Bungarus (krait) envenomings are well-known for their life-threatening neurotoxic effects. However, their impact on coagulation remains largely unexplored experimentally or clinically. This study, examined the effect of begins to examine venoms from four Bungarus species-B. caeruleus, B. candidus, B. fasciatus, and B. flaviceps on human platelet poor plasma coagulation parameters using thromboelastography and coagulation inhibition assays. B. flaviceps completely inhibited clotting, while B. caeruleus only delayed clot formation. In contrast, B. candidus and B. fasciatus did not affect clotting. Subsequent examinations into the anticoagulant biochemical mechanisms demonstrated divergent pathophysiological pathways. B. caeruleus venom anticoagulant effects were prevented by the addition of an excess of phospholipids, with anticoagulation thereby the result of phospholipid depletion. In contrast B. flaviceps anticoagulation was not affected by the addition of an excess of phospholipids. Further investigations demonstrated that B. flaviceps mediates its anticoagulant toxicity through the inactivation of coagulation enzymes. The anticoagulant effects of both B. flaviceps and B. caeruleus were nullified by varespladib, a phospholipase A (PLA) inhibitor, revealing the toxin class involved. These results uncover previously unrecognized and unexplored anticoagulant effects of Bungarus venoms.

Tityus caripitensis is an endemic scorpion species found in the northeastern region from Venezuela, being responsible for sting accidents in this area. This study describes for the first time a biological, biochemical and electrophysiological partial characterization of Tityus caripitensis scorpion venom. The venom is toxic to mice with a LD50 of 20.2 μg/gr mouse. Animals experimentally envenomed with Tityus caripitensis venom gradually manifested clinical signs in response to sublethal doses. SDS-PAGE of the venom resulted in 7 fractions ranging in size from ∼3.5 to ≥38 kDa. The 6-8 kDa proteins could correspond to neurotoxins. In addition, the components of Tityus caripitensis venom were similar to those obtained in the electrophoretic profile of Tityus discrepans. The commercial anti- Tityus discrepans IgG showed reactivity against Tityus caripitensis venom. Tityus caripitensis venom could induce hematological changes such as hyperamylasemia and hyperglycemia. The venom modified voltage dependent Na  1.4 channels and blocked K + channels. Although Tityus caripitensis venom is less toxic than Tityus discrepans, they share molecular and antigenic components. This aspect should be considered in the application of antivenom treatment.

A 68-year-old woman, after an Indian cobra (Naja naja) bite, developed anaphylaxis, Takotsubo cardiomyopathy, and Kounis syndrome. She was initially diagnosed with acute coronary syndrome after anaphylaxis due to exposure to cobra venom, indicating Kounis syndrome. The echocardiogram, electrocardiogram, and almost complete reversal of dyskinetic myocardium established Takotsubo cardiomyopathy. Adrenaline, initially given for anaphylaxis, and noradrenaline as an intravenous infusion for hypotension potentially precipitated the ATAK complex. The diagnosis was established by history, low blood pressure, elevated troponin, numerous dyskinetic segments in the echocardiogram, and normal coronary vessels in the angiogram.

Green pit viper (Peltopelor trigonocephalus) is a medically important endemic snake in Sri Lanka. Its envenoming commonly causes local effects such as pain, swelling, blistering, and lymphadenopathy and rarely causes venom-induced consumption coagulopathy as a systemic effect. Despite its frequent encounters in estates, commonly tea and cinnamon plantations, reports of envenoming are rare and limited to nine reports in the literature. An extensive literature review confirms no previous reports of compartment syndrome following Sri Lankan Green pit viper bites. We report two cases of acute compartment syndrome leading to fasciotomy, of which, in addition, case 1 patient developed venom-induced consumption coagulopathy.

Apis dorsata stings are amongst the most frequent insect-stings in Sri Lanka. A. dorsata venom consists of a mixture of components including PLA, melittin, hyaluronidase and apamin. However, there are no studies done in Sri Lanka to evaluate the environmental influence in venom production. We, herein, tried to correlate the variations in those four venom components of A. dorsata with environmental factors (temperature, rainfall, wind speed and relative humidity). The venom components were analyzed using high-performance liquid chromatography (HPLC) and variations in environmental factors were gathered from the Department of Meteorology, Sri Lanka. Of the four components, PLA (r = 0.718; p = 0.009 and r = 0.636; p = 0.026) and melittin r = 0.734; p = 0.007 and r = 0.582; p = 0.047) showed significant correlations with temperature and wind speed, respectively. Whilst relative humidity showed significant negative correlations with PLA (r = - 0.634; p = 0.027) and melittin (r = -0.643; p = 0.024). There was no significant correlation of climatic parameters with hyaluronidase or apamin. The results indicated a variation in the composition of venom components with the month in which the venom was collected due to climatic influence and it should be considered when therapeutic grade venom preparations are produced.

Intraspecific phenotypic variation can be used as a window into the ecological differences among individuals of a species and lead to a better understanding of adaptive evolution. Adaptive traits, such as venom, that play an important ecological role for a species are useful models for understanding the sources of intraspecific variation. Intraspecific studies on front-fanged venomous snakes have offered deeper insights into the diverse mechanisms and adaptations that support the effectiveness of venom across species. Despite the extensive research on front-fanged venomous snakes, rear-fanged snakes, representing two-thirds of all snake species, have been largely overlooked. To test for sex and age-based intraspecific venom variation, we sequenced the messenger RNA from the Duvernoy's gland of 9 male and 10 female Common Garter Snakes, Thamnophis sirtalis, of different sizes from a single location. Our data represent the most venom gland transcriptomes of any venomous snake species from a single location and represent the first Duvernoy's venom gland transcriptomes for Thamnophis sirtalis. We found four toxin families dominate the Thamnophis sirtalis transcriptome: Snake Venom Metalloproteinases (SVMPs), Three-finger toxins (3FTxs), Cysteine-Rich Secretory Proteins (CRISPs), and C-type lectins (CTLs). Thamnophis sirtalis exhibits a unique balance in toxin expression, with approximately 30% each of neurotoxic (3FTx-dominated) and enzymatic (SVMP-dominated) components. No other published RFS Duvernoy's gland transcriptome displays this ratio, rather they are dominated by one or the other. Additionally, venom expression varies with sex and size, with differences in toxin gene expression between males and females as they grow. Our study provides new insights on venom composition in a RFS species and highlights the amount of intraspecific variation possible among individuals from a single population.

Coralsnakes of the genus Micrurus include more than 80 species distributed in the American continent. They produce potent neurotoxic venoms acting at the neuromuscular junction and potentially leading to respiratory paralysis and death. The vast majority of proteins in coralsnake venoms belong to the three-finger toxin (3FTx) and the group I phospholipase A (PLA) families. Previous studies using 'bottom-up' proteomic strategies have revealed a compositional dichotomy of toxin expression by which different Micrurus species display a predominance of either 3FTx or PLA proteins in their venoms, possibly linked to the phylogeographic structure of the genus radiation. 'Top-down' proteomics (TDP) allows the direct analysis of intact proteins in a high resolution mass spectrometer, circumventing the limitations of the 'peptide-to-protein inference problem' inherent to the bottom-up approach. Here, we analyzed the venoms of five out of the six Micrurus species that inhabit Costa Rica, by using a TDP approach. Results unveil venom proteoforms that are shared between these species, and provide additional insights into the variable compositional complexity of these venoms and relationships to their 3FTx/PLA dichotomy.

Naja kaouthia is a medically important snake, widely distributed throughout Southeast Asia, with a diverse venom composition. N. kaouthia venom is subject to significant intraspecific variation, caused by several factors, such as the wide geographic distribution of the species, sexual and ontogenetic factors. However, individual variation is a factor that has only been studied with small sample size groups and/or with pooled samples. With this in mind, this study evaluates the composition and in-vitro enzymatic activities of 29 individual venom samples from specimens born in captivity, with a similar genetic background caused by inbreeding, using SDS-PAGE under reducing conditions, RP-HPLC profiles and enzymatic activities of PLA, LAAO and proteolytic activity over azocasein. Even in this scenario, we were able to observe significant variations in abundance and activity of PLA. Individual variations in LAAO activity, as well as a sexual dimorphism in which males present a significantly higher LAAO activity than females were observed. Phosphodiasterase and CRiSP abundance were also found and considered to have multiple effects in the clinical manifestations of envenomation by presenting synergistic effects with other proteins from N. kaouthia venom. The RP-HPLC profiles were better at detecting compositional differences than SDS-PAGE profiles and better correlated with enzymatic activities, being a better technique to screen variation profiles and reinforcing the importance of individual venom analysis prior to pooling.

Despite the numerous incidents of scorpion envenoming worldwide, little is known about the effects of maternal venom exposure and serotherapy on fetal development. The impact of antivenom on pregnant rats envenomed by Tityus serrulatus venom was examined. The venom caused alterations in the development of the offspring, yet the antivenom protected against these adverse effects and does not cause harm in itself, indicating the potential benefits of serotherapy.

Our previous studies have demonstrated the analgesic effects of botulinum toxin type A (BoNT/A) in a pre-clinical model of rheumatoid arthritis of the temporomandibular joint, where we proposed that BoNT/A decreases the neurogenic milieu after reaching the subnucleus caudalis. However, it is unknown whether BoNT/A directly regulates microglial cell activity. Therefore, the present study investigates the effects of BoNT/A on a microglial murine cell lineage (BV-2) in different inflammatory conditions. Cellular viability and proliferation were carried out with different concentrations of BoNT/A (ranging from 0.3125 to 20 U/mL) for 24 h. Cells were primed with carrageenan (300 μg/mL) or Lipopolysaccharides (LPS) (20 ng/mL). The gene expression of IL-1β, IL-6, IL-18, TNF-α, Ikkβ, p65, Iba1 were quantified using PCR-RT. The supernatant was used to determine IL-1β, IL-6, and TNF-α levels. For all data, the significance level was set at 5%. Overall, data analysis revealed that BoNT/A 1.25 U/mL exhibited the greatest effect cell viability and proliferation. In addition, genes associated with inflammatory response in both stimuli (carrageenan and LPS) were downregulated in the presence of BoNT/A. Lastly, BoNT/A mitigates the protein levels of IL-1β and TNF-α in a time and dose-dependent manner. In conclusion, our results revealed that BoNT/A directly modulates the microglial cells' activities in an inflammatory context, opening new perspectives for using BoNT/A, considering its potential immunomodulatory effect.

This study investigates the toxicity of bioactive compounds isolated from the halophytic plant Halocnemum strobilaceum against A549 lung cancer cells. Sequential extraction using petroleum ether, chloroform, and methanol yielded various fractions, with the petroleum ether extract demonstrating the highest cytotoxicity. Through bioassay-guided fractionation and isolation techniques, including vacuum liquid chromatography and column chromatography, three compounds were identified: (1) Di(2-ethylhexyl) phthalate, (2) isorhamnetin-3-glucoside, and (3) quercetin-3-glucoside. The cytotoxic effects of these compounds were assessed using the MTT assay, revealing significant toxicity on A549 cells, with quercetin-3-glucoside exhibiting 78% cytotoxicity and isorhamnetin-3-glucoside showing 69% cytotoxicity at a concentration of 100 μg/mL. These findings suggest that the toxic effects of H. strobilaceum may be attributed to the presence of bioactive compounds, such as flavonoids and polyphenols, known for their antioxidant and free-radical scavenging capabilities. This highlights the potential of H. strobilaceum as a source of novel anti-cancer agents, warranting further studies to elucidate the mechanisms of action and explore therapeutic applications.

Scorpion envenomation's ignored public health problem in tropical and subtropical countries is alarming. Particularly dangerous for small children and the elderly, it can cause severe problems and even death. Recent studies have proposed the creation of rapid, easy, species-specific, and sensitive detection kits as an alternative to the methods currently used to identify scorpions. Unfortunately, there is currently no commercially available technology for detecting scorpion envenomation in clinical settings, especially in remote tropical health centres. This study delineates the most dangerous scorpion species globally and the advancements in identifying their stings in vitro or in envenomed plasma. Furthermore, we have highlighted the practical challenges associated with scorpion venom detection and the necessity for innovative, expedited, and more accessible detection kits in countries where scorpion envenomation poses a significant issue.

This study describes the epidemiological, clinical, and pathological aspects of an outbreak of ruminal acidosis and ruminitis caused by the ingestion of hedge lucerne (Desmanthus virgatus L.) in 70 cattle in the state of Paraiba, Northeastern Brazil. The herd had been transported from the state of Piauí to Paraiba. The deaths of the cattle occurred 15 days after the animals were introduced to a native pasture containing D. virgatus. All animals exhibited ruminal atony, which ranged from mild to severe. A total of 35 cattle died, with five undergoing necropsy. Initial clinical signs included apathy, followed by a marked increase in left abdominal volume, consistent with ruminal distension, absence of rumination (ruminal atony), lateral recumbency, and ultimately death. All affected animals were treated with oral administration of rumen fluid, enteral fluid therapy, and oral antacids. During this period, twenty animals succumbed to the condition, and an additional 15 died after being relocated, resulting in a 50% fatality rate. Significant gross pathological findings were observed primarily in the digestive system. The forestomachs were markedly distended, containing large amounts of reddish, pasty, and serous ingesta. A demarcation line was evident in the esophagus, separating the pale and bloodless distal esophagus from the congested proximal esophagus at the thoracic inlet, corresponding to the "bloat line." Frothy material was present in the tracheal lumen, indicating pulmonary edema. Additionally, rectal prolapse was noted. Histopathological examination revealed marked edema and severe hydropic (ballooning) degeneration of the basal layer in the forestomachs, along with intercellular edema. Separation of the epithelium from the lamina propria, forming multiple clefts, was observed, accompanied by areas of lymphoplasmacytic inflammatory infiltrate in the submucosa. This study demonstrates that this plant can cause severe gastrointestinal disturbances in cattle unaccustomed to its consumption and ingesting large quantities of the plant's shoots.

Poisonous plants are naturally found in the environment and are easily reachable especially by children. These plants pose significant risks ranging from mild or asymptomatic to severe and even life-threatening. Data on poisonous plants of Lebanon is scarce and scattered; therefore, there remains a significant gap in the literature concerning poisonous plants in Lebanon. This study relied on a thorough review of existing literature on poisonous plants of Lebanon and their effects. Based on our experience in the field and on leveraging available data from the literature, a list of important potentially toxic plants in Lebanon was compiled. Toxic plants in Lebanon were categorized based on their chemical properties into groups such as alkaloids; glycosides; proteins, peptides, and lectins; phenols and phenylpropanoids; terpenes and resins; carboxylic acids; and other (uncategorized). The clinical effects of these plants were discussed in detail to provide an overview of the toxicity that they can cause. This study is part of our ongoing work on poisonous plants of Lebanon. It aims to fill a gap pertaining to poisonous plant; it will benefit healthcare workers and the public at the same time. Prompt recognition of plant exposure and their manifestations will allow for better clinical management especially among emergency healthcare workers and professionals. In addition, this review will increase awareness of Lebanese public about the poisonous plants of Lebanon with the ultimate aim to prevent these toxic occurrences from the beginning.

As global warming and water eutrophication, the multiple proliferation of harmful cyanobacteria can form algal blooms and cause serious ecological problems. In recent years, the large-scale and persistent cyanobacterial blooms occur frequently worldwide and have attracted widespread attention due to the harmful impacts. Among these harmful bloom-forming cyanobacteria, the ecological and toxicological impacts of planktonic cyanobacteria have been extensively studied. However, research on the ecological risks and adverse effects of harmful benthic cyanobacteria is lagging. Filter-feeding fish could suffer from more toxic stimuli than other fish due to their special feeding habits. To investigate and compare the complex toxic effects of different kinds of harmful cyanobacteria on fish, three different-sized (i.e. small, medium, and large) juvenile silver carp (Hypophthalmichthys molitrix) and bighead carp (Aristichthys nobilis) were exposed to cyanobacterial blooms-related density (1 × 10 cells/mL) of Microcystis aeruginosa ( i.e. generating microcystins) and Oscillatoria sp. (i.e. generating cylindrospermopsin) for 3 d, after which biomarkers of oxidative stress and inflammation in the liver of fish were detected. The silver carp and bighead carp can effectively ingest Microcystis cells but cannot effectively ingest Oscillatoria cells through the measurement of the levels of cyanotoxins. Both Microcystis and Oscillatoria cells can induce different levels of oxidative stress and inflammatory responses in the liver of these juvenile filter-feeding fish via altering the biochemical parameters of the antioxidant system (e.g. superoxide dismutase activity) and immune system (e.g. interleukin-1β level). Therefore, our research identified potential data gaps that how the different types of cyanobacteria induce toxic effects in the liver of juvenile filter-feeding fish in a short time. This study contributes to a better understanding of the short-term adverse effects of different cyanobacterial species on juvenile fish, suggesting that the benthic toxic cyanobacteria-induced ecological and health risks require further attention.

Tissue repair and regeneration present significant clinical challenges. Despite the array of treatments currently available in this domain, the urgent demand for innovative therapies persists, with the goal of enhancing patient quality of life. Recently, the application of botulinum neurotoxin type A (BoNT/A) has expanded within the realm of tissue repair and regeneration. This review critically examines the utilization of BoNT/A, specifically focusing on its vascular effects, potential in nerve regeneration, and contributions to bone healing. This analysis not only offers fresh insights into the diverse mechanisms of action of BoNT/A but also explores additional therapeutic possibilities for patients.

Evidence-based therapies to manage the clinical signs of intoxication caused by toxic plants in livestock are lacking. For that reason, the aim of this work was to develop a drug-based intervention for the management of clinical signs of piperidine alkaloid intoxication in livestock. The actions of anabasine, coniine, γ-coniceine, and two total alkaloid extracts from Lupinus sulphureus were compared in the presence and absence of the nicotinic acetylcholine receptor partial agonist varenicline in RD cells, mice and goats. Pretreatment of RD cells with 10.0 μM varenicline significantly shifted the anabasine fifty percent effective concentration (EC) value to a greater concentration and blocked the response of the cells to coniine. γ-coniceine did not have any effect on RD cells as measured by membrane potential sensing dye. Swiss Webster mice median lethal dose (LD) values for anabasine, coniine, γ-coniceine were 1.5, 5.5, and 3.7 mg/kg respectively, and pretreatment with 10.0 mg/kg i. p. dosed varenicline shifted the LD values to 4.2, 9.1, and 4.3 mg/kg respectively. The rodent LD value of the Pendelton, WA L. sulphureus quinolizidine alkaloid extract was shifted to a lesser concentration by varenicline while the Ritzville, WA L. sulphureus piperidine alkaloid extract was shifted to a greater concentration by varenicline. The clinical signs of intoxication in goats orally dosed with Conium maculatum were exacerbated by 0.5, 1.0 and 10.0 mg/kg i. v. dosed varenicline. These results suggest that varenicline was effective at shifting piperidine alkaloid EC values in RD cells and increasing piperidine but not quinolizidine alkaloid LD values in mice and was not useful at managing the clinical signs of poison hemlock intoxication in goats.

Foothill death camas (Z. paniculatus) grows on the foothill ranges of western North America and is acutely toxic to livestock grazing these ranges. The toxic alkaloids in foothill death camas are zygadenine and a series of zygadenine esters, with zygacine, the 3-acetyl ester of zygadenine, being the most abundant. In this study, earwax was evaluated as a specimen to determine livestock exposure to foothill death camas. Death camas alkaloids were detected in the earwax of sheep administered oral doses of foothill death camas alkaloids. In addition, death camas alkaloids were detected in the earwax of sheep that grazed rangeland with abundant death camas. This study demonstrates the potential of earwax as a noninvasive specimen for chemical analyses to aid in the diagnosis of livestock that may have been exposed to and poisoned by death camas. The results from this study indicate that diagnosticians should analyze for zygacine and zygadenine in the earwax of livestock suspected to have been poisoned by foothill death camas.

To analysis repair function of mucin-2(MUC2) and glycoprotein particles on the tight junction protein of uterus under bacterial endotoxins. In this experiment, we showed that the thicker mucus layer of the uterus is used to prevent the translocation of endotoxin at 21d postdelivery. When endotoxin acts on the uterus to thin its mucous layer, the cells in the lamina propria of the uterus secrete a large number of glycoprotein particles at 27d postdelivery. Due to a significantly decrease in the expression of glycosyltransferase, the glycoprotein particles are incompletely glycosylation MUC2, which can interact with the cell membrane and are released in large quantities in the form of exocytosis. These glycoprotein particles can significantly repair tight junction proteins in the inter-cellular space and significantly increase the expression of Claudin-1, JAM (Junction adhesion molecule-A), E-cadherin, ZO-1(Zonula occludens-1) and desmosome proteins after endotoxin treatment. The results of the present study show that endotoxins can thin the uterine mucus layer and accelerate the release of incompletely glycosylated MUC2 from lamina propria cells. In inter-cellular spaces, MUC2 can increase its expression levels and distribution area to repair the tight junction structure of cells with larger gaps. Further strengthening of the barrier prevents endotoxin translocation by repairing the tight junction structure of uterine epithelial cells.