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Comparative immunotoxicity on physicochemical properties of single-walled carbon nanotubes: In vitro and in vivo
S240
Abstracts / Toxicology Letters 221S (2013) S59–S256
P24-04 Biodistribution and toxicological effects of intranasally instilled polyamidoamine (PAMAM) dendrimers in BALB/c mouse brain Tin-Tin Win-Shwe ∗ , Yoshika Kurokawa, Hiroshi Nitta, Seishiro Hirano, Hideko Sone National Institute for Environmental Studies, 16-2 Onogawa, Tsukuba, Ibaraki, Japan Background and aims: Current understanding of the toxicological and pharmacological effects of dendrimers is limited. We hypothesized that intranasally instilled dendrimers may reach the brain and induce inflammatory response in the brain. In the present study we investigated the effects of exposure to polyamidoamine (PAMAM) dendrimers on biodistribution and toxicological effects using neuroimmune biomarkers in the brain of mice. Methods: Male BALB/c mice (8-week-old) were administered a single dose of 30 l of Alexa 488 labeled PAMAM-dendrimers (3 or 15 g/mouse; Sigma) intranasally. Twenty four hours after intranasal instillation, olfactory bulb, hippocampus and cerebral cortex were collected to detect the potential biomarkers in the blood and brain by hematological analysis, real-time RT-PCR. We also examined the biodistribution of PAMAM dendrimers by confocal laser microscope and gene expressions by microarray method. Results: The fluorescent signals which have the possibility of dendrimers in hippocampus were observed. Any remarkable changes of hematological and inflammatory markers were not observed in the blood and brain. However, brain derivedneurotrophic factor (BDNF) mRNA was up-regulated in the hippocampus and cerebral cortex of high dose dendrimer-treated mice. Moreover, microarray analysis showed up-regulation of the expression level of genes related to blood coagulation cascade, peroxisome proliferator-activated receptor signaling and neurotransmitter monoamine pathway. Discussion and conclusion: We suggest that PAMAM dendrimers may reach the brain via systemic circulation or olfactory nerve route after intranasal instillation. Our present findings indicate that single intranasal administration of PAMAM-NH2 dendrimers may have potential neurotoxicity by modulating the expression of neurological related biomarkers. http://dx.doi.org/10.1016/j.toxlet.2013.05.589
P24-05 Comparative immunotoxicity on physicochemical properties of single-walled carbon nanotubes: In vitro and in vivo Soyoung Lee 1 , Dongwoo Khang 2 , Sang-Hyun Kim 1,∗ 1 Department of Pharmacology School of Medicine, Kyungpook National University, Daegu 700-422, Republic of Korea, 2 School of Materials Science and Engineering and Center for NBECS, Gyeongsang National University, Jinju 660-701, Republic of Korea
Purpose: In this study, in vitro and in vivo response on differently modified swCNTs (such as functionalization and dispersion) and their immunotoxic effects were demonstrated. Methods: For immunotoxicity of swCNTs, MTT assay, ROS production, SOD activity and confocal microscope were used in macrophages. In vivo study, we investigated body weight, organ weight, hematological change and lymphocyte population. Results and conclusions: swCNTs samples functionalized to swCNT-COOH, swCNT-OH, and swCNT-NH2 . As observed in the
MTT and NO assay, swCNT-COOH induced greater cytotoxicity than other functionalized swCNTs in macrophages. swCNT-COOH showed higher cellular uptake and ROS production than others. Then, we examined immunotoxic effects of differently dispersed swCNT-COOHs (such as COOH-1, COOH-2, and COOH-3) using MTT assay and ROS production. We found that as the degree of dispersion increased, swCNT-COOHs become less cytotoxic. Although differently dispersed swCNT-COOHs induce similar cellular uptake in macrophages, swCNT-COOH-3 dramatically decreased ROS production and SOD activity. For in vivo study, female BALB/c mice were exposed to 1 mg/kg/day of swCNT-COOH-1, COOH-2 and COOH-3 for 2 weeks by i.v. Differently dispersed swCNTCOOHs have no significant effect on body weight, organ weight and hematological change. However, different dispersed swCNTCOOHs altered T lymphocyte and B lymphocyte populations. swCNT-COOH-3 significantly decreased B lymphocyte population compared with swCNT-COOH-1 in spleen and lymph node, and increased T lymphocyte population in spleen and thymus. Further, swCNT-COOH-3 significantly decreased expression of TNF-␣ and IL-2. These results suggest that properties of functionalization and dispersion were relevant factors on regulating immunotoxicity of swCNTs. http://dx.doi.org/10.1016/j.toxlet.2013.05.590
P24-06 Ecotoxicity of engineered nanomaterials: Known facts and data gaps Katre Juganson ∗ , Angela Ivask, Meelika Koitjärv, Monika Mortimer, Olesja Bondarenko, Kaja Kasemets, Anne Kahru National Institute of Chemical Physics and Biophysics, Tallinn, Estland The increasing production and use of engineered nanomaterials (ENMs) in consumer products inevitably leads to their release into the environment. Thus, the ecotoxicological effects of ENMs need to be assessed. Indeed, according to Thomson Reuters ISI WoS the topic is gaining interest as half of the papers on ‘nano* AND ecotoxic*’ (241/471, search made on 29.04.2013) have been published within the past two years. Unfortunately, most of the available ecotoxicity data even for the same test species are highly variable. This is mostly due to a wide range of ENMs and test conditions used. We suggest that systematic collection and analysis of nanotoxicity data combined with detailed description of physico-chemical properties of ENMs and test conditions enable to elucidate the causes of variability in toxicity data. For this purpose we are currently creating a database on available data in nanoecotoxicity. This database, developed as a part of the Estonian Research Council’s ‘Environmental Conservation and Environmental Technology R&D Program’ project ‘TERIKVANT’ includes information on carbon nanotubes, fullerenes, Ag, TiO2 , ZnO, CeO2 , and CuO NMs which all are industrially relevant and/or have high technological potential. Detailed information on the physico-chemical properties and toxicity of ENMs, and biotesting conditions is collected from carefully selected peer-reviewed articles. The resulting database will allow the comparison of toxicity of ENMs across different test species, ENMs, and in addition, will provide valuable input for computational analysis (e.g. QSARs) and risk assessment. http://dx.doi.org/10.1016/j.toxlet.2013.05.591
Abstracts / Toxicology Letters 221S (2013) S59–S256
P24-04 Biodistribution and toxicological effects of intranasally instilled polyamidoamine (PAMAM) dendrimers in BALB/c mouse brain Tin-Tin Win-Shwe ∗ , Yoshika Kurokawa, Hiroshi Nitta, Seishiro Hirano, Hideko Sone National Institute for Environmental Studies, 16-2 Onogawa, Tsukuba, Ibaraki, Japan Background and aims: Current understanding of the toxicological and pharmacological effects of dendrimers is limited. We hypothesized that intranasally instilled dendrimers may reach the brain and induce inflammatory response in the brain. In the present study we investigated the effects of exposure to polyamidoamine (PAMAM) dendrimers on biodistribution and toxicological effects using neuroimmune biomarkers in the brain of mice. Methods: Male BALB/c mice (8-week-old) were administered a single dose of 30 l of Alexa 488 labeled PAMAM-dendrimers (3 or 15 g/mouse; Sigma) intranasally. Twenty four hours after intranasal instillation, olfactory bulb, hippocampus and cerebral cortex were collected to detect the potential biomarkers in the blood and brain by hematological analysis, real-time RT-PCR. We also examined the biodistribution of PAMAM dendrimers by confocal laser microscope and gene expressions by microarray method. Results: The fluorescent signals which have the possibility of dendrimers in hippocampus were observed. Any remarkable changes of hematological and inflammatory markers were not observed in the blood and brain. However, brain derivedneurotrophic factor (BDNF) mRNA was up-regulated in the hippocampus and cerebral cortex of high dose dendrimer-treated mice. Moreover, microarray analysis showed up-regulation of the expression level of genes related to blood coagulation cascade, peroxisome proliferator-activated receptor signaling and neurotransmitter monoamine pathway. Discussion and conclusion: We suggest that PAMAM dendrimers may reach the brain via systemic circulation or olfactory nerve route after intranasal instillation. Our present findings indicate that single intranasal administration of PAMAM-NH2 dendrimers may have potential neurotoxicity by modulating the expression of neurological related biomarkers. http://dx.doi.org/10.1016/j.toxlet.2013.05.589
P24-05 Comparative immunotoxicity on physicochemical properties of single-walled carbon nanotubes: In vitro and in vivo Soyoung Lee 1 , Dongwoo Khang 2 , Sang-Hyun Kim 1,∗ 1 Department of Pharmacology School of Medicine, Kyungpook National University, Daegu 700-422, Republic of Korea, 2 School of Materials Science and Engineering and Center for NBECS, Gyeongsang National University, Jinju 660-701, Republic of Korea
Purpose: In this study, in vitro and in vivo response on differently modified swCNTs (such as functionalization and dispersion) and their immunotoxic effects were demonstrated. Methods: For immunotoxicity of swCNTs, MTT assay, ROS production, SOD activity and confocal microscope were used in macrophages. In vivo study, we investigated body weight, organ weight, hematological change and lymphocyte population. Results and conclusions: swCNTs samples functionalized to swCNT-COOH, swCNT-OH, and swCNT-NH2 . As observed in the
MTT and NO assay, swCNT-COOH induced greater cytotoxicity than other functionalized swCNTs in macrophages. swCNT-COOH showed higher cellular uptake and ROS production than others. Then, we examined immunotoxic effects of differently dispersed swCNT-COOHs (such as COOH-1, COOH-2, and COOH-3) using MTT assay and ROS production. We found that as the degree of dispersion increased, swCNT-COOHs become less cytotoxic. Although differently dispersed swCNT-COOHs induce similar cellular uptake in macrophages, swCNT-COOH-3 dramatically decreased ROS production and SOD activity. For in vivo study, female BALB/c mice were exposed to 1 mg/kg/day of swCNT-COOH-1, COOH-2 and COOH-3 for 2 weeks by i.v. Differently dispersed swCNTCOOHs have no significant effect on body weight, organ weight and hematological change. However, different dispersed swCNTCOOHs altered T lymphocyte and B lymphocyte populations. swCNT-COOH-3 significantly decreased B lymphocyte population compared with swCNT-COOH-1 in spleen and lymph node, and increased T lymphocyte population in spleen and thymus. Further, swCNT-COOH-3 significantly decreased expression of TNF-␣ and IL-2. These results suggest that properties of functionalization and dispersion were relevant factors on regulating immunotoxicity of swCNTs. http://dx.doi.org/10.1016/j.toxlet.2013.05.590
P24-06 Ecotoxicity of engineered nanomaterials: Known facts and data gaps Katre Juganson ∗ , Angela Ivask, Meelika Koitjärv, Monika Mortimer, Olesja Bondarenko, Kaja Kasemets, Anne Kahru National Institute of Chemical Physics and Biophysics, Tallinn, Estland The increasing production and use of engineered nanomaterials (ENMs) in consumer products inevitably leads to their release into the environment. Thus, the ecotoxicological effects of ENMs need to be assessed. Indeed, according to Thomson Reuters ISI WoS the topic is gaining interest as half of the papers on ‘nano* AND ecotoxic*’ (241/471, search made on 29.04.2013) have been published within the past two years. Unfortunately, most of the available ecotoxicity data even for the same test species are highly variable. This is mostly due to a wide range of ENMs and test conditions used. We suggest that systematic collection and analysis of nanotoxicity data combined with detailed description of physico-chemical properties of ENMs and test conditions enable to elucidate the causes of variability in toxicity data. For this purpose we are currently creating a database on available data in nanoecotoxicity. This database, developed as a part of the Estonian Research Council’s ‘Environmental Conservation and Environmental Technology R&D Program’ project ‘TERIKVANT’ includes information on carbon nanotubes, fullerenes, Ag, TiO2 , ZnO, CeO2 , and CuO NMs which all are industrially relevant and/or have high technological potential. Detailed information on the physico-chemical properties and toxicity of ENMs, and biotesting conditions is collected from carefully selected peer-reviewed articles. The resulting database will allow the comparison of toxicity of ENMs across different test species, ENMs, and in addition, will provide valuable input for computational analysis (e.g. QSARs) and risk assessment. http://dx.doi.org/10.1016/j.toxlet.2013.05.591