Venom-Induced Tissue Damage

A special issue of Toxins (ISSN 2072-6651). This special issue belongs to the section "Animal Venoms".

Deadline for manuscript submissions: closed (31 December 2022) | Viewed by 44399

Special Issue Editors


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Guest Editor
School of Biological Sciences, University of Reading, Reading RG5 4EW, UK
Interests: regeneration; stem cells; muscle; venom; human; necrosis; therapy; snake

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Guest Editor
School of Pharmacy, University of Reading, Reading RG6 6UB, UK
Interests: venom research; sequence, structure and functional analysis of venom proteins; development of diagnostic and improved therapeutic strategies for snakebites; the impact of venoms on the cardiovascular system; clinical man-agement of snakebites in patients; policy development for snakebites
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Special Issue Information

Dear Colleagues,

Venoms from diverse species including snakes, spiders, scorpions, centipedes and jellyfish contain a complex mixture of toxins. While the systemic effects (such as coagulotoxicity and neurotoxicity) of venoms are relatively well understood, there is a paucity of information regarding their impacts on specific tissues or cell types. Therefore, this Special Issue focusses on the direct effects of a broad range of venoms and/or their toxins from any venomous species (both vertebrates and invertebrates) on tissue damage. We welcome manuscripts reporting the cytotoxic actions of venoms and/or their isolated components on any tissues including, but not limited to, skeletal muscle, vasculature, lymphatic system, kidneys, lungs, liver and heart. The manuscript may report robust results using experimental animals under in vivo settings, cultured or isolated cells in ex vivo conditions or any tissue damage-related issues from envenomed human victims. We hope to build this Special Issue with a range of different articles reporting the toxicity of distinctive venoms on various tissues to exemplify the spectrum of venom-induced damage in several tissues/organs. Hence, we would be very grateful if colleagues in the field of venom research could consider submitting their manuscripts to this Special Issue, in order to make this a beneficial to a wide range of researchers in this field.

Prof. Dr. Ketan Patel
Dr. Sakthivel Vaiyapuri
Guest Editors

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Keywords

  • venom
  • venom-induced tissue damage
  • venomous animals
  • tissue damage
  • muscle damage
  • kidney damage
  • liver damage
  • snakebite
  • venomous bite
  • invertebrate venom

Published Papers (14 papers)

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17 pages, 4433 KiB  
Article
Comparative Study of Toxic Effects and Pathophysiology of Envenomations Induced by Carybdea brevipedalia (Cnidaria: Cubozoa) and Nemopilema nomurai (Cnidaria: Scyphozoa) Jellyfish Venoms
by Du Hyeon Hwang, Phil-Ok Koh, Ramachandran Loganathan Mohan Prakash, Jinho Chae, Changkeun Kang and Euikyung Kim
Toxins 2022, 14(12), 831; https://doi.org/10.3390/toxins14120831 - 28 Nov 2022
Viewed by 2012
Abstract
Jellyfish stings can result in local tissue damage and systemic pathophysiological sequelae. Despite constant occurrences of jellyfish stings in oceans throughout the world, the toxinological assessment of these jellyfish envenomations has not been adequately reported in quantitative as well as in qualitative measurements. [...] Read more.
Jellyfish stings can result in local tissue damage and systemic pathophysiological sequelae. Despite constant occurrences of jellyfish stings in oceans throughout the world, the toxinological assessment of these jellyfish envenomations has not been adequately reported in quantitative as well as in qualitative measurements. Herein, we have examined and compared the in vivo toxic effects and pathophysiologic alterations using experimental animal models for two representative stinging jellyfish classes, i.e., Cubozoa and Scyphozoa. For this study, mice were administered with venom extracts of either Carybdea brevipedalia (Cnidaria: Cubozoa) or Nemopilema nomurai (Cnidaria: Scyphozoa). From the intraperitoneal (IP) administration study, the median lethal doses leading to the deaths of mice 24 h post-treatment after (LD50) for C. brevipedalia venom (CbV) and N. nomurai venom (NnV) were 0.905 and 4.4697 mg/kg, respectively. The acute toxicity (i.e., lethality) of CbV was much higher with a significantly accelerated time to death value compared with those of NnV. The edematogenic activity induced by CbV was considerably (83.57/25 = 3.343-fold) greater than NnV. For the evaluation of their dermal toxicities, the epidermis, dermis, subcutaneous tissues, and skeletal muscles were evaluated toxinologically/histopathologically following the intradermal administration of the venoms. The minimal hemorrhagic doses (MHD) of the venoms were found to be 55.6 and 83.4 μg/mouse for CbV and NnV, respectively. Furthermore, the CbV injection resulted in extensive alterations of mouse dermal tissues, including severe edema, and hemorrhagic/necrotic lesions, with the minimum necrotizing dose (MND) of 95.42 µg/kg body weight. The skin damaging effects of CbV appeared to be considerably greater, compared with those of NnV (MND = 177.99 µg/kg). The present results indicate that the toxicities and pathophysiologic effects of jellyfish venom extracts may vary from species to species. As predicted from the previous reports on these jellyfish envenomations, the crude venom extracts of C. brevipedalia exhibit much more potent toxicity than that of N. nomurai in the present study. These observations may contribute to our understanding of the toxicities of jellyfish venoms, as well as their mode of toxinological actions, which might be helpful for establishing the therapeutic strategies of jellyfish stings. Full article
(This article belongs to the Special Issue Venom-Induced Tissue Damage)
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16 pages, 3105 KiB  
Article
Experimental Bothrops atrox Envenomation: Blood Plasma Proteome Effects after Local Tissue Damage and Perspectives on Thromboinflammation
by Joeliton S. Cavalcante, Ingrid Mayara da Cunha Brito, Laudicéia Alves De Oliveira, Luciana Curtolo De Barros, Cayo Almeida, Bruno Cesar Rossini, Duaran Lopes Sousa, Renata Sousa Alves, Roberta Jeane Bezerra Jorge and Lucilene Delazari dos Santos
Toxins 2022, 14(9), 613; https://doi.org/10.3390/toxins14090613 - 01 Sep 2022
Cited by 11 | Viewed by 2032
Abstract
The clinical manifestations of Bothrops atrox envenoming involve local and systemic changes, among which edema requires substantial attention due to its ability to progress to compartmental syndromes and sometimes cause tissue loss and amputations. However, the impact of edema on the poisoned body’s [...] Read more.
The clinical manifestations of Bothrops atrox envenoming involve local and systemic changes, among which edema requires substantial attention due to its ability to progress to compartmental syndromes and sometimes cause tissue loss and amputations. However, the impact of edema on the poisoned body’s system has not been explored. Thus, the present study aimed to explore the systemic pathological and inflammatory events that are altered by intraplantar injection of B. atrox venom in a mouse model through hematologic, lipidic, and shotgun proteomics analysis. Plasma samples collected showed a greater abundance of proteins related to complement, coagulation, lipid system, platelet and neutrophil degranulation, and pathways related to cell death and ischemic tolerance. Interestingly, some proteins, in particular, Prdx2 (peroxiredoxin 2), Hba (hemoglobin subunit alpha), and F9 (Factor IX), increased according to the amount of venom injected. Our findings support that B. atrox venom activates multiple blood systems that are involved in thromboinflammation, an observation that may have implications for the pathophysiological progression of envenomations. Furthermore, we report for the first time a potential role of Prdx2, Hba, and F9 as potential markers of the severity of edema/inflammation in mice caused by B. atrox. Full article
(This article belongs to the Special Issue Venom-Induced Tissue Damage)
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18 pages, 5263 KiB  
Article
Histopathological Changes in the Liver, Heart and Kidneys Following Malayan Pit Viper (Calloselasma rhodostoma) Envenoming and the Neutralising Effects of Hemato Polyvalent Snake Antivenom
by Wipapan Khimmaktong, Nazmi Nuanyaem, Nissara Lorthong, Wayne C. Hodgson and Janeyuth Chaisakul
Toxins 2022, 14(9), 601; https://doi.org/10.3390/toxins14090601 - 30 Aug 2022
Cited by 4 | Viewed by 2468
Abstract
Calloselasma rhodostoma (Malayan pit viper) is a medically important snake species that is widely distributed across Southeast Asia. Systemic coagulopathy causing severe haemorrhage and local tissue injury is commonly observed following C. rhodostoma envenoming. However, nephrotoxicity and congestive heart failure were previously reported [...] Read more.
Calloselasma rhodostoma (Malayan pit viper) is a medically important snake species that is widely distributed across Southeast Asia. Systemic coagulopathy causing severe haemorrhage and local tissue injury is commonly observed following C. rhodostoma envenoming. However, nephrotoxicity and congestive heart failure were previously reported in a patient who had a long length of hospital stay. In this study, we determined the effect of C. rhodostoma envenoming on cardiovascular disturbances and the associated morphological changes in the liver, heart and kidneys using animal models. We also evaluated the efficacy of Hemato polyvalent antivenom (HPAV; Queen Saovabha Memorial Institute (QSMI) of the Thai Red Cross Society, Thailand) in neutralising the histopathological effects of C. rhodostoma venom. The intravenous (i.v.) administration of C. rhodostoma venom (1000 µg/kg) caused a rapid decrease in mean arterial pressure (MAP) followed by complete cardiac collapse in anaesthetized rats. Moreover, the intraperitoneal (i.p.) administration of C. rhodostoma venom (11.1 mg/kg; 3 × LD50) for 24 h caused cellular lesions in the liver and heart tissues. C. rhodostoma venom also induced nephrotoxicity, as indicated by the presence of tubular injury, interstitial vascular congestion and inflammatory infiltration in the whole area of the kidney. The administration of HPAV, at manufacturer-recommended doses, 15 min prior to or after the addition of C. rhodostoma venom reduced the extent of the morphological changes in the liver, heart and kidneys. This study found that experimental C. rhodostoma envenoming induced cardiovascular disturbances, hepatotoxicity and nephrotoxicity. We also highlighted the potential broad utility of HPAV to neutralise the histopathological effects of C. rhodostoma venom. The early delivery of antivenom appears capable of preventing envenoming outcomes. Full article
(This article belongs to the Special Issue Venom-Induced Tissue Damage)
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13 pages, 2204 KiB  
Article
Altered RNome expression in Murine Gastrocnemius Muscle following Exposure to Jararhagin, a Metalloproteinase from Bothrops jararaca Venom
by Andrezza Nascimento, Bianca Cestari Zychar, Rodrigo Pessôa, Alberto José da Silva Duarte, Patricia Bianca Clissa and Sabri Saeed Sanabani
Toxins 2022, 14(7), 472; https://doi.org/10.3390/toxins14070472 - 09 Jul 2022
Cited by 1 | Viewed by 1337
Abstract
Small RNAs (sRNAs) and microRNAs (miRNAs) are small endogenous noncoding single-stranded RNAs that regulate gene expression in eukaryotes. Experiments in mice and humans have revealed that a typical small RNA can affect the expression of a wide range of genes, implying that small [...] Read more.
Small RNAs (sRNAs) and microRNAs (miRNAs) are small endogenous noncoding single-stranded RNAs that regulate gene expression in eukaryotes. Experiments in mice and humans have revealed that a typical small RNA can affect the expression of a wide range of genes, implying that small RNAs function as global regulators. Here, we used small RNA deep sequencing to investigate how jararhagin, a metalloproteinase toxin produced from the venom of Bothrops jararaca, affected mmu-miRNAs expression in mice 2 hours (Jar 2hrs) and 24 hours (Jar 24hrs) after injection compared to PBS control. The findings revealed that seven mmu-miRNAs were substantially differentially expressed (p value (p (Corr) cut-off 0.05, fold change ≥ 2) at 2 hrs after jararhagin exposure and that the majority of them were upregulated when compared to PBS. In contrast to these findings, a comparison of Jar 24hrs vs. PBS 24hrs demonstrated that the majority of identified mmu-miRNAs were downregulated. Furthermore, the studies demonstrated that mmu-miRNAs can target the expression of several genes involved in the MAPK signaling pathway. The steady antithetical regulation of mmu-miRNAs may correlate with the expression of genes that trigger apoptosis via MAPK in the early stages, and this effect intensifies with time. The findings expand our understanding of the effects of jararhagin on local tissue lesions at the molecular level. Full article
(This article belongs to the Special Issue Venom-Induced Tissue Damage)
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8 pages, 1494 KiB  
Article
Ultrasound-Guided Compression Method Effectively Counteracts Russell’s Viper Bite-Induced Pseudoaneurysm
by Subramanian Senthilkumaran, Stephen W. Miller, Harry F. Williams, Rajendran Vaiyapuri, Ravi Savania, Namasivayam Elangovan, Ponniah Thirumalaikolundusubramanian, Ketan Patel and Sakthivel Vaiyapuri
Toxins 2022, 14(4), 260; https://doi.org/10.3390/toxins14040260 - 06 Apr 2022
Cited by 6 | Viewed by 4946
Abstract
Russell’s viper (Daboia russelii), one of the ‘Big Four’ venomous snakes in India, is responsible for the majority of snakebite-induced deaths and permanent disabilities. Russell’s viper bites are known to induce bleeding/clotting abnormalities, as well as myotoxic, nephrotoxic, cytotoxic and neurotoxic [...] Read more.
Russell’s viper (Daboia russelii), one of the ‘Big Four’ venomous snakes in India, is responsible for the majority of snakebite-induced deaths and permanent disabilities. Russell’s viper bites are known to induce bleeding/clotting abnormalities, as well as myotoxic, nephrotoxic, cytotoxic and neurotoxic envenomation effects. In addition, they have been reported to induce rare envenomation effects such as priapism, sialolithiasis and splenic rupture. However, Russell’s viper bite-induced pseudoaneurysm (PA) has not been previously reported. PA or false aneurysm is a rare phenomenon that occurs in arteries following traumatic injuries including some animal bites, and it can become a life-threatening condition if not treated promptly. Here, we document two clinical cases of Russell’s viper bites where PA has developed, despite antivenom treatment. Notably, a non-surgical procedure, ultrasound-guided compression (USGC), either alone, or in combination with thrombin was effectively used in both the cases to treat the PA. Following this procedure and additional measures, the patients made complete recoveries without the recurrence of PA which were confirmed by subsequent examination and ultrasound scans. These data demonstrate the development of PA as a rare complication following Russell’s viper bites and the effective use of a simple, non-surgical procedure, USGC for the successful treatment of PA. These results will create awareness among healthcare professionals on the development of PA and the use of USGC in snakebite victims following bites from Russell’s vipers, as well as other viper bites. Full article
(This article belongs to the Special Issue Venom-Induced Tissue Damage)
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11 pages, 1410 KiB  
Article
Local Cytotoxic Effects in Cobra Envenoming: A Pilot Study
by Jing-Hua Lin, Wang-Chou Sung, Han-Wei Mu and Dong-Zong Hung
Toxins 2022, 14(2), 122; https://doi.org/10.3390/toxins14020122 - 07 Feb 2022
Cited by 14 | Viewed by 3003
Abstract
The cobra (genus Naja (N.)) is one of the most common venomous snakes. Due to its frequency and deadly complications of muscle paralysis, local necrosis, and chronic musculoskeletal disability, it should not be ignored. The pathology of devastating tissue destruction, even [...] Read more.
The cobra (genus Naja (N.)) is one of the most common venomous snakes. Due to its frequency and deadly complications of muscle paralysis, local necrosis, and chronic musculoskeletal disability, it should not be ignored. The pathology of devastating tissue destruction, even though specific antivenoms exist, is not fully clear. Here, we attempted to dig in envenomed tissues to study the clinical toxicology of cobra venom. Four cases of N. atra snake envenomation, in which the subjects developed advanced tissue injury, were involved in this study. We used enzyme-ligand sandwich immunoassay (ELISA) to assay the whole venom, cytotoxin A3 and short-chain neurotoxin (sNTX) in blood, bullae, wound discharge, and debrided tissue. We found that persistently high concentrations of venom and toxins, especially cytotoxin A3, were detected in bullae, wound discharge fluid and necrotic tissue of these patients even after large doses of specific antivenom treatment, and wide excision and advanced debridement could largely remove these toxins, lessen the size of necrosis, and promote wound healing. We also found that the point-of-care apparatus, ICT-Cobra kit, might be used to promptly monitor the wound condition and as one of the indicators of surgical intervention in cases of cobra envenomation in Taiwan. Full article
(This article belongs to the Special Issue Venom-Induced Tissue Damage)
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17 pages, 3354 KiB  
Article
Isolation and Characterization of A2-EPTX-Nsm1a, a Secretory Phospholipase A2 from Malaysian Spitting Cobra (Naja sumatrana) Venom
by Nur Atiqah Haizum Abdullah, Muhamad Rusdi Ahmad Rusmili, Syafiq Asnawi Zainal Abidin, Mohd Farooq Shaikh, Wayne C. Hodgson and Iekhsan Othman
Toxins 2021, 13(12), 859; https://doi.org/10.3390/toxins13120859 - 02 Dec 2021
Cited by 5 | Viewed by 3069
Abstract
Phospholipase A2 (PLA2) toxins are one of the main toxin families found in snake venom. PLA2 toxins are associated with various detrimental effects, including neurotoxicity, myotoxicity, hemostatic disturbances, nephrotoxicity, edema, and inflammation. Although Naja sumatrana venom contains substantial quantities [...] Read more.
Phospholipase A2 (PLA2) toxins are one of the main toxin families found in snake venom. PLA2 toxins are associated with various detrimental effects, including neurotoxicity, myotoxicity, hemostatic disturbances, nephrotoxicity, edema, and inflammation. Although Naja sumatrana venom contains substantial quantities of PLA2 components, there is limited information on the function and activities of PLA2 toxins from the venom. In this study, a secretory PLA2 from the venom of Malaysian N. sumatrana, subsequently named A2-EPTX-Nsm1a, was isolated, purified, and characterized. A2-EPTX-Nsm1a was purified using a mass spectrometry-guided approach and multiple chromatography steps. Based on LC-MSMS, A2-EPTX-Nsm1a was found to show high sequence similarity with PLA2 from venoms of other Naja species. The PLA2 activity of A2-EPTX-Nsm1 was inhibited by 4-BPB and EDTA. A2-EPTX-Nsm1a was significantly less cytotoxic in a neuroblastoma cell line (SH-SY5Y) compared to crude venom and did not show a concentration-dependent cytotoxic activity. To our knowledge, this is the first study that characterizes and investigates the cytotoxicity of an Asp49 PLA2 isolated from Malaysian N. sumatrana venom in a human neuroblastoma cell line. Full article
(This article belongs to the Special Issue Venom-Induced Tissue Damage)
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13 pages, 2335 KiB  
Article
Neutrophil Gelatinase–Associated Lipocalin Acts as a Robust Early Diagnostic Marker for Renal Replacement Therapy in Patients with Russell’s Viper Bite–Induced Acute Kidney Injuries
by Subramanian Senthilkumaran, Ketan Patel, Anika Salim, Pradeep Vijayakumar, Harry F. Williams, Rajendran Vaiyapuri, Ravi Savania, Namasivayam Elangovan, Ponniah Thirumalaikolundusubramanian, M. Fazil Baksh and Sakthivel Vaiyapuri
Toxins 2021, 13(11), 797; https://doi.org/10.3390/toxins13110797 - 12 Nov 2021
Cited by 3 | Viewed by 2419
Abstract
Snakebite-induced acute kidney injury (AKI) is frequently observed in patients following bites from vipers such as Russell’s viper (Daboia russelii) in India. Currently, the levels of serum creatinine are mainly used as a marker to determine the necessity for renal replacement [...] Read more.
Snakebite-induced acute kidney injury (AKI) is frequently observed in patients following bites from vipers such as Russell’s viper (Daboia russelii) in India. Currently, the levels of serum creatinine are mainly used as a marker to determine the necessity for renal replacement therapy (RRT) (haemodialysis) in severe cases of AKI. However, it takes up to 48 h to ascertain a distinct change in creatinine levels compared to its baseline level upon admission. The time lost between admission and the 48 h timepoint significantly affects the clinical management of snakebite victims. Moreover, early diagnosis of AKI and decision on the necessity for RRT in snakebite victims is critical in saving lives, reducing long-term complications, and minimising treatment costs arising from expensive haemodialysis. Neutrophil gelatinase–associated lipocalin (NGAL) has been recently studied as a robust early marker for AKI in non-snakebite patients. However, its suitability for clinical use in snakebite victims has not been rigorously established. Here, we demonstrate the clinical significance of plasma NGAL as a robust marker for RRT following AKI using a large cohort (309) of Russell’s viper victims without any pre-existing health conditions. NGAL levels upon admission are positively correlated with creatinine levels at 48 h in different stages of AKI. Overall, NGAL acts as a robust early marker to ascertain the need for RRT following Russell’s viper bites. The quantification of NGAL can be recommended as a routine test in hospitals that treat snakebites to decide on RRT at early time points instead of waiting for 48 h to confirm the increase in creatinine levels. The diagnostic use of NGAL in Russell’s viper victims with pre-existing comorbidities and for other vipers should be evaluated in future studies. Full article
(This article belongs to the Special Issue Venom-Induced Tissue Damage)
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12 pages, 2947 KiB  
Article
Analysis of the Necrosis-Inducing Components of the Venom of Naja atra and Assessment of the Neutralization Ability of Freeze-Dried Antivenom
by Cheng-Hsuan Ho, Liao-Chun Chiang, Yan-Chiao Mao, Kuo-Cheng Lan, Shih-Hung Tsai, Yu-Jen Shih, Yuan-Sheng Tzeng, Chin-Sheng Lin, Wen-Loung Lin, Wei-Hsuan Fang, Kuang-Ting Chen, Chi-Hsin Lee, Dapi Meng-Lin Chiang and Shing-Hwa Liu
Toxins 2021, 13(9), 619; https://doi.org/10.3390/toxins13090619 - 02 Sep 2021
Cited by 10 | Viewed by 3595
Abstract
Patients bitten by Naja atra who are treated with bivalent freeze-dried neurotoxic antivenom in Taiwan have an improved survival rate but develop necrotic wound changes. The World Health Organization (WHO) has suggested using the minimum necrotizing dose (MND) of venom as a method [...] Read more.
Patients bitten by Naja atra who are treated with bivalent freeze-dried neurotoxic antivenom in Taiwan have an improved survival rate but develop necrotic wound changes. The World Health Organization (WHO) has suggested using the minimum necrotizing dose (MND) of venom as a method of evaluating the neutralization effect of antivenom. The aim of this study was to evaluate the effectiveness of antivenom for the prevention of necrosis based on the MND and clarify which component of the venom of N. atra induces necrosis. The neurotoxins (NTXs) were removed from the crude venom (deNTXs), and different concentrations of deNTXs were injected intradermally into the dorsal skin of mice. After three days, the necrotic lesion diameter was found to be approximately 5 mm, and the MND was calculated. A reduction in the necrotic diameter of 50% was used to identify the MND50. Furthermore, both phospholipase A2 (PLA2) and cytotoxins (CTXs) were separately removed from the deNTXs to identify the major necrosis-inducing factor, and the necrotic lesions were scored. All mice injected with deNTXs survived for three days and developed necrotic wounds. The MND of the deNTXs for mice was 0.494 ± 0.029 µg/g, that of the deNTXs-dePLA2 (major component retained: CTXs) was 0.294 ± 0.05 µg/g, and that of the deNTX-deCTX (major component retained: PLA2) venom was greater than 1.25 µg/g. These values show that CTX is the major factor inducing necrosis. These results suggest that the use of the deNTXs is necessary to enable the mice to survive long enough to develop venom-induced cytolytic effects. CTXs play a major role in N. atra-related necrosis. However, the MND50 could not be identified in this study, which meant that the antivenom did not neutralize venom-induced necrosis. Full article
(This article belongs to the Special Issue Venom-Induced Tissue Damage)
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18 pages, 97477 KiB  
Article
A Biochemical and Pharmacological Characterization of Phospholipase A2 and Metalloproteinase Fractions from Eastern Russell’s Viper (Daboia siamensis) Venom: Two Major Components Associated with Acute Kidney Injury
by Janeyuth Chaisakul, Orawan Khow, Kulachet Wiwatwarayos, Muhamad Rusdi Ahmad Rusmili, Watcharamon Prasert, Iekhsan Othman, Syafiq Asnawi Zainal Abidin, Mongkon Charoenpitakchai, Wayne C. Hodgson, Lawan Chanhome and Narongsak Chaiyabutr
Toxins 2021, 13(8), 521; https://doi.org/10.3390/toxins13080521 - 26 Jul 2021
Cited by 12 | Viewed by 2947
Abstract
Acute kidney injury (AKI) following Eastern Russell’s viper (Daboia siamensis) envenoming is a significant symptom in systemically envenomed victims. A number of venom components have been identified as causing the nephrotoxicity which leads to AKI. However, the precise mechanism of nephrotoxicity [...] Read more.
Acute kidney injury (AKI) following Eastern Russell’s viper (Daboia siamensis) envenoming is a significant symptom in systemically envenomed victims. A number of venom components have been identified as causing the nephrotoxicity which leads to AKI. However, the precise mechanism of nephrotoxicity caused by these toxins is still unclear. In the present study, we purified two proteins from D. siamensis venom, namely RvPLA2 and RvMP. Protein identification using LCMS/MS confirmed the identity of RvPLA2 to be snake venom phospholipase A2 (SVPLA2) from Thai D. siamensis venom, whereas RvMP exhibited the presence of a factor X activator with two subunits. In vitro and in vivo pharmacological studies demonstrated myotoxicity and histopathological changes of kidney, heart, and spleen. RvPLA2 (3–10 µg/mL) caused inhibition of direct twitches of the chick biventer cervicis muscle preparation. After administration of RvPLA2 or RvMP (300 µg/kg, i.p.) for 24 h, diffuse glomerular congestion and tubular injury with minor loss of brush border were detected in envenomed mice. RvPLA2 and RvMP (300 µg/kg; i.p.) also induced congestion and tissue inflammation of heart muscle as well as diffuse congestion of mouse spleen. This study showed the significant roles of PLA2 and SVMP in snake bite envenoming caused by Thai D. siamensis and their similarities with observed clinical manifestations in envenomed victims. This study also indicated that there is a need to reevaluate the current treatment strategies for Thai D. siamensis envenoming, given the potential for irreversible nephrotoxicity. Full article
(This article belongs to the Special Issue Venom-Induced Tissue Damage)
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11 pages, 3800 KiB  
Article
Influential Factors of Local Tissue Necrosis after Taiwan Cobra Bites: A Secondary Analysis of the Clinical Significance of Venom Detection in Patients of Cobra Snakebites
by Chih-Chuan Lin, Chung-Hsien Chaou and Shi-Ying Gao
Toxins 2021, 13(5), 338; https://doi.org/10.3390/toxins13050338 - 07 May 2021
Cited by 4 | Viewed by 4501
Abstract
Local tissue swelling, inflammation, and wound necrosis are observed in Taiwan cobra bites. Knowledge of the factors influencing local tissue necrosis after cobra bites might improve the cobra bite treatment strategy. Therefore, we aimed to explore the factors influencing local tissue necrosis after [...] Read more.
Local tissue swelling, inflammation, and wound necrosis are observed in Taiwan cobra bites. Knowledge of the factors influencing local tissue necrosis after cobra bites might improve the cobra bite treatment strategy. Therefore, we aimed to explore the factors influencing local tissue necrosis after cobra bites. This was a retrospective observational cohort study. All patients clinical presentations including serum venom levels for determining the influential factors in this study were obtained from Hung et al.’s previous study. Clinical features, such as bite information, initial swelling, patient presentation time, serum venom levels, and antivenom, use were extracted. The measurement outcome was the development of wound necrosis. The factors influencing wound necrosis were investigated using univariate and logistic regression analyses. The influential factors of local tissue necrosis and their areas under the curve were: initial limb swelling, 0.88; presentation time × serum level, 0.80; initial necrosis, 0.75; patient presentation time, 0.70. Serum venom level alone cannot be used as a predictive factor. The development of tissue necrosis might be associated with the venom factor, time factor, and their interaction. These influential factors can be used in future studies to evaluate antivenom efficacy. Full article
(This article belongs to the Special Issue Venom-Induced Tissue Damage)
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22 pages, 4393 KiB  
Article
A Comprehensive Study Monitoring the Venom Composition and the Effects of the Venom of the Rare Ethiopian Endemic Snake Species Bitis parviocula
by Vladimír Petrilla, Magdaléna Polláková, Barbora Bekešová, Zuzana Andrejčáková, Radoslava Vlčková, Dana Marcinčáková, Monika Petrillová, Eva Petrovová, Drahomíra Sopková and Jaroslav Legáth
Toxins 2021, 13(5), 299; https://doi.org/10.3390/toxins13050299 - 22 Apr 2021
Cited by 2 | Viewed by 2770
Abstract
The Ethiopian endemic snake of the species Bitis parviocula, recognized for its colorful patterns, might be more interesting as we look deeper into the venom activity. We assayed the effects of venoms from the most widespread venomous African Bitis arietens and closely related [...] Read more.
The Ethiopian endemic snake of the species Bitis parviocula, recognized for its colorful patterns, might be more interesting as we look deeper into the venom activity. We assayed the effects of venoms from the most widespread venomous African Bitis arietens and closely related species Bitis parviocula using The Hen’s Egg Test—Chorioallantoic membrane test (HET-CAM) and Chicken embryotoxicity screening test (CHEST), acetylcholinesterase (AChE) analysis, cytotoxicity assay performed on cell lines and protein analysis of selected venoms. Our results indicated that B. parviocula venom contains vasoactive compounds that have a direct effect on blood vessels. The AChE analysis showed significant ability inhibiting AChE activity in embryonic tissue. Cytotoxicity observed on A549 ATCC® CCL-185™ cells indicates the possible presence of cytotoxic agents in B. parviocula venom. We proved previously described differences in the composition of venom obtained from B. arietans and B. parviocula by using electrophoresis and total protein concentration. Based on similarities in vasoactive effects observed after administration of venoms onto a chicken chorioallantoic membrane, we suggest that venom from B. arietans and B. parviocula might share certain venom proteins responsible for haemotoxicity. The main active components of B. parviocula venom are unknown. Our results suggest that it might be worth performing proteomic analysis of B. parviocula venom as it might contain medically valuable compounds. Full article
(This article belongs to the Special Issue Venom-Induced Tissue Damage)
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8 pages, 2975 KiB  
Case Report
An Unnecessary Russell’s Viper Bite on the Tongue Due to Live Snake Worship and Dangerous First Aid Emphasise the Urgent Need for Stringent Policies
by Subramanian Senthilkumaran, S. V. Arathisenthil, Jarred Williams, Harry F. Williams, Ponniah Thirumalaikolundusubramanian, Ketan Patel and Sakthivel Vaiyapuri
Toxins 2022, 14(12), 817; https://doi.org/10.3390/toxins14120817 - 22 Nov 2022
Cited by 1 | Viewed by 3228
Abstract
India suffers the highest incidence of snakebite envenomation (SBE) in the world. Rural communities within India and other countries have long-held cultural beliefs surrounding snakes and SBE treatments, with snake statues present in numerous Hindu temples. While most cultural beliefs are well respected [...] Read more.
India suffers the highest incidence of snakebite envenomation (SBE) in the world. Rural communities within India and other countries have long-held cultural beliefs surrounding snakes and SBE treatments, with snake statues present in numerous Hindu temples. While most cultural beliefs are well respected and do not affect anyone, some people worship live venomous snakes without any safety precautions. Moreover, they practice various inappropriate first aid and traditional treatments that exacerbate SBE-induced complications. We report an unusual case of SBE on the tongue of a patient who was bitten while worshipping Russell’s viper following the advice of an astrologer based on the appearance of a snake in the patient’s dream. Following the bite, the tongue was deeply incised by the priest as a first aid to mitigate SBE-induced complications. The patient suffered profuse bleeding and swelling of the tongue resulting in difficulties in intubating them. The patient regained consciousness after antivenom administration, intranasal ventilation, and blood removal from the mouth. The tongue underwent extensive surgery to restore movement and function. This report advises caution to those undertaking the extremely risky practice of worshipping live snakes and emphasises the urgent need to develop and enforce policies to mitigate such actions and educate rural communities. Full article
(This article belongs to the Special Issue Venom-Induced Tissue Damage)
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5 pages, 3270 KiB  
Case Report
Envenoming by a Marine Blood Worm (Glycera)
by Daniela M. Durkin, Alison N. Young, Kent Khtikian, Zuzana Karjala, Arin L. Isenstein, Bryan G. Fry and Matthew R. Lewin
Toxins 2022, 14(7), 495; https://doi.org/10.3390/toxins14070495 - 17 Jul 2022
Cited by 2 | Viewed by 3959
Abstract
Bites from venomous marine annelid ‘bloodworms’ (e.g., Glycera spp.) do not appear to have been described in the medical literature despite being seemingly well-known to bait diggers and fishermen. The few laboratory study reports describe their venom composition and physiological effects in vitro [...] Read more.
Bites from venomous marine annelid ‘bloodworms’ (e.g., Glycera spp.) do not appear to have been described in the medical literature despite being seemingly well-known to bait diggers and fishermen. The few laboratory study reports describe their venom composition and physiological effects in vitro to be primarily proteolytic enzymes and neurotoxins apparently used for predation and defense. Herein, we present the report of a symptomatic envenoming suffered by a marine ecologist bitten while performing her field research. The local effects included a rapid onset of pain, swelling, and numbness at the bite site “as if injected with local anesthetic”. Additional signs and symptoms appearing over a two-week period were consistent with both delayed venom effects and potentially secondary infection. The late signs and symptoms resolved during a course of antibiotic treatment with doxycycline prescribed as a precaution and lack of resources to consider a wound culture. Comments about annelid bites sporadically appear in the popular literature, especially pertaining to the fishing industry, under names such as ‘bait-diggers hand’. While these bites are not known to be dangerously venomous, they seem to produce painful local symptoms and possibly increase the risk of marine bacterial infections that could be associated with more serious outcomes. More cases need to be formally described to better understand the natural history of these types of envenomation. Full article
(This article belongs to the Special Issue Venom-Induced Tissue Damage)
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