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A combinação de nanopartículas de dióxido de titânio com nanotubos de carbono de parede múltiplas possibilita a geração de um nanomaterial híbrido, com atividade fotocatalítica aprimorada, denominado TiO2-MWCNT. Existe um grande interesse científico e tecnológico em materiais fotocatalíticos, estes apresentam potencial para o desenvolvimento de novos agentes antimicrobianos, nanocompósitos, catalisadores e remediação ambiental. Apesar de muitos trabalhos enfatizarem os benefícios na utilização de nanohíbridos, ainda são escassos estudos de impactos ambientais e toxicidade. O objetivo deste trabalho foi sintetizar e caracterizar o nanohíbrido TiO2-MWCNT, bem como avaliar sua ecotoxicidade aquática através de ensaios in vivo (embriões de Zebrafish - Danio rerio) e in vitro (linhagem celular RTG-2 - fibroblastos de Oncorhynchus mykiss). O TiO2-MWCNT foi sintetizado pelo método mecanoquímico (moagem em estado sólido) e caracterizado empregando as seguintes técnicas: microscopia eletrônica de varredura e de transmissão, espectroscopia Raman, análise termogravimétrica, espalhamento dinâmico de luz e espalhamento de luz eletroforético. O nanohíbrido sintetizado apresentou atividade fotocatalítica aprimorada, confirmada através de ensaios de fotocatálise. Nos ensaios in vivo, o TiO2-MWCNT não apresentou ecotoxicidade aguda até 100 µg mL-1 (na presença ou ausência de radiação UV). No entanto, foi observada a ingestão do nanohíbrido pelos embriões (via oral) através da técnica microfluorescência de raios-X (µ-XRF). Também não foi observado ecotoxicidade para o nanohíbrido nos ensaios in vitro até 100 µg mL-1; porém foi verificado a capacidade de internalização celular deste material. Em geral, aspectos coloidais (agregação/aglomeração) e a formação de protein corona apresentaram importantes implicações para a determinação precisa da ecotoxicidade. Os resultados obtidos neste trabalho suportam futuras aplicações do nanohíbrido TiO2-MWCNT na área de fotocatálise, e contribui de maneira proativa para sua avaliação ecotoxicológica / The combination of titanium dioxide nanoparticles with multiwall carbon nanotubes enables the generation of a hybrid nanomaterial with improved photocatalytic activity, called TiO2-MWCNT. There is great scientific and technological interest in photocatalytic materials, which present potential for the development of new antimicrobial agents, nanocomposites, catalysts and environmental remediation. Although many papers emphasize the benefits of using nanohybrids, there are still a small number of studies about its environmental impacts and toxicity. The objective of this work was to synthesize and characterize a TiO2-MWCNT nanohybrid. As well as to evaluate its aquatic ecotoxicity through in vivo (Zebrafish embryos - Danio rerio) and in vitro (RTG-2 cell line - Oncorhynchus mykiss fibroblasts) assays. TiO2-MWCNT was synthesized by the mechanochemical method (solid state milling) and characterized using the following techniques: scanning and transmission electron microscopy, Raman spectroscopy, thermogravimetric analysis, dynamic scattering light and electrophoretic scattering light. The synthesized nanohybrid showed enhanced photocatalytic activity, confirmed by photocatalysis studies. In the in vivo assays, TiO2-MWCNT did not show acute ecotoxicity up to 100 ?g mL-1 (in the presence or absence of UV radiation). However, the ingestion of the nanohybrid by the embryos (oral route) was observed through ?-probe X-ray fluorescence spectroscopy (?-XRF). Also, no toxicity was observed in the in vitro assays up to 100 ?g mL-1; however, the cellular internalization capacity of this material was verified. In general, colloidal aspects (aggregation / agglomeration) and the formation of protein corona presented important implications for the precise determination of ecotoxicity. The results obtained in this work support future applications of the nanohybrid TiO2-MWCNT in the area of photocatalysis and contributes proactively to its ecotoxicological evaluation

Orientador: Leonardo Fernandes Fraceto / Resumo: Para o controle de pragas, contínuamente se faz o uso de elevadas quantidades de agroquímicos que muitas vezes possuem efeitos adversos tanto para o ambiente quanto para a saúde humana. Este fato tem motivado a busca por alternativas menos impactantes. Neste cenário, diversos mecanismos estão sendo estudados a fim de minimizar estes danos, como por exemplo, o desenvolvimento de sistemas carreadores utilizando polímeros biodegradáveis e proteínas. Aliado a isto, a utilização de inseticidas botânicos também tem demonstrado potencialidade para o combate a pragas, devido aos possíveis menores impactos causados por esses produtos de origem natural. Portanto, o presente trabalho descreve o preparo e caracterização de um nanobiopesticida baseado em nanopartículas de zeína carreadas com óleo de neem junto com a avaliação da sua toxicidade contra organismos não alvos (usando Allium cepa, microbiota do solo envolvida no ciclo do nitrogênio e Caenorhabditis elegans) e da sua fitotoxicidade (usando Phaseolus vulgaris). Ademais, a atividade biológica desse novo sistema em pragas agrícolas (Acanthoscelides obtectus, Bemisia tabaci and Tetranychus urticae) também foi investigada. As nanopartículas esféricas apresentaram diâmetro médio de 278 ± 61,5 nm, alta eficiência de encapsulação (> 80%) e boa estabilidade durante os experimentos. Nos ensaios de toxicidade com A. cepa, as nanopartículas de zeína carregadas com óleo de neem mitigaram o aumento do índice de danos relativo ao DNA causado p... (Resumo completo, clicar acesso eletrônico abaixo) / Doutor

Due to the rapid expansion of nanotechnology and the increasing applications of nanomaterials under production and development, it is essential evaluate the potential impacts on human health, ecosystems and the environment. This study is specifically focused on the interactions between metal-based nanoparticles (NPs) and target cells, aiming at exploration of the fundamental knowledge essentially useful for understanding nanotoxicity and its connections with particle properties. The whole structure of this study can be divided into three levels: the first level is to quantitatively understand physicochemical properties of NPs of interest and their dynamic changes under varying environmental conditions. The second level is to evaluate the biological interactions of representative NPs with a specific focus on the size-dependent adsorption processes, interfacial forces, cellular disruption, and membrane damages. The third level is to develop effective, accurate, and valid tools based on atomic force microscopy (AFM) to characterize NPs in terms of the nanoscale hydrophobicity and the nanoscale electric properties, which are most relevant and important properties in the bio-nano interactions. Overall, this study systematically investigated the kinetic environmental behaviors, biological interactions, and unique nano-properties of metal-based NPs, which should be of interest to people in application and implication of nanotechnology.

Submitted by Marlene Santos (marlene.bc.ufg@gmail.com) on 2017-09-21T19:58:03Z No. of bitstreams: 2 Tese - Fernanda Craveiro Franco - 2017.pdf: 4803005 bytes, checksum: 35b5c5c99f5a0689a4c30ebe8ea513cd (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2017-09-22T11:38:57Z (GMT) No. of bitstreams: 2 Tese - Fernanda Craveiro Franco - 2017.pdf: 4803005 bytes, checksum: 35b5c5c99f5a0689a4c30ebe8ea513cd (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Made available in DSpace on 2017-09-22T11:38:57Z (GMT). No. of bitstreams: 2 Tese - Fernanda Craveiro Franco - 2017.pdf: 4803005 bytes, checksum: 35b5c5c99f5a0689a4c30ebe8ea513cd (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2017-09-04 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / The interaction of some compounds and DNA molecule can cause genotoxic changes. The tests used to evaluate genotoxicity have evolved over the years, and they have great efficiency. Currently, several traditional methodologies are used, such as the comet assay, and some more modern, based on molecular biology. Considering the importance of detecting the effects caused by exposure to potentially genotoxic agents, this thesis presents three chapters with different approaches to this topic. The first chapter aimed at evaluating published studies on the mutagenic, genotoxic and oxidative effects caused by occupational exposure to pesticides. For this, a systematic review of articles published between the years of 2011 and 2015 was carried out, focusing on these exposure conditions. The results showed that 44% of the studies addressed only men and 44% approached men and women, and 78% used rural workers as an exposed population. The most evaluated class of pesticide was organophosphorus. The studies were separated by methodologies of analysis used and all showed some type of alteration in the populations occupationally exposed to pesticides. The second chapter, published in the journal Environmental Science and Pollution Research, considered the dengue scene in the state of Goias and techniques of mosquitoes control, and sought to understand the genotoxic effects caused by exposure of endemic agents to pesticides used against Aedes aegypti, being the first study published with this group of workers. The main pesticides used were insecticides and larvicides and an increase in DNA damage was observed in the exposed population, without influence of the lifestyle factors. In the whole transcriptome assay the differential expression of genes related to various chronic diseases was observed. Finally, the third chapter was carried out in collaboration with the Institute of Experimental Medicine of the Czech Academy of Sciences, aiming the determination of cytotoxic and genotoxic effects caused by in vitro exposure to different types of metallic nanomaterials. In nanomaterials that showed cell viability reduction (cytotoxic), an increase in genotoxicity was also identified. In addition, three of the four non-cytotoxic nanomaterials evaluated showed genotoxic effects. Studies aimed at detecting the compounds genotoxic potential are extremely important for the regulatory definition and identification of risks caused by exposure. In this study, the toxicological and genotoxic effects of different compounds and mixtures were evaluated using traditional and modern techniques, in vitro or by human biomonitoring, seeking to understand and determine the risks involved in exposure to these substances. / Compostos que interagem com a molécula de DNA podem provocar alterações genotóxicas. Os testes utilizados para avaliação de genotoxicidade evoluíram ao longo dos anos, apresentando grande eficiência. Atualmente, utilizam-se várias metodologias tradicionais, como o ensaio cometa, e também algumas mais modernas, baseadas na biologia molecular. Considerando a importância de detectar os efeitos causados pela exposição a agentes potencialmente genotóxicos, essa tese apresenta três capítulos com formas de abordagem distintas, referente a essa temática. O primeiro capítulo visou a avaliação de estudos publicados acerca dos efeitos mutagênicos, genotóxicos e oxidativos causados pela exposição ocupacional a pesticidas pela realização uma revisão sistemática de artigos publicados entre os anos de 2011 a 2015. Observou-se que 44% dos estudos abordaram exclusivamente indivíduos do sexo masculino e 44% abordaram ambos os sexos, e 78% utilizaram trabalhadores rurais como população exposta. A classe de pesticida mais avaliada foi a de organofosforado. Os estudos foram separados por metodologias de análise utilizada e todos apresentaram algum tipo de alteração nas populações expostas a pesticidas no ambiente de trabalho. O segundo capítulo, publicado na revista Environmental Science and Pollution Research, considerou o cenário da dengue no estado de Goiás e as formas de combate ao mosquito, e buscou compreender os efeitos genotóxicos causados pela exposição de Agentes de combate a endemias aos pesticidas utilizados contra o mosquito, sendo o primeiro estudo publicado com esse grupo de trabalhadores na região centro-oeste. Os principais pesticidas utilizados foram inseticidas e larvicidas e foi observado um aumento no dano ao DNA na população exposta, sem influência dos fatores relacionados ao estilo de vida. No ensaio de transcritoma foi observada a expressão diferencial de genes relacionados a diversas doenças crônicas. Finalmente, o terceiro capítulo foi realizado em colaboração com o Instituto de Medicina Experimental, da Academia Tcheca de Ciências, visando a determinação de efeitos citotóxicos e genotóxicos, causados pela exposição in vitro a diferentes tipos de nanomateriais metálicos. Nos nanomateriais que apresentaram redução na viabilidade celular (citotóxicos) também foi identificado aumento na genotoxicidade. Além disso, três dos quatro nanomateriais não citotóxicos avaliados apresentaram efeitos genotóxicos. Estudos que visam detectar o potencial gentoxicológico de compostos são de extrema importância para definição de normas e regulamentações de aplicação e identificação dos riscos causados pela exposição. Nesse estudo, foram avaliados os efeitos toxicológicos e genotóxicos de diferentes compostos e misturas, com a utilização de técnicas tradicionais e modernas, in vitro ou por biomonitoramento humano, buscando compreender e determinar os riscos envolvidos na exposição a essas substâncias.

Submitted by Renata Lopes (renatasil82@gmail.com) on 2016-04-08T14:09:56Z No. of bitstreams: 1 michelemunkpereira.pdf: 6330020 bytes, checksum: 446922b21f5355bdcbfc26ac618f8e7c (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2016-04-24T03:40:43Z (GMT) No. of bitstreams: 1 michelemunkpereira.pdf: 6330020 bytes, checksum: 446922b21f5355bdcbfc26ac618f8e7c (MD5) / Made available in DSpace on 2016-04-24T03:40:43Z (GMT). No. of bitstreams: 1 michelemunkpereira.pdf: 6330020 bytes, checksum: 446922b21f5355bdcbfc26ac618f8e7c (MD5) Previous issue date: 2013-12-17 / CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Os nanotubos de carbono multicamadas (MWCNT) e as nanofibras de celulose (NFCs) são interessantes nanomateriais (NMs) que possuem grande potencial de aplicação em áreas como tratamento de água, reforço de materiais, engenharia tecidual e entrega de moléculas terapêuticas. Em especial, os MWCNT são promissores vetores de DNA em células e embriões de mamíferos. Porém, o desenvolvimento desta área está relacionado à padronização de sistemas para avaliar o potencial impacto dos NMs na saúde humana e ambiental. O objetivo geral deste estudo foi avaliar a toxicidade de MWCNT e NFC em diferentes modelos biológicos (fibroblastos e embriões bovinos; microalgas) e o potencial de carreamento gênico de MWCNT-COOH em fibroblastos e embriões bovinos. No experimento 1, foi avaliada a viabilidade e a morfologia dos fibroblastos cultivados in vitro expostos às NFCs e aos MWCNT-COOHs. Os resultados deste experimento revelaram que em baixas concentrações (0,02-100μg ml-1) as NFC não foram citotóxicas (P = 0,06). Porém, concentrações acima de 200 μg ml-1 NFC diminuíram a viabilidade celular e causaram mudanças na morfologia das células. Para os MWCNT-COOH, a exposição dos fibroblastos a 100μg ml-1 reduziram a viabilidade (P= 0,001) e alteram a morfologia celular. No experimento 2, foram analisados os efeitos desses NMs no desenvolvimento, expressão gênica e apoptose in situ de embriões bovinos produzidos in vitro. Neste ensaio, os NMs não influenciaram o desenvolvimento (P=0,24) e o índice de apoptose embrionária (P=0,82). Contudo, os MWCNT-COOH alteraram a expressão de genes (P=0,02) relacionados à totipotência, diferenciação e estresse celular de forma mais acentuada quando comparada às NFCs. No experimento 3, o potencial ecotóxico das NFCs e dos MWCNTs foi estudado em microalgas Chlorella vulgaris e Klebsormidium flaccidum mediante análise de Potencial Zeta, viabilidade celular, atividade fotossintética e de enzimas antioxidativas, quantificação dos níveis de ATP e microscopia eletrônica. Os resultados revelaram que os MWCNTs e as NFCs afetaram a viabilidade (P<0,001), a fotossíntese (P<0,05), a atividade de enzimas antioxidativas (P<0,05), os níveis de ATP (P<0,05) e a morfologia celular das microalgas em concentrações, tempos e sistemas de cultura específicos. No experimento 4, os fibroblastos e embriões bovinos foram transfectados com MWCNT-COOH complexados ao plasmídeo contendo o gene que codifica a proteína verde fluorescente (pGFP). As análises de microscopia de fluorescência detectaram que o gene GFP foi expresso nas células e nos embriões no estágio inicial de desenvolvimento (2 a 8 células). Entretanto, a expressão de GFP não foi observada no estágio de blastocisto. A análise por PCR confirmou a presença do gene GFP nos fibroblastos (3,30% GFP+) e embriões de 2-8–células (46,67% GFP+). Em conclusão, nas condições testadas, a exposição de fibroblastos a baixas concentrações de MWCNT-COOH ou NFC não causaram impacto na viabilidade e morfologia celular. Entretanto, os MWCNTs e as NFCs foram citotóxicas para as microalgas estudadas. O uso de MWCNT-COOH como vetor de DNA em embriões bovinos mostrou-se promissora, o que abre possibilidades de geração de animais transgênicos por este método. / Multi-walled carbon nanotubes (MWCNTs) and cotton cellulose nanofibers (CNFs) are interesting nanomaterials (NMs) which possess great potential for applications in various fields such as in water treatment, reinforcement materials, tissue engineering and therapeutic molecule delivery. In particular, MWCNT have emerged as a new method for gene delivery and they can be an alternative for cell and embryos transfection. However, while engineered NMs provide great benefits, we know very little about the potential effects on human health and the environment. Thus, the objectives of this study were to evaluate the potential toxicity of MWCNT and CNF in various biological model organisms (bovine fibroblast and embryo, and green microalgaes) and whether MWCNT is able to deliver exogenous DNA molecules into bovine fibroblast and embryos. In experiment 1, we evaluated in vitro the effects of NMs on bovine fibroblast viability and morphology. The results showed that low concentrations of CNF (0.02-100μg ml-1) did not cause viability loss (P>0.05) or change in cell morphology. However, at concentrations above 200μg ml-1, NFC significantly decreased cell viability (P<0.05) and changes in cell shape. Fibroblasts exposed at concentrations above 100μg ml-1 MWCNT-COOH exhibited a reduced cell viability (P<0.05) and their cell morphology was altered. In experiment 2, we examined gene expression, apoptosis response and developmental rates of in vitro produced bovine embryos that were exposed to NMs. There was no difference (P > 0.05) in the hatching, degeneration and apoptosis rate among the control, MWCNT-COOH or cotton CNF- exposed embryos. In contrast, in embryos exposed at 0.2 μg ml-1 MWCNT-COOH showed relatively higher levels (P<0.05) of the genes associated with totipotency, differentiation and response to stress. In experiment 3, we analyzed the cytotoxic response of C. vulgaris and K. flaccidum cells (green microalgae) to NMs by investigating the zeta potential, trypan blue exclusion assay, photosynthetic activity, superoxide dismutase activity, quantification of ATP levels and microscopic investigations. NMs decreased viability, photosynthetic activity and ATP levels of microalgaes cells, depending on concentration and time. Addition of NMs further induced an increase of superoxide dismutase activity and ultrastructural damage cell. In experiment 4, we have used plasmid DNA of green fluorescent protein (pGFP) in combination with MWCNT-COOH to transfect bovine fibroblast and embryos. Detection of GFP accumulation by fluorescence microscopy examination revealed that this gene was expressed in the fibroblast and the embryo (2 to 8-cell stage). However, the expression GFP was not observed in blastocyst stage. The PCR result confirmed the presence of the pGFP gene in the transfected cells (3.30% GFP+) and embryos of 2-8–cell stage (46.67% GFP+). In conclusion, under the conditions tested, the exposures to MWCNTs or CNFs in low concentrations are not toxic to bovine fibroblast cells. However, these NMs have toxic effects in green microalgaes. Especially, this work showed that MWCNT-COOH-transfection of embryo could be a simple and suitable method to introduce foreign genes in embryos and perhaps could be also useful to generate transgenic animals.

This thesis is focused on nanoparticles produced by internal combustion engines utilized in vehicles. It deals with spatial distribution of nanoparticles within urban areas, impact of alternative fuels usage on particle production and toxicity, and a particle toxicological testing methodology. Monitoring of airborne nanoparticles identified traffic as the main source of airborne nanoparticles in places with heavy traffic load (Prague), as well as in a small city with only local traffic (Čelákovice). Most particles were likely emitted during short episodes of high emissions (e.g. uphill acceleration). During the measurements, high-emission vehicles responsible for a large fraction of the air pollution were also identified. On the other hand, small non-road internal combustion engines, which are not subject to any limit on particle emissions, such as a lawn mower, were operated during the measurement and generated a large number of nanoparticles. The amount and characteristics of the particles produced by combustion depend on the combustion technology and the fuel composition. A large part of the thesis deals with alternative fuels and their effects on the quantity of produced particles and toxicity of organic matter adsorbed on the particles. Hydrotreated vegetable oil (HVO) exhibited the lowest...

In recent years, respiratory diseases have emerged as a leading cause of mortality across the globe. In the United States alone respiratory diseases are the fourth leading cause of deaths annually. Moreover, with the rapid increase of industrialization and urbanization, the occurrences of respiratory diseases are expected to remain high with strong chances of increasing in the future. To ameliorate the epidemic of respiratory disease, it is first important to understand its underlying mechanisms. Respiratory research studies in animals have elucidated the chronological order of the pathological events and systemic responses inside the lung, but understanding the response of individual cell types inside the lung is necessary to outline the initiators and mediators of the pathological events. Many research studies have aimed to understand the behavior of individual cell types, from the lung, under different pathological conditions specific to the respiratory system. However, the cell culture systems used in most of these studies were limited by the absence of the dynamic cell growth environment present in actual lung tissues. The lung exists in a mechanically active environment, where different amounts of circumferential and longitudinal expansion and contraction occur during breathing movements. Thus, simulating the biomechanical environment in in vitro cell culture models may improve the cellular functionality and the outcome of the research studies. Moreover, the stimulation of biomechanical forces in in vitro cell cultures provides the advantage of mimicking the mechanical environment, related to different pathological conditions. In our study we used a dynamic in vitro cell culture system capable of implementing cyclic equibiaxial deformation in cell monolayers to stimulate different biomechanical environments similar to conditions inside the lung. The dynamic cell growth condition was used to determine the effects of ventilator-induced lung injury and nano-material/pollutant exposure in A549 cell cultures. Examples of such pollutants are diesel particulate matter, multi-walled carbon nanotubes, and single-walled carbon nanotubes. Our results indicated that the dynamic cell growth condition specific to ventilator induced lung injury facilitated an increase in inflammatory and tissue remodeling activities in A549 cells. Under the nano-material/pollutant exposure assessment studies, the dynamic cell growth condition induced changes in inflammation and oxidative stress level which closely resembled those in in vivo studies.

Cardiovascular disease (CVD) is the leading cause of death for people of most ethnicities on a global scale, and countless research efforts on the pathology of CVD has been well-characterized over the years. However, advancement in modern technologies, such as nanotechnology, has generated environmental and occupational health concerns within the scientific community. Current investigation of nanotoxicity calls into question the negative effects nanomaterials may invoke from their environmental, commercial, and therapeutic usage. As a result, further research is needed to investigate and characterize the toxicological implications associated with nanomaterial-exposure and CVD. We investigated the toxicity of multi-walled carbon nanotubes (MWCNT) and titanium dioxide (TiO2), which are two prominently used nanomaterials that have been previously linked to upregulation of inflammatory and atherogenic factors. However, the mechanistic pathways involved in these nanomaterials mediating detrimental effects on the heart and/or coronary vasculature have not yet been fully determined. Thus, we utilized two different routes of exposure in rodent models to assess alterations in proinflammatory and proatherogenic signaling pathways, which are represented in contrast throughout the dissertation. In our MWCNT study, we used C57Bl/6 mice exposed to MWCNTs (1 mg/m3) or filtered air (FA-Controls), via inhalation, for 6 hr/d for 14d. Conversely, intravenous TiO2 was administered to F344 male fisher rats, following 24h and 28d post-exposure to a single injection of TiO2-NPs (1 mg/kg), compared to control animals. MWCNT-exposed endpoints investigated the alterations in cholesterol transport, such as lectin-like oxidized low-density lipoprotein receptor (LOX)-1 and ATP-binding cassette transporter (ABCA)-1, inflammatory markers [tumor necrosis factor (TNF)-α], interleukin (IL)-1β/IL-6, nuclear-factor kappa-light-chain-enhancer of activated B cells (NF-κB) and signaling factors involved in activation of the pathway, as well as intracellular/vascular adhesion molecule(s) (VCAM-1, ICAM-1), and miRNAs (miR-221/-21/-1), associated with CVD, were analyzed in cardiac tissue and coronary vasculature. Cardiac fibrotic deposition, matrix-metalloproteinases (MMP)-2/9, and reactive oxygen species (ROS) were also assessed. TiO2-exposure endpoints also involved alterations on cholesterol transport proteins via LOX-1 and ABCA-1, factors of inflammation, namely intracellular macrophages and interleukin (IL)-1β, MMP-2/9 activity and protein expression, fibrotic deposition, and ROS generation were analyzed via quantitative detection or histologically in both cardiac tissue and coronary vasculature. Results from both studies found alterations in fibrotic deposition, upregulation in LOX-1 expression and MMP-2/9 activity, and ROS generation; with a concurrent decrease in ABCA-1 expression in cardiac tissue and coronary vasculature. Individually, MWCNT-exposed endpoints had shown induction of cardiac TNF-α, MMP-9, IκB Kinase (IKK)-α/β, and miR-221 mRNAs; as well as increased coronary expression of TNF-α and VCAM-1. TiO2 studies found increases in IL-1β and MMP-9 protein expression, as well as intracellular macrophage induction. Both studies also found, through pre-treatment of NADPH oxidase inhibitor, apocynin, resulted in attenuation of nanomaterial-exposure mediated ROS production; with nitric oxide synthase inhibitor, L-NNA, also showing attenuation, but only in our MWCNT-exposed inhalation study. The results from both studies have demonstrated, through different routes of administration, exposures, and rodent models; that exposure to nanomaterials can mediate signaling pathways involved in initiation and/or progression of CVD.