Final published version
Licence: CC BY: Creative Commons Attribution 4.0 International License
Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
}
TY - JOUR
T1 - Proteomics and histological assessment of an organotypic model of human skin following exposure to Naja nigricollis venom
AU - Ahmadi, Shirin
AU - Pachis, Spyridon T
AU - Kalogeropoulos, Konstantinos
AU - McGeoghan, Farrell
AU - Canbay, Vahap
AU - Hall, Steven R
AU - Crittenden, Edouard P
AU - Dawson, Charlotte A
AU - Bartlett, Keirah E
AU - Gutiérrez, José María
AU - Casewell, Nicholas R
AU - Keller, Ulrich Auf dem
AU - Laustsen, Andreas H
N1 - .
PY - 2022/12/31
Y1 - 2022/12/31
N2 - Snakebite envenoming was reintroduced as a Category A Neglected Tropical Disease by the World Health Organization in 2017. Since then, increased attention has been directed towards this affliction and towards the development of a deeper understanding of how snake venoms exert their toxic effects and how antivenoms can counter them. However, most of our in vivo generated knowledge stems from the use of animal models which do not always accurately reflect how the pathogenic effects of snake venoms manifest in humans. Moreover, animal experiments are associated with pain, distress, and eventually animal sacrifice due to the toxic nature of snake venoms. Related to this, the implementation of the 3Rs principle (Replacement, Reduction, and Refinement) in the use of experimental animals in snakebite envenoming research is recommended by the World Health Organization. Therefore, more humane experimental designs and new in vitro/ex vivo alternatives for experimental animals are sought after. Here, we report the use of an organotypic model of human skin to further elucidate the pathophysiology of the dermonecrotic effects caused by the venom of the black-necked spitting cobra, Naja nigricollis, in humans. The goal of this study is to expand the repertoire of available models that can be used to study the local tissue damages induced by cytotoxic venoms.
AB - Snakebite envenoming was reintroduced as a Category A Neglected Tropical Disease by the World Health Organization in 2017. Since then, increased attention has been directed towards this affliction and towards the development of a deeper understanding of how snake venoms exert their toxic effects and how antivenoms can counter them. However, most of our in vivo generated knowledge stems from the use of animal models which do not always accurately reflect how the pathogenic effects of snake venoms manifest in humans. Moreover, animal experiments are associated with pain, distress, and eventually animal sacrifice due to the toxic nature of snake venoms. Related to this, the implementation of the 3Rs principle (Replacement, Reduction, and Refinement) in the use of experimental animals in snakebite envenoming research is recommended by the World Health Organization. Therefore, more humane experimental designs and new in vitro/ex vivo alternatives for experimental animals are sought after. Here, we report the use of an organotypic model of human skin to further elucidate the pathophysiology of the dermonecrotic effects caused by the venom of the black-necked spitting cobra, Naja nigricollis, in humans. The goal of this study is to expand the repertoire of available models that can be used to study the local tissue damages induced by cytotoxic venoms.
KW - Animals
KW - Humans
KW - Snake Bites/complications
KW - Proteomics
KW - Elapid Venoms/toxicity
KW - Antivenins/pharmacology
KW - Naja
KW - Snake Venoms
U2 - 10.1016/j.toxicon.2022.106955
DO - 10.1016/j.toxicon.2022.106955
M3 - Journal article
C2 - 36309071
VL - 220
JO - Toxicon
JF - Toxicon
SN - 0041-0101
M1 - 106955
ER -