CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / O uso clÃnico de indometacina, embora eficaz na supressÃo da dor, febre e inflamaÃÃo, à frequentemente associado a efeitos deletÃrios sobre o sistema gastrointestinal, hematolÃgico e renal, que limitam o seu uso terapÃutico. Este estudo analisou se a talidomida poderia reduzir a letalidade induzida pela indometacina e as alteraÃÃes hematolÃgicas e bioquÃmicas no sangue, os danos intestinais, alÃm do efeito da talidomida sobre o epitÃlio intestinal e o aumento nos nÃveis de fibrinogÃnio plasmÃtico induzido pela indometacina em ratos. Os ratos foram tratados com indometacina (5,0 mg/kg), talidomida 100,0 mg/kg e 200,0 mg/kg, e ampicilina (200,0 mg/kg), via oral, num perÃodo de cinco dias. Os animais foram submetidos à coleta de sangue no quinto dia de tratamento, mediante a punÃÃo do plexo-orbital do olho. Os parÃmetros estudados foram: eritrograma, contagem de leucÃcitos, tempo de protrombina (TP), tempo de tromboplastina parcial ativada (TTPA), fibrinogÃnio, contagem de plaquetas, cultura do lavado peritoneal e dosagem de mieloperoxidase (MPO) nesse lavado, avaliaÃÃo hepÃtica (ALT, AST, FA, GGT) e glicose. Os resultados do TP, TTPA, antitrombina, contagem de plaquetas, mantiveram-se normais em relaÃÃo ao grupo controle. Nos animais tratados com indometacina, observamos um aumento (p <0,001) nos nÃveis de fibrinogÃnio (637,50Â13,19 mg/dL) sendo o mesmo revertido pelo tratamento com talidomida 100,0 mg/kg e 200,0 mg/kg, (381,80  50,79 mg/dL; 389,30 65,13 mg/dL) respectivamente. Os animais que receberam indometacina apresentaram positividade em 100% das culturas realizadas para enterobactÃrias, demonstrando assim a presenÃa de bactÃrias do trato gastrintestinal na cavidade peritoneal. A atividade da MPO no lÃquido peritoneal dos ratos que receberam indometacina (5,0 mg/kg, v.o, 5d) foi significativamente maior (1217  341,4 U/mL) quando comparada com o grupo-controle (3,33  3,33 U/mL). O tratamento com talidomida (100 e 200 mg / kg, v.o, 5d) reduziu significativamente (p <0,05) este aumento (375,8  149,1 U/ mL), sendo a inibiÃÃo de 69,2%. Os resultados demonstram que a lesÃo intestinal inflamatÃria induzida pela indometacina foi revertida parcialmente pelo tratamento com a talidomida. AlÃm disso, os dados obtidos evidenciam o efeito hepatoprotetor da talidomida contra a indometacina, provavelmente por sua atividade antiinflamatÃria diminuindo ou minimizando o aumento do fibrinogÃnio e recrutamento leucocitÃrio no ambiente hepÃtico. / The clinical use of indomethacin, although effective in suppressing pain, fever and inflammation is often associated with deleterious effects for the gastrointestinal system, and hematological and renal functions, which limit its therapeutic use. This study examined in rats whether thalidomide could reduced the lethality induced by indomethacin and hematological, biochemical, blood, and intestinal damage. This study analyzed the effect of thalidomide on the intestinal epithelium and increased levels of plasma fibrinogen induced by indomethacin in rats. The rats were treated with indomethacin (5.0 mg / kg), thalidomide 100.0 mg / kg or 200.0 mg / kg, and ampicillin (200.0 mg / kg) orally over a period of 5 days. The animals were submitted to blood collection on the fifth day of treatment by puncturing the orbital plexus of the eye, after being anesthetized with ether. The blood was placed in tubes containing anticoagulant, EDTA, sodium citrate and 3.8% in tubes without anticoagulant. The parameters studied were: erythrogram, leukocyte count, prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen, platelet count, and culture of peritoneal lavage, measurement of MPO and evaluation of liver function (ALT, AST, FA, GGT and glucose). The results of the PT, APTT, antithrombin, platelet counts remained normal in the control group. In animals treated with indomethacin, we observed a significant increase (p <0.001) in fibrinogen levels (637.50  13.19 mg / dL) and this increase reversed by treatment with thalidomide 100.0 mg / kg or 200.0 mg / kg, (381.80  50.79 mg / dL, 389.30  65.13 mg / dL, respectively). Animals that received indomethacin were positive in 100% of the cultures performed for enterobacteria, thus demonstrating the presence of bacteria in the gastrointestinal tract into the peritoneal cavity, probably due to a drug-induced intestinal perforation. The MPO activity in peritoneal fluid of rats given indomethacin (5.0 mg / kg, po, 5d) was significantly higher (1217  341.4 U / mL) compared with the control group (3.33  3, 33 U / mL). Treatment with thalidomide (100 or 200 mg / kg, vo, 5d) significantly reversed this effect (p <0.05), (375.8  149.1 U / mL). As inhibition of 69.2%. The results showed that inflammatory intestinal injury in rats induced by indomethacin was partially reversed by treatment with thalidomide. In addition, the data showed a hepatoprotective effect of thalidomide against indomethacin, by its anti-inflammatory activity that might prevent the increase of fibrinogen and leukocyte recruitment in the liver environment.
| Identifer | oai:union.ndltd.org:IBICT/oai:www.teses.ufc.br:5884 |
| Date | 08 July 2011 |
| Creators | Marcos AntÃnio Martins da Silva |
| Contributors | Geanne Matos de Andrade, Vietla Satyanarayana Rao, Adriana da Rocha Tomà |
| Publisher | Universidade Federal do CearÃ, Programa de PÃs-GraduaÃÃo em CiÃncias MÃdicas, UFC, BR |
| 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 UFC, instname:Universidade Federal do Ceará, instacron:UFC |
| Rights | info:eu-repo/semantics/openAccess |
Page generated in 0.002 seconds