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Previous issue date: 2004-03-03 / Pacientes com Insuficiência Renal Crônica (IRC) freqüentemente apresentam nível plasmático de triiodotironina (LT3) diminuído, tiroxina (LT4) normal ou diminuído e o hormônio estimulante da tireóide (TSH) normal. Estudos sobre o transporte de hormônios tireoideanos (HTs) em diferentes células de mamíferos indicam que a membrana citoplasmática constitui um ponto regulatório na modulação da concentração intracelular e conseqüentemente na ação celular. Entretanto, não há estudos examinando se o transporte de HTs tem algum papel na disfunção tireoideana observada na IRC. O propósito dessa investigação foi caracterizar o influxo e efluxo de HTs em hemácias de pacientes com IRC antes e depois de uma sessão de hemodiálise e verificar os efeitos de análogos ao LT3 (rT3 e Triac) e Verapamil (VRP) no transporte de LT3 em eritrócitos de pacientes com IRC. As hemácias obtidas de sujeitos controles e de pacientes urêmicos em pré-hemodiálise (pré-HD) e pós-hemodiálise (pós-HD) foram submetidas a experimentos de influxo e efluxo utilizando-se HTs marcados com 125I. Os dados foram submetidos à Análise de Variância (ANOVA) e aplicado o teste Newman-Keuls Multiple Comparison. Os resultados demonstraram que o influxo de LT3 em pacientes urêmicos pré-HD foi 50% e 55% maior em relação aos sujeitos controles aos 1 e 5 minutos, respectivamente. Entretanto, o influxo de LT4 em hemácias de pacientes urêmicos foi significativamente menor após 1 minuto (88%) e 5 minutos (63%). O influxo de LT3 foi menor e o de LT4 foi significativamente maior nos sujeitos controles. Após 60 minutos de efluxo, o LT3 remanescente nos eritrócitos foi 80% maior e de LT4 foi 57% menor em relação aos sujeitos controles. A hemodiálise não corrigiu o influxo e efluxo de LT3 e LT4 nas hemácias de pacientes urêmicos em relação aos sujeitos controles. A adição de análogos ao LT3 (rT3 e Triac) e VRP diminuiu o influxo de LT3 em hemácias de sujeitos controles em 45%, 26% e 8%, respectivamente, e em 24%, 24% e 23% em hemácias de pacientes urêmicos pré-HD e ainda 32%, 37% e 35% pós-HD. Ainda, os análogos ao LT3 e o VRP mostraram um significante efeito inibitório no efluxo de LT3 em hemácias de sujeitos controles assim como de pacientes urêmicos pré e pós-HD. Concluindo, estes achados representam a primeira demonstração que a diferença no transporte dos HTs em hemácias pode indicar um mecanismo compensatório mantendo o eutiroidismo em pacientes com IRC. Outro aspecto relevante é que a sensibilidade do influxo e efluxo de LT3 ao rT3, Triac e VRP difere entre os pacientes urêmicos e sujeitos controles. Os resultados indicam que o transporte de HTs em hemácias de pacientes urêmicos e sujeitos controles ocorre por meio de mecanismos distintos. O estudo destes mecanismos abre novos caminhos farmacológicos que podem ser desenvolvidos para o controle da concentração intracelular dos hormônios tireoideanos em hemácias de urêmicos. ____________________________________________________________________________________ ABSTRACT / Patients with Chronic Renal Failure (CRF) frequently show diminished levels of triidothyronine (LT3), normal or low thyroxine (LT4) and normal thyroid-stimulating hormone (TSH). Studies on the transport of thyroid hormones (THs) in different mammalian cells indicate that the cytoplasmic membrane constitutes a regulatory point in the modulation of intracellular concentration and consequently in cellular action. However, there are no studies examining whether THs transport plays a role in the thyroid dysfunction observed in CRF. The aim of this investigation was to characterize the uptake and efflux in erythrocytes of patients with CRF before and after hemodialysis and to investigate whether LT3 analogs (rT3 and Triac) and Verapamil (VRP) have an effect or not on thyroid hormone uptake and efflux of LT3 in red blood cells from uremic patients on hemodialysis. Erythrocytes obtained from the control subjects and uremic patients in pre-hemodialysis (pre-HD) and in post-hemodialysis (post-HD) were submitted to uptake and efflux experiments using THs labeled with 125I. The data were analyzed by one-way variance analyses (ANOVA) and Newman-Keuls Multiple Comparison. The results obtained demonstrated that LT3 uptake in erythrocytes from uremic patients pre-HD was 50% and 55% higher than control subjects at 1min and 5 min respectively. However, LT4 uptake in erythrocytes from uremic patients was significantly lower at 1min (88%) and 5 min (63%). The LT3 efflux rate was lower and LT4 efflux was significantly higher than in control subjects. After 60-min of efflux, the LT3 which remained in erythrocytes was 80% higher and that of LT4 was 57% lower than in control individuals. Hemodialysis did not correct the LT3 and LT4 uptake and efflux in RBC from uremic patients. The addition of LT3 analogs (Triac and rT3) and VRP decreased LT3 uptake by 45%, 26% and 8% in red blood cells from the control group, respectively, and by 24%, 24% and 23% in red blood cells from uremic patients pre-HD and by 32%, 37% and 35% in erythrocytes from uremic patients post-HD respectively. Also, LT3 analogs and Verapamil showed significant inhibitory effects on LT3 efflux in red blood cells from normal, pre- and post-HD patients. These results show that LT3 entry and exit in red blood cells of uremic patients and from the control group occur through distinct mechanisms, and that the sensitivity to LT3 analogs and VRP differs between uremic and control subjects. In conclusion, these findings represent the first demonstration that the difference in transport in erythrocytes can indicate a compensatory mechanism which maintains euthyroidism in patients with CRF. Another relevant aspect is that the sensitivity of efflux and uptake of LT3 to rT3, Triac and VRP differs between uremic patients and the control group. Results show that THs transport in red blood cells from uremic patients and from the control group occurs through distinct mechanisms. The study of these mechanisms can indicate novel pharmacological pathways to control the intracellular amount of the thyroid hormones in erythrocytes from uremic patients.
| Identifer | oai:union.ndltd.org:IBICT/oai:repositorio.unb.br:10482/1689 |
| Date | 03 March 2004 |
| Creators | Rodrigues, Maria Cristina Soares |
| Contributors | Simeoni, Luiz Alberto |
| Source Sets | IBICT Brazilian ETDs |
| Language | Portuguese |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/doctoralThesis |
| Source | reponame:Repositório Institucional da UnB, instname:Universidade de Brasília, instacron:UNB |
| Rights | info:eu-repo/semantics/openAccess |
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