Pub Date : 2024-11-22DOI: 10.1016/j.toxicon.2024.108187
Julián Fernández , Walter Chaves , David Vargas-Diaz , Daniel Petras , Bruno Lomonte
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 A2 (PLA2) 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 PLA2 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/PLA2 dichotomy.
{"title":"Top-down proteomics of venoms from five Micrurus species from Costa Rica: comparative composition of phospholipase A2-rich vs three-finger toxin-rich phenotypes","authors":"Julián Fernández , Walter Chaves , David Vargas-Diaz , Daniel Petras , Bruno Lomonte","doi":"10.1016/j.toxicon.2024.108187","DOIUrl":"10.1016/j.toxicon.2024.108187","url":null,"abstract":"<div><div>Coralsnakes of the genus <em>Micrurus</em> 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<sub>2</sub> (PLA<sub>2</sub>) families. Previous studies using ‘bottom-up’ proteomic strategies have revealed a compositional dichotomy of toxin expression by which different <em>Micrurus</em> species display a predominance of either 3FTx or PLA<sub>2</sub> 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 <em>Micrurus</em> 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<sub>2</sub> dichotomy.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"252 ","pages":"Article 108187"},"PeriodicalIF":2.6,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-21DOI: 10.1016/j.toxicon.2024.108184
Benedict T. Green, Stephen T. Lee, Kevin D. Welch, Daniel Cook, Clinton A. Stonecipher
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 (EC50) 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 (LD50) 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 LD50 values to 4.2, 9.1, and 4.3 mg/kg respectively. The rodent LD50 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 EC50 values in RD cells and increasing piperidine but not quinolizidine alkaloid LD50 values in mice and was not useful at managing the clinical signs of poison hemlock intoxication in goats.
{"title":"The actions of varenicline on alkaloids from Conium maculatum (poison hemlock), Lupinus sulphureus (sulphur lupine) and Nicotiana glauca (tree tobacco)","authors":"Benedict T. Green, Stephen T. Lee, Kevin D. Welch, Daniel Cook, Clinton A. Stonecipher","doi":"10.1016/j.toxicon.2024.108184","DOIUrl":"10.1016/j.toxicon.2024.108184","url":null,"abstract":"<div><div>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 <em>Lupinus sulphureus</em> 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<sub>50</sub>) 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<sub>50</sub>) 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<sub>50</sub> values to 4.2, 9.1, and 4.3 mg/kg respectively. The rodent LD<sub>50</sub> value of the Pendelton, WA <em>L. sulphureus</em> quinolizidine alkaloid extract was shifted to a lesser concentration by varenicline while the Ritzville, WA <em>L. sulphureus</em> piperidine alkaloid extract was shifted to a greater concentration by varenicline. The clinical signs of intoxication in goats orally dosed with <em>Conium maculatum</em> 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<sub>50</sub> values in RD cells and increasing piperidine but not quinolizidine alkaloid LD<sub>50</sub> values in mice and was not useful at managing the clinical signs of poison hemlock intoxication in goats.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"252 ","pages":"Article 108184"},"PeriodicalIF":2.6,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142693699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-20DOI: 10.1016/j.toxicon.2024.108181
Stephen T. Lee, Clinton A. Stonecipher, Kevin D. Welch, Daniel Cook
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.
{"title":"The evaluation of earwax as a noninvasive specimen to determine livestock exposure to death camas (Zigadenus paniculatus)","authors":"Stephen T. Lee, Clinton A. Stonecipher, Kevin D. Welch, Daniel Cook","doi":"10.1016/j.toxicon.2024.108181","DOIUrl":"10.1016/j.toxicon.2024.108181","url":null,"abstract":"<div><div>Foothill death camas (<em>Z. paniculatus</em>) 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.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"252 ","pages":"Article 108181"},"PeriodicalIF":2.6,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142688875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-19DOI: 10.1016/j.toxicon.2024.108180
W. Anura K. Wijesinghe , Thilina Rathnasekara , Ajith W. Wanniarachchi , Anjana Silva , Sisira Siribaddana
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.
一名 68 岁的妇女被印度眼镜蛇（Naja naja）咬伤后，出现了过敏性休克、塔克次博心肌病和库尼斯综合征。她最初被诊断为接触眼镜蛇毒液引起过敏性休克后的急性冠状动脉综合征，这表明她患有库尼斯综合征。通过超声心动图、心电图和几乎完全逆转的运动障碍心肌证实了塔克苏博心肌病。肾上腺素最初用于治疗过敏性休克，而去甲肾上腺素静脉注射用于治疗低血压，这可能会诱发 ATAK 综合征。根据病史、低血压、肌钙蛋白升高、超声心动图显示多个运动障碍节段以及血管造影显示冠状动脉血管正常，可以确诊该病。
{"title":"ATAK (Adrenaline, Takotsubo, anaphylaxis, and Kounis hypersensitivity-associated syndrome) following common cobra (Naja naja) bite: A case report from Sri Lanka","authors":"W. Anura K. Wijesinghe , Thilina Rathnasekara , Ajith W. Wanniarachchi , Anjana Silva , Sisira Siribaddana","doi":"10.1016/j.toxicon.2024.108180","DOIUrl":"10.1016/j.toxicon.2024.108180","url":null,"abstract":"<div><div>A 68-year-old woman, after an Indian cobra (<em>Naja naja</em>) 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.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"252 ","pages":"Article 108180"},"PeriodicalIF":2.6,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142682782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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.
{"title":"Acute compartment syndrome leading to fasciotomy, severe morbidity and long-term disabilities following Sri Lankan Green pit viper (Peltopelor trigonocephalus) envenomation","authors":"R.M.M.K. Namal Rathnayaka , P.E. Anusha Nishanthi Ranathunga , Y.N.M.P. Abeyrathne , Damsara A. Kularatne , S.A.M. Kularatne","doi":"10.1016/j.toxicon.2024.108179","DOIUrl":"10.1016/j.toxicon.2024.108179","url":null,"abstract":"<div><div>Green pit viper (<em>Peltopelor trigonocephalus</em>) 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.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"252 ","pages":"Article 108179"},"PeriodicalIF":2.6,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142668840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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 +v1.4 channels and blocked Kv + 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.
{"title":"Venom characterization of Venezuelan scorpion Tityus caripitensis","authors":"Amini Hudefe , Aurora Álvarez , Deyanell Hernández , Cecilia Castillo , Caridad Malave , Pedro Parrilla , Noraida Zerpa","doi":"10.1016/j.toxicon.2024.108174","DOIUrl":"10.1016/j.toxicon.2024.108174","url":null,"abstract":"<div><div><em>Tityus caripitensis</em> 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 <em>Tityus caripitensis</em> scorpion venom. The venom is toxic to mice with a LD50 of 20.2 μg/gr mouse. Animals experimentally envenomed with <em>Tityus caripitensis</em> 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 <em>Tityus caripitensis</em> venom were similar to those obtained in the electrophoretic profile of <em>Tityus discrepans.</em> The commercial anti- <em>Tityus discrepans</em> IgG showed reactivity against <em>Tityus caripitensis</em> venom. <em>Tityus caripitensis</em> venom could induce hematological changes such as hyperamylasemia and hyperglycemia. The venom modified voltage dependent Na <sup>+</sup> <sub>v</sub>1.4 channels and blocked K<sub>v</sub> + channels. Although <em>Tityus caripitensis</em> venom is less toxic than <em>Tityus discrepans</em>, they share molecular and antigenic components. This aspect should be considered in the application of antivenom treatment.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"252 ","pages":"Article 108174"},"PeriodicalIF":2.6,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142640006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-13DOI: 10.1016/j.toxicon.2024.108177
Tharwat El Zahran , Zeina Halabi , Alondra Barakat , Rony Imad El Hachem , Charbel Bou Nicolas , Sally Al Hassan , Aline Khalil
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.
{"title":"An overview of the poisonous plants of Lebanon and their effects","authors":"Tharwat El Zahran , Zeina Halabi , Alondra Barakat , Rony Imad El Hachem , Charbel Bou Nicolas , Sally Al Hassan , Aline Khalil","doi":"10.1016/j.toxicon.2024.108177","DOIUrl":"10.1016/j.toxicon.2024.108177","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"252 ","pages":"Article 108177"},"PeriodicalIF":2.6,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142640001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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 PLA2, LAAO and proteolytic activity over azocasein. Even in this scenario, we were able to observe significant variations in abundance and activity of PLA2. 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.
{"title":"Analysis of Naja kaouthia snake venom composition and in-vitro enzymatic activities of 29 specimens in captivity: Highlighting the importance of individual variation in venom pool production","authors":"Beatriz Kopel , Caroline Serino-Silva, Rebeca Barcelos Jantsch , Igor Castellar Sorila, Sávio S. Sant’Anna, Kathleen Fernandes Grego, Anita Mitico Tanaka-Azevedo","doi":"10.1016/j.toxicon.2024.108173","DOIUrl":"10.1016/j.toxicon.2024.108173","url":null,"abstract":"<div><div><em>Naja kaouthia</em> is a medically important snake, widely distributed throughout Southeast Asia, with a diverse venom composition. <em>N. kaouthia</em> 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<sub>2</sub>, LAAO and proteolytic activity over azocasein. Even in this scenario, we were able to observe significant variations in abundance and activity of PLA<sub>2</sub>. 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 <em>N. kaouthia</em> 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.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"252 ","pages":"Article 108173"},"PeriodicalIF":2.6,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142628973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-13DOI: 10.1016/j.toxicon.2024.108178
Abhinandan Chowdhury , Bryan G. Fry , Stephen P. Samuel , Ashish Bhalla , Sakthivel Vaiyapuri , Parul Bhargava , Rebecca W. Carter , Matthew R. Lewin
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 A2 (PLA2) inhibitor, revealing the toxin class involved. These results uncover previously unrecognized and unexplored anticoagulant effects of Bungarus venoms.
{"title":"In vitro anticoagulant effects of Bungarus venoms on human plasma which are effectively neutralized by the PLA2-inhibitor varespladib","authors":"Abhinandan Chowdhury , Bryan G. Fry , Stephen P. Samuel , Ashish Bhalla , Sakthivel Vaiyapuri , Parul Bhargava , Rebecca W. Carter , Matthew R. Lewin","doi":"10.1016/j.toxicon.2024.108178","DOIUrl":"10.1016/j.toxicon.2024.108178","url":null,"abstract":"<div><div>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 <em>Bungarus</em> species—<em>B. caeruleus, B. candidus, B. fasciatus,</em> and <em>B. flaviceps</em> on human platelet poor plasma coagulation parameters using thromboelastography and coagulation inhibition assays. <em>B. flaviceps</em> completely inhibited clotting, while <em>B. caeruleus</em> only delayed clot formation. In contrast, <em>B. candidus</em> and <em>B. fasciatus</em> did not affect clotting. Subsequent examinations into the anticoagulant biochemical mechanisms demonstrated divergent pathophysiological pathways. <em>B. caeruleus</em> venom anticoagulant effects were prevented by the addition of an excess of phospholipids, with anticoagulation thereby the result of phospholipid depletion. In contrast <em>B. flaviceps</em> anticoagulation was not affected by the addition of an excess of phospholipids. Further investigations demonstrated that <em>B. flaviceps</em> mediates its anticoagulant toxicity through the inactivation of coagulation enzymes. The anticoagulant effects of both <em>B. flaviceps</em> and <em>B. caeruleus</em> were nullified by varespladib, a phospholipase A<sub>2</sub> (PLA<sub>2</sub>) inhibitor, revealing the toxin class involved. These results uncover previously unrecognized and unexplored anticoagulant effects of <em>Bungarus</em> venoms.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"252 ","pages":"Article 108178"},"PeriodicalIF":2.6,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142640004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-13DOI: 10.1016/j.toxicon.2024.108172
Xuan-Zhu Guo , Ya-Nan Niu , Xuan Zhou , Qiao Wei , Meng Li , Jia-Ning Xia , Yu-Qi Cui , Chao-Xin Chai , Yi-Ming Wang , Li-Ping Chen
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.
{"title":"Application of botulinum toxin A in tissue repair and regeneration","authors":"Xuan-Zhu Guo , Ya-Nan Niu , Xuan Zhou , Qiao Wei , Meng Li , Jia-Ning Xia , Yu-Qi Cui , Chao-Xin Chai , Yi-Ming Wang , Li-Ping Chen","doi":"10.1016/j.toxicon.2024.108172","DOIUrl":"10.1016/j.toxicon.2024.108172","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"252 ","pages":"Article 108172"},"PeriodicalIF":2.6,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142628974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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