Efeitos renais induzidos pelas fosfolipases A2 Asp-49 e Lys-49 isoladas do veneno da serpente Bothropoides pauloensis

• Autor(a) principal: Marinho, Aline Diogo
• Data de Publicação: 2018
• Tipo de documento: Tese
• Idioma: por
• Título da fonte: Repositório Institucional da Universidade Federal do Ceará (UFC)
• Texto Completo: http://www.repositorio.ufc.br/handle/riufc/31400
• topic: Rim; Citotoxicidade Imunológica; Venenos de Serpentes

The Bothropoides pauloensis is a poisonous snake habituating area in the southeast of Brazil. The biological effects by envenomation show similar profile than those observed with other Bothrops, such as important severe local and systemic effects such as Acute Renal Failure (ARF). In this work, we investigated the renal effects of phospholipases Lys-49 and Asp-49 isolated from Bothropoides pauloensis snake venom in isolated rat kidney system and in renal cells lines MDCK and HEK-293. The PLA2s (3µg/mL) caused significant effects in isolated rat kidney, Asp-49 reducing perfusion pressure (PP) at 90 and 120min (101,0+2,6; 96,6+2,0, respectively), the Renal Vascular Resistence (RVR) at 90min (4,4+0,3), the Urinary Flow (UF) at 60min (0,17+0,02), the Glomerular Filtration Rate (GFR) at 60, 90 and 120min (0,44+0,08; 0,55+0,15 and 0,34+0,08, respectively) and the percentage of tubular sodium (%TNa+), chloride (%TCl-) and potassium (%TK+). The Lys-49 increased PP at 60, 90 and 120min (130+3,7; 132+7,6 and 142+10,5, respectively) and UF at 60, 90 and 120min (0,20+0,01; 0,22+0,01 and 0,23+0,01, respectively) and decreased the RFG at 60, 90 and 120min (0,50+0,15; 0,44+0,11 and 0,45+0,11, respectively) and the %TNa+, %TK+ and %TCl-. The PLA2 caused alterations in MDA Lys-49 (16,98+2,53), Nitrite in Asp-49 (301,9+15,51) and Lys-49 (354,3+39,9), GSH in Asp-49 (690,4+65,21) and Lys-49 (1314+37,34) and MPO in Asp-49 (3,133+0,636) and Lys-49 (6,863+0,834). The citokines pro-inflammatory (IL-1β e TNF-α) and anti- inflammatory (IL-10) are involvement in nephrotoxicity mechanism. The Asp-49, TNF- α (2,52+0,48) and IL-10 (4,153+0,261), the Lys-49, IL-1β (5,40+0,26), TNF-α (6,59+0,65) and IL-10 (5,86+0,60). The treatments (24h) of PLA2 were able to reduce cell viability in both cells lines. In MDCK cell, we verified the generation of reactive oxygen species with Asp-49, not induced membrane rupture, not showed the percentage of apoptotic, necrotic or secondary necrotic cells and not caused alteration in cell cycle. In HEK-293, not observed release of calcium from endoplasmatic reticulum