Pro-inflammatory response and hemostatic disorder induced by venom of the coral snake Micrurus tener tener IN C57BL/6 mice. (August 2018)

• Record Type: Journal Article
• Authors: Salazar, Emelyn; Salazar, Ana Maria; Taylor, Peter; Ibarra, Carlos; Rodríguez-Acosta, Alexis; Sánchez, Elda; Pérez, Karin; Brito, Beatriz; Guerrero, Belsy
• Is Part Of: Toxicon. Volume 150(2018)
• Page Start: 212
• Page End: 219
• Publication Date: 2018-08
• Subjects: Inflammation -- Micrurus tener tener -- Hemostasis -- Edema -- Snake venom; Mtt Micrurus tener tener -- LD50 lethal dose 50 -- i.p. intra peritoneal -- i.d. intra dermal -- NO nitric oxide -- TNF-α tumor necrosis factor alpha -- PT Prothrombin Time -- aPTT Activated Partial Thromboplastin Time -- FXIII factor XIII -- t-PA tissue plasminogen activator -- PAI-1 plasminogen activator inhibitor type 1 -- u-PA urokinase plasminogen activator -- IL-6 Interleukin 6 -- Cdc Crotalus durissus cumanensis -- Bi Bothrops isabelae; Toxins -- Periodicals; Venom -- Periodicals; 615.9
• DOI: 10.1016/j.toxicon.2018.06.063
• Languages: English
• ISSNs: 0041-0101

Abstract

Abstract: Micrurus venoms are known to induce mainly neurotoxicity in victims. However, other manifestations, including hemorrhage, edema, myotoxicity, complement activation, and hemostatic activity have been reported. In order to develop a more complete pharmacological profile of these venoms, inflammatory responses and hemostasis were evaluated in C57BL/6 mice treated with a sub-lethal dose of M. t. tener ( Mtt ) venom (8 μg/mouse), inoculated intraperitoneally. The venom induced moderate bleeding into the abdominal cavity and lungs, as well as infiltration of leukocytes into the liver. After 30 min, the release of pro-inflammatory mediators (TNF-α, IL-6, and NO) were observed, being most evident at 4 h. There was a decrease in hemoglobin and hematocrit levels at 72 h, a prolongation in coagulation times (PT and aPTT), a decrease in the fibrinogen concentration and an increase in fibrinolytic activity. In this animal model, it was proposed that Mtt venom induces inflammation with the release of mediators such as TNF-α, in response to the toxins. These mediators may activate hemostatic mechanisms, producing systemic fibrinolysis and hemorrhage. These findings suggest alternative treatments in Micrurus envenomations in which neurotoxic manifestations do not predominate. Highlights: Micrurus envenomation mainly manifests neurotoxicity, but inflammation and hemostasis activation have been clinically and experimentally described. C57BL/6 mice showed hemorrhage in the abdominal cavity and clots in the lungs at 72 h post-injection with Mtt venom. Mtt venom induced alterations in hematological and hemostatic parameters in mice at 72 h post-injection. Mtt venom induced an acute inflammatory response (4 h) and accumulation of mononuclear cells in liver (72 h). We documented other alterations, beside neurotoxicity, induced by sub-lethal doses of Micrurus tener tener venom in mice.