You're using an outdated browser. Please upgrade to a modern browser for the best experience.
Submitted Successfully!
Thank you for your contribution! You can also upload a video entry or images related to this topic. For video creation, please contact our Academic Video Service.
Version Summary Created by Modification Content Size Created at Operation
1
Yuri Utkin
 -- 1469 2023-02-23 21:26:44 |
2 layout & references
Sirius Huang
 Meta information modification 1469 2023-02-24 06:21:58 |

Video Upload Options

We provide professional Academic Video Service to translate complex research into visually appealing presentations. Would you like to try it?
No, upload directly Yes

Confirm

Are you sure to Delete?
Yes No
Cite
If you have any further questions, please contact Encyclopedia Editorial Office.
Osipov, A.; Utkin, Y. Neurological Signs Produced by Viperid Bites. Encyclopedia. Available online: https://encyclopedia.pub/entry/41600 (accessed on 17 July 2025).
Osipov A, Utkin Y. Neurological Signs Produced by Viperid Bites. Encyclopedia. Available at: https://encyclopedia.pub/entry/41600. Accessed July 17, 2025.
Osipov, Alexey, Yuri Utkin. "Neurological Signs Produced by Viperid Bites" Encyclopedia, https://encyclopedia.pub/entry/41600 (accessed July 17, 2025).
Osipov, A., & Utkin, Y. (2023, February 23). Neurological Signs Produced by Viperid Bites. In Encyclopedia. https://encyclopedia.pub/entry/41600
Osipov, Alexey and Yuri Utkin. "Neurological Signs Produced by Viperid Bites." Encyclopedia. Web. 23 February, 2023.
Neurological Signs Produced by Viperid Bites
Edit
This entry is adapted from the peer-reviewed paper 10.3390/ijms24032919

Snake venoms as tools for hunting are primarily aimed at the most vital systems of the prey, especially the nervous and circulatory systems. The venom of most viperids has a hemolytic effect; victims die from blood incoagulability and numerous hemorrhages in internal organs. However, neurological signs are often observed after viperid bites.

hemotoxic venom nervous system viper snake neurotoxicity

1. Introduction

Snakes (Serpentes) in Linnean taxonomy form a suborder in the order Squamata from the class Reptilia [1]. There are over 3500 species of snakes [2]. Snakes are legless predators and use a variety of hunting strategies. In practice, some snakes subdue and swallow large, often dangerous prey animals by constriction or using strike-and-release feeding strategies; this shields them from injuries during predatory encounters. Others use venoms to immobilize preys. Snake venom has evolved from saliva in the course of evolution. It is produced in a special organ venom gland and is delivered at the bite through the teeth that are often referred to as ‘fangs’, which have a channel or groove for the injection of venom. Various sources indicate different numbers of snake species which are considered as venomous. The World Health Organization (WHO) considers that about 300 species, mainly belonging to the families Viperidae, Elapidae and Colubridae, to be of medical importance [3]. It is believed that the evolution of snake venom is driven by an evolutionary arms race between venom toxins and prey physiology [4]. Since venom is an important functional feature of venomous snakes, its composition and activity has evolved in parallel with the physiology of prey [5]. Apparently, depending on which of the systems (nervous or cardiovascular) of the victim is most vulnerable, the venom was specialized as either neurotoxic or hemotoxic. In addition, the composition of venom depends not only on snake species, but also on some other factors, including habitat, season, age and size of the snake etc.
Snake venom is a complex lethal cocktail, composed mainly of peptides and proteins usually named “toxins” and targeting different systems of prey organism, including the nervous and cardiovascular systems [6][7]. Venoms that have a principal damaging effect on the nervous system or blood are considered as neurotoxic or hemotoxic, respectively. Most venomous snakes belong to the elapid or viperid families. In general, the elapid venoms comprise toxins affecting the nervous system and are considered as neurotoxic, while the action of viperid venoms is directed mainly on blood coagulation and they are regarded as hemotoxic. The venoms of kraits, mambas and most cobras are typical examples of neurotoxic venoms. The typical hemotoxic venoms are those of saw-scaled (carpet) vipers, Levantine viper, and most pit vipers, although the venoms of some pit vipers manifest neurotoxicity. However, the division into neurotoxic and hemotoxic venoms is entirely arbitrary because those from elapid may impair blood coagulation and, vice versa, the venoms from viperid can produce neurological signs. Interestingly, snakes from the Colubridae family, or rear-fanged snakes considered for a long time as non-venomous, are now recognized as venom-producing and include both species, which produce venom with prevalence neurotoxic components, such as elapid, and the species with hemotoxic venoms, such as viperid [8].
Components directly affecting the nervous system, in particular α-neurotoxins, β-neurotoxins, dendrotoxins, and some others, constitute a considerable part of neurotoxic (e.g., elapid) snake venom. According to proteomic data, α-neurotoxins may comprise more than a half of total proteins in some cobra venoms. For example, the venom of monocled cobra (Naja kaouthia) contains more than 53% α-neurotoxins [9] and Samar cobra (N. samarensis)—more than 65% [10]. Proteomic analysis revealed that β-neurotoxins called therein as β-bungarotoxins are among the main components of krait venoms. Thus, common krait (Bungarus caeruleus) venom contains about 13% of β-bungarotoxins [11], while in the venom of the many-banded krait (B. multicinctus) from Vietnam, the content of these toxins reaches up to 45% [12].
These toxins are responsible for both the predominant envenomation symptoms and the death of the victim. They have specific molecular targets, which are involved in nerve impulse transduction. For example, dendrotoxins target the presynaptic voltage-dependent potassium ion channels [13]. The α-neurotoxins disrupt the nerve impulse transduction at the nerve-muscle junctions and between neurons, primarily by blocking the reception of the mediator acetylcholine at postsynaptic nicotinic acetylcholine receptors [14].The β-neurotoxins act at the presynaptic site hampering primarily such an important process as the release of a mediator acetylcholine. Hence, in the narrow sense, neurotoxicity can be defined as a specific action on a molecular target within excitable tissue (it may be a membrane receptor or an ion channel) that affects directly the generation, transduction and reception of a nerve impulse. Based on this definition, a neurotoxin should not be obligatory highly toxic and lethal. For instance, neurotoxins, which disrupt nociception, sometimes manifest relatively lower lethality.
The components of hemotoxic venoms affecting blood coagulation are represented both by enzymes including serine and metalloproteinases, and non-enzymatic proteins such as disintegrins, as well as C-type lectin like proteins. According to proteomic data, these proteins dominate in viperid venoms. So, the venom of Nigerian carpet viper Echis ocellatus contains 30.84% metalloproteinase and 15.5% serine proteinase [15]. In the Nigerian puff adder Bitis arietans venom, these enzymes comprise 21.06% and 22.31%, respectively [15]. In the Saharan horned viper Cerastes cerastes venom, the content of disintegrins achieves 43.44% [16]. Hemotoxic viperid venom may affect the functions of the central nervous system by disturbing the blood clotting system and platelet aggregation, as well as by damaging vascular endothelium to cause severe intracranial bleeding and/or brain infarction [17]. Of course, this is accompanied by strong neurological disorders. Such complications are attributable to venom serine proteinases [18], metaloproteinases [19] and disintegrins [20], C-type lectin like proteins [21]. Should these compounds be considered as neurotoxins? Apparently, they should not, as they have no specific targets in excitable tissues. However, hemotoxic snake venoms do contain neurotoxins, i.e., compounds directed towards specific molecular targets involved in the propagation of the nerve impulse.
The neurotoxicity of snake venom is manifested mainly in the disruption of the neuromuscular transmission, primarily in the skeletal muscles. The explanation is simple: venomous snakes are predators who have neither claws nor powerful paws; but with victims’ skeletal muscle paralysis these are not necessary because a prey is unable to breathe, escape and resist. Therefore, the breakdown of movements is the leading strategy for the neurotoxins of snake venoms—both neurotoxic and hemotoxic [21]. The elements of the mechanism of transmission of an electrochemical impulse from nerve to muscle, which may be the targets for most neurotoxins of snake venom, are as follows: sodium and potassium channels of the nerve fiber; the release of the mediator from the pre-synaptic membrane; the passage of the released mediator in the synaptic cleft; the reception of the mediator by receptors on the post-synaptic membrane of the muscle; and the sodium, potassium and calcium channels of muscle fiber. With the specificity inherent in snake venom toxins, each neurotoxin usually affects only one such target. The neurotoxins present in elapid venoms affect practically all these targets, while viperid neurotoxins, being not so numerous, impact only some of the above targets.

2. Neurological Signs Produced by Viperid Bites

The venom of most viperids has a hemolytic effect; victims die from blood incoagulability and numerous hemorrhages in internal organs. However, neurological signs are often observed. The first documented report of neurotoxic manifestations after a viper bite that researchers could find dates back to the thirties of the last century. These were envenomings by the Serbian (Valley of the Sava River) Vipera berus bosniensis viper, described by Reuss as cited in [22].
The neurotoxic effects observed after the Russell’s viper (Daboia russelii) bites are well known. These effects were described mainly for Sri Lankan Russell’s viper and the neuromuscular dysfunction reported in patients was mild [23]. It was characterized by ptosis, blurred vision and ophthalmoplegia [24]; however, life-threatening paralysis was rare.
Among European vipers, the bites by V. ammodytes ammodytes (the longnosed viper) can result in life-threatening neurotoxicity [25], and the venom of this snake contains several neurotoxins which are discussed below. As mentioned earlier, the neurotoxic manifestations are observed after the bites by Serbian V. berus bosniensis. Recently a severe neurotoxic envenoming following this snake bite has been reported in South-Western Hungary [26]. Neurological complications after the bites of snakes from Vipera genus have been reported in Italy [27] and Switzerland [28]. In south-east France, human envenomation after V. aspis aspis bites produces neurological signs (mainly cranial nerve disturbances) [29]. Using zebrafish as a model animal, neurotoxic effects has been demonstrated for Montivipera bornmuelleri venom [30].
All these data suggest the presence of neurotoxic components in viperid venoms and may indicate a multitarget strategy during envenomation.
The venoms of snakes from the Crotalus genus produce neurotoxic signs in both humans [31] and animals [32]. Thus, after Mojave rattlesnake (Crotalus scutulatus) bites, respiratory paralysis may follow that suggest neurotoxic block [33]. In 1938, Slotta and Fraenkel-Conrat communicated the isolation of crotoxin from the venom of rattlesnake C. terrificus; this toxin became the first neurotoxin isolated from the viperid venom [34].

References

  1. Lock, B.A.; Wellehan, J. Chapter 8—Ophidia (Snakes). In Fowler’s Zoo and Wild Animal Medicine; Miller, R.E., Fowler, M.E., Eds.; W.B. Saunders: Philadelphia, PA, USA, 2015; Volume 8, pp. 60–74.
  2. Wallach, V.; Williams, K.L.; Boundy, J. Snakes of the World: A Catalogue of Living and Extinct Species, 1st ed.; CRC Press: Boca Raton, FL, USA, 2014; p. IX.
  3. World Health Organization (WHO). Snakebite Information and Data Platform. 2020. Available online: https://www.who.int/teams/control-of-neglected-tropical-diseases/snakebite-envenoming/snakebite-information-and-data-platform/overview#tab=tab_1,2020 (accessed on 10 January 2023).
  4. Casewell, N.R.; Jackson, T.N.W.; Laustsen, A.H.; Sunagar, K. Causes and consequences of snake venom variation. Trends Pharmacol. Sci. 2020, 41, 570–581.
  5. Barlow, A.; Pook, C.E.; Harrison, R.A.; Wüster, W. Coevolution of diet and prey-specific venom activity supports the role of selection in snake venom evolution. Proc. Biol. Sci. 2009, 276, 2443–2449.
  6. Ranawaka, U.K.; Lalloo, D.G.; de Silva, H.J. Neurotoxicity in snakebite—The limits of our knowledge. PLoS Negl. Trop. Dis. 2013, 7, e2302.
  7. Averin, A.S.; Utkin, Y.N. Cardiovascular effects of snake toxins: Cardiotoxicity and cardioprotection. Acta Nat. 2021, 13, 4–14.
  8. Modahl, C.M.; Mackessy, S.P. Venoms of rear-fanged snakes: New proteins and novel activities. Front. Ecol. Evol. 2019, 7, 279.
  9. Laustsen, A.H.; Gutiérrez, J.M.; Lohse, B.; Rasmussen, A.R.; Fernández, J.; Milbo, C.; Lomonte, B. Snake venomics of monocled cobra (Naja kaouthia) and investigation of human IgG response against venom toxins. Toxicon 2015, 99, 23–35.
  10. Palasuberniam, P.; Chan, Y.W.; Tan, K.Y.; Tan, C.H. Snake venom proteomics of Samar cobra (Naja samarensis) from the Southern Philippines: Short alpha-neurotoxins as the dominant lethal component weakly cross-neutralized by the Philippine cobra antivenom. Front. Pharmacol. 2021, 12, 727756.
  11. Patra, A.; Chanda, A.; Mukherjee, A.K. Quantitative proteomic analysis of venom from Southern India common krait (Bungarus caeruleus) and identification of poorly immunogenic toxins by immune-profiling against commercial antivenom. Expert Rev. Proteom. 2019, 16, 457–469.
  12. Ziganshin, R.H.; Kovalchuk, S.I.; Arapidi, G.P.; Starkov, V.G.; Hoang, A.N.; Thi Nguyen, T.T.; Nguyen, K.C.; Shoibonov, B.B.; Tsetlin, V.I.; Utkin, Y.N. Quantitative proteomic analysis of Vietnamese krait venoms: Neurotoxins are the major components in Bungarus multicinctus and phospholipases A2 in Bungarus fasciatus. Toxicon 2015, 107, 197–209.
  13. Harvey, A.L.; Robertson, B. Dendrotoxins: Structure-activity relationships and effects on potassium ion channels. Curr. Med. Chem. 2004, 11, 3065–3072.
  14. Nirthanan, S. Snake three-finger α-neurotoxins and nicotinic acetylcholine receptors: Molecules, mechanisms and medicine. Biochem Pharmacol. 2020, 181, 114168.
  15. Dingwoke, E.J.; Adamude, F.A.; Mohamed, G.; Klein, A.; Salihu, A.; Abubakar, M.S.; Sallau, A.B. Venom proteomic analysis of medically important Nigerian viper Echis ocellatus and Bitis arietans snake species. Biochem. Biophys. Rep. 2021, 28, 101164.
  16. Nguyen, G.T.T.; O’Brien, C.; Wouters, Y.; Seneci, L.; Gallissà-Calzado, A.; Campos-Pinto, I.; Ahmadi, S.; Laustsen, A.H.; Ljungars, A. High-throughput proteomics and in vitro functional characterization of the 26 medically most important elapids and vipers from sub-Saharan Africa. Gigascience 2022, 11, giac121.
  17. Del Brutto, O.H.; Del Brutto, V.J. Neurological complications of venomous snake bites: A review. Acta Neurol. Scand. 2012, 125, 363–372.
  18. Silva, G.M.; Berto, D.H.; Lima, C.A.; Waitman, K.B.; Lima, C.F.G.; Prezoto, B.C.; Vieira, M.L.; Rocha, M.M.T.; Gonçalves, L.R.C.; Andrade, S.A. Synergistic effect of serine protease inhibitors and a bothropic antivenom in reducing local hemorrhage and coagulopathy caused by Bothrops jararaca venom. Toxicon 2021, 199, 87–93.
  19. Gutiérrez, J.M.; Rucavado, A.; Escalante, T.; Díaz, C. Hemorrhage induced by snake venom metalloproteinases: Biochemical and biophysical mechanisms involved in microvessel damage. Toxicon 2005, 45, 997–1011.
  20. Huang, T.F.; Hsu, C.C.; Kuo, Y.J. Anti-thrombotic agents derived from snake venom proteins. Thromb. J. 2016, 14, 18.
  21. Tian, H.; Liu, M.; Li, J.; Xu, R.; Long, C.; Li, H.; Mwangi, J.; Lu, Q.; Lai, R.; Shen, C. Snake C-type lectins potentially contribute to the prey immobilization in Protobothrops mucrosquamatus and Trimeresurus stejnegeri venoms. Toxins 2020, 12, 105.
  22. Malina, T.; Krecsák, L.; Jelić, D.; Maretić, T.; Tóth, T.; Siško, M.; Pandak, N. First clinical experiences about the neurotoxic envenomings inflicted by lowland populations of the Balkan adder, Vipera berus bosniensis. Neurotoxicology 2011, 32, 68–74.
  23. Silva, A.; Kuruppu, S.; Othman, I.; Goode, R.J.; Hodgson, W.C.; Isbister, G.K. Neurotoxicity in Sri Lankan Russell’s Viper (Daboia russelii) Envenoming is Primarily due to U1-viperitoxin-Dr1a, a Pre-Synaptic Neurotoxin. Neurotox. Res. 2017, 31, 11–19.
  24. Silva, A.; Maduwage, K.; Sedgwick, M.; Pilapitiya, S.; Weerawansa, P.; Dahanayaka, N.J.; Buckley, N.A.; Siribaddana, S.; Isbister, G.K. Neurotoxicity in Russell’s viper (Daboia russelii) envenoming in Sri Lanka: A clinical and neurophysiological study. Clin. Toxicol. (Phila) 2016, 54, 411–419.
  25. Logonder, U.; Krizaj, I.; Rowan, E.G.; Harris, J.B. Neurotoxicity of ammodytoxin a in the envenoming bites of Vipera ammodytes ammodytes. J. Neuropathol. Exp. Neurol. 2008, 67, 1011–1019.
  26. Varga, C.; Malina, T.; Alföldi, V.; Bilics, G.; Nagy, F.; Oláh, T. Extending knowledge of the clinical picture of Balkan adder (Vipera berus bosniensis) envenoming: The first photographically-documented neurotoxic case from South-Western Hungary. Toxicon 2018, 143, 29–35.
  27. Lonati, D.; Giampreti, A.; Rossetto, O.; Petrolini, V.M.; Vecchio, S.; Buscaglia, E.; Mazzoleni, M.; Chiara, F.; Aloise, M.; Gentilli, A.; et al. Neurotoxicity of European viperids in Italy: Pavia Poison Control Centre case series 2001–2011. Clin. Toxicol. 2014, 52, 269–276.
  28. Fuchs, J.; Gessner, T.; Kupferschmidt, H.; Weiler, S. Indigenous venomous snakebites in Switzerland: Analysis of reports to the National Poisons Information Centre over 22 years. Swiss Med. Wkly. 2021, 151, w30085.
  29. Ferquel, E.; de Haro, L.; Jan, V.; Guillemin, I.; Jourdain, S.; Teynié, A.; d’Alayer, J.; Choumet, V. Reappraisal of Vipera aspis venom neurotoxicity. PLoS ONE 2007, 2, e1194.
  30. Sahyoun, C.; Krezel, W.; Mattei, C.; Sabatier, J.M.; Legros, C.; Fajloun, Z.; Rima, M. Neuro- and cardiovascular activities of Montivipera bornmuelleri snake venom. Biology 2022, 11, 888.
  31. Clark, R.F.; Williams, S.R.; Nordt, S.P.; Boyer-Hassen, L.V. Successful treatment of crotalid-induced neurotoxicity with a new polyspecific crotalid Fab antivenom. Ann. Emerg. Med. 1997, 30, 54–57.
  32. de Sousa-e-Silva, M.C.; Tomy, S.C.; Tavares, F.L.; Navajas, L.; Larsson, M.H.; Lucas, S.R.; Kogika, M.M.; Sano-Martins, I.S. Hematological, hemostatic and clinical chemistry disturbances induced by Crotalus durissus terrificus snake venom in dogs. Hum. Exp. Toxicol. 2003, 22, 491–500.
  33. Clement, J.F.; Pietrusko, R.G. Pit viper snakebite in the United States. J. Fam. Pract. 1978, 6, 269–279.
  34. Slotta, K.; Fraenkel-Conrat, H. Schlangengifte III. Mitteilung: Reiningung und Krystallisation des Klapperschlangengiftes. Ber. Dtsch. Chem. Ges. 1938, 71B, 1076–1081.
More
© Text is available under the terms and conditions of the Creative Commons Attribution (CC BY) license; additional terms may apply. By using this site, you agree to the Terms and Conditions and Privacy Policy.
Upload a video for this entry
Information
Subjects: Toxicology
Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register :
Alexey Osipov
,
Yuri Utkin
View Times: 678
Revisions: 2 times (View History)
Update Date: 24 Feb 2023
Table of Contents
    1000/1000
    Hot Most Recent
    Academic Video Service
    Feedback