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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

Efeitos biolÃgicos induzidos pelo veneno total de Tityus serrulatus e suas fraÃÃes TsTx-V, toxina gama e peptÃdeo natriurÃtico / Biological effects induced by Tityus serrulatus crude venom and its toxins TsTx-V, gamma toxin and natriuretic peptide

Renata de Sousa Alves 28 November 2008 (has links)
Conselho Nacional de Desenvolvimento CientÃfico e TecnolÃgico / O veneno do escorpiÃo Tityus serrulatus à uma mistura de peptÃdeos tÃxicos e nÃo tÃxicos com diversas aÃÃes locais e sistÃmicas. O objetivo deste trabalho foi estudar os efeitos cardiovasculares e renais induzidos pelo veneno total do escorpiÃo T. serrulatus e de suas fraÃÃes TsTx-V, Toxina &#947; e NatriurÃtica. Foram utilizados ratos Wistar machos (250-300g) para os experimentos de perfusÃo de rim isolado, leito mesentÃrico, pressÃo arterial e perfusÃo in vivo. Para os ensaios de canal deferente foram utilizados camundongos Swiss (30-40g). O veneno de T. serrulatus apresentou efeito sobre o sistema nervoso autÃnomo observado atravÃs da contraÃÃo do vaso deferente. O veneno total mostrou efeito adrenÃrgico demonstrado pela reversÃo dos seus efeitos renais apÃs prÃ-tratamento dos rins com antagonista &#945;-adrenÃrgico prazosin, especialmente sobre a resistÃncia vascular renal (RVRVTs = 7,51  0,96 vs RVRPz = 5,51  0,43 mmHg/mL.g-1.min-1*,*p<0,05) e pressÃo de perfusÃo (PPVTs = 150,1  18,40 vs PPPz = 118,1  4,00 mmHg*,*p<0,05). As fraÃÃes isoladas mostraram efeitos renais somatÃrios, haja visto que TsTx-V promoveu aumento da diurese e a Toxina &#947; causou efeitos pressÃricos. ApÃs avaliaÃÃo histopatolÃgica dos efeitos renais das fraÃÃes isolados do veneno de T. serrulatus, observamos a presenÃa de material protÃico nos espaÃos urinÃrios glomerulares e nos tÃbulos. Entretanto, no leito vascular mesentÃrico, somente a toxina &#947; mostrou-se ativa. Os efeitos renais induzidos pela fraÃÃo natriurÃtica (0,03 e 0,1Âg/mL) revelaram aumento da pressÃo e, de maneira concentraÃÃo-dependente, diminuiÃÃo da reabsorÃÃo de eletrÃlitos e aumento da excreÃÃo urinÃria de guanosina monofosfato cÃclico (GMPc). Nos experimentos in vivo, tanto o veneno total quanto a fraÃÃo natriurÃtica causaram aumento da pressÃo arterial mÃdia (PAM) e diminuiÃÃo do hematÃcrito. Em adiÃÃo, a fraÃÃo natriurÃtica causou ainda a elevaÃÃo do fluxo urinÃrio e da freqÃÃncia cardÃaca. O clearance de inulina foi utilizado para a avaliaÃÃo da funÃÃo renal in vivo. O veneno total diminui significativamente o clearance da inulina, enquanto a fraÃÃo natriurÃtica causou elevaÃÃo. O fluxo plasmÃtico renal cortical, avaliado atravÃs do clearance de p-aminohipurato, foi reduzido por aÃÃo do veneno total de T. serrulatus. Em conclusÃo, o veneno de Tityus serrulatus promoveu efeitos hemodinÃmicos renais que foram prontamente revertidos in vitro pelo prazosin. Os experimentos in vivo mostraram que o veneno de Tityus serrulatus induziu a elevaÃÃo da pressÃo arterial mÃdia, taquicardia e alteraÃÃo da funÃÃo renal. / The venom of Tityus serrulatus has a mixture of toxic and non toxic peptides presenting diverse systemic and local effects. The aim of this work was to investigate the cardiovascular and renal effects promoted by the crude venom of the scorpion Tityus serrulatus and its isolated components such as Tityus serrulatus toxin V (TsTx-V), Gamma Toxin and the newly isolated Natriuretic Peptide. The experiments of isolated perfused rat kidney, isolated mesenteric bed, arterial pressure and in vivo perfusion were performed using male Wistar rats weighing 250-300g. The assays with vas deferens were done using Swiss mice weighing 30-40g. The crude venom presented autonomic nervous system effects showed by the contraction of vas deferens. Adrenergic effects were demonstrated specially with the decrease of renal vascular resistance (RVRVTs = 7.51  0.96 vs RVRPz = 5.51  0.43 mmHg/mL.g-1.min-1*,*p<0.05) and renal perfusion pressure (PPVTs = 150.1  18.40 vs PPPz = 118.1  4.00 mmHg*,*p<0.05) induced by the crude venom after kidneys pre-treatment with prazosin. The venoms isolated components showed kidney addictional effects, where TsTx-V caused diuresis while Gamma Toxin increased perfusion pressure. We could also observe the presence of protein inside the tubules and in glomerular spaces after renal histopathologic evaluation in the groups treated with the isolated components. However, only Gamma Toxin promoted an increase of the mesenteric bed perfusion pressure. The Natriuretic Peptide (0.03 and 0.1Âg/mL) increased renal perfusion pressure. In addition, the natriuretic peptide increased cyclic guanosine monophosphate (cGMP) urinary excretion, but reduced electrolytes reabsorption in a dependent-concentration manner. The crude venom and the natriuretic peptide increased the arterial blood pressure, but decreased the hematocrit values, evaluated after in vivo experiments. However, the natriuretic peptide increased urinary flow and heartbeat frequency. In vivo renal function was evaluated by the clearance of inulin. The scorpion crude venom decreased the clearance of inulin, but this parameter was increased after natriuretic peptide treatment. The renal cortex blood flux, estimated by the clearance of p-aminohippurate, was reduced after the crude venom treatment. In conclusion, we demonstrated that Tityus serrulatus venom induced renal hemodynamic effects that were blocked in vitro by prasozin. In vivo experiments showed how the crude venom and its isolated components act increasing arterial blood pressure, heartbeat frequency and altered renal function.

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