CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / A insuficiÃncia renal aguda à uma das complicaÃÃes mais freqÃentes nos envenenamentos ofÃdicos. Contudo, a sua patogÃnese permanece obscura. Em nossos estudos foram avaliados os efeitos renais causados pelas miotoxinas purificadas dos venenos das serpentes Bothrops jararacussu (Bthtx I, Lys 49 e Bthtx II, Asp 49) e Bothrops moojeni (BmTx I, Lys 49), assim como pelas lectinas dos venenos de Bothrops moojeni (BmLec) e Bothrops jararacussu (BJcuL). Tentando avaliar o mecanismo envolvido nos efeitos renais das substÃncias acima mencionadas, foram testados os efeitos da indometacina, um bloqueador inespecÃfico de ciclooxigenase. Adicionalmente, foram avaliados os efeitos inibitÃrios do Tezosentan, um bloqueador de receptor de endotelina, nos efeitos renais causados pela miotoxina I da serpente Bothrops moojeni. Para tanto, as miotoxinas, na dosagem de 5Âg/mL, ou as lectinas, na dosagem de 10Âg/mL foram adicionadas 30 minutos depois do inÃcio dos experimentos. Contudo, a indometacina e o tezosentan foram adicionados no sistema de perfusÃo sempre no inÃcio de cada experimento na dosagem de 10Âg/mL. Os efeitos renais foram comparados com um grupo controle, onde os rins foram perfundidos somente com a soluÃÃo de Krebs-Henseleit modificada. Bthtx I, BthtxII e BmLec aumentaram a pressÃo de perfusÃo (C120= 110,28  3,09, Bthtx I120 = 171,20  6,3 *, Bthtx II120 = 175,50  7,20 * e BmLec120 = 152,50  2,10 *), a resistÃncia vascular renal (C120= 5,46  0,54, Bthtx I120= 8,62  0,37 *, Bthtx II120= 8,90  0,36 * e BmLec120= 7,77  0,30*), o fluxo urinÃrio (C120= 0,143  0,008, Bthtx I120= 0,326  0,048*, e Bthtx II120= 0,373  0,085*, BmLec120= 0,085  0,007* ), o ritmo de filtraÃÃo glomerular (C120= 0,678  0,065, Bthtx I120= 0,855  0,133 *, Bthtx II120= 1,224  0,282*, BmLec120=1,037  0,055*) e a excreÃÃo de sÃdio potÃssio e cloreto (ENa+, EK+, ECl-). PorÃm, diminuÃram os percentuais dos transportes tubulares de sÃdio (C120= 79,76  0,56, Bthtx I120= 62,23  4,12*, Bthtx II120= 70,96  2,93* e BmLec60= 77,25  1,36*) e potÃssio (C60= 66,38  3,31, Bthtx I60= 55,79  5,57 *, Bthtx II60= 50,86  6,16* e BmLec60= 59,78  3,49). A indometacina foi capaz de bloquear os efeitos causados pela miotoxina I da B. jararacussu e lectina da B. moojeni, mas reverteu parcialmente os efeitos causados pelas miotoxinas II e lectina da B. jararacussu e miotoxina I da B. moojeni. O tezosentan, por sua vez, bloqueou os efeitos causados pela miotoxina I da B. moojeni. Foi concluÃdo que prostaglandinas estÃo envolvidas nas alteraÃÃes renais promovidas pelas substÃncias isoladas das serpentes B. jararacussu e B. moojeni, enquanto que endotelina seria o principal mediador nas alteraÃÃes renais causadas pela miotoxina I da B. moojeni. / Acute renal failure is one of the most common systemic complications after snakebite. However, its pathogenesis remains obscure. In this study, we evaluated the renal effects of Bothrops jararacussu myotoxins I and II (Bthtx-I Lys 49 and BthtxII, Asp 49), Bothrops moojeni myotoxin I and the lectins from Bothrops moojeni and Bothrops jararacussu. Attempting to investigate the mechanisms involved in the renal effects of the mentioned toxins, we tested indomethacin, an unespecific cyclooxigenase inhibitor. Additionally, tezosentan, an endothelin receptor blocker, was used to evaluate the role of endothelin in the renal effects of Bothrops moojeni myotoxin I. All myotoxins (5 Âg/mL) and lectins (10Âg /mL) were added to the perfusion system 30 min after the beginning of each perfusion. Indomethacin (10Âg/mL) and tezosentan (10 Âg /mL) were always added 30 minutes before the tested substances. The renal effects were compared against a control group, where kidneys were perfused only with the modified Krebs-Henseleit solution. Myotoxins from Bothrops jararacussu and the lectin from Bothrops moojeni increased the perfusion pressure (C120= 110.28  3.09, Bthtx I120= 171.20  6.3 * ,Bthtx II120= 175.50  7.20 * and BmLec120= 152.50  2.10 *), the renal vascular resistance (C120= 5.46  0.54, Bthtx I120= 8.62  0.37 *, Bthtx II120= 8.90  0.36 * and BmLec120= 7.77  0.30*), the urinary flow (C120= 0.143  0.008, Bthtx I120= 0.326  0.048*, and Bthtx II120= 0.373  0.085* ), the glomerular filtration rate (C120= 0.678  0.065, Bthtx I120= 0.855  0.133 *, Bthtx II120= 1.224  0.282* and BmLec120= 1.037  0.055*) and the sodium, potassium and chloride excretion. On the other hand, the same substances decreased the percent of renal tubular transport of sodium (C120= 79.76  0.56, Bthtx I120= 62.23  4.12*, Bthtx II120= 70.96  2.93* and BmLec60= 77.25  1.36*), potassium (C60= 66.38  3.31, Bthtx I60= 55.79  5.57 *, Bthtx II60= 50.86  6.16* and BmLec60= 59.78  3.49*). Indomethacin inhibited the renal effects induced by Bothrops jararacussu myotoxin I and Bothrops moojeni lectin, but partially blocked the effects promoted by myotoxin II and the lectin of Bothrops jararacussu, and the effects of myotoxin I of Bothrops moojeni. Tezosentan inhibited the renal effects induced by B. moojeni myotoxin I. In conclusion, prostaglandins are involved in the renal alterations induced by myotoxins and lectins purified from the snake venoms of Bothrops jararacussu and Bothrops moojeni. In addition, endothelin is the main mediator of the renal alterations promoted by Bothrops moojeni myotoxin I