Investigating Snake-Venom-Induced Dermonecrosis and Inflammation Using an Ex Vivo Human Skin Model

Alsolaiss, Jaffar, Leeming, Gail, Da Silva, Rachael, Alomran, Nessrin ORCID: https://orcid.org/0000-0002-9916-8182, Casewell, Nicholas ORCID: https://orcid.org/0000-0002-8035-4719, Habib, Abdulrazaq G., Harrison, Robert and Modahl, Cassandra (2024) 'Investigating Snake-Venom-Induced Dermonecrosis and Inflammation Using an Ex Vivo Human Skin Model'. Toxins, Vol 16, Issue 6, e276.

Preview

Text toxins-16-00276.pdf - Published Version Available under License Creative Commons Attribution. Download (4MB) | Preview

Abstract

Snakebite envenoming is a neglected tropical disease that causes >100,000 deaths and >400,000 cases of morbidity annually. Despite the use of mouse models, severe local envenoming, defined by morbidity-causing local tissue necrosis, remains poorly understood, and human-tissue responses are ill-defined. Here, for the first time, an ex vivo, non-perfused human skin model was used to investigate temporal histopathological and immunological changes following subcutaneous injections of venoms from medically important African vipers (Echis ocellatus and Bitis arietans) and cobras (Naja nigricollis and N. haje). Histological analysis of venom-injected ex vivo human skin biopsies revealed morphological changes in the epidermis (ballooning degeneration, erosion, and ulceration) comparable to clinical signs of local envenoming. Immunostaining of these biopsies confirmed cell apoptosis consistent with the onset of necrosis. RNA sequencing, multiplex bead arrays, and ELISAs demonstrated that venom-injected human skin biopsies exhibited higher rates of transcription and expression of chemokines (CXCL5, MIP1-ALPHA, RANTES, MCP-1, and MIG), cytokines (IL-1β, IL-1RA, G-CSF/CSF-3, and GM-CSF), and growth factors (VEGF-A, FGF, and HGF) in comparison to non-injected biopsies. To investigate the efficacy of antivenom, SAIMR Echis monovalent or SAIMR polyvalent antivenom was injected one hour following E. ocellatus or N. nigricollis venom treatment, respectively, and although antivenom did not prevent venom-induced dermal tissue damage, it did reduce all pro-inflammatory chemokines, cytokines, and growth factors to normal levels after 48 h. This ex vivo skin model could be useful for studies evaluating the progression of local envenoming and the efficacy of snakebite treatments.

Item Type:	Article
Subjects:	QV Pharmacology > Toxicology > General Toxicology > QV 601 Antidotes and other therapeutic measures QV Pharmacology > Toxicology > General Toxicology > QV 602 Detection of poisons. Tests. Laboratory manuals. Technique WD Disorders of Systemic, Metabolic or Environmental Origin, etc > Animal Poisons > WD 410 Reptiles
Faculty: Department:	Biological Sciences > Department of Tropical Disease Biology
Digital Object Identifer (DOI):	https://doi.org/10.3390/toxins16060276
Depositing User:	Clare O'Neill
Date Deposited:	25 Jun 2024 14:30
Last Modified:	25 Jun 2024 14:30
URI:	https://archive.lstmed.ac.uk/id/eprint/24763

Statistics

View details

Actions (login required)

Edit Item