TY  - JOUR
PY  - 2016//
TI  - Pathogenesis of dermonecrosis induced by venom of the spitting cobra, naja nigricollis: an experimental study in mice
JO  - Toxicon: Journal of the International Society on Toxinology
A1  - Rivel, Mario
A1  - Solano, Daniela
A1  - Herrera, María
A1  - Vargas, Mariángela
A1  - Villalta, Mauren
A1  - Segura, Alvaro
A1  - Arias, Ana Silvia
A1  - León, Guillermo
A1  - Gutiérrez, José María
SP  - 171
EP  - 179
VL  - 119
IS  - 
N2  - The pathogenesis of dermonecrosis induced by the venom of the African spitting cobra Naja nigricollis was investigated in a mouse model. Intradermal injection of venom induced a macroscopic necrotic lesion. Histological examination revealed early edema of the dermis, followed by blistering, loss of skin appendages and reduction in cellularity. By 24 h, necrosis of the dermis was evident, sections of epidermis were lost, and a fibrinoid hyaline material filled the damaged areas. Abundant inflammatory infiltrate was present in the hypodermis and basal dermis, and there was an increment in the expression of matrix metalloproteinases (MMPs). Thrombi were observed in blood vessels. Abundant cells were present in the dermis by 7 days. By 14 and 28 days, re-epithelization had occurred, collagen was widespread in the dermis, and few skin appendages were present. The RP-HPLC fractions that reproduced the necrotic activity were composed of low molecular mass cytotoxins of the three-finger toxin family and, to a lesser extent, of phospholipases A2 (PLA2). Inhibition of PLA2 of venom by p-bromophenacyl bromide did not reduce the area of necrosis, but modified the appearance of necrotic regions. Depletion of neutrophils and inhibition of venom and MMPs did not affect dermonecrosis. IgG and F(ab')2 antivenoms were effective in the neutralization of dermonecrosis when incubated with venom prior to injection. However, when antivenoms were administered immediately after venom injection, dermonecrosis was reduced only to a partial extent, underscoring the difficulties in neutralizing this effect with antivenoms.<br><br>Copyright © 2016. Published by Elsevier Ltd.<p />  <p>Language: en</p>
LA  - en
SN  - 0041-0101
UR  - http://dx.doi.org/10.1016/j.toxicon.2016.06.006
ID  - ref1
ER  -