Previous studies have shown extensive cellular damage can activate poly(ADP-ribose) polymerase-1 (PARP-1) and cause a rapid decrease in the levels of NAD+ and ATP, thereby preventing apoptosis and promoting necrosis and inflammation. The purpose of this study was to extend previous observations that inhibitors of PARP-1 could alter acetaminophen and carbon tetrachloride-induced hepatotoxicity. Bromobenzene (BB) a glutathione dependent hepatotoxicant was tested. Groups of male mice were treated with a single dosage of 112mg/kg (0.075 ml/kg) BB by the intraperitoneal (ip) route. All animals were maintained in a controlled environment and provided food and water ad libitum. This dosage of BB resulted in hepatotoxicity as measured by an increase in serum alanine transferase (ALT). BB treatment resulted in a 5-fold increase in ALT. Moderate hepatotoxicity was detected with this treatment regime. Subsequently, another group of mice were treated with three treatments of nicotinamide at 0.5, 1 and 2 hours following BB treatment. Serum ALT elevations were reduced by 90% at 24 hours following BB and nicotinamide treatments. BB-induced liver pathology was also blocked by nicotinamide. Mortality among BB treated animals was also significantly reduced by nicotinamide treatment. Mortality among mice treated with BB and nicotinamide was near control. The model was verified with a more potent and specific inhibitor, Phen. BB treatment was keep at the same level as in the previous study, and Phen was administered concomitantly. Serum ALT elevations were reduced by 75%. Phen also blocked BB-induced liver pathology. Mortality among mice treated with BB and Phen was reduced 75%. PARP-1 inhibitors appear to alter chemical-induced hepatotoxicity that has either a glutathione dependent or independent mechanism.

We previously observed that postnatal exposure of mice to the procarcinogen 4-aminobiphenyl (ABP) produced liver tumors only in wild-type males, while arylamine N-acetyltransferase deficient males and females of either strain were protected. Others have also observed a sex difference in liver tumors in mice using the procarcinogen diethylnitrosamine (DEN). Reasons for these sex and strain differences are unclear, but differences in acute hepatotoxicity and inflammation may be involved. In this thesis we found that neither ABP nor DEN produced overt hepatotoxicity in postnatally exposed mice, and only DEN caused an increase in levels of the pro-inflammatory cytokine interleukin-6 but was not sex-dependent. The lack of sex difference suggests that sex hormone modulation of inflammation following sexual maturation might favour growth of initiated cells in males. However, the lack of detectable inflammation following ABP exposure may be due to localized responses, or that inflammation may be a DEN-specific effect.

We previously observed that postnatal exposure of mice to the procarcinogen 4-aminobiphenyl (ABP) produced liver tumors only in wild-type males, while arylamine N-acetyltransferase deficient males and females of either strain were protected. Others have also observed a sex difference in liver tumors in mice using the procarcinogen diethylnitrosamine (DEN). Reasons for these sex and strain differences are unclear, but differences in acute hepatotoxicity and inflammation may be involved. In this thesis we found that neither ABP nor DEN produced overt hepatotoxicity in postnatally exposed mice, and only DEN caused an increase in levels of the pro-inflammatory cytokine interleukin-6 but was not sex-dependent. The lack of sex difference suggests that sex hormone modulation of inflammation following sexual maturation might favour growth of initiated cells in males. However, the lack of detectable inflammation following ABP exposure may be due to localized responses, or that inflammation may be a DEN-specific effect.

Black Cohosh (Actaea racemosa) is one of the highest selling medicinal plants, ranking as the sixth best seller in the US in 2015 (Smith et al., 2016). However, this popularity has been tarnished by claims of hepatotoxicity. The investigation of these reports has determined that implicated products did not contain Black Cohosh plant material. Other reports were shown to be incomplete or had other factors contributing. This has led to the suspicion that cases of adverse reactions may in fact be linked to cases of substitution or adulterations with Asian species of Actaea, rather than to A. racemosa. (Jordan et al., 2010). This shows the need for authentication of Black Cohosh products. In this study various DNA based authentication methods were developed. The first, PlantID is capable of discriminating between Actaea racemosa and four potential adulterant species; Actaea cimicifuga, Actaea cordifolia, Actaea podocarpa and Caulophyllum thalictroides, in a single PCR reaction. The resulting fragments are scrutinized using gel electrophoresis. Other platforms of analysis were trialled with little success. The second was a qPCR based method. These assays are competent in detecting A. racemosa, A. cimicifuga and A. dahurica species and are compared to a generic primer capable of amplification of ten Actaea species. This enables the user to detect specific species in comparison to how much Actaea species are present as a whole. This assay was extensively tested on many materials and products available in the UK and the USA. Out of 34 products assessed it was possible to extract DNA from 32. From the UK market it was found that five products contained undeclared species. From the US market it was found that six products contained undeclared species. All of the THR registered products were found to contain only the authentic species Actaea racemosa. This was a reassuring result from the analysis and adds further value to the scheme of THR. Sequence data from GenBank was used to assist in assigning species to sequenced DNA samples. The data contained on GenBank was scrutinised using various bioinformatics tools. Sequences were organised into molecular taxonomic units using tree diagram software. This showed efficiently and iii visually which sequence entries were reliable to use based upon grouping. This analysis showed that the nuclear internal transcribed spacer (nrITS) was an ideal barcoding region and that maturase K (MatK) was a poor choice for Actaea species. To address the issue of hepatotoxicity claims, cultured human hepatocyte derived cells were treated with 60% ethanol extracts of Actaea racemosa and Asian Actaea. A qPCR array was utilised to assess 84 genes associated with hepatotoxicity across various concentrations of extract. The collective array output gave a plethora of data which was analysed using bespoke online software from the manufacturer. Stringent quality controls were included on the arrays which gave confidence of results. There were small changes noted for Actaea racemosa and some activity for the Asian Actaea treated cells was also seen. An LDH and MTT assay were used to assess cell viability and toxicity in two human hepatocyte derived cell lines. Actaea racemosa showed no significant effects whereas the Asian Actaea extract showed a notable decrease in cell viability and significant release of LDH indicating toxicity. The Asian Actaea material used to manufacture extracts was of questionable species origin but determined to be either A. dahurica or A. cimicifuga. The results from these experiments were unfortunately not as conclusive as hoped, but did show some evidence of a more likely culprit of toxicity originating from Asian Actaea species.

Submitted by Ana Maria Fiscina Sampaio (fiscina@bahia.fiocruz.br) on 2013-11-06T17:30:24Z No. of bitstreams: 1 Felipe Miranda Santos Potencial terapeutico das S-nitroglutationa-.pdf: 5390094 bytes, checksum: 048e66640081905e53e87d3353d7c25c (MD5) / Made available in DSpace on 2013-11-06T17:30:24Z (GMT). No. of bitstreams: 1 Felipe Miranda Santos Potencial terapeutico das S-nitroglutationa-.pdf: 5390094 bytes, checksum: 048e66640081905e53e87d3353d7c25c (MD5) Previous issue date: 2012 / Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Farmácia. Salvador, BA, Brasil / A intoxicação pelo paracetamol é a principal causa de insuficiência hepática aguda (IHA) em vários países do ocidente. A hepatotoxicidade é mediada por um metabólito intermediário reativo que depleta as reservas do antioxidante endógeno glutationa (GSH). O tratamento precoce com n-acetilcisteína (NAC) é recomendado para restabelecer a concentração fisiológica de GSH. A snitrosoglutationa (GSNO) é uma molécula antioxidante derivada do GSH capaz de reduzir o estresse oxidativo em diversos sistemas celulares e modelos experimentais. OBJETIVO: Avaliar se GSNO é capaz de reduzir a taxa de mortalidade, extensão da necrose hepática, manifestações bioquímicas e comparar sua eficácia com NAC e GSH no tratamento da IHA experimental induzida por paracetamol. METODOLOGIA: Camundongos isogênicos machos da linhagem C57Bl/6 foram tratados por três semanas com água suplementada com etanol a 10%. Os animais foram divididos em cinco grupos. O grupo 1 (controle negativo) recebeu solução salina 0,9%. Os demais grupos receberam 300 mg/Kg de paracetamol para indução de IHA. Após 3 horas, o grupo 2 (controle positivo) foi tratado com salina tamponada com fosfato (PBS) e os grupos 3, 4 e 5 foram tratados, respectivamente, com 600 Umol/kg de NAC, GSH e GSNO. A eutanásia foi feita 12 horas após a indução de IHA. A extensão da necrose hepática foi avaliada por morfometria através do software IMAGEPRO-PLUS. Os níveis séricos de transaminases e fosfatase alcalina foram avaliados como marcadores bioquímicos de lesão hepática. A taxa de mortalidade foi avaliada em um experimento independente, após uma dose de 350 mg/Kg de paracetamol. RESULTADOS: O tratamento com GSNO 600 Umol/kg aumentou a taxa de sobrevida em relação aos grupos tratados com NAC ou PBS. Entretanto, não houve diferença de mortalidade entre os grupos GSNO e GSH. A avaliação morfométrica revelou menor extensão de necrose hepática nos animais tratados com GSNO em comparação com NAC e PBS. Houve redução de atividade sérica de ALT, mas não de AST no grupo GSNO em comparação com PBS e NAC. Os níveis séricos de fosfatase alcalina, albumina, ureia e creatinina não apresentaram diferenças entre os diversos grupos. CONCLUSÃO: O tratamento com GSNO aumenta a taxa de sobrevida e reduz a extensão de necrose hepática na IHA experimental por paracetamol. O GSNO apresenta eficácia superior à NAC e idêntica ao GSH em dose equimolar. Estes achados sugerem que o efeito protetor do GSNO parece independer da porção nitroso da molécula. Possíveis mecanismos de proteção extra-hepáticos merecem ser investigados / Paracetamol overdose is the main cause of acute liver failure (ALF) in western countries. The hepatotoxicity is mediated by a reactive metabolite that depletes the pool of glutathione (GSH), an endogenous antioxidant molecule. Early treatment with n-acetylcysteine (NAC) is recommended to replenish the pool of GSH. S-nitrosoglutathione (GSNO) is a potent antioxidant molecule that reduces oxidative stress in several cellular systems and experimental models. OBJECTIVE: To evaluate if GSNO reduces the mortality rate, the hepatocelular necrosis extension and to compare its therapeutic efficacy with NAC and GSH in experimental ALF induced by paracetamol. METHODS: Male mice were treated for three weeks with alcohol 10% orally. The animals were divided in five groups. Group 1 (negative control) received saline 0.9%. All the other groups received 300 mg/Kg paracetamol for induction of ALF. After 3 hours, group 2 (positive control) received phosphate buffered saline (PBS) and groups 3, 4 and 5 were treated respectively with 600 Umol/kg of NAC, GSH and GSNO. The animals were sacrificed after 12 hours of induction of ALF. The area of liver necrosis was evaluated by morphometric analysis with the software IMAGEPRO. Transaminases and alkaline phosfatase were determined as markers of liver injury. Mortality rate was evaluated in an independent experiment after a dose of 350 mg/Kg of paracetamol. RESULTS: GSNO treatment (600 Umol/kg) significantly improved the survival rate compared to PBS and NAC treatments. There was no statistical difference in survival rate between GSNO and GSH groups. In addition, GSNO attenuated the area of liver necrosis in comparison to NAC and PBS, but not to GSH. GSNO reduced the serum ALT, but not AST activity in comparison to PBS and NAC. There was no statistical difference in alkaline phosphatase, urea, creatinine and albumin among the groups that received paracetamol. CONCLUSION: GSNO treatment augmented survival rate and reduced the area of liver necrosis in comparison to NAC, but was equally as effective as GSH. These findings suggest that the hepatoprotector effect of GSNO is independent of the nitroso moiety of the molecule. Potential extra-hepatic mechanisms remain to be evaluated.

Introdução: A Insuficiência Hepática Aguda Grave (IHAG) é uma síndrome clínica rara, caracterizada por uma disfunção grave e súbita das células do fígado. A tioacetamida (TAA) é uma hepatotoxina, cuja administração em ratos causa a morte de células hepáticas por necrose centro lobular e promove o aumento da formação de espécies reativas de oxigênio (ERO). A glutamina é um aminoácido precursor para a síntese de glutationa. Objetivo: Avaliar o efeito antioxidante da glutamina em modelo experimental IHAG induzida por TAA em ratos. Métodos: Foram utilizados ratos machos Wistar, divididos em 4 grupos por tempo de avaliação: controle, glutamina (25 mg/kg), tioacetamida (400 mg/kg) e animais que receberam tioacetamida e glutamina. Os animais foram avaliados em 24, 36 e 48 horas. Foi coletado sangue para análises de AST, ALT, FA, BT e CRE e amostras de fígado para avaliar a lipoperoxidação (TBARS), a atividade das enzimas antioxidantes (SOD, GPx, CAT e GST), avaliação histológica e análise imuno-histoquímica de NF-kB, TNF-a e iNOS. Resultados: Os níveis de TBARS e a atividade das enzimas antioxidantes SOD e GST mostraram-se significativamente diminuídos nos animais dos grupos tratados com glutamina quando comparados com os animais dos grupos TAA. A atividade da CAT mostrou-se aumentada nos animais que receberam a glutamina em comparação aos animais dos grupos TAA. A atividade da GPx diminuiu significativamente nos grupos tratados com glutamina quando avaliada em 36 e 48 horas quando comparada com os animais dos grupos TAA, nestes tempos. O dano tecidual e a expressão de NF-kB, TNF-a e iNOS foram significativamente menores nos animais tratados com glutamina. Conclusão: A tioacetamida causa alterações em alguns parâmetros bioquímicos, histológicos e no processo inflamatório, por sua vez a glutamina exerce ação protetora ao fígado dos danos gerados pela tioacetamida no modelo de IHAG. / Introduction: Severe acute liver failure (SALF) is a rare clinical syndrome characterized by severe and sudden dysfunction of liver cells. The administration of the hepatotoxin thioacetamide (TAA) in rats causes the death of liver cells by necrosis and lobular center promotes increased formation of reactive oxygen species (ROS). Glutamine is a precursor for the synthesis of glutathione amino acid. Objective: To evaluate the antioxidant effect of glutamine in IHAG experimental model in rats induced by TAA. Methods: Male Wistar rats were divided into 4 groups by evaluation period: control, glutamine (25 mg / kg), thioacetamide (400 mg / kg) and animals that received thioacetamide and glutamine. Animals were evaluated at 24, 36 and 48 hours. Blood was collected for analysis of AST, ALT, ALP, BT and CRE and liver samples to assess lipid peroxidation (TBARS), the activity of antioxidant enzymes (SOD, GPx, CAT and GST), histological and immunohistochemical analysis NF-kB, iNOS and TNF-a. Results: The levels of TBARS and the activity of antioxidant enzymes SOD and GST were significantly decreased in animals in groups treated with glutamine compared with those for groups TAA. CAT activity was shown to be increased in animals receiving glutamine compared to groups TAA. The GPx activity decreased significantly in the groups treated with glutamine when evaluated at 36 and 48 hours compared with those for groups TAA in these times. The tissue damage and the expression of NF-kB, iNOS and TNF-a were significantly lower in animals treated with glutamine. Conclusion: The thioacetamide causes changes in some biochemical, and histological parameters in the inflammatory process, in turn glutamine exerts protective of the liver damage caused by thioacetamide in IHAG model action.

Introdução: A Insuficiência Hepática Aguda Grave (IHAG) é uma síndrome clínica rara, caracterizada por uma disfunção grave e súbita das células do fígado. A tioacetamida (TAA) é uma hepatotoxina, cuja administração em ratos causa a morte de células hepáticas por necrose centro lobular e promove o aumento da formação de espécies reativas de oxigênio (ERO). A glutamina é um aminoácido precursor para a síntese de glutationa. Objetivo: Avaliar o efeito antioxidante da glutamina em modelo experimental IHAG induzida por TAA em ratos. Métodos: Foram utilizados ratos machos Wistar, divididos em 4 grupos por tempo de avaliação: controle, glutamina (25 mg/kg), tioacetamida (400 mg/kg) e animais que receberam tioacetamida e glutamina. Os animais foram avaliados em 24, 36 e 48 horas. Foi coletado sangue para análises de AST, ALT, FA, BT e CRE e amostras de fígado para avaliar a lipoperoxidação (TBARS), a atividade das enzimas antioxidantes (SOD, GPx, CAT e GST), avaliação histológica e análise imuno-histoquímica de NF-kB, TNF-a e iNOS. Resultados: Os níveis de TBARS e a atividade das enzimas antioxidantes SOD e GST mostraram-se significativamente diminuídos nos animais dos grupos tratados com glutamina quando comparados com os animais dos grupos TAA. A atividade da CAT mostrou-se aumentada nos animais que receberam a glutamina em comparação aos animais dos grupos TAA. A atividade da GPx diminuiu significativamente nos grupos tratados com glutamina quando avaliada em 36 e 48 horas quando comparada com os animais dos grupos TAA, nestes tempos. O dano tecidual e a expressão de NF-kB, TNF-a e iNOS foram significativamente menores nos animais tratados com glutamina. Conclusão: A tioacetamida causa alterações em alguns parâmetros bioquímicos, histológicos e no processo inflamatório, por sua vez a glutamina exerce ação protetora ao fígado dos danos gerados pela tioacetamida no modelo de IHAG. / Introduction: Severe acute liver failure (SALF) is a rare clinical syndrome characterized by severe and sudden dysfunction of liver cells. The administration of the hepatotoxin thioacetamide (TAA) in rats causes the death of liver cells by necrosis and lobular center promotes increased formation of reactive oxygen species (ROS). Glutamine is a precursor for the synthesis of glutathione amino acid. Objective: To evaluate the antioxidant effect of glutamine in IHAG experimental model in rats induced by TAA. Methods: Male Wistar rats were divided into 4 groups by evaluation period: control, glutamine (25 mg / kg), thioacetamide (400 mg / kg) and animals that received thioacetamide and glutamine. Animals were evaluated at 24, 36 and 48 hours. Blood was collected for analysis of AST, ALT, ALP, BT and CRE and liver samples to assess lipid peroxidation (TBARS), the activity of antioxidant enzymes (SOD, GPx, CAT and GST), histological and immunohistochemical analysis NF-kB, iNOS and TNF-a. Results: The levels of TBARS and the activity of antioxidant enzymes SOD and GST were significantly decreased in animals in groups treated with glutamine compared with those for groups TAA. CAT activity was shown to be increased in animals receiving glutamine compared to groups TAA. The GPx activity decreased significantly in the groups treated with glutamine when evaluated at 36 and 48 hours compared with those for groups TAA in these times. The tissue damage and the expression of NF-kB, iNOS and TNF-a were significantly lower in animals treated with glutamine. Conclusion: The thioacetamide causes changes in some biochemical, and histological parameters in the inflammatory process, in turn glutamine exerts protective of the liver damage caused by thioacetamide in IHAG model action.

Introdução: A Insuficiência Hepática Aguda Grave (IHAG) é uma síndrome clínica rara, caracterizada por uma disfunção grave e súbita das células do fígado. A tioacetamida (TAA) é uma hepatotoxina, cuja administração em ratos causa a morte de células hepáticas por necrose centro lobular e promove o aumento da formação de espécies reativas de oxigênio (ERO). A glutamina é um aminoácido precursor para a síntese de glutationa. Objetivo: Avaliar o efeito antioxidante da glutamina em modelo experimental IHAG induzida por TAA em ratos. Métodos: Foram utilizados ratos machos Wistar, divididos em 4 grupos por tempo de avaliação: controle, glutamina (25 mg/kg), tioacetamida (400 mg/kg) e animais que receberam tioacetamida e glutamina. Os animais foram avaliados em 24, 36 e 48 horas. Foi coletado sangue para análises de AST, ALT, FA, BT e CRE e amostras de fígado para avaliar a lipoperoxidação (TBARS), a atividade das enzimas antioxidantes (SOD, GPx, CAT e GST), avaliação histológica e análise imuno-histoquímica de NF-kB, TNF-a e iNOS. Resultados: Os níveis de TBARS e a atividade das enzimas antioxidantes SOD e GST mostraram-se significativamente diminuídos nos animais dos grupos tratados com glutamina quando comparados com os animais dos grupos TAA. A atividade da CAT mostrou-se aumentada nos animais que receberam a glutamina em comparação aos animais dos grupos TAA. A atividade da GPx diminuiu significativamente nos grupos tratados com glutamina quando avaliada em 36 e 48 horas quando comparada com os animais dos grupos TAA, nestes tempos. O dano tecidual e a expressão de NF-kB, TNF-a e iNOS foram significativamente menores nos animais tratados com glutamina. Conclusão: A tioacetamida causa alterações em alguns parâmetros bioquímicos, histológicos e no processo inflamatório, por sua vez a glutamina exerce ação protetora ao fígado dos danos gerados pela tioacetamida no modelo de IHAG. / Introduction: Severe acute liver failure (SALF) is a rare clinical syndrome characterized by severe and sudden dysfunction of liver cells. The administration of the hepatotoxin thioacetamide (TAA) in rats causes the death of liver cells by necrosis and lobular center promotes increased formation of reactive oxygen species (ROS). Glutamine is a precursor for the synthesis of glutathione amino acid. Objective: To evaluate the antioxidant effect of glutamine in IHAG experimental model in rats induced by TAA. Methods: Male Wistar rats were divided into 4 groups by evaluation period: control, glutamine (25 mg / kg), thioacetamide (400 mg / kg) and animals that received thioacetamide and glutamine. Animals were evaluated at 24, 36 and 48 hours. Blood was collected for analysis of AST, ALT, ALP, BT and CRE and liver samples to assess lipid peroxidation (TBARS), the activity of antioxidant enzymes (SOD, GPx, CAT and GST), histological and immunohistochemical analysis NF-kB, iNOS and TNF-a. Results: The levels of TBARS and the activity of antioxidant enzymes SOD and GST were significantly decreased in animals in groups treated with glutamine compared with those for groups TAA. CAT activity was shown to be increased in animals receiving glutamine compared to groups TAA. The GPx activity decreased significantly in the groups treated with glutamine when evaluated at 36 and 48 hours compared with those for groups TAA in these times. The tissue damage and the expression of NF-kB, iNOS and TNF-a were significantly lower in animals treated with glutamine. Conclusion: The thioacetamide causes changes in some biochemical, and histological parameters in the inflammatory process, in turn glutamine exerts protective of the liver damage caused by thioacetamide in IHAG model action.

Made available in DSpace on 2018-06-27T18:56:38Z (GMT). No. of bitstreams: 2 Delita Vania Bock Almeida.pdf: 1328786 bytes, checksum: 2c33bf461a3b3566365bb92e30e6826b (MD5) Delita Vania Bock Almeida.pdf.jpg: 3645 bytes, checksum: 646c02170c5e61727474716ed25b1fb7 (MD5) Previous issue date: 2012-03-30 / Carbon nanotubes are among the most promising nanomaterials with special features for use both as biomedical engineering. Several studies on the toxicity and feasibility are performed to assess its application in humans for delivery of drugs. In this study, we performed the evaluation of the hepatotoxic effect of carbon nanotubes multi-wall (MWCNT) by biochemical markers (albumin (ALB), total protein (TP), transaminases (ALT / AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH)) after administration via the intraperitoneal and intragastric in female mice at a dose of 1.5 mg / kg suspended in saline. Blood samples were analyzed one day, 7 and 30 days after treatment with MWCNT. The results after intraperitoneal administration showed a rise in serum total protein after 1 and 7 days. Serum albumin showed an increase in concentration after 7 days and 30 days after reduction. The activity of ALT levels increased only after 1 day, whereas the activity of AST showed an increase after 7 and 30 days. The LDH activity also increased significantly after 7 and 30 days. The FAL showed an increase in its activity after 1 and 7 days and a reduction after 30 days. The results obtained after intragastric administration of MWCNT showed an increase in serum total protein after 7 days and 30 days after reduction. Albumin did not show significant variations. The ALT activity increased significantly after 1 day and a reduction after 30 days. AST activity showed no significant differences in this way. The activity of LDH showed an increase after 7 days, no significant difference after 1 day and 30 days. The activity of ALP showed an increase after only one day. Serum albumin and total protein indicate an acute inflammatory process by both intraperitoneal and through activities of liver enzymes intragastric. As intraperitoneally showed severe liver injury while intragastrically showed mild reversible liver damage. / Nanotubos de carbono estão entre os nanomateriais mais promissores, com características especiais tanto para uso biomédico quanto para engenharia. Vários estudos sobre a sua toxicidade e viabilidade são realizados para avaliar sua aplicação em seres humanos para entrega de fármacos. Neste estudo, realizamos a avaliação do efeito hepatotóxico de nanotubos de carbono de parede múltipla (NTCPM) através de marcadores bioquímicos albumina (ALB), proteínas totais (PT), transaminases (ALT/AST), fosfatase alcalina (FAL), lactato desidrogenase (LDH)), após administração via intraperitoneal e via intragástrica em camundongos fêmeas na dose de 1,5mg/Kg suspensos em solução salina. As amostras de sangue foram analisadas 1 dia, 7 e 30 dias após o tratamento com NTCPM. Os resultados obtidos após administração intraperitoneal demonstraram uma elevação na concentração sérica de proteínas totais após 1 e 7dias. A albumina sérica apresentou um aumento na sua concentração após 7 dias e uma redução após 30 dias. A atividade de ALT apresentou aumento somente após 1 dia, enquanto que a atividade da AST apresentou aumento após 7 e 30 dias. A atividade de LDH também apresentou um aumento significativo após 7 e 30 dias. A FAL apresentou aumento em sua atividade após 1 e 7 dias e uma redução após 30 dias. Os resultados obtidos após a administração via intragástrica de NTCPM apresentaram um aumento na concentração sérica de proteínas totais após 7dias e uma redução após 30 dias. A albumina não apresentou variações significativas. A atividade de ALT apresentou um aumento significativo após 1 dia e uma redução após 30 dias. A atividade da AST não apresentou diferenças consideráveis por esta via. A atividade de LDH apresentou um aumento após 7dias, não apresentando diferença após 1 dia e 30 dias. A atividade da FAL apenas apresentou aumento após 1 dia. Os valores séricos de albumina e proteínas totais indicam um processo inflamatório agudo tanto pela via intraperitoneal quanto pela via intragástrica.As atividades das enzimas hepáticas por via intraperitoneal indicaram lesão hepática grave enquanto que por via intragástrica indicaram lesão hepática leve reversível.

Submitted by MARCIA ROVADOSCHI (marciar@unifra.br) on 2018-08-16T17:15:53Z No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Dissertacao_DelitaVaniaBockAlmeida.pdf: 1331570 bytes, checksum: e3f48f82f1362d8c3eeda21314c80887 (MD5) / Made available in DSpace on 2018-08-16T17:15:53Z (GMT). No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Dissertacao_DelitaVaniaBockAlmeida.pdf: 1331570 bytes, checksum: e3f48f82f1362d8c3eeda21314c80887 (MD5) Previous issue date: 2012-03-30 / Carbon nanotubes are among the most promising nanomaterials with special features for use both as biomedical engineering. Several studies on the toxicity and feasibility are performed to assess its application in humans for delivery of drugs. In this study, we performed the evaluation of the hepatotoxic effect of carbon nanotubes multi-wall (MWCNT) by biochemical markers (albumin (ALB), total protein (TP), transaminases (ALT / AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH)) after administration via the intraperitoneal and intragastric in female mice at a dose of 1.5 mg / kg suspended in saline. Blood samples were analyzed one day, 7 and 30 days after treatment with MWCNT. The results after intraperitoneal administration showed a rise in serum total protein after 1 and 7 days. Serum albumin showed an increase in concentration after 7 days and 30 days after reduction. The activity of ALT levels increased only after 1 day, whereas the activity of AST showed an increase after 7 and 30 days. The LDH activity also increased significantly after 7 and 30 days. The FAL showed an increase in its activity after 1 and 7 days and a reduction after 30 days. The results obtained after intragastric administration of MWCNT showed an increase in serum total protein after 7 days and 30 days after reduction. Albumin did not show significant variations. The ALT activity increased significantly after 1 day and a reduction after 30 days. AST activity showed no significant differences in this way. The activity of LDH showed an increase after 7 days, no significant difference after 1 day and 30 days. The activity of ALP showed an increase after only one day. Serum albumin and total protein indicate an acute inflammatory process by both intraperitoneal and through activities of liver enzymes intragastric. As intraperitoneally showed severe liver injury while intragastrically showed mild reversible liver damage. / Nanotubos de carbono estão entre os nanomateriais mais promissores, com características especiais tanto para uso biomédico quanto para engenharia. Vários estudos sobre a sua toxicidade e viabilidade são realizados para avaliar sua aplicação em seres humanos para entrega de fármacos. Neste estudo, realizamos a avaliação do efeito hepatotóxico de nanotubos de carbono de parede múltipla (NTCPM) através de marcadores bioquímicos albumina (ALB), proteínas totais (PT), transaminases (ALT/AST), fosfatase alcalina (FAL), lactato desidrogenase (LDH)), após administração via intraperitoneal e via intragástrica em camundongos fêmeas na dose de 1,5mg/Kg suspensos em solução salina. As amostras de sangue foram analisadas 1 dia, 7 e 30 dias após o tratamento com NTCPM. Os resultados obtidos após administração intraperitoneal demonstraram uma elevação na concentração sérica de proteínas totais após 1 e 7dias. A albumina sérica apresentou um aumento na sua concentração após 7 dias e uma redução após 30 dias. A atividade de ALT apresentou aumento somente após 1 dia, enquanto que a atividade da AST apresentou aumento após 7 e 30 dias. A atividade de LDH também apresentou um aumento significativo após 7 e 30 dias. A FAL apresentou aumento em sua atividade após 1 e 7 dias e uma redução após 30 dias. Os resultados obtidos após a administração via intragástrica de NTCPM apresentaram um aumento na concentração sérica de proteínas totais após 7dias e uma redução após 30 dias. A albumina não apresentou variações significativas. A atividade de ALT apresentou um aumento significativo após 1 dia e uma redução após 30 dias. A atividade da AST não apresentou diferenças consideráveis por esta via. A atividade de LDH apresentou um aumento após 7dias, não apresentando diferença após 1 dia e 30 dias. A atividade da FAL apenas apresentou aumento após 1 dia. Os valores séricos de albumina e proteínas totais indicam um processo inflamatório agudo tanto pela via intraperitoneal quanto pela via intragástrica.As atividades das enzimas hepáticas por via intraperitoneal indicaram lesão hepática grave enquanto que por via intragástrica indicaram lesão hepática leve reversível.