title: Activities against hemostatic proteins and adrenal gland ultrastructural changes caused by the brown widow spider Latrodectus geometricus (Araneae: Theridiidae) venom.
abstract: Brown widow spider (BrWS) (Latrodectus geometricus) venom produces intense systemic reactions such as cramps, harsh muscle nociceptive, nauseas, vomiting and hypertension. The proposed pathogenic mechanisms resulting in these accidents have principally been damages occurring at the nervous system. However, it is suspected that there is also damage of the adrenal glands, as a result of the experimental animal's clinical manifestations, which developed symptoms compatible with acute adrenal insufficiency. We have currently found that the adrenal gland is damaged by this venom gland homogenates (VGH) producing severe alterations on cortex cells resulting in death by acute adrenal insufficiency. In general, the ultrastructural study on the glands of mice under transmission electronic microscopy observations showed alterations in the majority of the intracellular membranes within 3 to 24h. BrWSVGH also showed specific actions on extracellular matrix proteins such as fibronectin, laminin and fibrinogen. In addition, zymogram experiments using gelatin as substrates detected gelatinolytic activity. The molecular exclusion fractionation of crude BrWSVGH resulted in 15 fractions, of which F1 and F2 presented alpha/beta-fibrinogenase and fibronectinolytic activities. Fractions F6, F14 and F15 showed only alpha-fibrinogenase activity; in contrast, the gelatinolytic action was only observed in fraction F11. Only metalloproteinase inhibitors abolished all these proteolytic activities. Our results suggest that adrenal cortex lesions may be relevant in the etiopathogenesis of severe brown widow spider envenoming. To our knowledge, this is the first report on adrenal gland damages, fibrinogenolytic activity and interrelations with cell-matrix adhesion proteins caused by L.geometricus VGH. The venom of this spider could be inducing hemostatic system damages on envenomed patients.
authors.affiliation: Pathophysiology Laboratory, Medicine Experimental Center, Instituto Venezolano de Investigaciones Científicas, Caracas, Venezuela.
authors.forename: Belsy
authors.initials: B
authors.lastname: Guerrero
authors.forename: Hector J
authors.initials: HJ
authors.lastname: Finol
authors.forename: Matias
authors.initials: M
authors.lastname: Reyes-Lugo
authors.forename: Ana M
authors.initials: AM
authors.lastname: Salazar
authors.forename: Elda E
authors.initials: EE
authors.lastname: Sánchez
authors.forename: Amalid
authors.initials: A
authors.lastname: Estrella
authors.forename: Antonio
authors.initials: A
authors.lastname: Roschman-González
authors.forename: Carlos
authors.initials: C
authors.lastname: Ibarra
authors.forename: Ivan
authors.initials: I
authors.lastname: Salvi
authors.forename: Alexis
authors.initials: A
authors.lastname: Rodríguez-Acosta
mesh_terms: D000302:Adrenal Cortex / Q000187:drug effects* / Q000201:enzymology / Q000648:ultrastructure; D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism; D021982:Cell-Matrix Junctions / Q000187:drug effects / Q000378:metabolism; D002850:Chromatography, Gel; D004591:Electrophoresis, Polyacrylamide Gel; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D006487:Hemostasis / Q000187:drug effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D046529:Microscopy, Electron, Transmission; D001098:Spider Bites / Q000097:blood / Q000201:enzymology / Q000209:etiology* / Q000473:pathology; D013111:Spider Venoms / Q000201:enzymology / Q000633:toxicity*
chemical_list: D015815:Cell Adhesion Molecules; D016326:Extracellular Matrix Proteins; D013111:Spider Venoms