O hipertireoidismo leva o fígado a uma situação de proteção antioxidante limítrofe, que pode aumentar a susceptibilidade do órgão a ações deletérias de xenobióticos ou fenômenos que impliquem em estresse oxidativo. Tal ocorre em ratos Sprague-Dawley tratados simultaneamente com hormônio tireoidiano L-3,3\',5-triiodotironina (T3) e o inseticida lindano (gama-hexaclorociclohexano). Enquanto a dose única de lindano (20 mg/kg peso corpóreo) não alterou a maioria dos parâmetros estudados, a administração de T3 estabeleceu a condição de estresse oxidativo hepático pelo aumento da atividade da NADPH-citocromo c redutase, acompanhado do aumento nos índices de lipoperoxidação e da produção microssomal de ânion superóxido (O2-) e da diminuição da atividade de defesas antioxidantes enzimáticas (superóxido dismutase e catalase) e não-enzimáticas (diminuição dos níveis hepáticos de alfa-tocoferol, beta-caroteno e licopeno). A administração de lindano teve seu efeito potenciado pelo hipertireoidismo, como indicado pelo aumento das razões O2-/SOD e SRAT/GSHT e pela diminuição dos níveis de alfa-tocoferol hepático, ambos efeitos maiores do que a soma dos obtidos nos tratamentos isolados. Devido à importância da atividade dos macrófagos residentes no fígado, observada em vários modelos de dano hepático, a função das células de Kupffer (CK) foi estudada neste modelo. Ao contrário do observado em experimentos no fígado íntegro, a luminescência das CK isoladas sofreu decréscimo nos animais tratados com T3 e lindano separadamente, apresentando uma tendência ao aumento no tratamento conjunto. Todos os tratamentos diminuíram a atividade fungicida das CK. É possível que os tratamentos utilizados estejam prejudicando a ação das CK, sendo restaurada na presença dos dois tratamentos. Por outro lado, a importância das CK no aumento do efeito do lindano no hipertireoidismo experimental foi evidenciada pela supressão dos efeitos acima mencionados após a administração do inativador de CK, o GdCl3. Estudos morfológicos corroboram este dado, mostrando uma supressão de sinais inflamatórios e necróticos nos animais hipertiroídeos tratados com GdCl3. / Hyperthyroidism elicits a borderline antioxidant protection state in the liver, which may increase its susceptibility to deleterious effects of xenobiotics or situations that cause oxidative stress. This happens to Sprague-Dawley rats treated concurrently with thyroid hormone L-3,3\',5-triiodothyronine (T3) and the pesticide lindane (gama-hexachlorocyclohexane). While a single dose of 20 mg/kg body weight of lindane did not alter most of the assessed parameters, T3 administration established a hepatic oxidative stress condition by means of an increase in NADPH-cytochrome c reductase activity, with a concomitant increase in lipoperoxidation (increase of thiobarbituric acid reactants) and microsomal generation of superoxide anion (O2-) and lower enzymatic (decreased activities of superoxide dismutase (SOD) and catalase) and non-enzymatic antioxidant defenses (decreased hepatic levels of alpha-tocopherol, beta-carotene, and lycopene). Lindane administration had potentiated effects on hyperthyroid animals, as indicated by the increased O2-/SOD ratio and further lowering of alpha-tocopherol levels in the liver; both effects greater than the sum of the ones observed after isolated treatments. As liver resident macrophages have been shown to play an important role in several hepatic damage models, Kupffer cell (KC) function was also studied in this model. Contrary to what was observed in experiments in the whole liver, Kupffer cell (KC) luminescence was diminished in separately T3 and lindane treated rats, revealing a tendency to increase after joint treatment. All treatments decreased KC fungicidal activity. It is possible that the separate treatments impair KC function, which is restored after the joint treatment. KC role in the potentiation of lindane-induced oxidative stress was evidenced by the suppression of this effect after KC inactivator, gadolinium chloride, administration. Morphological aspects of liver corroborate these data, showing a suppression of inflammatory and necrotic signals, present in hyperthyroid animals treated with lindane.

Organochlorine (OC) compounds that include several pesticides as well as an array of industrial chemicals were very efficacious for their intended use but were also characterized by deleterious environmental impacts when released either intentionally or inadvertently. Their lipophilic nature, long persistence in the environment and threat to human health caused all the developed countries to ban the production of these chemicals as well as restricted the use of formulations containing these material for food production. / A number of scientists have become involved in the development of intentional degradation methods/techniques for these compounds using zero-valent metals or bimetallic mixtures. To date, there is no single, simple and continuous procedure available to completely dechlorinate lindane or pentachlorophenol (PCP). This work describes the complete dechlorination of lindane and pentachlorophenol by zero-valent Zn, Fe and Fe/Ag bimetallic mixture as well as a supercritical fluid extraction technique for a more efficient mass transfer of the substrates to the surfaces of the metal catalyst. The dechlorination reaction occurs on the surface of metal particles with the removal of all the chlorine atoms from lindane and PCP in a matter of minute, and yields completely dechlorinated hydrocarbon molecules and chloride as products. (Abstract shortened by UMI.)

Thesis (M.Sc.(Chemistry))--University of Pretoria, 2007. / Includes bibliographical references (leaves 80-85).

Diss. (sammanfattning) Uppsala : Sveriges lantbruksuniversitet, 2009. / Härtill 3 uppsatser.

No description available.

The immunotoxic effects of multiple pesticide exposure were evaluated. C57BL/6 mouse thymocytes were exposed to lindane, malathion, and permethrin, either separately or in mixtures of two pesticides, in concentrations ranging from 37.5 uM to 1mM. These exposures caused both apoptotic and necrotic cell death in thymocytes as evaluated by 7-aminoactinomycin-D, Annexin-V/PI, and lactate dehydrogenase release assays. When cells were exposed to lindane+malathion, or lindane+permethrin, a significantly greater-than-additive cytotoxicity was observed. The pesticide exposure caused DNA ladder formation with increased laddering in mixtures. Further, the effect of these pesticides on thymocyte oxidative stress was investigated. Thymocytes treated with any of these pesticides generated superoxide and H2O2. The lindane + malathion caused more-than-additive increase in superoxide production compared to single treatments of these pesticides. However, the effect of the lindane + permethrin was not significantly different from individual components of this mixture. The effects of pesticides on antioxidant enzymes were also investigated and only mixtures were found to have significant effects. Alteration in transcription factor NFkB level was measured as an indicator of oxidative stress in thymocytes following 12 h pesticide exposure, in vitro. Only lindane + malathion was found to increase the protein level. Furthermore, the effects of pesticides and their mixtures on immune functions of mice were studied in vivo. Animals (8-12 week old, male mice) were randomly divided into groups of six and injected intraperitoneally with three different doses (one-half, one-third, one-fourth, or one-eight of LD50) of individual pesticides. Exposure to individual pesticides did not alter the thymus/body or spleen/body weight ratios, thymic or splenic cell counts, or CD4/CD8 or CD45/CD90 ratios. However, anti-sRBC plaque forming cell (PFC) counts were significantly lowered with all treatments. Two other groups of animals were injected with lindane + malathion or lindane + permethrin at one-third of the LD50 of each pesticide. Exposure to pesticide mixtures did not alter the CD4/CD8 or CD45/CD90 ratios. However, the thymus/ and spleen/body weight ratios, thymic and splenic cell counts, and PFC counts were significantly lowered. These data indicate that lindane, malathion, and permethrin are immunotoxic and their mixtures can cause higher toxicity compared to individual exposures. In addition, these data support the hypothesis that oxidative stress were induced in thymocytes by exposure to these pesticides in vitro. / Ph. D.

Le travail présenté dans cette thèse porte sur l'adaptation bactérienne aux molécules chlorées, tant au niveau des ressources génétiques nécessaires à la mise en place des gênes de dégradation qu'au niveau de la structure de la communauté microbienne observée durant la dégradation de ces composés. La première partie de ce document est une bibliographie qui se focalise sur les mécanismes développés par les bactéries pour répondre aux stress environnementaux, et sur les possibles origines des gènes responsables des premières étapes de dégradation des composés chlorés : les dehalogenases (qui réalisent les étapes de déchloration). Le deuxième chapitre de cette thèse porte sur des essais expérimentaux de remodelage génétique, dans le but de valider les hypothèses présentées lors de la bibliographie quant aux mécanismes qui ont pu conduire à la génération de nouveaux gênes de dégradation. Ces remodelages in vitro et in vivo ont été effectués en utilisant les gènes linB et dhaA. Le chapitre suivant examine la structure de la communauté bactérienne lors de la dégradation réductive du tetrachloroéthylène (PCE). Pour cette étude, des outils de biologie moléculaire, plus spécifiquement des puces phylogénétiques, ont été utilisés pour étudier la structure de la communauté microbienne depuis l'introduction du polluant jusqu'à sa dégradation. Afin d'élucider les fonctions métaboliques qui peuvent être corrélées avec la dégradation du PCE, les résultats des puces phylogénétiques ont été comparés avec un suivi chimique des métabolites de dégradation de ce composé, lors d'une étude en microcosmes. L'objectif du dernier chapitre de la thèse a été de relier la structure de la communauté microbienne avec la cinétique de dégradation des composés chimiques étudiés. Pour cela, une étude globale comportant à la fois un suivi chimique des métabolites de dégradation, une quantification des gènes de dégradation impliqués dans la déchloration réductive du PCE ainsi que l'étude de la structure de la communauté microbienne ont été mis en place. Cette étude a permis de corréler les conditions environnementales nécessaires à la déchloration et la communauté microbienne associée avec l'expression des déhalogénases quantifiées. En résumé, cette thèse explore à la fois les mécanismes mis en place par les bactéries pour dégrader ces composés polluants et la structure de la communauté bactérienne durant la dégradation de ce polluant. Comprendre ces deux étapes dans l'adaptation bactérienne peut contribuer à améliorer l'utilisation des capacités bactériennes utilisées en bioremédiation. / This thesis concerns the bacterial adaptation to the chlorinated compounds at both the gene level and the microbial community level. The bibliography will focus on the adaptation mechanisms developed by bacteria to respond to environmental stresses and on the possible origins of the genes responsible for the first steps of chlorinated compound degradation, those encoding for the dehalogenases, which perform the dechlorination or chlorine removal step. The second chapter of the thesis consists of an experimental exploration of the gene shuffling hypothesis presented in the bibliography, using linB and dhaA genes. The next chapter examines the bacterial community structure in relation to compound degradation using the reductive dechlorination of tetrachloroethylene. For this study, molecular biology tools, specifically phylochip microarrays were used to examine bacterial community structure from the moment of pollutant introduction to the environment and during bioremediation. In order to elucidate the metabolic functions, which correlate the PCE degradation, phylogenetic results were compared with functional genes in the microcosms studied. The last chapter of this global study on chlorinated compound degradation genes was to link the microbial community structure kinetics with the chemical degradation kinetics. In order to evaluate the molecular biological parameters of the microbial community, all the genes known to be involved in the entire pathway of PCE reductive dechlorination were quantified. This global study, incorporating chemical monitoring, dehalogenase quantification and microbial community structure, produced correlations between the environmental conditions necessary for dechlorination and the microbial community associated with dehalogenase expression. In summary, both the mechanisms implemented by the bacteria to degrade this compound pollutant and the bacterial community structure during the pollutant degradation were addressed. Improving the understanding of these two steps in bacterial adaptation can contribute to the understanding of bacterial and environmental cleanup capabilities.

Le travail présenté dans cette thèse porte sur l'adaptation bactérienne aux molécules chlorées, tant au niveau des ressources génétiques nécessaires à la mise en place des gênes de dégradation qu'au niveau de la structure de la communauté microbienne observée durant la dégradation de ces composés. La première partie de ce document est une bibliographie qui se focalise sur les mécanismes développés par les bactéries pour répondre aux stress environnementaux, et sur les possibles origines des gènes responsables des premières étapes de dégradation des composés chlorés : les dehalogenases (qui réalisent les étapes de dechloration). Le deuxième chapitre de cette thèse porte sur des essais expérimentaux de remodelage génétique, dans le but de valider les hypothèses présentées lors de la bibliographie quant aux mécanismes qui ont pu conduire à la génération de nouveaux gênes de dégradation. Ces remodelages in vitro et in vivo ont été effectués en utilisant les gènes linB et dhaA. Le chapitre suivant examine la structure de la communauté bactérienne lors de la dégradation réductive du tetrachloroéthylène (PCE). Pour cette étude, des outils de biologie moléculaire, plus spécifiquement des puces phylogénétiques, ont été utilisés pour étudier la structure de la communauté microbienne depuis l'introduction du polluant jusqu'à sa dégradation. Afin d'élucider les fonctions métaboliques qui peuvent être corrélées avec la dégradation du PCE, les résultats des puces phylogénétiques ont été comparés avec un suivi chimique des métabolites de dégradation de ce composé, lors d'une étude en microcosmes. L'objectif du dernier chapitre de la thèse a été de relier la structure de la communauté microbienne avec la cinétique de dégradation des composés chimiques étudiés. Pour cela, une étude globale comportant à la fois un suivi chimique des métabolites de dégradation, une quantification des gènes de dégradation impliqués dans la déchloration réductive du PCE ainsi que l'étude de la structure de la communauté microbienne ont été mis en place. Cette étude a permis de corréler les conditions environnementales nécessaires à la déchloration et la communauté microbienne associée avec l'expression des déhalogénases quantifiées. En résumé, cette thèse explore à la fois les mécanismes mis en place par les bactéries pour dégrader ces composés polluants et la structure de la communauté bactérienne durant la dégradation de ce polluant. Comprendre ces deux étapes dans l'adaptation bactérienne peut contribuer à améliorer l'utilisation des capacités bactériennes utilisées en bioremédiation.

Polybrominated flame retardants (BFRs), organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) were analysed in eggs of various wild bird species from industrialised areas in South Africa. Eggs were collected during the 2008 – 2009 breeding season, homogenised and sent to the Norwegian School of Veterinary Science (NVH) for gas chromatography-mass spectrometry (GC-MS) analysis. The concentration, contamination profile, and risk assessment were conducted for each pollutant class, while effects of species-specific variation, feeding guild, and feeding habitat were investigated. Levels of BFRs ranged between 2.6 – 44 ng g-1 wet mass (wm). The predominant congeners were BDE-153, -154, - 183 and -47. Results indicated species, in close contact to humans, had higher levels of BFRs, even at lower trophic levels. Therefore, diet was not the primary route of exposure. High concentrations and the occurrence of nona-PBDE congeners and HBCD indicated exposure to current use BFRs. There were measurable levels of OCPs and PCBs in all eggs analysed. Median OCP concentration ranged from 4.2 – 623 ng g-1 wm. DDE was the predominant compound in all species with the exception of the Crowned Lapwing (Vanellus coronatus) where chlordanes were predominant. This may indicate a species-specific attribute in the metabolic efficiency or diet of the genus, since these findings have been reported elsewhere in literature. Congener profiles indicated historic sources of lindane and DDT, while low levels of p,p’-DDT in al species indicate long-range or atmospheric transport. Even though levels of p,p’-DDE were approaching toxicological thresholds, no eggshell thinning was evident. Concentrations of OCPs and PCBs showed an increase with increasing tophic level. PCB concentrations ranged between 0.9 – 296.4 ng g-1 wm. When studying the metabolic potential of PCBs, metabolic groups showed good agreement with the biodegradability of the individual congeners. Phenobarbital-type (PB-type) inducer PCBs were prevalent, indicating the predominance of less toxic PCB congeners. However, non-ortho PCBs were not analysed. These congeners aslo could impact on the toxic potential of PCBs in wild bird eggs. Principle component analysis (PCA) indicated that variances within datasets could be attributed to congener profiles within species as they were affected by exposure, diet, position in the food web, and association with human activities. Although the individual groups of organohalogens were below no observed effect levels (NOELs), negative effects could occur through interactions of various compounds with each other, as well as the unique exposure profiles of South African bird populations. To assess the dietary exposure of low-income human populations living close to large industries, the occurrence of organohalogens was investigated in backyard chicken eggs. Levels of dioxins in these eggs were above the European Union (EU) recommended limits, whereas BFRs and OCPs levels were below levels of concern. Nevertheless, areas where DDT is actively applied to dwellings for malaria control should be urgently investigated. The presence of measureable levels of all the compounds considered, indicate an environment seriously impacted by anthropogenic activity that in the long term could negatively affect both the environment and human health, if it has not already done so. / Thesis (Ph.D. (Environmental Science))--North-West University, Potchefstroom Campus, 2011.

Polybrominated flame retardants (BFRs), organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) were analysed in eggs of various wild bird species from industrialised areas in South Africa. Eggs were collected during the 2008 – 2009 breeding season, homogenised and sent to the Norwegian School of Veterinary Science (NVH) for gas chromatography-mass spectrometry (GC-MS) analysis. The concentration, contamination profile, and risk assessment were conducted for each pollutant class, while effects of species-specific variation, feeding guild, and feeding habitat were investigated. Levels of BFRs ranged between 2.6 – 44 ng g-1 wet mass (wm). The predominant congeners were BDE-153, -154, - 183 and -47. Results indicated species, in close contact to humans, had higher levels of BFRs, even at lower trophic levels. Therefore, diet was not the primary route of exposure. High concentrations and the occurrence of nona-PBDE congeners and HBCD indicated exposure to current use BFRs. There were measurable levels of OCPs and PCBs in all eggs analysed. Median OCP concentration ranged from 4.2 – 623 ng g-1 wm. DDE was the predominant compound in all species with the exception of the Crowned Lapwing (Vanellus coronatus) where chlordanes were predominant. This may indicate a species-specific attribute in the metabolic efficiency or diet of the genus, since these findings have been reported elsewhere in literature. Congener profiles indicated historic sources of lindane and DDT, while low levels of p,p’-DDT in al species indicate long-range or atmospheric transport. Even though levels of p,p’-DDE were approaching toxicological thresholds, no eggshell thinning was evident. Concentrations of OCPs and PCBs showed an increase with increasing tophic level. PCB concentrations ranged between 0.9 – 296.4 ng g-1 wm. When studying the metabolic potential of PCBs, metabolic groups showed good agreement with the biodegradability of the individual congeners. Phenobarbital-type (PB-type) inducer PCBs were prevalent, indicating the predominance of less toxic PCB congeners. However, non-ortho PCBs were not analysed. These congeners aslo could impact on the toxic potential of PCBs in wild bird eggs. Principle component analysis (PCA) indicated that variances within datasets could be attributed to congener profiles within species as they were affected by exposure, diet, position in the food web, and association with human activities. Although the individual groups of organohalogens were below no observed effect levels (NOELs), negative effects could occur through interactions of various compounds with each other, as well as the unique exposure profiles of South African bird populations. To assess the dietary exposure of low-income human populations living close to large industries, the occurrence of organohalogens was investigated in backyard chicken eggs. Levels of dioxins in these eggs were above the European Union (EU) recommended limits, whereas BFRs and OCPs levels were below levels of concern. Nevertheless, areas where DDT is actively applied to dwellings for malaria control should be urgently investigated. The presence of measureable levels of all the compounds considered, indicate an environment seriously impacted by anthropogenic activity that in the long term could negatively affect both the environment and human health, if it has not already done so. / Thesis (Ph.D. (Environmental Science))--North-West University, Potchefstroom Campus, 2011.