Cytotoxicity of Venoms and Cytotoxins from Asiatic Cobras (Naja kaouthia, Naja sumatrana, Naja atra) and Neutralization by Antivenoms from Thailand, Vietnam, and Taiwan

Abstract

Envenoming by cobras (Naja spp.) often results in extensive local tissue necrosis when optimal treatment with antivenom is not available. This study investigated the cytotoxicity of venoms and purified cytotoxins from the Monocled Cobra (Naja kaouthia), Taiwan Cobra (Naja atra), and Equatorial Spitting Cobra (Naja sumatrana) in a mouse fibroblast cell line, followed by neutralization of the cytotoxicity by three regional antivenoms: the Thai Naja kaouthia monovalent antivenom (NkMAV), Vietnamese snake antivenom (SAV) and Taiwanese Neuro bivalent antivenom (NBAV). The cytotoxins of N. atra (NA-CTX) and N. sumatrana (NS-CTX) were identified as P-type cytotoxins, whereas that of N. kaouthia (NK-CTX) is S-type. All venoms and purified cytotoxins demonstrated varying concentration-dependent cytotoxicity in the following trend: highest for N. atra, followed by N. sumatrana and N. kaouthia. The antivenoms moderately neutralized the cytotoxicity of N. kaouthia venom but were weak against N. atra and N. sumatrana venom cytotoxicity. The neutralization potencies of the antivenoms against the cytotoxins were varied and generally low across NA-CTX, NS-CTX, and NK-CTX, possibly attributed to limited antigenicity of CTXs and/or different formulation of antivenom products. The study underscores the need for antivenom improvement and/or new therapies in treating local tissue toxicity caused by cobra envenomings.

Metabolomics analyses of serum metabolites perturbations associated with Naja atra bite

“…The sustained action of toxic proteins leads to both local tissue necrosis and systemic neurotoxicity [ 26 ]. Snake venom metalloproteinase primarily acts on type IV collagen and certain coagulation factors, causing collagen degradation, inducing apoptosis, and inhibiting platelet aggregation leading to bleeding [ 27 ]. When the basement membrane of the skin barrier is breached, phospholipase A2 binds to various receptors in the plasma and axonal membranes of myocytes, causing acute skeletal muscle necrosis, local tissue inflammation with edema and the painful influx of leukocytes into the wound [ 25 , 28 , 29 ].…”

De novo designed proteins neutralize lethal snake venom toxins

“…Cytotoxins, a prominent functional group within the 3FTx family found in cobra venoms, exert cytotoxic effects and induce local tissue damage by destabilizing phospholipid membranes 46 (Figure 1b). Neutralizing these toxins is crucial to prevent severe sequelae, such as limb deformity, amputation, and lasting disabilities in snakebite victims 47 .…”

Naja species Bite Injury- Pathophysiology of Envenomation and Multidisciplinary Approach in Management

“…In Malaysia, significant numbers of snake related injuries (SRI) in urban setting are from the Naja species and the reticulated python (1,2). Bite envenomation from the Naja species can cause local and/or systemic effects, depending on the amount of venom injected (1)(2)(3). Systemic effects include cardiotoxicity and neurotoxicity (1)(2)(3).…”

“…Bite envenomation from the Naja species can cause local and/or systemic effects, depending on the amount of venom injected (1)(2)(3). Systemic effects include cardiotoxicity and neurotoxicity (1)(2)(3). Local effects vary from mild pain and swelling of the affected bitten area to significant tissue injury and necrosis (1)(2)(3)(4)(5).…”