Traumatic brain injury (TBI) is a prominent disease in developed countries, and age is an important factor in functional outcome. Although aged patients typically show diminished recovery compared to young patients, and have higher mortality and morbidity following TBI, the mechanism is not well understood. To date, there is no effective therapeutic for TBI. Previous studies indicate a secondary injury in TBI begins immediately after impact, and is likely the major contribution to delayed neuron dysfunction and loss. Studies also suggest mitochondrial dysfunction and increased free radical species (ROS) production following TBI may play a key role in the process. To evaluate oxidative damage following TBI, especially in aging, young (3 months), middle aged (12 months) and aged (22 months) Fisher-344 rats were subjected to a unilateral controlled cortical impact (CCI) injury, and tissue sparing, 4-hydroxynonenal (HNE) and acrolein levels, and antioxidant enzyme activities, and DNA oxidative damage were measured. In order to evaluate changes in mitochondria following TBI, mitochondrial protein levels were investigated using young adult animals. To evaluate a potential therapeutic for TBI, the effect of creatine on oxidative damage was evaluated. These studies show an age dependent increase of oxidative damage following TBI, demonstrated by increased levels of 4-HNE, acrolein and 8-hydroxyguanine. Middle aged and aged animals showed increased tissue loss compared to young animals 7 days post injury. Mitochondrial proteins involved in the respiratory chain, carrier proteins and channel proteins were significantly decreased 24 h post injury in ipsilateral cortex, but increased in both ipsilateral and contralateral hippocampus. To study potentially protective compounds in TBI, animals were fed with creatine two weeks before TBI and showed less oxidative damage and increased antioxidant capacity, which suggests creatine may be a potential drug for clinical treatment of TBI. The work described in this dissertation is the first to show increased oxidative damage and diminished antioxidant capacity in TBI in aging. The study of mitochondriafollowing TBI using quantitative proteomics is also the first time to show multiple mitochondrial proteins change following TBI. These data are also the first to show creatine can increase antioxidant defenses. These studies contribute to our understanding the mechanisms of secondary injury in TBI in aging.

Abstract Antioxidants function as blockers of radical processes and eliminate harmful reactive oxygen species (ROS) produced during normal cellular metabolism. A complex antioxidant defence system has evolved to protect the cellular homeostasis. This system includes antioxidant enzymes (AOEs), such as superoxide dismutases (SODs), which are intracellular MnSOD and CuZnSOD and extracellular ECSOD, H2O2 scavenging enzymes catalase and glutathione peroxidase, and hemeoxygenase-1 (HO-1), an important enzyme in heme metabolism, which has also been suggested to have antioxidant capacities. ROS play an important role in the pathogenesis of interstitial lung diseases. These diseases represent a group of disorders with different etiology, histopathology, treatment and prognosis. Sarcoidosis, extrinsic allergic alveolitis and two different forms of idiopathic pulmonary fibrosis, usual interstitial pneumonia (UIP) and desquamative interstitial pneumonia (DIP) were included in this study. The purpose of this research was to evaluate the expressions of inducible nitric oxide synthase (i-NOS), endothelial nitric oxide synthase (e-NOS) and xanthine oxidase (XAO), oxidant generating enzymes commonly associated with tissue injury, and, on the other hand, the expressions of AOEs suggested to be involved in the defence of lung tissue against oxidant stress. The methods included immunohistochemistry on lung biopsies (n=48) and Western blotting, Northern blotting or reverse polymerase chain reaction (RT-PCR) on human inflammatory cells and cells obtained from bronchoalveolar lavage. I-NOS was intensively expressed in inflammatory, but not in fibrotic lesions, similar e-NOS expression was found in control lung and in all interstitial lung diseases, while XAO was mainly negative. MnSOD and HO-1 were highly expressed in the granulomas of sarcoidosis. In contrast the expressions of MnSOD and HO-1 in late fibrotic lesions of UIP were low or undetectable by immunohistochemistry. CuZnSOD and catalase showed similar immunoreactivity in healthy and diseased lung. A cell specific expression and regulation of various enzymes may play an important role during acute inflammatory diseases and also in the progression of lung fibrogenesis.

Abstract Manganese superoxide dismutase (MnSOD) is an important intracellular antioxidant enzyme, which has been suggested to play a role in tumour biology. In the present study, the expression and possible role of MnSOD in malignant pleural mesothelioma was investigated. Mesothelial cells in healthy visceral pleural tissue showed no MnSOD immunoreactivity in five out of six cases, whereas moderate or high immunoreactivity for MnSOD was detected in 30 out of 42 (71%) cases of mesothelioma. Only two of the 21 cases with metastatic adenocarcinoma of the pleura showed moderate MnSOD immunoreactivity, the remaining 19 (90.5%) showing negative or weak reactivity (p < 0.001, by Fisher's exact test compared to mesothelioma). The immunostaining of catalase, a hydrogen peroxide scavenging antioxidant enzyme, was detectable in 27 of the 35 (77%) mesothelioma cases studied, whereas all the five samples of healthy pleural mesothelium were negative. Reactive mesothelium showed positive immunoreactivity for MnSOD and catalase, suggesting that induction of these enzymes is not specific for mesothelioma. Two continuous human mesothelioma cell lines showed higher MnSOD activity, immunoreactive protein and mRNA levels than non-malignant mesothelial cells. In addition, mesothelioma cells expressing the highest MnSOD levels had the highest levels of catalase and copper-zinc superoxide dismutase. The mitochondria of these cells expressed higher MnSOD and lower superoxide levels than non-malignant mesothelial cells. The mesothelioma cells with the highest antioxidant enzyme levels were most resistant to oxidant- and drug-induced injury and to drug-induced apoptosis compared to non-malignant mesothelial cells and mesothelioma cells with lower MnSOD and catalase levels. The extent of cell proliferation and apoptosis of mesothelioma tissue were 14.1±13.2% and 1.1±1.2%, respectively. MnSOD expression was inversely associated with cell proliferation (p = 0.02 by t-test), and a tendency for a better prognosis among patients with moderate or strong MnSOD expression was demonstrated. Patients displaying a tumour with enhanced proliferation or apoptosis had a poorer prognosis (p < 0.001 by Log Rank test). In conclusion, the MnSOD level is usually high in pleural mesothelioma, which may affect the proliferation and drug-resistance of mesothelioma cells. MnSOD immunostaining can thus possibly be used to distinguish mesothelioma from metastatic adenocarcinoma but not from reactive mesothelium.

>Magister Scientiae - MSc / Drought is a major abiotic stress which causes not only differences between the mean yield and the potential yield but also yield variation from year to year. Although selection for genotypes with improved productivity under drought environments has been a central goal of numerous plant breeding programs, the molecular basis for plant tolerance towards drought stress is still poorly understood. Exposure of plants to this abiotic stress is known to trigger excessive formation of reactive oxygen species (ROS), which induce cell death and reduce growth. Part of the mechanism of plant responses to drought involves alterations in the expression of antioxidant enzymes and biosynthesis of different compatible solutes such as proline. Sorghum is regarded as generally more drought tolerant than maize, and it is a potential key model system for investigating the physiological and molecular mechanisms conferring drought tolerance. Comparative studies in crop plants to decipher differences in drought tolerance are essential for crop improvement to sustain a higher level of production, which in turn will improve food security, under severe drought conditions resulting from climate change. On this basis, the aim of this study is to determine molecular differences between Zea mays and Sorghum bicolor in response to drought stress in an attempt to identify novel biomarkers for drought tolerance. The physiological and molecular responses of maize and sorghum were studied for changes in growth, chlorophyll content, relative water content, ROS content, lipid peroxidation level, proline content, and antioxidant enzyme activity. Spectral Count Label-free Quantitation analysis was conducted to reveal the changes in protein profiles under drought in attempt to identify drought-responsive molecular mechanisms in the leaves of the two plant species. In this study, water deficit triggered mechanisms that resulted in overproduction of ROS in both Zea mays and Sorghum bicolor. However, Sorghum bicolor showed less oxidative damage under water stress compared to Zea mays. Drought-induced proline accumulation in the roots of Sorghum bicolor was associated with enhanced water retention. Significant changes were identified in the antioxidant enzyme activity between the two plant species in response to drought conditions. Proteomics results showed differing patterns for drought-responsive proteins in the two species. Together with the physiological, biochemical and proteomic profiling results between Zea mays and Sorghum bicolor, potential proteins and/or metabolic pathways underlying drought tolerance were identified. The findings obtained through this study provide insight towards understanding the molecular basis of crop drought tolerance.

Com o objetivo de avaliar o desempenho de diferentes doses e produtos fitossanitários utilizados no tratamento de sementes de soja, foi efetuada a caracterização do efeito fisiológico na germinação e no desenvolvimento das plântulas por intermédio dos testes de germinação e de vigor (índice de velocidade de germinação, envelhecimento acelerado, comprimento e massa de matéria seca de plântula, teste de frio e análise computadorizada de imagem) em laboratório, além da determinação do teor de clorofila (por intermédio do valor SPAD), fotossíntese líquida, condutância estomática, transpiração, temperatura foliar, conteúdo de peróxido de hidrogênio, peroxidação de lipídios, atividade da catalase (enzima antioxidante), e teor de proteína e de nitrogênio total. Com base nos resultados obtidos observou-se que todos os tratamentos apresentaram desempenho satisfatório no que diz respeito à germinação. Não se observaram diferenças em termos de índice de velocidade de germinação, envelhecimento acelerado, comprimento e massa de matéria seca de raiz, índice de vigor e de crescimento (análise de imagem) e peroxidação de lipídeos. O tratamento com Fipronil + Piraclostrobina + Tiofanato Metílico apresentou tendência de melhor desempenho em termos de comprimento de parte aérea, enquanto o tratamento Controle apresentou tendência de melhor desempenho, mas não diferiu dos tratamentos: Fipronil + Piraclostrobina + Tiofanato Metílico, Fluxapiroxade e Piraclostrobina em termos de massa de matéria seca de parte aérea. Os tratamentos Fipronil e Fluxapiroxade apresentaram melhor desempenho que o Controle, em termos de relação massa de matéria seca de raiz e de parte aérea. O tratamento com Fipronil apresentou melhor tendência de desempenho pelo teste de frio e juntamente com Fipronil + Piraclostrobina + Tiofanato Metílico e Fluxapiroxade apresentou desempenho melhor que o Controle no de índice de uniformidade. A Piraclostrobina apresentou desempenho melhor que o Controle em termos de teor de clorofila, fotossíntese líquida e temperatura foliar, enquanto o tratamento com Fipronil foi melhor que o Controle e os demais tratamentos em termos de condutância estomática e transpiração. Os tratamentos com Fipronil e Piraclostrobina apresentaram desempenho melhor que o Controle, em termos de conteúdo de peróxido de hidrogênio e os tratamentos com Fipronil + Piraclostrobina + Tiofanato Metílico e Fluxapiroxade e Piraclostrobina apresentaram desempenho melhor que o Controle, em termos da atividade da catalase. O Fluxapiroxade (50 g por 100 kg de sementes) apresentou melhor desempenho, mas não diferiu do Controle e dos tratamentos com Fipronil, Fluxapiroxade (25 e 75 g por 100 kg de sementes) e Piraclostrobina em termos do teor de proteína e nitrogênio total. Com os resultados apresentados, conclui-se que não houve prejuízo ao vigor das plântulas quando realizado o tratamento de sementes. Além disso, pode-se concluir que esta constitui prática agronômica eficiente não só no que diz respeito ao controle de doenças e pragas, mas também apresenta benefícios no que diz respeito à fisiologia das plântulas de soja, sobretudo para tratamento realizado com estrobilurinas. Esses benefícios podem favorecer um melhor estabelecimento das plântulas no campo. / This study aimed to evaluate the physiological effects of soybean seed treatment with different pesticides and doses on germination and seedling development. Germination and vigor tests, such as speed of germination index, accelerated aging, length and dry weight of seedling, cold test and computerized image analysis were performed in the laboratory, besides the determination of chlorophyll content (SPAD value), net photosynthesis, stomatal conductance, leaves transpiration and temperature, content of hydrogen peroxide, lipid peroxidation, catalase (an antioxidant enzyme) activity, protein and total nitrogen. The results obtained revealed that all treatments showed satisfactory performance in germination. No differences in terms of speed index, accelerated aging, root length and dry weight, vigor and growth index (image analysis) and lipid peroxidation were observed. Treatment with Fipronil + Pyraclostrobin + Methyl Tiophanate tended to perform better in terms of shoot, while control treatment tended to perform better, but did not differ from treatments with Fipronil + Pyraclostrobin + Methyl Tiophanate, Fluxapyroxad and Pyraclostrobin in terms of shoot dry matter. Fipronil and Fluxapyroxad treatments performed better than the control in terms of relationship between root and shoot dry weight. Treatment with Fipronil showed better performance trend for the cold test and along with Fipronil + Pyraclostrobin + Methyl Tiophanate and Fluxapyroxad performed better than control on the uniformity index. Pyraclostrobin showed better performance than the control in terms of chlorophyll content, net photosynthesis and leaf temperature, whereas treatment with Fipronil was better than the control and other treatments in terms of stomatal conductance and transpiration. Treatments with Fipronil and Pyraclostrobin performed better than the control in terms of content of hydrogen peroxide and treatments with Fipronil + Pyraclostrobin + Methyl Tiophanate, Fluxapyroxad and Pyraclostrobin performed better than the control in terms of catalase activity. Fluxapyroxad (50 g per 100 kg of seeds) performed better, but did not differ from control, Fipronil, Fluxapyroxad (25 and 75 g per 100 kg of seeds) and Pyraclostrobin in terms of protein content and total nitrogen. With the results presented, we conclude that there was no damage to seedling vigor when seed treatment was applied. Furthermore, it can be concluded that this is an efficient agronomic practice with regard to the control of diseases and pests and it also has benefits to the physiology of soybean seedlings, mainly when treatment is done with Strobilurins. These benefits can favorable to a better seedling establishment in the field.

Com o objetivo de avaliar o desempenho de diferentes doses e produtos fitossanitários utilizados no tratamento de sementes de soja, foi efetuada a caracterização do efeito fisiológico na germinação e no desenvolvimento das plântulas por intermédio dos testes de germinação e de vigor (índice de velocidade de germinação, envelhecimento acelerado, comprimento e massa de matéria seca de plântula, teste de frio e análise computadorizada de imagem) em laboratório, além da determinação do teor de clorofila (por intermédio do valor SPAD), fotossíntese líquida, condutância estomática, transpiração, temperatura foliar, conteúdo de peróxido de hidrogênio, peroxidação de lipídios, atividade da catalase (enzima antioxidante), e teor de proteína e de nitrogênio total. Com base nos resultados obtidos observou-se que todos os tratamentos apresentaram desempenho satisfatório no que diz respeito à germinação. Não se observaram diferenças em termos de índice de velocidade de germinação, envelhecimento acelerado, comprimento e massa de matéria seca de raiz, índice de vigor e de crescimento (análise de imagem) e peroxidação de lipídeos. O tratamento com Fipronil + Piraclostrobina + Tiofanato Metílico apresentou tendência de melhor desempenho em termos de comprimento de parte aérea, enquanto o tratamento Controle apresentou tendência de melhor desempenho, mas não diferiu dos tratamentos: Fipronil + Piraclostrobina + Tiofanato Metílico, Fluxapiroxade e Piraclostrobina em termos de massa de matéria seca de parte aérea. Os tratamentos Fipronil e Fluxapiroxade apresentaram melhor desempenho que o Controle, em termos de relação massa de matéria seca de raiz e de parte aérea. O tratamento com Fipronil apresentou melhor tendência de desempenho pelo teste de frio e juntamente com Fipronil + Piraclostrobina + Tiofanato Metílico e Fluxapiroxade apresentou desempenho melhor que o Controle no de índice de uniformidade. A Piraclostrobina apresentou desempenho melhor que o Controle em termos de teor de clorofila, fotossíntese líquida e temperatura foliar, enquanto o tratamento com Fipronil foi melhor que o Controle e os demais tratamentos em termos de condutância estomática e transpiração. Os tratamentos com Fipronil e Piraclostrobina apresentaram desempenho melhor que o Controle, em termos de conteúdo de peróxido de hidrogênio e os tratamentos com Fipronil + Piraclostrobina + Tiofanato Metílico e Fluxapiroxade e Piraclostrobina apresentaram desempenho melhor que o Controle, em termos da atividade da catalase. O Fluxapiroxade (50 g por 100 kg de sementes) apresentou melhor desempenho, mas não diferiu do Controle e dos tratamentos com Fipronil, Fluxapiroxade (25 e 75 g por 100 kg de sementes) e Piraclostrobina em termos do teor de proteína e nitrogênio total. Com os resultados apresentados, conclui-se que não houve prejuízo ao vigor das plântulas quando realizado o tratamento de sementes. Além disso, pode-se concluir que esta constitui prática agronômica eficiente não só no que diz respeito ao controle de doenças e pragas, mas também apresenta benefícios no que diz respeito à fisiologia das plântulas de soja, sobretudo para tratamento realizado com estrobilurinas. Esses benefícios podem favorecer um melhor estabelecimento das plântulas no campo. / This study aimed to evaluate the physiological effects of soybean seed treatment with different pesticides and doses on germination and seedling development. Germination and vigor tests, such as speed of germination index, accelerated aging, length and dry weight of seedling, cold test and computerized image analysis were performed in the laboratory, besides the determination of chlorophyll content (SPAD value), net photosynthesis, stomatal conductance, leaves transpiration and temperature, content of hydrogen peroxide, lipid peroxidation, catalase (an antioxidant enzyme) activity, protein and total nitrogen. The results obtained revealed that all treatments showed satisfactory performance in germination. No differences in terms of speed index, accelerated aging, root length and dry weight, vigor and growth index (image analysis) and lipid peroxidation were observed. Treatment with Fipronil + Pyraclostrobin + Methyl Tiophanate tended to perform better in terms of shoot, while control treatment tended to perform better, but did not differ from treatments with Fipronil + Pyraclostrobin + Methyl Tiophanate, Fluxapyroxad and Pyraclostrobin in terms of shoot dry matter. Fipronil and Fluxapyroxad treatments performed better than the control in terms of relationship between root and shoot dry weight. Treatment with Fipronil showed better performance trend for the cold test and along with Fipronil + Pyraclostrobin + Methyl Tiophanate and Fluxapyroxad performed better than control on the uniformity index. Pyraclostrobin showed better performance than the control in terms of chlorophyll content, net photosynthesis and leaf temperature, whereas treatment with Fipronil was better than the control and other treatments in terms of stomatal conductance and transpiration. Treatments with Fipronil and Pyraclostrobin performed better than the control in terms of content of hydrogen peroxide and treatments with Fipronil + Pyraclostrobin + Methyl Tiophanate, Fluxapyroxad and Pyraclostrobin performed better than the control in terms of catalase activity. Fluxapyroxad (50 g per 100 kg of seeds) performed better, but did not differ from control, Fipronil, Fluxapyroxad (25 and 75 g per 100 kg of seeds) and Pyraclostrobin in terms of protein content and total nitrogen. With the results presented, we conclude that there was no damage to seedling vigor when seed treatment was applied. Furthermore, it can be concluded that this is an efficient agronomic practice with regard to the control of diseases and pests and it also has benefits to the physiology of soybean seedlings, mainly when treatment is done with Strobilurins. These benefits can favorable to a better seedling establishment in the field.

In this study, effect of cold stress on physiology and biochemistry of two Turkish barley cultivars, winter type Tarm-92 and spring type Zafer-160, was studied. For chilling stress treatment, cultivars were exposed to +4 &ordm / C for 1, 3 and 7 days, and for freezing stress application acclimated cultivars (+4 &ordm / C for 3 days) were treated with -3 &ordm / C and -7 &ordm / C. After freezing stress treatment, a recovery period was applied for 4 days at 4 &ordm / C. Following analyses were performed on leaf and root tissues: growth parameters (length, wet-dry weights), malondialdehyde (MDA) content, proline content, hydrogen peroxide content (H2O2) electrolyte leakage, PS II fluorescence (Fv/Fm), antioxidant enzyme activities such as catalase (CAT: EC 1.11.1.6), ascorbate peroxidase (APX: EC 1.11.1.11) and glutathione reductase (GR: EC 1.6.4.2). It was observed that effect of cold was more at freezing temperatures than chilling temperature. Cold dependent damage was more obvious as the duration of chilling temperature increased. Growth retardation, membrane damage, leaf catalase deactivation were more apparent and leaf glutathione reductase activity increase was less in spring type cultivar Zafer than in winter type Tarm. These results indicated that winter type barley cultivar is more cold tolerant than spring type barley.

Magister Scientiae - MSc (Biotechnology) / Glycine max (soybean) is an important crop species globally as it is used as a protein-rich food and feed crop and as a source of oils used in the food and biofuel industry. However, the growth and yield of soybean is adversely affected by drought. Exposure of soybean to drought leads to accumulation of reactive oxygen species (ROS) and cell membrane instability. Sterols are membrane components that regulates membrane fluidity and permeability. Besides being major components of the cell membranes, sterols such as lanosterol appear to play a role in the regulation of ROS scavenging and some are precursors to brassinosteroids that act as signaling molecules with hormonal function that regulate growth, development and responses to abiotic stresses such as drought and salinity. In this study, the involvement of plant sterols, also known as phytosterols, in the regulation of soybean responses to drought stress was investigated in Glycine max by determining the effects of drought on the expression of a candidate lanosterol synthase gene (Glyma08g24160) and the content of a subset of phytosterols in soybean. The effects of inhibition of sterol synthesis on ROS production and on superoxide dismutase (SOD), ascorbate peroxidase (APX), catalase (CAT) and dehydroascorbate reductase (DHAR) were investigated. The concentration of hydrogen peroxide (H2O2) as well as superoxide (O2-) increased in response to drought and sterol synthesis inhibition, however, O2- concentration and sterol contents declined under drought stress and sterol synthesis inhibition.

Conselho Nacional de Desenvolvimento Científico e Tecnológico / The indiscriminate use of agricultural supplies can cause soil pollution, affecting the flora, fauna and ecological relationships. Among these chemical compounds used in agriculture, there is the Bordeaux mixture. The intense use of this fungicide results in a considerable copper addition in the soil, may cause damage to exposed organisms. This study aimed to evaluate the toxicological effects of different copper doses, (0, 35, 70, 105, 140 e 175 mg.Kg-1) applied in soil, at earthworms Eisenia andrei biomass and reproduction, through ecotoxicological tests as well as the effects of exposure to antioxidant enzyme activity, by the enzymes catalase and glutathione S-transferase (GST and CAT), on neurotransmission biomarkers such as acetylcholinesterase (AChE) and cell membrane lipid peroxidation through the levels of malondialdehyde (MDA). The ecotoxicological results showed that the largest copper doses tested, (140 e 175 mg.Kg-1) were toxic, because the worms had a mean biomass reduction and cocoons. In the enzyme assessments, an increase in the glutathione-S-transferase activity was observed as the antioxidant defense mechanism. The significant MDA levels increase and the acetylcholinesterase activity inhibition, indicating the cell membrane lipid peroxidation occurrence and neurotransmission changes as a result of oxidative stress caused by the metal. / O uso indiscriminado de insumos agrícolas pode causar a poluição dos solos, comprometendo a flora, fauna e as relações ecológicas. Dentre os insumos químicos utilizados na agricultura, destaca-se a calda bordalesa. Sua intensa utilização resulta em uma adição considerável de cobre ao solo, podendo causar danos aos organismos expostos. O presente estudo teve como objetivo determinar os efeitos toxicológicos de diferentes doses de cobre: 0, 35, 70, 105, 140 e 175 mg.Kg-1 aplicado ao solo, na biomassa e reprodução das minhocas Eisenia andrei, através dos testes ecotoxicológicos assim como os efeitos da exposição a nível enzimático antioxidante, através das enzimas catalase e glutationa S-transferase (CAT e GST), sobre biomarcadores de neurotransmissão como a acetil-colinesterase (AChE) e na peroxidação lipídica da membrana celular através dos níveis de malondialdeído (MDA). Os resultados ecotoxicológicos, evidenciaram que as maiores doses de cobre testadas, (140 e 175 mg.Kg-1) foram tóxicas, pois as minhocas apresentaram redução média na biomassa e no número de casulos. Em relação aos níveis enzimáticos, foi observado um incremento na atividade das enzimas glutationa-S-transferase, como mecanismo de defesa antioxidante. O aumento significativo nos níveis de MDA observados e a inibição da atividade da acetil-colinesterase, indicam a ocorrência da peroxidação lipídica da membrana celular e alterações na neurotransmissão em decorrência do estresse oxidativo ocasionado pela presença do metal.

Abstract Reactive oxygen species (ROS) can cause severe damage to cells and organs but they are also important mediators of inflammatory responses and cellular signalling. Due to the significant role of ROS, the cells have evolved a broad antioxidative system to regulate the concentration of these species. Peroxiredoxins (Prxs) are enzymes that participate in the regulation of the cellular redox-homeostasis by detoxifying hydrogen peroxide. Prxs are not classified as conventional antioxidant enzymes and their physiological role, whether protective or regulatory, is still unclear. The aim of this project was to study the localization and regulation of Prxs in normal human lung and also their role in selected lung disorders (pulmonary sarcoidosis, pleural mesothelioma, lung carcinomas and chronic obstructive disorder, COPD). Additionally the expression of thioredoxin (Trx) and thioredoxin reductase (TrxR) was analysed in the lung of smokers and COPD patients. These enzymes are important reductants in cell and Prxs are one of their targets. Lung is an important organ in the field of ROS and antioxidant research since it is especially vulnerable to exogenous oxidative stress caused by pollutants, cigarette smoke and also by high oxygen pressure. The results showed that all six human Prxs were expressed in healthy human lung but in a cell-specific manner. The most prominent expression was detected in the epithelium and in macrophages, the cells most prone to oxidative stress. There were also differences in subcellular locations of Prxs. The expression of Prxs in non-malignant lung diseases (pulmonary sarcoidosis and COPD) and in smoker's lung was very similar with that in normal lung. Higher expression of Prx V and VI was detected in a subpopulation of macrophages sampled from COPD patients' lung. In contrast, Trx expression was induced in the bronchial epithelium of smoker's lung. Differences in the expression compared to normal lung were seen in lung malignancies (pleural mesothelioma and lung carcinomas). Interestingly, different Prxs were highly expressed in different types of carcinomas. In pleural mesothelioma, all Prxs except Prx IV were highly expressed when compared to normal pleura, in adenocarcinoma Prxs I, II, VI and especially IV, and in squamous cell carcinoma Prxs I, II and IV were upregulated. Tests performed on cultured cells in vitro revealed only a minor increase in the Prx expression after severe oxidant stress in malignant lung cell line originating from alveolar type II pneumocytes (A549) or non-malignant cell line derived from bronchial epithelium. None of the tested growth factors or cytokines affected Prx expression or oxidation state, but severe oxidant stress influenced remarkably the oxidation state of the Prxs.