Teses em Neurociências e Biologia Celular (Doutorado) - PPGNBC/ICB

URI Permanente para esta coleçãohttps://repositorio.ufpa.br/handle/2011/2390

O Doutorado Acadêmico pertence ao Programa de Pós-Graduação em Neurociências e Biologia Celular (PPGNBC) do Instituto de Ciências Biológicas (ICB) da Universidade Federal do Pará (UFPA).

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    Toxicidade in vitro e in vivo do ortobenzamol, análogo do paracetamol
    (Universidade Federal do Pará, 2014-01-23) QUEIROZ, Luana Melo Diogo de; CRESPO LÓPEZ, Maria Elena; http://lattes.cnpq.br/9900144256348265
    Paracetamol (PAR) is the non-prescription medicine most used worldwide. However, high doses of PAR produce hepatic and/or renal toxicity. In order to minimize the toxicity of PAR and get better analgesic and anti-inflammatory activity, a previous study conducted by modifying the chemical structure of PAR through molecular modeling, gave rise to ortobenzamol (OBZ) – analog of PAR. Thus, the OBZ was synthesized and evaluated in models of nociception and inflammation in animals. The study showed central analgesic activity of OBZ, with superior potency when compared to PAR. In addition, tests showed a significant inhibition in the inflammatory process. However, to the OBZ be able to be considered as an important new therapeutic option for the treatment of pain and/or inflammation is necessary to determine its toxicity. Given that, this study aimed to evaluate the toxicity in vitro and in vivo OBZ and compare it with the PAR. For this purpose, in vitro neurotoxicity was evaluated in primary cultures of cortical neurons through cell viability assays, determination of the levels of total and reduced glutathione, as well as the possible neuroprotective capacity against oxidative stress. In vivo studies were performed in mice, initiated by determining the median effective dose (ED50) of PAR in order to compare it with the OBZ at toxicity models studied. It was determined the liver and brain oxidative stress by analyzing the levels of lipid peroxidation and nitrites. The possible hepatic and renal dysfunction was determined by analyzing plasma enzymes aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyl transferase (GGT) levels and creatinine in the blood. We evaluated changes in clinical parameters through the CBC, WBC and platelet parameters and was held to determine the acute toxicity. The results of this study showed that in the tested doses, ortobenzamol is safer than paracetamol. The ortobenzamol displayed absence of neurotoxicity, less hepatotoxic and hematotoxic potential, absence of nephrotoxicity and also was rated as a xenobiotic with low toxicity after evaluation of acute toxicity. Therefore, the ortobenzamol can be considered as a safer alternative to the treatment of pain and inflammation when compared to paracetamol.
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