Pub Date : 2022-09-01DOI: 10.1016/j.toxcx.2022.100134
E.P. O'Hara, D. Wilson, J.E. Seymour
{"title":"Erratum to “The influence of ecological factors on cnidarian venoms” [Toxicon: X 9–10C (2021) 100067]","authors":"E.P. O'Hara, D. Wilson, J.E. Seymour","doi":"10.1016/j.toxcx.2022.100134","DOIUrl":"10.1016/j.toxcx.2022.100134","url":null,"abstract":"","PeriodicalId":37124,"journal":{"name":"Toxicon: X","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/53/52/main.PMC9278439.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40512616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-09-01DOI: 10.1016/j.toxcx.2022.100126
Beraldo-Neto Emidio , Lebrun Ivo , Nencioni Ana Leonor Abrahao
Tb II-I isolated from Tityus bahiensis venom causes epileptic-discharges when injected into the hippocampus of rats. The involvement of neurotransmitters in this activity was investigated. Our results demonstrated that Tb II-I increases the concentrations of dopamine metabolite but does not alter other neurotransmitters. Thus, dopaminergic system seems to be partially responsible for the convulsive process. Specific action on particular neurotransmitter can make this toxin a useful tool to better understand the functioning of the system.
从巴海提鱼毒液中分离出的结核菌i - i注射到大鼠的海马体中会引起癫痫放电。研究了神经递质在这一活动中的作用。我们的研究结果表明,Tb i - i - i增加了多巴胺代谢物的浓度,但不改变其他神经递质。因此,多巴胺能系统似乎对抽搐过程负有部分责任。对特定神经递质的特定作用可以使这种毒素成为更好地了解系统功能的有用工具。
{"title":"Dopaminergic metabolism is affected by intracerebral injection of Tb II-I isolated from Tityus bahiensis scorpion venom","authors":"Beraldo-Neto Emidio , Lebrun Ivo , Nencioni Ana Leonor Abrahao","doi":"10.1016/j.toxcx.2022.100126","DOIUrl":"10.1016/j.toxcx.2022.100126","url":null,"abstract":"<div><p>Tb II-I isolated from <em>Tityus bahiensis</em> venom causes epileptic-discharges when injected into the hippocampus of rats. The involvement of neurotransmitters in this activity was investigated. Our results demonstrated that Tb II-I increases the concentrations of dopamine metabolite but does not alter other neurotransmitters. Thus, dopaminergic system seems to be partially responsible for the convulsive process. Specific action on particular neurotransmitter can make this toxin a useful tool to better understand the functioning of the system.</p></div>","PeriodicalId":37124,"journal":{"name":"Toxicon: X","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590171022000364/pdfft?md5=20a75145a8e6e76bc32c7f71b1224526&pid=1-s2.0-S2590171022000364-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42034253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-06-01DOI: 10.1016/j.toxcx.2022.100124
Mitchel Otieno Okumu , James Mucunu Mbaria , Joseph Kangangi Gikunju , Paul Gichohi Mbuthia , Vincent Odongo Madadi , Francis Okumu Ochola , Kenneth Narotso Maloba , Joseph Gichuki Nderitu
This study aimed to determine the efficacy of Inoserp, Vins bioproducts, and South African Institute of Medical Research (SAIMR) polyvalent antivenoms in neutralizing Naja ashei venom-induced lethality in mice. The neutralization efficacy of the antivenoms were expressed as effective dose, median effective ratio, potency, normalized potency, volume, and the number of vials of antivenom required to neutralize 100 mg of Naja ashei venom (NAV).
{"title":"Preclinical efficacy testing of three antivenoms against Naja ashei venom-induced lethality","authors":"Mitchel Otieno Okumu , James Mucunu Mbaria , Joseph Kangangi Gikunju , Paul Gichohi Mbuthia , Vincent Odongo Madadi , Francis Okumu Ochola , Kenneth Narotso Maloba , Joseph Gichuki Nderitu","doi":"10.1016/j.toxcx.2022.100124","DOIUrl":"10.1016/j.toxcx.2022.100124","url":null,"abstract":"<div><p>This study aimed to determine the efficacy of Inoserp, Vins bioproducts, and South African Institute of Medical Research (SAIMR) polyvalent antivenoms in neutralizing <em>Naja ashei</em> venom-induced lethality in mice. The neutralization efficacy of the antivenoms were expressed as effective dose, median effective ratio, potency, normalized potency, volume, and the number of vials of antivenom required to neutralize 100 mg of <em>Naja ashei</em> venom (NAV).</p></div>","PeriodicalId":37124,"journal":{"name":"Toxicon: X","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590171022000340/pdfft?md5=056b177fce2af29a9113781332daacb4&pid=1-s2.0-S2590171022000340-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42011867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-06-01DOI: 10.1016/j.toxcx.2022.100123
Jia Jin Hiu , Michelle Khai Khun Yap
Cobra venom cytotoxin (CTX) is a non-enzymatic three-finger toxin that constitutes 40–60% of cobra venom. Thus, it plays an important role in the pathophysiology of cobra envenomation, especially in local dermonecrosis. The three-finger hydrophobic loops of CTX determine the cytotoxicity. Nevertheless, the actual mechanisms of cytotoxicity are not fully elucidated as they involve not only cytolytic actions but also intracellular signalling-mediated cell death pathways. Furthermore, the possible transition cell death pattern remains to be explored. The actual molecular mechanisms require further studies to unveil the relationship between different CTXs from different cobra species and cell types which may result in differential cell death patterns. Here, we discuss the biophysical interaction of CTX with the cell membrane involving four binding modes: electrostatic interaction, hydrophobic partitioning, isotropic phase, and oligomerisation. Oligomerisation of CTX causes pore formation in the membrane lipid bilayer. Additionally, the CTX-induced apoptotic pathway can be executed via death receptor-mediated extrinsic pathways and mitochondrial-mediated intrinsic pathways. We also discuss lysosomal-mediated necrosis and the occurrence of necroptosis following CTX action. Collectively, we provided an insight into concentration-dependent transition of cell death pattern which involves different mechanistic actions. This contributes a new direction for further investigation of cytotoxic pathways activated by the CTXs for future development of biotherapeutics targeting pathological effects caused by CTX.
{"title":"The myth of cobra venom cytotoxin: More than just direct cytolytic actions","authors":"Jia Jin Hiu , Michelle Khai Khun Yap","doi":"10.1016/j.toxcx.2022.100123","DOIUrl":"10.1016/j.toxcx.2022.100123","url":null,"abstract":"<div><p>Cobra venom cytotoxin (CTX) is a non-enzymatic three-finger toxin that constitutes 40–60% of cobra venom. Thus, it plays an important role in the pathophysiology of cobra envenomation, especially in local dermonecrosis. The three-finger hydrophobic loops of CTX determine the cytotoxicity. Nevertheless, the actual mechanisms of cytotoxicity are not fully elucidated as they involve not only cytolytic actions but also intracellular signalling-mediated cell death pathways. Furthermore, the possible transition cell death pattern remains to be explored. The actual molecular mechanisms require further studies to unveil the relationship between different CTXs from different cobra species and cell types which may result in differential cell death patterns. Here, we discuss the biophysical interaction of CTX with the cell membrane involving four binding modes: electrostatic interaction, hydrophobic partitioning, isotropic phase, and oligomerisation. Oligomerisation of CTX causes pore formation in the membrane lipid bilayer. Additionally, the CTX-induced apoptotic pathway can be executed via death receptor-mediated extrinsic pathways and mitochondrial-mediated intrinsic pathways. We also discuss lysosomal-mediated necrosis and the occurrence of necroptosis following CTX action. Collectively, we provided an insight into concentration-dependent transition of cell death pattern which involves different mechanistic actions. This contributes a new direction for further investigation of cytotoxic pathways activated by the CTXs for future development of biotherapeutics targeting pathological effects caused by CTX.</p></div>","PeriodicalId":37124,"journal":{"name":"Toxicon: X","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590171022000339/pdfft?md5=61312ae33305725598ccccf13e5f19e3&pid=1-s2.0-S2590171022000339-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42870465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zearalenone (ZEA) is a toxic metabolite of the genus Fusarium, which causes hepatotoxicity and induces oxidative stress. Kefir is an important probiotic dairy-product showing important in vitro antioxidant potential. In this study, the effect of Kefir supplementation to mitigate ZEA toxicity in rats was investigated. Animals were divided into four groups of five rats each, which received sterile milk (200 μL/day) during the first week. Then, they were switched to Kefir (200 μL/day), ZEA (40 mg/kg b. w./day) and Kefir + ZEA for the second week. Hematological and biochemical parameters, as well as liver histological analysis were determined. Kefir administration prevented the changes occurred in the count of all blood cells, and improved the antioxidant enzymes in the liver, such as catalase, glutathione peroxidase and superoxide dismutase activities that increased by 6, 4.5 and 1.3 folds, respectively, compared to ZEA group. Interestingly, the concurrent regimen Kefir + ZEA removed ZEA residues in the serum and liver. Furthermore, the Kefir + ZEA group showed a reduction in the levels of bilirubin, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and hepatic malonaldehyde by ∼82, 54, 66, 50 and 36%, respectively, compared to the ZEA group. The histopathological analysis showed a normal liver histological architecture in Kefir + ZEA group, while degenerative changes were observed in ZEA group. These results suggest that Kefir as probiotic consortium may have a hepatoprotective effect against ZEA poisoning.
{"title":"Does probiotic Kefir reduce dyslipidemia, hematological disorders and oxidative stress induced by zearalenone toxicity in wistar rats?","authors":"Fadia Ben Taheur , Chalbia Mansour , Sondes Mechri , Sihem Safta Skhiri , Bassem Jaouadi , Ridha Mzoughi , Kamel Chaieb , Nacim Zouari","doi":"10.1016/j.toxcx.2022.100121","DOIUrl":"10.1016/j.toxcx.2022.100121","url":null,"abstract":"<div><p>Zearalenone (ZEA) is a toxic metabolite of the genus <em>Fusarium</em>, which causes hepatotoxicity and induces oxidative stress. Kefir is an important probiotic dairy-product showing important <em>in vitro</em> antioxidant potential. In this study, the effect of Kefir supplementation to mitigate ZEA toxicity in rats was investigated. Animals were divided into four groups of five rats each, which received sterile milk (200 μL/day) during the first week. Then, they were switched to Kefir (200 μL/day), ZEA (40 mg/kg b. w./day) and Kefir + ZEA for the second week. Hematological and biochemical parameters, as well as liver histological analysis were determined. Kefir administration prevented the changes occurred in the count of all blood cells, and improved the antioxidant enzymes in the liver, such as catalase, glutathione peroxidase and superoxide dismutase activities that increased by 6, 4.5 and 1.3 folds, respectively, compared to ZEA group. Interestingly, the concurrent regimen Kefir + ZEA removed ZEA residues in the serum and liver. Furthermore, the Kefir + ZEA group showed a reduction in the levels of bilirubin, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and hepatic malonaldehyde by ∼82, 54, 66, 50 and 36%, respectively, compared to the ZEA group. The histopathological analysis showed a normal liver histological architecture in Kefir + ZEA group, while degenerative changes were observed in ZEA group. These results suggest that Kefir as probiotic consortium may have a hepatoprotective effect against ZEA poisoning.</p></div>","PeriodicalId":37124,"journal":{"name":"Toxicon: X","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590171022000315/pdfft?md5=bb0d6a07c0b4baa91cd5696962ecd463&pid=1-s2.0-S2590171022000315-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45732435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-06-01DOI: 10.1016/j.toxcx.2022.100117
Björn M. von Reumont , Sebastien Dutertre , Ivan Koludarov
Modern venomics is increasing its focus on hymenopterans such as honeybees, bumblebees, parasitoid wasps, ants and true wasps. However solitary bees remain understudied in comparison and the few available venom studies focus on short melittin-like sequences and antimicrobial peptides. Herein we describe the first comprehensive venom profile of a solitary bee, the violet carpenter bee Xylocopa violacea, by using proteo-transcriptomics. We reveal a diverse and complex venom profile with 43 different protein families identified from dissected venom gland extracts of which 32 are also detected in the defensively injected venom. Melittin and apamin are the most highly secreted components, followed by Phospholipase A2, Icarapin, Secapin and three novel components. Other components, including eight novel protein families, are rather lowly expressed. We further identify multiple forms of apamin-like peptides. The melittin-like sequences of solitary bees separate into two clades, one comprised most sequences from solitary bees including xylopin (the variant in Xylocopa), while sequences from Lasioglossa appear closer related to melittin-like peptides from Bombus (Bombolittins). Our study suggests that more proteo-transcriptomic data from other solitary bees should be complemented with corresponding genome data to fully understand the evolution and complexity of bee venom proteins, and is of a particular need to disentangle the ambiguous phylogenetic relations of short peptides.
{"title":"Venom profile of the European carpenter bee Xylocopa violacea: Evolutionary and applied considerations on its toxin components","authors":"Björn M. von Reumont , Sebastien Dutertre , Ivan Koludarov","doi":"10.1016/j.toxcx.2022.100117","DOIUrl":"10.1016/j.toxcx.2022.100117","url":null,"abstract":"<div><p>Modern venomics is increasing its focus on hymenopterans such as honeybees, bumblebees, parasitoid wasps, ants and true wasps. However solitary bees remain understudied in comparison and the few available venom studies focus on short melittin-like sequences and antimicrobial peptides. Herein we describe the first comprehensive venom profile of a solitary bee, the violet carpenter bee <em>Xylocopa violacea</em>, by using proteo-transcriptomics. We reveal a diverse and complex venom profile with 43 different protein families identified from dissected venom gland extracts of which 32 are also detected in the defensively injected venom. Melittin and apamin are the most highly secreted components, followed by Phospholipase A2, Icarapin, Secapin and three novel components. Other components, including eight novel protein families, are rather lowly expressed. We further identify multiple forms of apamin-like peptides. The melittin-like sequences of solitary bees separate into two clades, one comprised most sequences from solitary bees including xylopin (the variant in <em>Xylocopa</em>), while sequences from <em>Lasioglossa</em> appear closer related to melittin-like peptides from <em>Bombus</em> (Bombolittins). Our study suggests that more proteo-transcriptomic data from other solitary bees should be complemented with corresponding genome data to fully understand the evolution and complexity of bee venom proteins, and is of a particular need to disentangle the ambiguous phylogenetic relations of short peptides.</p></div>","PeriodicalId":37124,"journal":{"name":"Toxicon: X","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8927852/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40308793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-06-01DOI: 10.1016/j.toxcx.2022.100100
Janna M. Schurer , Aleta Dam , Marie Thérèse Mutuyimana , Daniel Muhire Runanira , Richard Nduwayezu , J. Hellen Amuguni
Snakebite envenomation (SBE) is a serious medical condition with human, animal, and environmental factors driving occurrence. In Rwanda, the number of SBE cases reported by the medical system is far lower than regional estimates for SBE incidence, suggesting that victims might be seeking care outside of formal medical structures. Our goals were to describe circumstances surrounding snakebite and to explore experiences of snakebite victims in accessing treatment. For this qualitative study, our team recruited individuals bitten by snakes between 2013 and 2018, who sought care either from traditional healers (N = 40) or hospitals (N = 65). In-depth interviews based on a semi-structured interview guide were conducted by telephone in Kinyarwanda. Inductive thematic analysis was conducted by two team members. Our respondents reported similar environmental circumstances surrounding their snake encounters; namely, farm fields, roads, and their homes, as well as inadequate lighting. Unsafe First Aid practices, including burning/sucking/cutting the skin and tourniquet, were often performed immediately after bites. Respondents reported various reasons for seeking traditional or hospital care, such as perceived cost, distance, transportation, and especially, community beliefs and treatment outcomes of other victims. Respondents described envenomation of livestock as well as the sale of livestock to pay SBE-related medical expenses. Improving trust and use of formal medical services will require enhanced hospital delivery of high quality medical services for SBE through improved stocking of appropriate anti-venom and reduced delays during intake. Communities might also benefit from education campaigns that discourage unsafe First Aid practices and address the common misperception that physicians are not trained to treat SBE.
{"title":"“At the hospital they do not treat venom from snakebites”: A qualitative assessment of health seeking perspectives and experiences among snakebite victims in Rwanda","authors":"Janna M. Schurer , Aleta Dam , Marie Thérèse Mutuyimana , Daniel Muhire Runanira , Richard Nduwayezu , J. Hellen Amuguni","doi":"10.1016/j.toxcx.2022.100100","DOIUrl":"10.1016/j.toxcx.2022.100100","url":null,"abstract":"<div><p>Snakebite envenomation (SBE) is a serious medical condition with human, animal, and environmental factors driving occurrence. In Rwanda, the number of SBE cases reported by the medical system is far lower than regional estimates for SBE incidence, suggesting that victims might be seeking care outside of formal medical structures. Our goals were to describe circumstances surrounding snakebite and to explore experiences of snakebite victims in accessing treatment. For this qualitative study, our team recruited individuals bitten by snakes between 2013 and 2018, who sought care either from traditional healers (N = 40) or hospitals (N = 65). In-depth interviews based on a semi-structured interview guide were conducted by telephone in Kinyarwanda. Inductive thematic analysis was conducted by two team members. Our respondents reported similar environmental circumstances surrounding their snake encounters; namely, farm fields, roads, and their homes, as well as inadequate lighting. Unsafe First Aid practices, including burning/sucking/cutting the skin and tourniquet, were often performed immediately after bites. Respondents reported various reasons for seeking traditional or hospital care, such as perceived cost, distance, transportation, and especially, community beliefs and treatment outcomes of other victims. Respondents described envenomation of livestock as well as the sale of livestock to pay SBE-related medical expenses. Improving trust and use of formal medical services will require enhanced hospital delivery of high quality medical services for SBE through improved stocking of appropriate anti-venom and reduced delays during intake. Communities might also benefit from education campaigns that discourage unsafe First Aid practices and address the common misperception that physicians are not trained to treat SBE.</p></div>","PeriodicalId":37124,"journal":{"name":"Toxicon: X","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590171022000108/pdfft?md5=3bb16fac681d1a56eff945f00711b97d&pid=1-s2.0-S2590171022000108-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44640751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-06-01DOI: 10.1016/j.toxcx.2022.100120
Umberto Zottich , Isadora Sousa de Oliveira , Isabela Gobbo Fereira , Felipe Augusto Cerni , Bordon Karla de Castro Figueiredo , Eliane Candiani Arantes , Valdirene Moreira Gomes , Germana Bueno Dias , Manuela Berto Pucca
Fungal infections are becoming a serious problem of human diseases, being one of the most important fungal pathogens the yeast of the genus Candida. So far, fungal infection treatment faces different challenges, including the limited number of therapeutic drugs. Scorpions are known to be a valuable source of biologically active molecules, especially of peptide-derived molecules with a variety of biological effects and useful, lead compounds for drugs development. Here, we pioneer described the antifungal effect of venom, mucus, and the major toxin (Rc1) from Rhopalurus crassicauda scorpion. These results support the potential for Rc1 to be further investigated as a novel antifungal therapeutic to treat Candida infections.
{"title":"Antifungal activity of Rhopalurus crassicauda venom against Candida spp.","authors":"Umberto Zottich , Isadora Sousa de Oliveira , Isabela Gobbo Fereira , Felipe Augusto Cerni , Bordon Karla de Castro Figueiredo , Eliane Candiani Arantes , Valdirene Moreira Gomes , Germana Bueno Dias , Manuela Berto Pucca","doi":"10.1016/j.toxcx.2022.100120","DOIUrl":"10.1016/j.toxcx.2022.100120","url":null,"abstract":"<div><p>Fungal infections are becoming a serious problem of human diseases, being one of the most important fungal pathogens the yeast of the genus <em>Candida</em>. So far, fungal infection treatment faces different challenges, including the limited number of therapeutic drugs. Scorpions are known to be a valuable source of biologically active molecules, especially of peptide-derived molecules with a variety of biological effects and useful, lead compounds for drugs development. Here, we pioneer described the antifungal effect of venom, mucus, and the major toxin (Rc1) from <em>Rhopalurus crassicauda</em> scorpion. These results support the potential for Rc1 to be further investigated as a novel antifungal therapeutic to treat <em>Candida</em> infections.</p></div>","PeriodicalId":37124,"journal":{"name":"Toxicon: X","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590171022000303/pdfft?md5=c78539d4b6e34e3c2da98db660c8d54d&pid=1-s2.0-S2590171022000303-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47428997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-06-01DOI: 10.1016/j.toxcx.2022.100125
Ernest Z. Manson , Mutinda C. Kyama , Joseph K. Gikunju , Josephine Kimani , James H. Kimotho
Neutralization of lethality in mice model at the preclinical level has been established by the World Health Organization as the gold standard for the evaluation of antivenom efficacy. The assessment of the neutralization profiles of antivenoms helps to discern the efficacy or otherwise of these antivenoms at neutralizing the toxic effects induced by medically significant snake venoms. However, for many antivenoms, information on their preclinical efficacy remains limited. Therefore, to strengthen global efforts at reducing the impact of snakebite envenoming, the provision of information on the preclinical efficacy of antivenoms, especially in parts of the world where antivenom availability and accessibility is problematic, including sub-Saharan Africa is crucial. This study presents the lethal and toxic activities of N. ashei venom and the neutralizing capacity of two commonly used commercial antivenoms in Kenya; VINS™ and Inoserp™. Median lethal dose (LD50), minimum necrotizing dose (MND) and minimum edema-forming dose (MED) of N. ashei venom as well as the neutralization of these effects were evaluated in mice. The LD50 of N. ashei venom was found to be 4.67 (3.34–6.54) mg/kg while MND and MED were 11.00 μg and 0.80 μg respectively. Both VINS™ and Inoserp™ antivenoms demonstrated capacity to neutralize the lethal and toxic effects induced by Naja ashei venom albeit at varying efficacies. Our results thus confirm the toxic effects of N. ashei venom as previously observed with other Naja sp. venoms and also underscore the relevance of para-specific neutralizing capacity of antivenoms in the design of antivenoms.
{"title":"Evaluation of lethality and cytotoxic effects induced by Naja ashei (large brown spitting cobra) venom and the envenomation-neutralizing efficacy of selected commercial antivenoms in Kenya","authors":"Ernest Z. Manson , Mutinda C. Kyama , Joseph K. Gikunju , Josephine Kimani , James H. Kimotho","doi":"10.1016/j.toxcx.2022.100125","DOIUrl":"https://doi.org/10.1016/j.toxcx.2022.100125","url":null,"abstract":"<div><p>Neutralization of lethality in mice model at the preclinical level has been established by the World Health Organization as the gold standard for the evaluation of antivenom efficacy. The assessment of the neutralization profiles of antivenoms helps to discern the efficacy or otherwise of these antivenoms at neutralizing the toxic effects induced by medically significant snake venoms. However, for many antivenoms, information on their preclinical efficacy remains limited. Therefore, to strengthen global efforts at reducing the impact of snakebite envenoming, the provision of information on the preclinical efficacy of antivenoms, especially in parts of the world where antivenom availability and accessibility is problematic, including sub-Saharan Africa is crucial. This study presents the lethal and toxic activities of <em>N. ashei</em> venom and the neutralizing capacity of two commonly used commercial antivenoms in Kenya; VINS™ and Inoserp™. Median lethal dose (LD<sub>50</sub>), minimum necrotizing dose (MND) and minimum edema-forming dose (MED) of <em>N. ashei</em> venom as well as the neutralization of these effects were evaluated in mice. The LD<sub>50</sub> of <em>N. ashei</em> venom was found to be 4.67 (3.34–6.54) mg/kg while MND and MED were 11.00 μg and 0.80 μg respectively. Both VINS™ and Inoserp™ antivenoms demonstrated capacity to neutralize the lethal and toxic effects induced by <em>Naja ashei</em> venom albeit at varying efficacies. Our results thus confirm the toxic effects of <em>N. ashei</em> venom as previously observed with other <em>Naja</em> sp. venoms and also underscore the relevance of para-specific neutralizing capacity of antivenoms in the design of antivenoms.</p></div>","PeriodicalId":37124,"journal":{"name":"Toxicon: X","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590171022000352/pdfft?md5=e818b86c13cb615b56c74308a0142170&pid=1-s2.0-S2590171022000352-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91956909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-06-01DOI: 10.1016/j.toxcx.2022.100113
Anna M.L. Klompen , Steven M. Sanders , Paulyn Cartwright
Cnidarians (jellyfish, hydroids, sea anemones, and corals) possess a unique method for venom production, maintenance, and deployment through a decentralized system composed of different types of venom-filled stinging structures called nematocysts. In many species, nematocyst types are distributed heterogeneously across functionally distinct tissues. This has led to a prediction that different nematocyst types contain specific venom components. The colonial hydrozoan, Hydractinia symbiolongicarpus, is an ideal system to study the functional distribution of nematocyst types and their venoms, given that they display a division of labor through functionally distinct polyps within the colony. Here, we characterized the composition and distribution of nematocysts (cnidome) in the different polyp types and show that the feeding polyp (gastrozooid) has a distinct cnidome compared to the reproductive (gonozooid) and predatory polyp (dactylozooid). We generated a nematocyst-specific reporter line to track nematocyst development (nematogenesis) in H. symbiolongicarpus, and were able to confirm that nematogenesis primarily occurs in the mid-region of the gastrozooid and throughout stolons (tubes of epithelia that connect the polyps in the colony). This reporter line enabled us to isolate a nematocyst-specific lineage of cells for de novo transcriptome assembly, annotate venom-like genes (VLGs) and determine differential expression (DE) across polyp types. We show that a majority of VLGs are upregulated in gastrozooids, consistent with it being the primary site of active nematogenesis. However, despite gastrozooids producing more nematocysts, we found a number of VLGs significantly upregulated in dactylozooids, suggesting that these VLGs may be important for prey-capture. Our transgenic Hydractinia reporter line provides an opportunity to explore the complex interplay between venom composition, nematocyst diversity, and ecological partitioning in a colonial hydrozoan that displays a division of labor.
{"title":"Venom system variation and the division of labor in the colonial hydrozoan Hydractinia symbiolongicarpus","authors":"Anna M.L. Klompen , Steven M. Sanders , Paulyn Cartwright","doi":"10.1016/j.toxcx.2022.100113","DOIUrl":"https://doi.org/10.1016/j.toxcx.2022.100113","url":null,"abstract":"<div><p>Cnidarians (jellyfish, hydroids, sea anemones, and corals) possess a unique method for venom production, maintenance, and deployment through a decentralized system composed of different types of venom-filled stinging structures called nematocysts. In many species, nematocyst types are distributed heterogeneously across functionally distinct tissues. This has led to a prediction that different nematocyst types contain specific venom components. The colonial hydrozoan, <em>Hydractinia symbiolongicarpus,</em> is an ideal system to study the functional distribution of nematocyst types and their venoms, given that they display a division of labor through functionally distinct polyps within the colony. Here, we characterized the composition and distribution of nematocysts (cnidome) in the different polyp types and show that the feeding polyp (gastrozooid) has a distinct cnidome compared to the reproductive (gonozooid) and predatory polyp (dactylozooid). We generated a nematocyst-specific reporter line to track nematocyst development (nematogenesis) in <em>H. symbiolongicarpus</em>, and were able to confirm that nematogenesis primarily occurs in the mid-region of the gastrozooid and throughout stolons (tubes of epithelia that connect the polyps in the colony). This reporter line enabled us to isolate a nematocyst-specific lineage of cells for <em>de novo</em> transcriptome assembly, annotate venom-like genes (VLGs) and determine differential expression (DE) across polyp types. We show that a majority of VLGs are upregulated in gastrozooids, consistent with it being the primary site of active nematogenesis. However, despite gastrozooids producing more nematocysts, we found a number of VLGs significantly upregulated in dactylozooids, suggesting that these VLGs may be important for prey-capture. Our transgenic <em>Hydractinia</em> reporter line provides an opportunity to explore the complex interplay between venom composition, nematocyst diversity, and ecological partitioning in a colonial hydrozoan that displays a division of labor.</p></div>","PeriodicalId":37124,"journal":{"name":"Toxicon: X","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590171022000236/pdfft?md5=f2cfbd2fe7402ca88a0403a0132ad428&pid=1-s2.0-S2590171022000236-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92095877","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}