ToxiconPub Date : 2024-11-05DOI: 10.1016/j.toxicon.2024.108164
Bayram Alparslan, Murat Şentürk, Cengiz Erkan
{"title":"Bee venom and melittin: Potent key enzyme inhibitors with promising therapeutic potential.","authors":"Bayram Alparslan, Murat Şentürk, Cengiz Erkan","doi":"10.1016/j.toxicon.2024.108164","DOIUrl":"https://doi.org/10.1016/j.toxicon.2024.108164","url":null,"abstract":"<p><p>Bee venom (BV) is a versatile product with extensive applications, boasting antibacterial and anticancer properties. Within this study, we focused on isolating melittin (Mel) from Apis mellifera L. venom and exploring the influence of both BV and Mel on specific enzymes, namely carbonic anhydrase (CA) I, CA II, CA IX, glutathione reductase (GR), acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and neuraminidase (NA). The rationale for selecting these enzymes is that their inhibitors have a particular interest in medicinal chemistry in the treatment of several diseases. BV was obtained using a poison collection apparatus, and Mel was isolated by means of High-Performance Liquid Chromatography (HPLC). All enzymes, except for CA I and CA II, were commercially sourced and of high purity, and the enzyme assays were carried out spectrophotometrically. Our findings showed that BV inhibited the enzymes with IC<sub>50</sub> values of 0.583-3.32 ng/mL, and Mel showed an inhibition range of 0.528-3.2 ng/mL. These results underscore the potential therapeutic promise of BV and Mel as robust enzyme inhibitors, offering prospects for addressing diverse health conditions.</p>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142606281","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}
ToxiconPub Date : 2024-11-02DOI: 10.1016/j.toxicon.2024.108161
Subramanian Senthilkumaran , Jarred Williams , José R. Almeida , Harry F. Williams , Ketan Patel , Ponniah Thirumalaikolundusubramanian , Sakthivel Vaiyapuri
{"title":"Snakebite-induced reversible cerebral vasoconstriction syndrome: Report of three cases","authors":"Subramanian Senthilkumaran , Jarred Williams , José R. Almeida , Harry F. Williams , Ketan Patel , Ponniah Thirumalaikolundusubramanian , Sakthivel Vaiyapuri","doi":"10.1016/j.toxicon.2024.108161","DOIUrl":"10.1016/j.toxicon.2024.108161","url":null,"abstract":"<div><div>Envenomings from Russell's viper typically result in local tissue damage and bleeding complications, but the bites from common krait and cobra primarily cause neurotoxic effects. While most symptoms can be treated with appropriate antivenom, additional support is necessary for several snakebite victims to tackle a broad range of unusual complications that they develop following bites. Reversible vasoconstriction syndrome (RCVS), characterised by the constriction of cerebral arteries, is a rare but serious issue, presenting with severe headaches and, in extreme cases, haemorrhagic/ischaemic stroke. This report presents three cases of RCVS in snakebite victims following Russell's viper, krait and cobra bites. The patients were admitted to the hospital with neurological and/or haematological complications, and they were treated with polyvalent antivenom. After two days of antivenom treatment, all the patients developed intense headaches that lasted for several hours and failed to respond to commonly used analgesics. While the physical, laboratory and computed tomography examinations were normal, the RCVS was diagnosed with multimodal magnetic resonance angiography. All patients were successfully treated with oral nimodipine, and during their follow-ups, physical and laboratory examinations were unremarkable, and the magnetic resonance imaging confirmed the reversal of RCVS. To achieve positive outcomes in patients, clinicians must swiftly identify such rare complications and make accurate diagnoses to provide prompt treatments. Overall, this report presents an unusual complication of RCVS in snakebite patients and appropriate diagnosis and treatment approaches to tackle this condition.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569289","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}
{"title":"Intramuscular injection of Bothrops jararaca venom provoked acute kidney injury (AKI): Underpinned by impaired renal filtration, Na+ handling, and tissue damage","authors":"Taissa Nunes Guerrero , Mayara Amorim Romanelli , Dayene Santos Gomes , Russolina Benedeta Zingali , Lucienne da Silva Lara","doi":"10.1016/j.toxicon.2024.108159","DOIUrl":"10.1016/j.toxicon.2024.108159","url":null,"abstract":"<div><div>Globally, about 2.5 million people are victims of snakebites annually. In Brazil, the most clinically relevant snake is the <em>Bothrops jararaca</em>. The symptoms of envenomation are acute inflammation at the bite site and bleeding disorders. Despite kidney failure being the main cause of death after envenomation, kidney damage is not completely understood, and there are no clinically representative <em>in vivo</em> models. This work aimed to characterize the acute kidney injury (AKI) induced by intramuscular injection (IM) of <em>Bothrops jararaca</em> (Bjc) venom in male Wistar rats. The control group received 0.9% saline solution. Three doses of venom (3.5, 6.0, and 8.0 mg/kg) were administered IM into the posterior region of the right knee. After the injection, the rats were kept in metabolic cages. The following parameters were analyzed after 24 h: the extent of muscle damage and kidney damage (urinary creatinine, proteinuria, plasma creatinine, and renal tissue histology). All rats presented a hemorrhagic lesion at the injection site in a dose-dependent manner. Biochemical parameters indicated kidney damage: plasma creatinine accumulation, decreased glomerular filtration rate, albuminuria and proteinuria, and disturbance in Na<sup>+</sup> homeostasis. Histological analyses showed glomerular injury, tissue discontinuity more evident in the cortex and tubular dilatation, and collagen deposition. The decline in renal function and tissue damage indicated the occurrence of AKI. Therefore, a Bjc venom-induced <em>in vivo</em> model of renal injury has been established for future studies.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569258","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}
ToxiconPub Date : 2024-11-01DOI: 10.1016/j.toxicon.2024.108160
Abdel Azeim A. Khalaf , Mohamed A. Elhady , Marwa A. Ibrahim , Eman I. Hassanen , Rehab E. Abdelrahman , Peter A. Noshy
{"title":"Quercetin protects the liver of broiler chicken against oxidative stress and apoptosis induced by ochratoxin A","authors":"Abdel Azeim A. Khalaf , Mohamed A. Elhady , Marwa A. Ibrahim , Eman I. Hassanen , Rehab E. Abdelrahman , Peter A. Noshy","doi":"10.1016/j.toxicon.2024.108160","DOIUrl":"10.1016/j.toxicon.2024.108160","url":null,"abstract":"<div><div>Ochratoxin A (OTA) is a mycotoxin that causes major health concerns in human and animals. Quercetin (QUE) is a flavonoid that possesses antioxidant, anti-inflammatory and anti-apoptotic properties. This report aims to investigate the ameliorative effects of QUE against OTA-induced hepatotoxicity in broiler chicken. Forty broiler chicks were equally allocated into 4 groups: Group I (control), Group II (OTA), Group III (QUE) and Group IV (OTA + QUE). OTA (0.5 mg/kg) and QUE (0.5 g/kg) were incorporated into the chicken feed for 42 days. The results presented a significant decrease in body weight and elevation in feed conversion ratio, and a significant elevation of the activities of serum alanine aminotransferase and aspartate aminotransferase enzymes in the OTA birds. Additionally, there was a significant decrease in catalase activity and reduced glutathione content and a significant elevation in malondialdehyde level in the liver of OTA-exposed birds. Various hepatocellular lesions were also noticed in the OTA-exposed birds. OTA exposure up-regulated the phosphatase and tensin homologue (PTEN) and the pro-apoptotic genes and down-regulated the anti-apoptotic genes in the liver. The addition of QUE ameliorated most of the hepatotoxic effects of OTA.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569265","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}
ToxiconPub Date : 2024-10-28DOI: 10.1016/j.toxicon.2024.108157
Federico Camicia , Rocío I. Miguez , Néstor R. Lago , Carlos F. Damin , Adolfo R. de Roodt
{"title":"A simple method to determine proteolytic activity of snake venoms","authors":"Federico Camicia , Rocío I. Miguez , Néstor R. Lago , Carlos F. Damin , Adolfo R. de Roodt","doi":"10.1016/j.toxicon.2024.108157","DOIUrl":"10.1016/j.toxicon.2024.108157","url":null,"abstract":"<div><div>In this work, we describe an easy, simple, and cost-effective method to assess the proteolytic activity of snake venoms. The method is based on measuring the hydrolytic halo formed by gelatin radial hydrolysis following the incubation of venoms on a solid gelatin-agarose plate. Venoms from <em>Bothrops (B.) alternatus</em>, <em>B. diporus</em>, <em>B. neuwiedi</em>, <em>B. jararaca</em>, <em>B. jararacussu</em>, <em>Crotalus atrox,</em> and <em>Trimeresurus albolabris</em> were tested. A dose-response relationship was observed for each venom tested, with proteolytic capacity values, determined as GD (gelatinolytic dose, the dose causing a 15 mm hydrolytic halo) ranging from 21 to 222 μg. A correlation between hydrolysis and hemorrhagic activity in rat skin (minimal hemorrhagic dose) was found, with an r<sup>2</sup> value of 0.8774 (p < 0.0001). The venoms’ hydrolytic activity was significantly, though not completely, inhibited by EDTA. This methodology was also deployed to assess venom neutralization by antivenoms on the hydrolytic activity of the different venoms, demonstrating its usefulness in evaluating antivenom neutralizing capacity. The method presented is simple, cheap and useful for preliminary screening of venom proteolytic activity and its inhibition and may also predict gross differences in hemorrhagic activity, contributing to the reduction of the number of animals used for these determinations.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142547667","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}
{"title":"Environmental determinants of venom variability in captive scorpions: A comprehensive analysis of diet, temperature, and humidity effects.","authors":"Zineb Agourram, Razana Zegrari, Anass Kettani, Bouabid Badaoui, Mouad Mkamel","doi":"10.1016/j.toxicon.2024.108151","DOIUrl":"10.1016/j.toxicon.2024.108151","url":null,"abstract":"<p><p>This study examines the effects of environmental conditions on venom production in four prevalent scorpion species in Morocco: Androctonus amoreuxi, Androctonus mauretanicus, Buthus mardochei, and Scorpio maurus. The research focuses on how climatic factors such as temperature, humidity, and diet-specifically mealworm consumption-affect physical parameters including size and weight, and ultimately venom yield. We conducted a comprehensive investigation involving the capture, acclimatization, and systematic venom extraction from 480 scorpions. Our findings indicate considerable variations in venom volumes, with Scorpio maurus showing a reduced yield compared to Androctonus amoreuxi. Key determinants of venom production were identified as humidity and dietary intake, pointing to significant implications for interspecific diversity and acclimatization processes. These insights have crucial implications for medical and pharmaceutical applications, emphasizing the need for species-specific husbandry protocols to optimize venom extraction for therapeutic use.</p>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142547668","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}
ToxiconPub Date : 2024-10-28DOI: 10.1016/j.toxicon.2024.108156
Kavi Ratanabanangkoon
{"title":"Effective production of snake antivenom by targeting epidermal dendritic cells via the ‘low dose, low volume, multi-site’ immunization","authors":"Kavi Ratanabanangkoon","doi":"10.1016/j.toxicon.2024.108156","DOIUrl":"10.1016/j.toxicon.2024.108156","url":null,"abstract":"<div><div>Snakebite envenomation (SBE) is a serious neglected tropical disease that affects about 3 million people every year and causes over 100,000 deaths annually, mostly in developing countries. WHO has pledged to cut in half the morbidity and mortality due to SBE by 2030. Animal plasma-derived antivenoms, produced mostly in horses and sheep, are the main treatment modality. However, for over a century, equine plasma antivenom production has faced many problems<del>.</del> These include: low neutralizing potency, failure of horses to develop a satisfactory immune response, and a long immunization period. These problems have led to antivenom shortages and higher costs resulting in otherwise avoidable morbidity and mortality in snake bite victims. Attempts have been made to improve the antivenom production process. For example, a number of adjuvants designed to improve the immune response have been tested. In 1997, an immunization protocol involving the use of multi-site, low-volume and venom doses was developed and is currently used in antivenom production. This protocol constituted a significant innovation that has resulted in highly potent antivenoms within much shortened immunization periods, with all the immunized horses responding and with much less venom immunogen used. It has resulted in an ample antivenom supply for use in Thailand and neighboring countries and has led to no reported deaths from snakebite in Thailand in the past few years. The effectiveness of this immunization protocol was the result of a strategy based on targeting dendritic cells which play a pivotal role in the immune response process. This communication summarizes the basis and results of this immunization strategy.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142555543","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}
ToxiconPub Date : 2024-10-26DOI: 10.1016/j.toxicon.2024.108152
Bernd Krock , Elizabeth M. Mudge , Annegret Müller , Stefanie Meyer , Jan Tebben , Pearse McCarron , Doris Abele , Urban Tillmann
{"title":"Azaspiracid-59 accumulation and transformation in mussels (Mytilus edulis) after feeding with Azadinium poporum (Dinophyceae)","authors":"Bernd Krock , Elizabeth M. Mudge , Annegret Müller , Stefanie Meyer , Jan Tebben , Pearse McCarron , Doris Abele , Urban Tillmann","doi":"10.1016/j.toxicon.2024.108152","DOIUrl":"10.1016/j.toxicon.2024.108152","url":null,"abstract":"<div><div>Azaspiracid-59 (AZA-59) was detected in plankton in coastal waters of the Pacific Northwest USA. Given that bivalves metabolize and transform accumulated phycotoxins, a strain of <em>Azadinium poporum</em> isolated from the coast of Washington State that is a known producer of AZA-59 was used in a controlled feeding experiment with mussels (<em>Mytilus edulis</em>) to assess AZA-59 accumulation rates and transformation into shellfish metabolites. Mussels started feeding immediately after the addition of <em>A. poporum</em>. Mussels were generally healthy during the entire experimental exposure of 18 days with prevailingly high rates of clearance (approx. 100 mL per mussel per hour) and ingestion. Mussels were extracted after different exposure times and were analyzed by liquid chromatography coupled with low- and high-resolution mass spectrometry. In the course of the experiment a number of putative AZA-59 metabolites were detected including hydroxyl and carboxy analogues that corresponded with previously reported mussel metabolites of AZA-1. A significant formation of 3-OH fatty acid acyl esters relative to free AZAs was observed through the time course of the study, with numerous fatty acid ester variants of AZA-59 confirmed. These results illustrate the potential for metabolism of AZA-59 in shellfish and provide important information for local AZA monitoring and toxicity testing along the Northern Pacific US coast.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569315","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}
ToxiconPub Date : 2024-10-26DOI: 10.1016/j.toxicon.2024.108155
Grigorii V. Malykin, Peter V. Velansky, Timur Yu Magarlamov
{"title":"First data on tetrodotoxins in Cephalothrix mokievskii (palaeonemertea, nemertea) and possible involvement OF POISONOUS nemerteans in toxification of marine bioresources","authors":"Grigorii V. Malykin, Peter V. Velansky, Timur Yu Magarlamov","doi":"10.1016/j.toxicon.2024.108155","DOIUrl":"10.1016/j.toxicon.2024.108155","url":null,"abstract":"<div><div>We for the first time have recorded the presence of TTX and 11 of its analogues (TTXs) and determined the profile of these toxins by high-performance liquid chromatography–tandem mass spectrometry (HPLC-MS/MS) in <em>Cephalothrix mokievskii</em>, collected off the coast of Sakhalin Island and also revealed differences in the TTXs profile between <em>C</em>. <em>mokievskii</em> and sibling <em>Cephalothrix</em> cf, <em>simula</em>. We discuss the features of the TTXs profile in <em>C</em>. <em>mokievskii</em>, geographical distribution of TTX-containing nemerteans and its possible implication for toxification of marine bioresources.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142555542","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}