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Previous issue date: 2014-01-02 / Paraquat (PQ) is an agrochemical agent commonly used worldwide, which is allied to potential risks of intoxication. This herbicide induces the formation of reactive oxygen species (ROS) that ends up compromising various organs, particularly the lungs (by the polyamine uptake system), and the brain (by dopaminergic neuronal cell loss). This study evaluated the deleterious effects of paraquat on the central nervous system (CNS) (changes in physiologic parameters, nociceptive responses, locomotor activity and motor coordination, and expression profile of some inflammatory markers), or peripherally (inflammatory cells in the blood and lungs), with special attempts to assess the putative protective effects of the selective CXCR2 receptor antagonist SB225002 on these parameters. PQ-toxicity was induced in male Wistar rats, in a total dose of 50 mg/kg, given by the intraperitoneal (i.p.) route (10 mg/kg each three days). Control animals received saline solution (10 ml/kg) at the same schedule of administration. Separate groups of animals were treated with the selective CXCR2 antagonist SB225002 (1 or 3 mg/kg, i.p.), administered 30 min before each paraquat injection. The major changes found in paraquat-treated animals were: decreased body weight and hypothermia, nociception behavior, impairment of locomotor and gait capabilities, enhanced TNF-α and IL-1β expression in the striatum, and cell migration to the lungs and blood. Some of these parameters were reversed when the antagonist SB225002 was administered, including recovery of physiological parameters, decreased nociception, improvement of gait abnormalities, modulation of striatal TNF-α and IL-1β expression, and decrease of neutrophil migration to the lungs and blood. Taken together, our results demonstrate that damage to the central and peripheral systems elicited by paraquat can be prevented by the pharmacological inhibition of CXCR2 chemokine receptors. The experimental evidence presented herein extends the comprehension on the toxicodynamic aspects of paraquat, and opens new avenues to treat intoxication induced by this herbicide. / O paraquat (PQ) ? um composto qu?mico bastante utilizado no mundo, o qual ? aliado a potenciais riscos de intoxica??o. Este herbicida induz a forma??o de esp?cies reativas de oxig?nio (ROS) que podem comprometer v?rios ?rg?os, especialmente os pulm?es (atrav?s da recapta??o de poliaminas), e o c?rebro (pela perda de neur?nios dopamin?rgicos). Este trabalho avaliou os efeitos delet?rios do paraquat frente ao Sistema Nervoso Central (SNC) (como mudan?as nos par?metros fisiol?gicos, respostas nociceptivas, atividade locomotora e coordena??o motora, e o perfil de express?o de alguns marcadores moleculares de inflama??o), e perif?rico (como c?lulas inflamat?rias no sangue e pulm?es), com o objetivo de avaliar o poss?vel papel protetor do antagonista de receptores de quimiocinas CXCR2, o SB225002, nestes par?metros. A toxicidade ao paraquat foi induzida em ratos machos Wistar, em uma dose total de 50 mg/kg, administrada intraperitonealmente (i.p.) (10 mg/kg a cada tr?s dias). Animais do grupo controle receberam solu??o salina (10 ml/kg) no mesmo protocolo de administra??o. Diferentes grupos de animais foram tratados com o antagonista SB225002 (1 ou 3 mg/kg, i.p.), administrado 30 minutos antes de cada aplica??o do paraquat. As prinicpais mudan?as encontradas nos animais tratados com paraquat foram: diminui??o do peso corporal e hipotermia, aumento da resposta nociceptiva, diminui??o da capacidade de marcha e locomo??o, aumento da express?o de TNF-α e IL-1β no estriado, e a migra??o de c?lulas inflamat?rias no sangue e pulm?es. Alguns destes par?metros foram revertidos quando administrado o antagonista SB225002, como recupera??o dos par?metros fisiol?gicos, diminui??o da nocicep??o, melhora na atividade de marcha, modula??o da express?o estriatal de TNF-α e IL-1β, e diminui??o da migra??o neutrof?lica para o sangue e pulm?es. Em conjunto, nossos resultados demonstram que os danos causados pelo paraquat ao sistema central e perif?rico podem ser prevenidos atrav?s da inibi??o farmacol?gica dos receptores de quimiocinas CXCR2. A evid?ncia experimental aqui apresentada extende a compreens?o dos efeitos toxicodin?micos do paraquat, e proporciona novas possibilidades para tratar a intoxica??o causada por este herbicida.
| Identifer | oai:union.ndltd.org:IBICT/oai:tede2.pucrs.br:tede/1758 |
| Date | 02 January 2014 |
| Creators | Costa, Kesiane Mayra da |
| Contributors | Bogo, Maur?cio Reis |
| Publisher | Pontif?cia Universidade Cat?lica do Rio Grande do Sul, Programa de P?s-Gradua??o em Medicina e Ci?ncias da Sa?de, PUCRS, BR, Faculdade de Medicina |
| Source Sets | IBICT Brazilian ETDs |
| Language | Portuguese |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/masterThesis |
| Format | application/pdf |
| Source | reponame:Biblioteca Digital de Teses e Dissertações da PUC_RS, instname:Pontifícia Universidade Católica do Rio Grande do Sul, instacron:PUC_RS |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 7620745074616285884, 500, 600, -8624664729441623247 |
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