title: Mechanisms of acute kidney injury induced by experimental Lonomia obliqua envenomation.
abstract: Lonomia obliqua caterpillar envenomation causes acute kidney injury (AKI), which can be responsible for its deadly actions. This study evaluates the possible mechanisms involved in the pathogenesis of renal dysfunction. To characterize L. obliqua venom effects, we subcutaneously injected rats and examined renal functional, morphological and biochemical parameters at several time points. We also performed discovery-based proteomic analysis to measure protein expression to identify molecular pathways of renal disease. L. obliqua envenomation causes acute tubular necrosis, which is associated with renal inflammation; formation of hematic casts, resulting from intravascular hemolysis; increase in vascular permeability and fibrosis. The dilation of Bowman's space and glomerular tuft is related to fluid leakage and intra-glomerular fibrin deposition, respectively, since tissue factor procoagulant activity increases in the kidney. Systemic hypotension also contributes to these alterations and to the sudden loss of basic renal functions, including filtration and excretion capacities, urinary concentration and maintenance of fluid homeostasis. In addition, envenomed kidneys increase the expression of proteins involved in cell stress, inflammation, tissue injury, heme-induced oxidative stress, coagulation and complement system activation. Finally, the localization of the venom in renal tissue agrees with morphological and functional alterations, suggesting also a direct nephrotoxic activity. In conclusion, the mechanisms of L. obliqua-induced AKI are complex involving mainly glomerular and tubular functional impairment and vascular alterations. These results are important to understand the mechanisms of renal injury and may suggest more efficient ways to prevent or attenuate the pathology of Lonomia's envenomation.
authors.affiliation: Laboratório de Bioquímica Farmacológica, Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul (UFRGS), Av. Bento Gonçalves, 9500, CEP 91501-970, Porto Alegre, RS, Brazil.
authors.forename: Markus
authors.initials: M
authors.lastname: Berger
authors.forename: Lucélia
authors.initials: L
authors.lastname: Santi
authors.forename: Walter O
authors.initials: WO
authors.lastname: Beys-da-Silva
authors.forename: Fabrício Marcus Silva
authors.initials: FM
authors.lastname: Oliveira
authors.forename: Marcelo Vidigal
authors.initials: MV
authors.lastname: Caliari
authors.forename: John R
authors.initials: JR
authors.lastname: Yates
authors.forename: Maria Aparecida Ribeiro
authors.initials: MA
authors.lastname: Vieira
authors.forename: Jorge Almeida
authors.initials: JA
authors.lastname: Guimarães
mesh_terms: D000818:Animals; D001180:Arthropod Venoms / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D002199:Capillary Permeability / Q000187:drug effects; D004195:Disease Models, Animal; D006439:Hemodynamics / Q000187:drug effects; D007150:Immunohistochemistry; D007279:Injections, Subcutaneous; D007299:Insect Bites and Stings / Q000473:pathology; D007668:Kidney / Q000098:blood supply / Q000187:drug effects / Q000473:pathology; D007677:Kidney Function Tests; D007683:Kidney Tubular Necrosis, Acute / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D009036:Moths; D017208:Rats, Wistar; D053719:Tandem Mass Spectrometry
chemical_list: D001180:Arthropod Venoms