Estudo experimental da exposição ao PCB126 sobre a indução de Diabetes mellitus tipo II / Experimental study of PCB126 exposure on induction of Diabetes mellitus type II

A exposição ambiental aos poluentes orgânicos persistentes tem recebido amplo destaque na literatura recentemente devido à extensa associação entre o desenvolvimento de doenças metabólicas, obesidade e/ou diabetes mellitus, e a presença destes poluentes, principalmente os organoclorados, como as bifenilas policloradas (PCBs), no organismo. Por outro lado, os mecanismos de ação destes poluentes é controverso devido à elevada quantidade de representantes destas classes, gerando diversidade de protocolos de exposição e escassez de estudos experimentais. Por isto, foi objetivo deste trabalho elucidar os mecanismos de ação tóxica do PCB126, nas doses de 0,1; 1 ou 10 µg/kg de massa corpórea, em ratos Wistar machos, durante quinze dias, expostos por instilação intranasal. O procotolo de exposição empregado foi caracterizado e considerado suficiente para causar toxicidade, uma vez que foram observadas alterações no sistema imune, metabolismo e em parâmetros relacionados à gênese do diabetes mellitus. A caracterização da exposição foi determinada pela quantificação da concentração de PCB126 no fígado e pulmão (CG/MS) e pelo aumento da expressão do receptor aril hidrocarboneto (AhR) no rim, fígado, pulmão e tecido adiposo (Western Blot). O efeito imunossupressor do PCB126 foi evidenciado pelo comprometimento da produção de células na medula óssea e, consequentemente, no número de células totais no sangue circulante. Adicionalmente, foi evidenciada a interferência do poluente na via de ativação mediada por receptores acoplados à proteína G (GPCRs), principalmente em neutrófilos, alterando importantes funções destas células, como a expressão de moléculas de adesão, geração de espécies reativas de oxigênio e migração. Entre as alterações metabólicas observadas, destacamos o aumento dos níveis de triglicerídeos e colesterol sérico, aumento da liberação de ácidos graxos livres; aumento da atividade da enzima hepática gama glutamil transferase; aumento da resistência à insulina e aumento da geração de óxido nítrico pelas ilhotas de Langerhans, dados estes, possivelmente relacionados ao comprometimento das células beta (ß) pancreáticas, confirmados pelo aumento da expressão de GLUT4 no tecido adiposo, aumento da concentração de insulina sérica e aumento do estresse oxidativo nas ilhotas de Langerhans. Em conjunto, os dados obtidos destacam importantes alterações causadas pela exposição intranasal ao PCB126, evidenciando a participação do poluente na gênese do diabetes mellitus do tipo II

The environmental exposure to persistent organic pollutants has been widely highlighted in recent literature due to the extensive association between the development of metabolic diseases, obesity and/or diabetes mellitus, and presence of these pollutants, especially organochlorines such as polychlorinated biphenyls (PCBs) in organism. Moreover, the mechanisms of action of these pollutants are controversial due to the high number of PCBs congeners, diversity of exposure protocols and lack of experimental studies. Therefore, the aim of this study was to elucidate the mechanisms of PCB126's toxic action at doses of 0.1; 1 or 10 µg/kg body weight in male Wistar rats exposed by intranasal instillation for 15 days. The established exposure procotol was characterized and considered sufficient to cause toxicity since changes were observed in the immune system, metabolism and in parameters related to the pathogenesis of diabetes mellitus. Characterization of exposure was determined by quantifying the concentration of PCB126 in liver and lung (GC-MS) and by the increased expression of aryl hydrocarbon receptor (AhR) in kidney, liver, lung, and adipose tissue (Western blot). The immunosuppressive effect of PCB126 was evidenced by impairment of cell production in the bone marrow and thus the total number of cells in the circulation. In addition, the interference of the pollutant in the activation pathway mediated by G-protein coupled receptors (GPCRs), in particular in neutrophils, was observed by changing important functions of these cells such as the expression of adhesion molecules, reactive oxygen species generation, and migration. Among the metabolic changes observed, we highlight the increased levels of triglycerides and serum cholesterol, increased release of free fatty acids; increased gamma glutamyl transferase hepatic enzyme activity; increased insulin resistance and increased generation of nitric oxide by the islets of Langerhans, these data possibly related to the impairment of beta cells (ß) pancreatic function, suggested by the increased expression of GLUT4 in adipose tissue, increased serum insulin concentration and increased oxidative stress in the islets of Langerhans. Altogether, these results highlight important changes caused by intranasal exposure to PCB126, suggesting participation of the pollutant in the genesis of diabetes mellitus type II

Diplomado en toxicología ambiental, microbiología y química sanitaria a distancia: opción de superación profesional / Masterliness on environmental toxicology, microbiology, and distant health chemistry: an option of professional excelling

La actualización de los recursos humanos en el campo de la salud ambiental en Cuba es una necesidad. El diplomado que se propone posibilita el desarrollo de competencias y habilidades en temáticas utilizadas en las funciones laborales de quienes optan por esta modalidad de superación profesional. El Diplomado en Toxicología Ambiental, Microbiología y Química Sanitaria constituye una contribución en la búsqueda de la excelencia en la gestión de los laboratorios de ensayo de muestras ambientales en el país. El diseño curricular elaborado está acorde con los objetivos propuestos para el perfil del egresado y se caracteriza por la actualización en los temas tratados y la inserción de lecturas complementarias que apoyan el estudio independiente del diplomante. La modalidad a distancia le concede al diplomado un valor de generalización del conocimiento amplio en estas ramas del saber, por la capacidad de acceso a través de las redes telemáticas del país.

Updating of human resources in the environmental health field in Cuba is a need. Masterliness proposed allows the development of competences and abilities in the subjects used in labour tasks of those opting by this modality of professional excelling. Masterliness in Environmental Toxicology, Microbiology, and Health Chemistry is a contribution in search of excellence in management of laboratories of environmental samples assays in our country. Curriculum design elaborated is in agreement to objectives proposed for graduate profile and it is characterized by the updating of the subjects discussed, and the insertion of complementary readings supporting the independent study of diplomate. Distant modality allows to student to value the generalization of extensive wisdom in these branches of knowledge by access ability through telematic networks of the country.

Evaluación de los efectos tóxicos y concentración letal 50 del surfactante Cosmoflux® 411F sobre juveniles de cachama blanca (Piaractus brachypomus) / Assessment of toxic effects and lethal concentration 50 of surfactant Cosmoflux® 411F on juveniles of cachama blanca (Piaractus brachypomus)

En Colombia, el surfactante Cosmoflux® 411F es usado en fumigaciones de cultivos ilícitos para mejorar la efectividad del glifosato. El uso del Cosmoflux® 411F no está soportado por estudios toxicológicos. Los objetivos del presente trabajo fueron determinar las lesiones anatomopatológicas derivadas de la exposición al Cosmoflux® 411F y establecer la concentración letal 50 (CL50) a 96 horas en cachama blanca (Piaractus brachypomus). Se utilizaron juveniles de cachama blanca (40 g) en dos experimentos: 1) toxicidad subletal (n =126) y, 2) determinación de la CL50 (n =84). Las concentraciones del ensayo de toxicidad subletal fueron: 0 mg/l (Tratamiento 0), 0.17 mg/l (Tratamiento 1), 0.34 mg/l (Tratamiento 2), 0.68 mg/l (Tratamiento 3), 1.36 mg/l (Tratamiento 4), y 2.72 mg/l (Tratamiento 5), en sistema semiestático. Para determinar la CL50 las dosis fueron: 3000, 3450, 3900, 4350 y 4800 mg/l de Cosmoflux® 411F. La CL50 obtenida fue de 4417.99 mg/l. En los peces se evidenció leve disminución de la actividad de nado. A la necropsia se halló palidez del hígado y acumulación de material mucoso en las branquias. Por histopatología se halló: vacuolización de hepatocitos, hiperplasia de células epiteliales, de cloro y caliciformes branquiales, vacuolización de enterocitos, aumento de centros melanomacrófagos renales, gliosis, degeneración neuronal e infiltración de células granulares eosinofílicas/células mastocitos en telencéfalo. Los hallazgos concuerdan con lo reportado en peces expuestos a surfactantes, exceptuando las lesiones del sistema nervioso central que pueden tener consecuencias sobre interacciones sociales, de alimentación y reproducción de la especie; siendo necesario profundizar la investigación sobre dicho efecto. El hígado, branquias y piel constituyen órganos blanco de la acción tóxica. La CL50 hallada (4417.99 mg/l) es alta comparada con lo reportado en surfactantes no-iónicos.

In Colombia, surfactant Cosmoflux® 411F is used for the fumigation of illicit crops in order to improve the glyphosate herbicide activity. The use of Cosmoflux® 411F is not supported by toxicological surveys. The aims of this study were to determinate the anatomopathological lesions due to the exposure to Cosmoflux® 411F and to establish lethal concentration 50 (LC50) to 96 hours in cachama blanca (Piaractus brachypomus). Juveniles of cachama blanca (40 g) in two assays were used: 1) sublethal toxicity (n= 126) and 2) determination of LC50 (n=84). Sublethal toxicity assay concentrations were: 0 mg/l (Treatment 0) 0.17 mg/l (Treatment 1), 0.34 mg/l (Treatment 2), 0.68 mg/l (Treatment 3), 1.36 mg/l (Treatment 4), and 2.72 mg/l (Treatment 5); through semi-static system. For the determination of LC50 of Cosmoflux® 411F 3000, 3450, 3900, 4350 y 4800 mg/l concentrations were used. LC50 was 4417.99 mg/l. Animals showed slight decrease in swimming activity. At necropsy examination were found paleness in liver and whitish material accumulation in top of gill filament. Histopathologically, it was found fatty degeneration and hepatocyte vacuolization, epithelial cells, chloride cells and mucous cells hyperplasia, enterocyte vacuolization, increase in the expression of melanomacrophage centres in kidney, gliosis, neuronal degeneration and infiltration of eosinophilic granule cells/mast cells in telencephalon. With exception of central nervous system lesions, the findings are according to the reported in literature about surfactant exposure in fish. Central nervous system effects can have consequences on feeding, reproductive and social interactions, due to close telencephalon/olfactory system relationship, being necessary to deep in research to these processes. In same way, liver, gills and skin are target organs of toxic action of this xenobiotic. LC50 is high (4417.99 mg/l) compared with that reported for other nonionic surfactants.

A técnica de Blue rayon in situ associada ao teste de Salmonella/microssoma como estratégia para o monitoramento de águas estuarinas quanto à presença de compostos policíclicos genotóxicos / Blue rayon anchored technique in situ associated with Salmonella/microsome assay as a strategy for estuary waters monitoring in relation to the presence of genotoxins polycyclics compounds

O estuário de Santos abriga o maior porto da América Latina e um dos maiores complexos industriais do Brasil. Na década de 1970 foi considerado um dos maiores exemplos de degradação ambiental em ambientes costeiros, e apesar da melhora na qualidade ambiental observada nos últimos anos algumas áreas deste estuário apresentam sedimentos ainda altamente contaminados com compostos tóxicos e genotóxicos, especialmente os Hidrocarbonetos Policíclicos Aromáticos (HPA). Operações de dragagem para manutenção das atividades portuárias são necessárias e consequentemente durante este processo pode ocorrer a ressuspensão de contaminantes presentes nesses sedimentos, tornando-os disponíveis novamente na coluna d'água. Desta forma é interessante ter uma estratégia eficiente e aplicável no monitoramento da qualidade dessas águas...

Santos estuary is the major Latin American harbor and one of the largest industrial complex of Brazil. In the 1970s, it was considered one of the major examples of coastal degradation. Due to enforcement actions the quality of the environment has improved in the last years in relation to the chemical parameters and toxicity but unfortunately the sediment is still contaminated with toxic and genotoxic compounds especially Polycyclic Aromatic Hydrocarbons (PAHs). For the maintenance of the port activities sediment dredging is needed and during this process contaminants resuspension can occur, leading to the contamination of the water column. Therefore it is interesting to have an efficient strategy that can be used for the water quality monitoring of this area. The Blue rayon is a selective adsorbent to polycyclic compounds containing three or more fused rings and has been successfully used in the monitoring of PAHs and mutagenic activity in aquatic environments. The objective of this work was to evaluate a modified blue rayon hanging technique, denominated in this work "Blue rayon anchored technique", where the fibers are placed at a fixed distance from the sediment, associated with the Salmonella/microsome microsuspension assay in order to monitor the water quality of Santos estuary. Three sites with different sources and sediment contamination levels were selected in this study. Two initial samplings were performed in order to evaluate the efficiency of the BR modified technique and find the most sensitive strain of Salmonella typhimurium to the mutagens possibly present in the those waters as well as verify the presence of PAHs. Five subsequent samplings were performed to verify the performance and efficiency of the defined strategy in the estuary water quality monitoring using dose response experiments. In the two initial samplings, the water from the site containing the most contaminated sediment and under influence of COSIPA (site 1) presented higher mutagenic activity and higher levels of PAHs. It was also possible to verify the highest sensitivity of the YG1041 strain in the detection of the mutagenic activity in both sites analyzed. In the subsequent five samplings, higher mutagenic potencies were again observed for site 1, reaching 5,100 and 36,000 revertants per gram of BR for the YG1 041 strain in the absence and presence of S9 respectively. Sites 2 and: presented similar potencies, around 1000 revertants per gram of BR. Based on the obtained results we can conclude that the Blue rayon anchored technique associated with the Salmonella/microsome microsuspension assay with the YG1041 strain in the presence and absence of S9 is an suitable tool to monito Santos estuarine waters.