title: Impairment of the cell-to-matrix adhesion and cytotoxicity induced by Bothrops moojeni snake venom in cultured renal tubular epithelia.
abstract: Bothrops moojeni snake venom induces acute renal failure (ARF) as a consequence of morphological and functional alterations in glomerular and tubular cells. It is still unclear whether the ARF results from a direct cytotoxic effect on renal epithelia or from a renal ischemia due to systemic hemodynamic disturbances. This work investigated the in vitro effect of B. moojeni crude venom, using cultured Madin-Darby canine kidney (MDCK) monolayers as a model. The crude venom induced a significant time- and dose-dependent decrease in transepithelial electrical resistance across MDCK monolayers. In addition, the exposure to the venom resulted in cell detachment from the substratum, as revealed by transmission electron microscopy. Immunocytochemical analysis showed no change in the distribution of some junctional proteins, such as occludin, ZO-1, and E-cadherin. Nevertheless, the staining with labeled phalloidin revealed a disarray of the cytoskeleton, specifically of the stress fibers and of the focal adhesion-associated F-actin at the cell-to-matrix contact region. The treatment with B. moojeni venom also increased the cell release of lactate dehydrogenase and decreased cellular uptake of the vital neutral red. In conclusion, B. moojeni crude venom appears to have a direct cytotoxic effect on a renal tubule-derived cell line, also inducing impairment of the cell-matrix interaction.
authors.affiliation: Department of Histology and Embryology, State University of Campinas, Campinas, SP, Brazil.
authors.forename: Carla B
authors.initials: CB
authors.lastname: Collares-Buzato
authors.forename: Luciana
authors.initials: L
authors.lastname: de Paula Le Sueur
authors.forename: Maria Alice
authors.initials: MA
authors.lastname: da Cruz-Höfling
mesh_terms: D000818:Animals; D017837:Bothrops; D015820:Cadherins / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003435:Crotalid Venoms / Q000633:toxicity*; D003599:Cytoskeleton / Q000187:drug effects / Q000648:ultrastructure; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D017097:Electric Impedance; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D005109:Extracellular Matrix / Q000187:drug effects* / Q000378:metabolism; D007150:Immunohistochemistry; D007684:Kidney Tubules / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D062793:Occludin; D010750:Phosphoproteins / Q000378:metabolism; D013997:Time Factors; D062826:Zonula Occludens-1 Protein
chemical_list: D015820:Cadherins; D003435:Crotalid Venoms; D008565:Membrane Proteins; D062793:Occludin; D010750:Phosphoproteins; D062826:Zonula Occludens-1 Protein; D007770:L-Lactate Dehydrogenase