Transient Hematotoxicity After Emerald Horned Pitviper (Ophryacus smaragdinus) Envenomation: A Case Report.

BACKGROUND: A minority of snake envenomations in the United States involve non-native snakes. In this report, we describe what we believe is the first documented human envenoming from an emerald horned pitviper, Ophryacus smaragdinus. CASE REPORT: A previously healthy 36-year-old woman was bitten on her left index finger by a captive emerald horned pitviper she was medicating at work. Swelling to the entire hand was present on emergency department arrival. She had no systemic symptoms and her initial laboratory studies were unremarkable. The affected limb was elevated. We administered five vials of Antivipmyn TRIⓇ (Bioclon), which specifically lists Ophryacus among the envenomations for which it is indicated. She developed pruritus and was treated with IV diphenhydramine and famotidine. Her swelling improved, but her repeat laboratory studies were notable for a platelet count of 102 K/µL and a fibrinogen level of 116 mg/dL. She declined additional antivenom because of the previous allergic reaction. She was admitted for further monitoring and pain control. Subsequent laboratory tests were better, but a small hemorrhagic bleb developed at the bite site. She was discharged the next day and followed up as an outpatient. Her swelling had resolved, her bleb had healed, and her laboratory studies continued to improve. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Emergency physicians may be required to treat bites from non-native snakes. Many of these bites will warrant treatment with non-U.S. Food and Drug Administration-approved antivenoms. Consultation with a regional poison center or medical toxicologist may be necessary to procure the proper antivenom.

Merrem's Hump-Nosed Viper (Hypnale hypnale) Bite on the Tongue of an Infant Leading to Upper Airway Obstruction: An Unusual Presentation.

Snakebites in unusual anatomical locations may lead to life-threatening consequences. Merrem's hump-nosed viper (Hypnale hypnale) is a medically important snake in Sri Lanka and India that causes many bites and envenomings. Their bites occur almost exclusively on upper and lower limbs and commonly result in local effects, with some patients developing systemic envenoming. No antivenom is available for treating envenoming by H. hypnale. We report an unusual case of H. hypnale bite on the tongue of a 10-month-old infant resulting in rapid local swelling of the tongue and floor of the mouth, requiring prompt intervention to prevent life-threatening upper airway obstruction. Early tracheostomy prevented upper airway obstruction and, along with supportive steroid therapy and antibiotics, led to a complete resolution of the local effects of the infant without permanent disability, despite the unavailability of antivenom.

Study of defensive behavior of a venomous snake as a new approach to understand snakebite.

Snakebites affect millions of people worldwide. The majority of research and management about snakebites focus on venom and antivenom, with less attention given to snake ecology. The fundamental factor in snakebites is the snakes' defensive biting behavior. Herein we examine the effects of environmental variables (temperature, time of day, and human stimulus) and biological variables (sex and body size) on the biting behavior of a medically significant pit viper species in Brazil, Bothrops jararaca (Viperidae), and associate it with the epidemiology of snakebites. Through experimental simulations of encounters between humans and snakes, we obtained behavioral models applicable to epidemiological situations in the State of São Paulo, Brazil. We found a significant overlap between behavioral, morphological, environmental, and epidemiological data. Variables that increase snakebites in epidemiological data also enhance the tendency of snakes to bite defensively, resulting in snakebites. We propose that snakebite incidents are influenced by environmental and morphological factors, affecting the behavior of snakes and the proportion of incidents. Thus, investigating behavior of snakes related to snakebite incidents is a valuable tool for a better understanding of the epidemiology of these events, helping the prediction and, thus, prevention of snakebites.

Ultrasound-guided selective peripheral nerve block for the snakebite pain management in the emergency department: Our experience.

Envenomation from snakebites (SBs) is a significant public health hazard globally. The venomous SB is associated with moderate-to-severe pain. Weak opioids such as tramadol or acetaminophen are commonly used for pain management but often provide inadequate analgesia. We hereby report our experience of using ultrasound-guided selective superficial peroneal, sural, and saphenous nerve blocks for pain management following SBs in nine patients. The selective peripheral nerve blocks are achieved with a small amount of local anesthesia and without loss of motor functions.

Presentation, treatment profiles, and outcome of snake bite patients presented in emergency department at a tertiary hospital in Eastern Nepal.

Background: Snake bite is one of the most common animal bites in Nepal. Different species of snake cause different clinical presentations. The incidence of snakebite is very high in rural Nepal. The objectives were to assess the presenting pattern, demographic profile, outcome, and treatment profiles of snakebite victims admitted to the emergency ward. Materials and Methods: A retrospective cross-sectional study was conducted among the patients who presented in emergency department with alleged history of snake bites from 2015 to 2016. The patient's record files were reviewed and the relevant data were recorded on a self-designed proforma. Descriptive statistics were calculated using SPSS version 11.5. Results: Out of 137 snakebite victims, 73 (53.3%) were female. The mean age was 35.17 ± 18.27 years. The upper limb (59%) was the most common site for snake bites followed by the lower limb (35.1%). Fifty patients (36.2%) were bitten by snakes during night (20.00-2.59 AM). Twenty-eight (20.4%) patients presented with ptosis as the most common sign and symptom followed by diplopia (15.3%). Out of 137 patients, 39 (28.5%) were admitted, 65 (47.4%) discharged, and 12 (8.8%) patients expired. Antisnake venom was given to 30 patients among which 23 patients (76.7%) were improved. Conclusions: Snake bite is one of the major problems in rural Nepal. It can be easily managed if treatment is given properly and in a timely manner. The importance of effective first aid management and effective treatment have to be disseminated among the peoples in rural areas via social media and radio.

A review on snake venom extracellular vesicles: Past to present.

Around 95% of snake venom is protein. Along with the soluble proteins, snake venom also contains proteins encapsulated in vesicles known as Snake Venom Extracellular Vesicles (SVEV). SVEVs are nano-sized membrane-bound vesicles released from the snake venom gland cells. The available published research works on SVEVs are minimal. Extracellular vesicles in the Snake Venom gland were initially discovered during the histopathological analysis of the Crotalus durissus terrificus snakes' venom gland. Later, various techniques were employed to isolate and characterize the SVEVs. The cargo of SVEV consists of a variety of proteins like Phospholipase A-2, C-type Lectins, L-Amino Acid Oxidase, Cysteine-Rich Secretory Proteins, Serine Proteinases, Dipeptidyl Peptidase-IV, Aminopeptidase-A, Ecto-5'-nucleotidases, Disintegrins. Proteomic data revealed the presence of some exclusive proteins in the SVEVs, and the other proteins are in varying concentrations in the SVEVs compared to their whole Venom. Interaction of SVEVs with mammalian cell lines showed the disruption of primary physiological functions leads to host immune modulation, and long-term effects of envenoming. Snakebite victim's blood showed variations in the specific Extracellular vesicle concentration. It has been hypothesized that SVEVs are responsible for long-term toxicity. The current review focuses on the various techniques adopted to isolate and characterize SVEVs and discusses the exclusiveness and variations of SVEV proteins and their role in snakebites.

Preclinical evaluation of single domain antibody efficacy in mitigating local tissue damage induced by Bothrops snake envenomation.

Camelid single-domain antibodies (VHH) represent a promising class of immunobiologicals for therapeutic applications due to their remarkable stability, specificity, and therapeutic potential. To enhance the effectiveness of antivenoms for snakebites, various methods have been explored to address limitations associated with serum therapy, particularly focusing on mitigating local damage and ensuring sustainable production. Our study aimed to characterize the pharmacological profile and neutralization capacity of anti-Phospholipase A2 (PLA2) monomeric VHH (Genbank accessions: KC329718). Using a post-envenoming mouse model, we used intravital microscopy to assess leukocyte influx, measured CK and LDH levels, and conducted a histopathology analysis to evaluate VHH KC329718's ability to neutralize myotoxic activity. Our findings demonstrated that VHH KC329718 exhibited heterogeneous distribution in muscle tissue. Treatment with VHH KC329718 reduced leukocyte influx caused by BthTX-I (a Lys-49 PLA2) by 28 %, as observed through intravital microscopy. When administered at a 1:10 ratio [venom or toxin:VHH (w/w)], VHH KC329718 significantly decreased myotoxicity, resulting in a 35-40 % reduction in CK levels from BthTX-I and BthTX-II (an Asp-49 PLA2) and a 60 % decrease in CK levels from B. jararacussu venom. LDH levels also showed reductions of 60%, 80%, and 60% induced by BthTX-I, BthTX-II, and B. jararacussu venom, respectively. Histological analysis confirmed the neutralization potential, displaying a significant reduction in tissue damage and inflammatory cell count in mice treated with VHH KC329718 post B. jararacussu venom inoculation. This study underscores the potential of monomeric anti-PLA2 VHH in mitigating myotoxic effects, suggesting a promising avenue for the development of new generation antivenoms to address current therapeutic limitations.

Pulmonary Thromboembolism following Russell's Viper Bites.

Snakebite envenoming and its resulting complications are serious threats to the health of vulnerable people living in rural areas of developing countries. The knowledge of the heterogeneity of symptoms associated with snakebite envenoming and their management strategies is vital to treat such life-threatening complications to save lives. Russell's viper envenomation induces a diverse range of clinical manifestations from commonly recognised haemotoxic and local effects to several rare conditions that are often not reported. The lack of awareness about these unusual manifestations can affect prompt diagnosis, appropriate therapeutic approaches, and positive outcomes for patients. Here, we report pulmonary thromboembolism that developed in three patients following Russell's viper envenomation and demonstrate their common clinical features and diagnostic and therapeutic approaches used. All patients showed clinical signs of local (oedema) and systemic (blood coagulation disturbances) envenomation, which were treated using polyvalent antivenom. They exhibited elevated heart rates, breathlessness, and reduced oxygen saturation, which are non-specific but core parameters in the diagnosis of pulmonary embolism. The recognition of pulmonary embolism was also achieved by an electrocardiogram, which showed sinus tachycardia and computed tomography and echocardiogram scans further confirmed this condition. Anti-coagulant treatment using low-molecular-weight heparin offered clinical benefits in these patients. In summary, this report reinforces the broad spectrum of previously unreported consequences of Russell's viper envenomation. The constant updating of healthcare professionals and the dissemination of major lessons learned in the clinical management of snakebite envenoming through scientific documentation and educational programs are necessary to mitigate the adverse impacts of venomous snakebites in vulnerable communities.

Alkaloids from Siparuna (Siparunaceae) are predicted as the inhibitors of proteolysis and plasma coagulation caused by snake venom and potentially counteract phospholipase A2 activity of Bothrops jararaca.

ETHNOPHARMACOLOGICAL RELEVANCE: Snakebite envenomation (SBE) is the world's most lethal neglected tropical disease. Bothrops jararaca is the species that causes the greatest number of SBEs in the South and Southeastern of Brazil. The main symptoms are local (inflammation, edema, hemorrhage, and myonecrosis) and systemic (hemorrhage, hemostatic alterations with consumptive coagulopathy, and death) effects. Species of the genus Siparuna, Siparunaceae, are used in folk and traditional medicine to treat SBE. However, limited information is available concerning Brazilian Siparuna species against SBE. AIM OF THE STUDY: To investigate the correlation between the compounds present in the extracts of five Siparuna species as potential agents against proteolytic activity, plasma coagulation, and phospholipase A2 (PLA2) activity caused by B. jararaca venom, using data obtained by UHPLC-MS/MS, biological activity, and multivariate statistics. MATERIALS AND METHODS: The ethanol extracts from leaves of S. ficoides, S. decipiens, S. glycycarpa, S. reginae, and S. cymosa were fractionated by liquid-liquid extraction using different solvents of increasing polarity (hexane, dichloromethane, ethyl acetate, and n-butanol), affording their respective extracts, totaling 25 samples that were assayed through in vitro plasma coagulation and proteolytic activity assays. Moreover, the extracts were analyzed by UHPLC-MS/MS, using electrospray ionization (ESI) and atmospheric-pressure chemical ionization (APCI) in negative and positive ionization modes. The data was processed in MZmine v. 2.53 and evaluated by multivariate statistical tests (PLS) using the software UnscramblerX v. 10.4. These data were also used to build molecular networks (GNPS), and some ions of interest could be annotated using the library of molecules on the GNPS platform. RESULTS: A total of 19 extracts inhibited B. jararaca-induced plasma coagulation, with emphasis on S. cymosa and S. reginae (800 s). The inhibition of the proteolytic activity was also promising, ranging from 16% (S. glycycarpa) to 99% (S. cymosa, S. decipiens, and S. reginae). In addition, most extracts from S. cymosa and S. reginae inhibited 70-90% of PLA2 activity. Based on data from positive mode APCI analyses, it was possible to obtain a statistic model with reliable predictive capacity which exhibited an average R2 of 0.95 and a Q2 of 0.88, indicating a robust fit. This process revealed five ions, identified as the alkaloids: coclaurine (1), stepholidine (2) O-methylisopiline (3), nornantenine (4) and laurolitsine (5). This is the first study to evidence the potential antivenom of alkaloids from Siparuna species. CONCLUSIONS: Altogether, our results give support to the popular use of Siparuna extracts in SBE accidents, suggesting their potential as an alternative or complementary strategy against envenoming by B. jararaca venom. The predicted ions in the chemometric analysis for the assayed activities can also be correlated with the blocking activity and encourage the continuation of this study for possible isolation and testing of individual compounds on the used models.

Protobothrops jerdonii (Jerdon's pit viper) and Protobothrops himalayanus (Himalayan lance-headed pit viper) bites: Clinical report on envenomings from North-East India, managed through remote consultation by a national-level Poison control center.

Members of the genus Protobothrops are amongst the more than twenty-eight range-restricted Indian pit viper species. Their bites and envenomings are rarely documented from India. Pit viper envenomings can be challenging to treat in the Indian setting, since available antivenoms do not satisfactorily neutralize their venoms. Herein, we present the first Indian reports on bites and envenoming by Protobothrops jerdonii and Protobothrops himalayanus resulting in local effects, coagulopathy and acute kidney injury in the case of the former and possible mild, isolated coagulopathy in the case of the latter; and discuss management-related challenges in the context of absent specific antivenoms.

Development of a membrane-disruption assay using phospholipid vesicles as a proxy for the detection of cellular membrane degradation.

Snakebite envenoming is a global health issue that affects millions of people worldwide, and that causes morbidity rates surpassing 450,000 individuals annually. Patients suffering from snakebite morbidities may experience permanent disabilities such as pain, blindness and amputations. The (local) tissue damage that causes these life-long morbidities is the result of cell- and tissue-damaging toxins present in the venoms. These compounds belong to a variety of toxin classes and may affect cells in various ways, for example, by affecting the cell membrane. In this study, we have developed a high-throughput in vitro assay that can be used to study membrane disruption caused by snake venoms using phospholipid vesicles from egg yolk as a substrate. Resuspended chicken egg yolk was used to form these vesicles, which were fluorescently stained to allow monitoring of the degradation of egg yolk vesicles on a plate reader. The assay proved to be suitable for studying phospholipid vesicle degradation of crude venoms and was also tested for its applicability for neutralisation studies of varespladib, which is a PLA2 inhibitor. We additionally made an effort to identify the responsible toxins using liquid chromatography, followed by post-column bioassaying and protein identification using high-throughput venomics. We successfully identified various toxins in the venoms of C. rhodostoma and N. mossambica, which are likely to be involved in the observed vesicle-degrading effect. This indicates that the assay can be used for screening the membrane degrading activity of both crude and fractionated venoms as well as for neutralisation studies.

Venomous snakebites in children: a 10 year experience in South China.

INTRODUCTION: Many studies have focused on snakebites in adults, but very few have described snakebites in children. METHODS: We reviewed the clinical characteristics and outcomes of children with venomous snakebites aged less than 15 years who presented to a regional medical centre in South China from January 2013 to December 2022. RESULTS: A total of 69 envenomed patients were analyzed in our study; 42 (60.9 per cent) patients were male, and 59 (85.5 per cent) reported lower limb bites. Most bites (89.8 per cent) occurred between April and October. Twenty-seven patients received first aid management, and 47 required admission to the general ward. Antivenom was administered to 58 patients, glucocorticoids to 43 patients, antibiotics to 48 patients, and tetanus antitoxin to 40 patients. No fatalities were reported. The most common snake identified was Trimeresurus albolabris. Four were classified as dry bites, 15 as mild, 43 as moderate, and seven as severe. The most common local signs were pain and swelling, while the most common systemic effects were haematological complications. Patients with high severity scores had significantly higher lactate dehydrogenase activities, creatine kinase isoenzyme activities, aspartate aminotransferase activities, D-dimer concentrations, prothrombin times and lower fibrinogen concentrations. In a receiver operating characteristic curve analysis of the values with the highest Youden index, the following cut-offs proved significant: lactate dehydrogenase activity > 248.1 U/L, creatine kinase isoenzyme activities > 17.5 U/L, fibrinogen concentration < 1,455 mg/L, D-dimer concentration > 437.0 µg/L, aspartate aminotransferase activity > 26.1 U/L, and prothrombin time > 15.2 seconds. DISCUSSION: This study provides insight into the epidemiology, clinical profile, and management of snakebites in children. Data from the present study were compared with those from our previous adult study. Limitations include that 50.7 per cent of our snakebites were attributed to Trimeresurus albolabris. Therefore, the results of our study may not be generalizable to all snakebites. CONCLUSION: The clinical symptoms were more severe in children than in adults in our previous study. Even though there were no fatalities, close monitoring should be performed to detect haematological and other potentially fatal complications promptly.

Assessing the Incidence of Snakebites in Rural Gabon-A Community-Based, Cross-Sectional Pilot Survey.

Snakebite envenoming (SBE) is a neglected tropical disease (NTD). Community-based studies from sub-Saharan Africa are urgently required as data on the incidence are scarce. This study aimed to determine the lifetime prevalence of snakebites in rural Gabon by preparing the conduct of a larger regional survey. A cross-sectional community-based epidemiological survey in Sindara, Ngounie province, was conducted. Households were interviewed about the history of snakebites of household members to calculate lifetime prevalence. In addition, the average annual incidence rate per 100,000 over the last 5 years was calculated. A total of 771 inhabitants were enrolled, of which 5 (0.65%; 95% confidence interval (95% CI: 0.2-1.5%)) were victims of snakebites. Over the past 5 years, annual incidence was 77 bites per 100,000 (95% CI: 0-620). This study provides a first rough estimate of the incidence of SBE from rural central Gabon, demonstrating the importance of this NTD. Key Contribution: The estimated annual incidence of snakebites found was 77 per 100,000. Snakebites occurred mainly during agricultural activities.

Understanding Local Reactions Induced by Bothrops jararaca Venom: The Role of Inflammatory Mediators in Leukocyte-Endothelium Interactions.

In recent years, extensive research has delved into the pathophysiology of local reactions triggered by Bothrops snake venoms. Even though antivenom works well at reducing death and systemic effects, it is still not very effective in treating local reactions because it cannot counteract damage that has already been triggered. This limitation might be attributed to certain molecules that amplify the venom-induced innate response. While evidence suggests endogenous mediators at the venom site play a role in this envenomation, in Brazil, the concurrent use of anti-inflammatory agents or other drugs alongside antivenom remains uncommon. This study evaluated the pharmacological mediation of alterations in leukocyte-endothelium interactions following the experimental envenomation of mice with Bothrops jararaca venom, the main culprit of snake-related accidents in Southeast Brazil. We treated envenomed mice with inhibitors of different pharmacological pathways and observed the cremaster muscle microcirculation with intravital microscopy. We found that eicosanoids related to cyclooxygenase pathways and nitric oxide significantly contributed to B. jararaca venom-induced alterations in leukocyte-endothelium interactions. Conversely, lipoxygenase-mediated eicosanoids, histamine, and serotonin had minimal participation. Notably, dexamethasone and antivenom treatment diminished B. jararaca venom-induced alterations in leukocyte-endothelium interactions. The limited efficacy of the antivenom in managing Bothrops venom-induced local reactions emphasizes the critical need for supplementary treatments to enhance therapeutic outcomes.

Clinico-Epidemiological Profile, Trends, and Health-Related Outcomes of Snakebite Victims: A One-Year Prospective Study from Eastern India.

INTRODUCTION: Snakebite envenomation is a significant life-threatening public health problem in Southeast Asia (SEA). In this region, India reported the largest number of snakebite deaths from 2000 to 2019 (1.2 million), with an average of 58,000 deaths yearly. METHODS: This prospective observational study was carried out among snakebite victims at the emergency department (ED) of a tertiary care public sector hospital in eastern India. RESULTS: A total of 145 cases of venomous snakebite were investigated. More than half (n = 81, 56%) of the snakebite victims were between 17 to 45 years. Most of the snakebite victims were male (68%) and were farmers (53%) by occupation. The majority of snakebites occurred during the daytime (76%) and while outdoors (67%). Most victims sustained a bite on the lower extremity (71%). The peak incidence of snakebites occurred from June to September (69%). Three-quarters of all patients were unaware of the required first aid measures following a snakebite. Among the 145 venomous snakebites, 48 were presumptively identified as the Indian cobra, 32 by the Indian krait, 56 by the Russel's viper, and 9 by saw-scaled viper. The mean duration from the snakebite to the onset of systemic effects in the Indian cobra was 52 ± 14.28 min, 66 ± 18.35 min in the Indian krait, 42 ± 13.47 min in Russel's viper, and 48 ± 16.38 min in saw-scaled viper. Respiratory failure was the commonly observed complication following an elapid envenomation. The mortality rate was 2.1% among the patients treated with antivenom. CONCLUSIONS: Snakebite is considered an occupational hazard in India, commonly affecting the young population in their productive period. The peak incidence was during monsoon season, and the majority had neurotoxic envenomation following an elapid bite (55%) that contributed to the increased mortality and morbidity among young adults. Of the 145 patients, the majority (84%) recovered fully with treatment; 16% of the victims developed morbidity viz cellulitis, respiratory failure, acute renal failure, compartment syndrome, local tissue necrosis, intracerebral hemorrhage, and disseminated intravascular coagulation. Appropriate first aid measures and timely medical intervention can significantly improve the treatment outcome following snakebites.

Snakebites in Cameroon: Tolerance of a Snake Antivenom (Inoserp™ PAN-AFRICA) in Africa in Real-Life Conditions.

Snakebite envenomation (SBE) is a public health issue in sub-Saharan countries. Antivenom is the only etiological treatment. Excellent tolerance is essential in managing SBE successfully. This study aimed to evaluate tolerance of InoserpTM PAN-AFRICA (IPA). It was conducted on fourteen sites across Cameroon. IPA was administered intravenously and repeated at the same dose every two hours if needed. Early and late tolerance was assessed by the onset of clinical signs within two hours and at a visit two weeks or more after the first IPA administration, respectively. Over 20 months, 447 patients presenting with a snakebite were included. One dose of IPA was administered to 361 patients and repeated at least once in 106 patients. No significant difference was shown between the proportion of adverse events in patients who received IPA (266/361, 73.7%) and those who did not (69/85, 81.2%) (p = 0.95). Adverse reactions, probably attributable to IPA, were identified in four (1.1%) patients, including one severe (angioedema) and three mild. All these reactions resolved favorably. None of the serious adverse events observed in twelve patients were attributed to IPA. No signs of late intolerance were observed in 302 patients. Tolerance appears to be satisfactory. The availability of effective and well-tolerated antivenoms would reduce the duration of treatment and prevent most disabilities and/or deaths.

Deciphering the interactions of scopoletin and scopolin from Catunaregam nilotica roots against Naja nigricollis phospholipase A2 enzyme.

Catuneragam nilotica has been used in ethnomedicine to treat snakebite, inflammation, and diarrhea among others. The aim of this research is to isolate, and characterize potential potential phospholipase A2 (PLA2) inhibitors from the roots of C. nilotica. The plant material was collected, authenticated, and sequentially extracted using solvents of increasing polarity starting from n-hexane, ethyl acetate, and methanol. The extracts as reported in our previous work, were screened in vitro for their inhibitory activity against PLA2 enzyme from N. nigricollis venom using acidimetric assay. In line with the bio-activity guided isolation, methanol extract (being the most active) was subjected to chromatographic separation using silica gel and sephadex LH-20 which resulted in the isolation and characterization of scopoletin, and scopolin; the compounds were able to inhibit the hydrolytic actions of PLA2 enzyme with percentage inhibition ranging from 67.82 to 100.00 % and 65.76-93.15 %, respectively while the standard Antisnake Venom (ASV) had 74.96-85.04 % after 10 min incubation at 37 °C. The molecular docking of the compounds against PLA2 enzyme was performed using Auto Dock Vina while ADME-Tox analysis was evaluated using swissADME and ProTox-II online servers; The findings indicated that both compounds were able to bind to the active site of PLA2 enzyme with high affinity (-6.5 to -6.2 kcal/mol) and they exhibited favorable drug-likeness and pharmacokinetic properties, and according to toxicity predictions, scopolin was found to be non-toxic (LD50 of 5000 mg/kg) while scopoletin has a slight chance of being toxic (LD50 of 3800 mg/kg). In conclusion, the findings of the research revealed that the roots of C. nilotica contains phytoconstituents with anti-PLA2 enzyme activity and thus, validates the ethnomedicinal claim of the use of the plant as herbal therapy against N. nigricollis envenomation.

Dermonecrosis caused by a spitting cobra snakebite results from toxin potentiation and is prevented by the repurposed drug varespladib.

Snakebite envenoming is a neglected tropical disease that causes substantial mortality and morbidity globally. The venom of African spitting cobras often causes permanent injury via tissue-destructive dermonecrosis at the bite site, which is ineffectively treated by current antivenoms. To address this therapeutic gap, we identified the etiological venom toxins in Naja nigricollis venom responsible for causing local dermonecrosis. While cytotoxic three-finger toxins were primarily responsible for causing spitting cobra cytotoxicity in cultured keratinocytes, their potentiation by phospholipases A2 toxins was essential to cause dermonecrosis in vivo. This evidence of probable toxin synergism suggests that a single toxin-family inhibiting drug could prevent local envenoming. We show that local injection with the repurposed phospholipase A2-inhibiting drug varespladib significantly prevents local tissue damage caused by several spitting cobra venoms in murine models of envenoming. Our findings therefore provide a therapeutic strategy that may effectively prevent life-changing morbidity caused by snakebite in rural Africa.

Acute compartment syndrome and fasciotomy after a viper bite in Italy: a case report.

BACKGROUND: Bites caused by European vipers are rare medical emergencies but can occasionally cause life-threatening complications. Viper venom causes local symptoms, which can be accompanied by systemic manifestations in severe cases. The local effects of snakebites include edema and, more rarely, necrosis and compartment syndrome. The consequences of envenomation are often more pronounced in children due to their smaller body size. CASE PRESENTATION: We present the case of a 6-year-old girl who experienced multiple viper bites in the lower limb in northwest Italy. The girl received supportive care but progressed to develop compartment syndrome that required emergency fasciotomy. The patient's condition improved promptly after surgical decompression and administration of antivenom, but full recovery required prolonged hospitalization and rehabilitation. CONCLUSIONS: This case highlights the importance of obtaining a timely assessment of the severity of viper envenomation without delaying the administration of antivenom in most serious cases. The presence of multiple bite marks on the patient is one factor that may help to predict the clinical severity of snakebites and anticipate symptom progression.

Varespladib mitigates acute liver injury via suppression of excessive mitophagy on Naja atra envenomed mice by inhibiting PLA2.

Snakebite envenomation often leads to severe visceral injuries, including acute liver injury (ALI). However, the toxicity mechanism remains unclear. Moreover, varespladib can directly inhibit phospholipase A2 (PLA2) in snake venom, but its protective effect on snakebite-induced ALI and the mechanism have not been clarified. Previous studies have shown that snake venom PLA2 leads to neuron cell death via reactive oxygen species (ROS), one of the initial factors related to the mitophagy pathway. The present study group also found that ROS accumulation occurred after Naja atra envenoming. Hematoxylin and eosin (H/E) staining and immunohistochemistry (IHC) were performed to identify the expression of inflammatory factors in the liver tissue, and flow cytometry and immunofluorescence were used to detect ROS levels and mitochondrial function. Immunofluorescence and western blotting were also used for detecting mitophagy pathway-related proteins. The results showed that N. atra bite induced ALI by activating mitophagy and inducing inflammation and that varespladib had a protective effect. Collectively, these results showed the pathological mechanism of ALI caused by N. atra bite and revealed the protective effect of varespladib.