, kémiai és biokémiai módszerekkel, patkánymodellben. Módszer: Az általános toxicitást (test-és szervtömegváltozás), a lokális (alveolaris üregekben/epithelben, hilusi nyirokcsomóban zajló) akut és krónikus celluláris toxicitást (gyulladás, sejtpusztulás), továbbá az oxidatív stresszt fényés elektronmikroszkópiával, valamint biokémiai (lipidperoxidáció, reaktívoxigén-gyök, proinflammatoricus citokin expressziója) úton mértük. Eredmények: A kezelt csoportok testtömegében dózis-és időfüggő eltérés nem volt, azonban a tüdők tömege és Titartalma a dózissal arányosan nőtt. A tüdőszövet fény-és elektronmikroszkópos vizsgálata igazolta a nanorészecskék jelenlétét az alveolaris térben szabadon és az alveolaris epitheltől független macrophagok phagosomáiban. A lokális akut alveolitis krónikussá válását alátámasztotta az alveolaris régió macrophagszámának dózisfüggő növekedése, az interstitium ödémája és megvastagodása, valamint egyes proinflammatoricus citokinek (interleukin-1a, LIX, L-szelektin, vascularis endothelialis növekedési faktor) fokozott expressziója. A kezelt állatok tüdőszövetében az oxidatív stressz és a lipidperoxidáció jelentősen fokozódott. A kezelt tüdők tömege, Ti-tartalma és a lipidperoxidáció mértéke között korrelációt találtunk. Az alveolaris epithel-capillaris endothel barrier elégtelenségére utaltak a nanorészecskékkel telt falósejtek a hilusi nyirokcsomóban, ami felveti a nanorészecskék szisztémás keringésbe és távolabbi szervekbe jutásának és akut szisztémás gyulladás kialakulásának lehetőségét. Következtetés: Az alsó légutakba jutott TiO 2-nanorészecskék etiológiai tényezőként szerepelhetnek az akut, illetve idült légúti gyulladással és/vagy progrediáló fibrosissal és obstrukcióval járó légzőszervi betegségek (például idült obstruktív tüdőbetegség, asztma) kialakulásában és/vagy progressziójában, melyben jelentősége lehet az autophagiának és az immunválasz (lymphocytaműködés) károsodásának.
Background: Titanium dioxide nanoparticles have numerous applications, resulting in human exposur... more Background: Titanium dioxide nanoparticles have numerous applications, resulting in human exposure. Nonetheless, available toxicological and safety data are insufficient regarding aspherical particles, such as rod-shaped nanoparticles. Methods: In a combined in vitro-in vivo approach, cultured A549 lung alveolar adenocarcinoma cells were treated with approximately 15×65 nm TiO 2 nanorod-containing medium, while young adult rats received the same substance by intratracheal instillation for 28 days in 5 and 18 mg/kg bodyweight doses. Nanoparticle accumulation in the lungs and consequent oxidative stress, cell damage, and inflammation were assessed by biochemical and histopathological methods. Results: Titanium was detected in tissue samples by single-particle inductively coupled plasma mass spectrometry. Nanoparticles were visualized inside cultured A549 cells, within pulmonary macrophages, and in hilar lymph nodes of the rats. A549 cells showed dose-dependent oxidative stress and lethality, and the observed nanoparticle-laden endosomes suggested deranged lysosomal function and possible autophagy. Strongly elevated Ti levels were measured in the lungs of nanorod-treated rats and moderately elevated levels in the blood of the animals. Numerous cytokines, indicating acute and also chronic inflammation, were identified in the lung samples of TiO 2-exposed rodents. Conclusion: Several signs of cell and tissue damage were detected in both the cultured alveolar cells and in treated rats' lungs. Rod-shaped nanoparticulate TiO 2 may consequently be more harmful than has generally been supposed. The occupational health risk suggested by the results calls for improved safety measures.
A szkizofrénia multilőkusz genetikai vizsgálata az idegfejlődés és az immunrendszer zavarának oki... more A szkizofrénia multilőkusz genetikai vizsgálata az idegfejlődés és az immunrendszer zavarának oki szerepére utal(hat) (Hungárián)
3-nitropropionic acid (3-NP), a substance used for modelling Huntington's disease, was given to m... more 3-nitropropionic acid (3-NP), a substance used for modelling Huntington's disease, was given to male Wistar rats in a single 20 mg/kg b.w. dose, and the resulting behavioral alterations in spontaneous locomotor activity were measured after 30 minutes. To detect the involvement of neurotransmitter systems in this immediate effect, the NMDA antagonist MK-801 (0.8 mg/kg); as well as an agonist, quinpirole (QP, 5 mg/kg) and an antagonist, sulpiride (SP, 80 mg/kg) of the dopamine D2 receptors, were given before 3-NP to separate groups of rats. Controls were given saline. All substances were injected ip. 3-NP decreased the rats' locomotor, especially vertical, activity, whereas local activity was increased. Based on the further changes of 3-NP effects in the combination groups it could be concluded that dopaminergic rather than glutamatergic mechanisms were possibly involved in the acute behavioral effect of 3-NP.
In this study, the acute effect of 3-nitropropionic acid was investigated on open field and start... more In this study, the acute effect of 3-nitropropionic acid was investigated on open field and startle behavior of rats, and on their cortical electrical activity. Spontaneous locomotor activity, acoustic startle response, and pre-pulse inhibition of acoustic startle were measured in male Wistar rats (10 weeks old, 180200 g body weight) after a single dose of 10 or 20 mg/kg i.p. 3-nitropropionic acid. After the behavioral tests, the rats were anaesthetized, and spontaneous cortical electrical activity was recorded. The vertical, horizontal and local open field performance showed dose-dependent deterioration in the rats treated with 3-nitropropionic acid. The number of noise-positive startle responses showed non-significant changes, but the inhibition by pre-pulse was significantly reduced in the high dose animals. High dose also increased the proportion of low-frequencies in the cortical activity. 3-nitropropionic acid, known primarily to act in repeated doses (e.g., in animal models of Huntingtons disease) had also some clear-cut acute effects on behavioral and electrophysiological parameters of the treated rats.
ABSTRACT Heavy metals have been known and used by mankind for over 3000 years. The large amounts ... more ABSTRACT Heavy metals have been known and used by mankind for over 3000 years. The large amounts mined, smeltered, processed and finally discarded resulted in massive occupational and environmental exposure. Certain metal-induced diseases have been well-described but the knowledge on toxic, first of all neurotoxic mechanisms of the heavy metals is far from complete. In this work, an inorganic and an organic form of lead, mercury and manganese was orally administered to rats for 12 weeks. It was found that at comparable doses the effects of the same metal were of different strength and/or direction. Conclusion: The actual chemical form may be decisive in the neurotoxic damage induced by human exposure to heavy metals, and the most sensitive functional indicator may be different.
Environmental Toxicology and Pharmacology, May 1, 2005
Young adult male Wistar rats (24/group) were treated for 5 weeks with methyl mercury(II)chloride ... more Young adult male Wistar rats (24/group) were treated for 5 weeks with methyl mercury(II)chloride (corresponding to 0.5 and 2.0 mgHg • /kg b.w., control: distilled water) by gavage, followed by a 19 weeks post-treatment period. Spontaneous motility, psychomotor performance and sensorimotor gating was repeatedly tested, electrophysiological recordings done, in the rats throughout the whole experiment. Decreased horizontal open field activity, reduced number of "noise positive" startle responses, as well as increase of startle response onset latency and peak time, and decrease of peak amplitude, was seen in the treated animals. Most changes disappeared in the post-treatment period. In the spontaneous cortical and hippocampal activity, altered distribution of the frequency bands was seen after 5 weeks of treatment but not at the end of the post-treatment period. Hippocampal population spikes in the treated animals were depressed and showed less potentiation, which effect was still present 19 weeks after finishing the treatment. The duration of the sensory cortical evoked potentials was shorter than in the controls. In the treated rats, tyrosine hydroxylase-immunoreactive boutons in the substantia nigra pars reticulata were shrunk; blood and brain Hg levels were significantly higher and decreased only slowly. Considering the continuous presence of low levels of mercurials in the human environment, effects of this kind may be supposed as the background of some human neurobehavioral abnormalities.
Heavy metals, due to their numerous applications in industrial processes, agrochemicals and house... more Heavy metals, due to their numerous applications in industrial processes, agrochemicals and household articles, have caused a widespread pollution and can be found in different foods. One of their target organs is the central nervous system. The toxic effects of heavy metals can be modified by lifestyleoriginated factors such as consumption of alcohol. The aim of this study was to investigate the changes in spontaneous cortical activity (ECoG), cortical sensory evoked potentials (EPs) and peripheral nerve action potentials, recorded in rats pre-treated with alcohol and acutely treated with lead, mercury and manganese by intraperitoneal injection. In the ECoG, Hg2+ caused a massive shift to lower frequencies while the effect of Mn2+ and Pb2+ was slight, and alcohol pre-treatment altered the effect of the metals minimally. The amplitude of EPs increased upon the application of heavy metals, and the peak latency lengthened. The effect of Hg2+ was the strongest and that of Pb2+ the weak...
Heavy metals have been known and used by mankind for over 3000 years. The large amounts mined, sm... more Heavy metals have been known and used by mankind for over 3000 years. The large amounts mined, smeltered, processed and finally discarded resulted in massive occupational and environmental exposure. Certain metal-induced diseases have been well-described but the knowledge on toxic, first of all neurotoxic mechanisms of the heavy metals is far from complete. In this work, an inorganic and an organic form of lead, mercury and manganese was orally administered to rats for 12 weeks. It was found that at comparable doses the effects of the same metal were of different strength and/or direction. Conclusion: The actual chemical form may be decisive in the neurotoxic damage induced by human exposure to heavy metals, and the most sensitive functional indicator may be different.
Oral exposure of humans by excess amounts of arsenic and/or fluorine may cause disturbances of th... more Oral exposure of humans by excess amounts of arsenic and/or fluorine may cause disturbances of the nervous system. In the present experiment, such exposure was modelled in rats, with general and behavioral endpoints being examined. Seven weeks old adult male SPF Crl:WI BR Wistar rats (160±20 g, 4 groups of 12 rats each) were treated with sodium (meta)arsenite (10 mg/kg b.w.; As), sodium-fluoride (5 mg/kg b.w.; F) and their combinations (As+F) per os by gavage, 5 days a week once a day for 6 weeks. An untreated control group was also used (Control). General toxicological parameters (body weight gain, food and water consumption) were measured daily. Behavioral investigations (rota-rod and open field) were done in the 4th and 6th weeks of treatment.Weekly body weight gain was significantly reduced in the As (vs. F) and As+F (vs. Control and F) groups from the first week on. This difference was seen during the whole treatment period, and was more prominent from the second week on (As an...
I. Vezer, T., Schulz, H., Nagymajtenyi, L.: memory effects following subchronic organic and inorg... more I. Vezer, T., Schulz, H., Nagymajtenyi, L.: memory effects following subchronic organic and inorganic lead administration in rats. J. Physiol. (London) 526: 162P-163P (2000) Impact factor: 4,455 II. Vezer, T., Papp, A., Nagymajtenyi, L.: Behavioral and neurotoxicological alterations induced by subchronic inorganic lead and mercury treatment in rats. Neurobiology 9: 273 (2001) III. Vezer, T., Papp, A., Nagymajtenyi, L.: Behavioral alterations in male Wistar rats induced by subchronic treatment with organic lead and mercury compounds. Toxicol. Lett. 123 Suppl 1: 77 (2001) Impact factor: 1,587 IV. Papp, A., Vezer, T., Nagymajtenyi, L.: The effect of subacute mercury exposure on behavioural and neurophysiological parameters in rats. NeuroToxicol. 222: 543 (2001) Impact factor: 1,576 V. Vezer, T., Papp, A., Nagymajtenyi, L.: Subchronic exposure by methyl mercury in male Wistar rats: effects on neurobehavioral performance. Pflugers Arch. Eur. J. Physiol., 442 Suppl: 369 (2002) Impact fact...
Background: Non-spherical titanium dioxide (TiO 2) nanoparticles have been increasingly applied i... more Background: Non-spherical titanium dioxide (TiO 2) nanoparticles have been increasingly applied in various biomedical and technological fields. Their toxicological characterization is, however, less complete than that of roundish nanoparticles. Materials and Methods: Anatase form TiO 2 nanorods, ca. 15x65 nm in size, were applied to cultured astrocytes in vitro and to the airways of young adult Wistar rats in vivo in 5, 10, and 8 mg/kg BW dose for altogether 28 days. Presence of nanorods and cellular damage was investigated in the astrocytes and in rat lungs and kidneys. Functional damage of the nervous system was studied by electrophysiological methods. Results: The treated astrocytes showed loss of viability without detectable apoptosis. In rats, TiO 2 nanorods applied to the airways reached the blood and various organs including the lungs, kidneys, and the central nervous system. In lung and kidney samples, nanorods were observed within (partly damaged) phagolysosomes and attached to organelles, and apoptotic cell death was also detected. In cortical and peripheral electrophysiological activity, alterations corresponding to energy shortage (resulting possibly from mitochondrial damage) and astrocytic dysfunction were detected. Local titanium levels and relative weight of the investigated organs, apoptotic cell death in the lungs and kidneys, and changes in the central and peripheral nervous activity were mostly proportional to the applied doses, and viability loss of the cultured astrocytes was also dose-dependent, suggesting causal relationship of treatments and effects. Conclusion: Based on localization of the visualized nanorods, on neuro-functional changes, and on literature data, the toxic mechanism involved mitochondrial damage, oxidative stress, and apoptotic cell death. These indicate potential human toxicity and occupational risk in case of exposure to rod-shaped TiO 2 nanoparticles.
Introduction and aims-Nanoparticles of titanium dioxide are suspected neurotoxic agents and have ... more Introduction and aims-Nanoparticles of titanium dioxide are suspected neurotoxic agents and have numerous applications possibly resulting in human exposure by several ways including inhalation. In the present work, rats were exposed to spherical TiO 2 nanoparticles of two different sizes by the intratracheal route. It was investigated how the neuro-functional alterations, detected by electrophysiological and behavioral methods, were related to the concentration of Ti in the tissue samples and what the influence of the size of the NPs was. Materials and methods-Rats (young adult Wistar males, 10/group) were exposed to TiO 2 nanoparticles of ca. 10 and 100 nm diameter (suspension medium: neutral PBS with 1% hydroxyethyl cellulose) by intratracheal instillation in 5 and 18 mg/kg b.w. dose; 5 days per week for 6 weeks. Controls were instilled with saline, and vehicle controls, with the suspension medium. To see general toxicity, body weight was checked daily, and organ weights were measured at the end of experiment. Grip strength test, to assess motor function damage, was done before and after the 6-week treatment. Finally, the rats were anesthetized with urethane, spontaneous cortical activity and sensory evoked potentials were recorded, then the rats were dissected and tissue samples were taken for Ti level measurement. Results-Body weight gain indicated no general toxicity, and no significant change in the relative organ weights, except that of the lungs, was seen. However, change of time-to-fall in the grip strength test, and latency of cortical evoked potentials, were altered in the treated groups, indicating functional damage. Correlation of these alterations with the cortical Ti level was dissimilar for the two sizes of nanoparticles.
Bevezetés: Napjainkban a nanotechnológia intenzív terjedésével nő a munkahelyi és lakossági nanor... more Bevezetés: Napjainkban a nanotechnológia intenzív terjedésével nő a munkahelyi és lakossági nanorészecske-expozíció veszélye. Jelenleg azonban kevés tudományosan megalapozott, ellentmondásmentes ismeret áll rendelkezésre a nehézfém nanorészecskék toxicitásáról és potenciális egészségkárosító hatásairól. Célkitűzés: Szubakut, intratrachealisan instillált, pálcika alakú titán-dioxid (TiO 2)-nanorészecskék indukálta tüdőszövet-károsodás vizsgálata morfológiai, kémiai és biokémiai módszerekkel, patkánymodellben. Módszer: Az általános toxicitást (test-és szervtömegváltozás), a lokális (alveolaris üregekben/epithelben, hilusi nyirokcsomóban zajló) akut és krónikus celluláris toxicitást (gyulladás, sejtpusztulás), továbbá az oxidatív stresszt fényés elektronmikroszkópiával, valamint biokémiai (lipidperoxidáció, reaktívoxigén-gyök, proinflammatoricus citokin expressziója) úton mértük. Eredmények: A kezelt csoportok testtömegében dózis-és időfüggő eltérés nem volt, azonban a tüdők tömege és Titartalma a dózissal arányosan nőtt. A tüdőszövet fény-és elektronmikroszkópos vizsgálata igazolta a nanorészecskék jelenlétét az alveolaris térben szabadon és az alveolaris epitheltől független macrophagok phagosomáiban. A lokális akut alveolitis krónikussá válását alátámasztotta az alveolaris régió macrophagszámának dózisfüggő növekedése, az interstitium ödémája és megvastagodása, valamint egyes proinflammatoricus citokinek (interleukin-1a, LIX, L-szelektin, vascularis endothelialis növekedési faktor) fokozott expressziója. A kezelt állatok tüdőszövetében az oxidatív stressz és a lipidperoxidáció jelentősen fokozódott. A kezelt tüdők tömege, Ti-tartalma és a lipidperoxidáció mértéke között korrelációt találtunk. Az alveolaris epithel-capillaris endothel barrier elégtelenségére utaltak a nanorészecskékkel telt falósejtek a hilusi nyirokcsomóban, ami felveti a nanorészecskék szisztémás keringésbe és távolabbi szervekbe jutásának és akut szisztémás gyulladás kialakulásának lehetőségét. Következtetés: Az alsó légutakba jutott TiO 2-nanorészecskék etiológiai tényezőként szerepelhetnek az akut, illetve idült légúti gyulladással és/vagy progrediáló fibrosissal és obstrukcióval járó légzőszervi betegségek (például idült obstruktív tüdőbetegség, asztma) kialakulásában és/vagy progressziójában, melyben jelentősége lehet az autophagiának és az immunválasz (lymphocytaműködés) károsodásának.
Background: Titanium dioxide nanoparticles have numerous applications, resulting in human exposur... more Background: Titanium dioxide nanoparticles have numerous applications, resulting in human exposure. Nonetheless, available toxicological and safety data are insufficient regarding aspherical particles, such as rod-shaped nanoparticles. Methods: In a combined in vitro-in vivo approach, cultured A549 lung alveolar adenocarcinoma cells were treated with approximately 15×65 nm TiO 2 nanorod-containing medium, while young adult rats received the same substance by intratracheal instillation for 28 days in 5 and 18 mg/kg bodyweight doses. Nanoparticle accumulation in the lungs and consequent oxidative stress, cell damage, and inflammation were assessed by biochemical and histopathological methods. Results: Titanium was detected in tissue samples by single-particle inductively coupled plasma mass spectrometry. Nanoparticles were visualized inside cultured A549 cells, within pulmonary macrophages, and in hilar lymph nodes of the rats. A549 cells showed dose-dependent oxidative stress and lethality, and the observed nanoparticle-laden endosomes suggested deranged lysosomal function and possible autophagy. Strongly elevated Ti levels were measured in the lungs of nanorod-treated rats and moderately elevated levels in the blood of the animals. Numerous cytokines, indicating acute and also chronic inflammation, were identified in the lung samples of TiO 2-exposed rodents. Conclusion: Several signs of cell and tissue damage were detected in both the cultured alveolar cells and in treated rats' lungs. Rod-shaped nanoparticulate TiO 2 may consequently be more harmful than has generally been supposed. The occupational health risk suggested by the results calls for improved safety measures.
A szkizofrénia multilőkusz genetikai vizsgálata az idegfejlődés és az immunrendszer zavarának oki... more A szkizofrénia multilőkusz genetikai vizsgálata az idegfejlődés és az immunrendszer zavarának oki szerepére utal(hat) (Hungárián)
Uploads
Papers by Tünde Vezér