Pub Date : 2025-02-01DOI: 10.1016/j.toxicon.2025.108272
Amin Haghighat Naeini , Ehsan Nassireslami , Marjan Shariatpanahi , Mohsen Chamanara , Ali Abdolali , Mehdi Aghsami
Aflatoxin B1 is the most toxic form of aflatoxins found in food. Nitric oxide in the hippocampus is essential for learning and memory. Necroptosis plays a role in cell death and pathology of many diseases, including neurodegenerative diseases. This study aimed to explore the role of the nitric oxide pathway and necroptosis signaling in Aflatoxin B1 neurotoxicity. A total of 35 male NMRI mice were divided into 5 groups as follows: Control group, Aflatoxin B1, Aflatoxin B1+L-Arginine, Aflatoxin B1+Aminoguanidine, and Aflatoxin B1+L-NAME. The spatial memory of the mice was assessed using the Barnes Maze test, and Western blot was conducted to evaluate the expression of RIP1, RIP3 and MLKL biomarkers in the hippocampus of mice brain. The behavioral tests indicated a significant memory impairment caused by Aflatoxin B1, which was significantly altered by L-Name and Aminoguanidine. The molecular tests showed an elevation of RIP1, RIP3 and MLKL biomarkers triggered by Aflatoxin B1 and a significant neutralization was then observed by L-Name. This study demonstrated that necroptosis pathway could be a possible mechanism of AFB1-induced memory damages and the nitric oxide pathway could play a role in altering these changes.
{"title":"Necroptosis signaling in spatial memory impairment caused by Aflatoxin B1 in male mice; involvement of the nitric oxide pathway","authors":"Amin Haghighat Naeini , Ehsan Nassireslami , Marjan Shariatpanahi , Mohsen Chamanara , Ali Abdolali , Mehdi Aghsami","doi":"10.1016/j.toxicon.2025.108272","DOIUrl":"10.1016/j.toxicon.2025.108272","url":null,"abstract":"<div><div>Aflatoxin B1 is the most toxic form of aflatoxins found in food. Nitric oxide in the hippocampus is essential for learning and memory. Necroptosis plays a role in cell death and pathology of many diseases, including neurodegenerative diseases. This study aimed to explore the role of the nitric oxide pathway and necroptosis signaling in Aflatoxin B1 neurotoxicity. A total of 35 male NMRI mice were divided into 5 groups as follows: Control group, Aflatoxin B1, Aflatoxin B1+L-Arginine, Aflatoxin B1+Aminoguanidine, and Aflatoxin B1+L-NAME. The spatial memory of the mice was assessed using the Barnes Maze test, and Western blot was conducted to evaluate the expression of RIP1, RIP3 and MLKL biomarkers in the hippocampus of mice brain. The behavioral tests indicated a significant memory impairment caused by Aflatoxin B1, which was significantly altered by L-Name and Aminoguanidine. The molecular tests showed an elevation of RIP1, RIP3 and MLKL biomarkers triggered by Aflatoxin B1 and a significant neutralization was then observed by L-Name. This study demonstrated that necroptosis pathway could be a possible mechanism of AFB1-induced memory damages and the nitric oxide pathway could play a role in altering these changes.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"256 ","pages":"Article 108272"},"PeriodicalIF":2.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143081054","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 : 2025-02-01DOI: 10.1016/j.toxicon.2025.108251
Tsz Kit Chow , Rex Pui Kin Lam , Chi Keung Chan , Man Li Tse , Yibin Feng , Timothy Hudson Rainer
Sophora alkaloids, including matrine, oxymatrine, and sophoridine, are quinolizidines found in plants used in traditional Chinese medicine such as Sophora flavescens and Sophora tonkinensis. Reports on acute Sophora alkaloid poisoning in humans outside of mainland China are lacking. This study aimed to characterize the clinical presentations, management, and outcomes of acute poisoning involving Sophora alkaloids in Hong Kong. We conducted a retrospective study of patients who were reported to the Hong Kong Poison Control Centre from all public emergency departments (EDs) in Hong Kong for acute poisoning involving Sophora alkaloids. Exposure was confirmed by laboratories, and data were collected between July 1, 2008 and June 30, 2021. We also analyzed patient demographics, clinical, management, and outcome characteristics. Among the 83 cases analyzed, S. flavescens was the major source (77.1%) of Sophora alkaloids and excessive dose was common (39.0%). Most patients (90.4%) had minor effects. Common clinical presentations were dizziness (83.1%), vomiting (72.3%), and palpitations (32.5%). No acute liver or kidney injuries or adverse skin reactions were observed. Treatment was primarily supportive and no patients underwent gastrointestinal decontamination, organ support treatment, or renal replacement therapy. Most patients (74.7%) were observed in the ED and only one required close monitoring in a cardiac care unit for prolonged QT interval after concurrent ciprofloxacin use. In contrast to the intravenous administration of S. flavescens, no adverse skin reactions were seen after oral consumption. Hepatoxicity, reported in in vitro and animal studies, and isolated human case reports, was not observed. In conclusion, excessive dose of S. flavescens is a common cause of acute Sophora alkaloid poisoning. Although most patients had mild symptoms, discrepancies in clinical presentations resulting from different formulations and varied experimental/clinical conditions call for further studies to evaluate the real-world risks of skin reactions and hepatoxicity of Sophora alkaloids.
{"title":"Acute Sophora alkaloid poisoning in Hong Kong","authors":"Tsz Kit Chow , Rex Pui Kin Lam , Chi Keung Chan , Man Li Tse , Yibin Feng , Timothy Hudson Rainer","doi":"10.1016/j.toxicon.2025.108251","DOIUrl":"10.1016/j.toxicon.2025.108251","url":null,"abstract":"<div><div><em>Sophora</em> alkaloids, including matrine, oxymatrine, and sophoridine, are quinolizidines found in plants used in traditional Chinese medicine such as <em>Sophora flavescens</em> and <em>Sophora tonkinensis</em>. Reports on acute <em>Sophora</em> alkaloid poisoning in humans outside of mainland China are lacking. This study aimed to characterize the clinical presentations, management, and outcomes of acute poisoning involving <em>Sophora</em> alkaloids in Hong Kong. We conducted a retrospective study of patients who were reported to the Hong Kong Poison Control Centre from all public emergency departments (EDs) in Hong Kong for acute poisoning involving <em>Sophora</em> alkaloids. Exposure was confirmed by laboratories, and data were collected between July 1, 2008 and June 30, 2021. We also analyzed patient demographics, clinical, management, and outcome characteristics. Among the 83 cases analyzed, <em>S. flavescens</em> was the major source (77.1%) of <em>Sophora</em> alkaloids and excessive dose was common (39.0%). Most patients (90.4%) had minor effects. Common clinical presentations were dizziness (83.1%), vomiting (72.3%), and palpitations (32.5%). No acute liver or kidney injuries or adverse skin reactions were observed. Treatment was primarily supportive and no patients underwent gastrointestinal decontamination, organ support treatment, or renal replacement therapy. Most patients (74.7%) were observed in the ED and only one required close monitoring in a cardiac care unit for prolonged QT interval after concurrent ciprofloxacin use. In contrast to the intravenous administration of <em>S. flavescens</em>, no adverse skin reactions were seen after oral consumption. Hepatoxicity, reported in <em>in vitro</em> and animal studies, and isolated human case reports, was not observed. In conclusion, excessive dose of <em>S. flavescens</em> is a common cause of acute <em>Sophora</em> alkaloid poisoning. Although most patients had mild symptoms, discrepancies in clinical presentations resulting from different formulations and varied experimental/clinical conditions call for further studies to evaluate the real-world risks of skin reactions and hepatoxicity of <em>Sophora</em> alkaloids.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"255 ","pages":"Article 108251"},"PeriodicalIF":2.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143012428","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 : 2025-02-01DOI: 10.1016/j.toxicon.2025.108259
Aicha Mouane , Alia Telli , Aicha Tedjani , Djouhain Achab , Raba Djehiche , Abdelouahab Gahtar , Mounira Kadri , Asma Abid , Moufida Saoucen Alayat , Nour El Houda Mekhadmi , Abdallah Aouadi , Maria Chikha , Lotfi M'Hamdi , Amar Djemoui , Ayomide Victor Atoki , Mohammed Messaoudi
Snakebites present a significant health risk in the Sahara, where access to modern medical facilities is limited, leading local populations to rely on traditional remedies. The medicinal plants used by indigenous communities in the Oued Righ region of the Northern Algerian Sahara are vital for treating envenomation from snakebites. This study provides an ethnobotanical inventory of medicinal plants used by local communities in the Oued Righ region for snakebite treatment and evaluates their therapeutic potential. Ethnobotanical data were collected through structured surveys of 200 local residents, herbalists, and healers. Data were analyzed using ethnobotanical indices, including relative citation frequency (RFC), use value (UV), and family importance value (FIV). A total of 41 plant species from 23 families were identified, and their uses for snake envenomation were documented. The most frequently used plants were Citrullus colocynthis (14.95%) and Nigella sativa (10.74%), with Asteraceae being the most represented family. The remedies are predominantly prepared using aerial parts and seeds in various forms, such as poultices and decoctions. The ethnobotanical indices highlight the cultural importance and pharmacological potential of these plants. This study documents traditional knowledge on snakebite treatments, creating a foundational database for future pharmacological studies. The identified plant species hold significant potential for developing new antivenom therapies.
{"title":"Exploring ethnobotanical remedies: Medicinal plants for snakebite envenoming treatments in the Oued Righ region (Northern Algerian Sahara)","authors":"Aicha Mouane , Alia Telli , Aicha Tedjani , Djouhain Achab , Raba Djehiche , Abdelouahab Gahtar , Mounira Kadri , Asma Abid , Moufida Saoucen Alayat , Nour El Houda Mekhadmi , Abdallah Aouadi , Maria Chikha , Lotfi M'Hamdi , Amar Djemoui , Ayomide Victor Atoki , Mohammed Messaoudi","doi":"10.1016/j.toxicon.2025.108259","DOIUrl":"10.1016/j.toxicon.2025.108259","url":null,"abstract":"<div><div>Snakebites present a significant health risk in the Sahara, where access to modern medical facilities is limited, leading local populations to rely on traditional remedies. The medicinal plants used by indigenous communities in the Oued Righ region of the Northern Algerian Sahara are vital for treating envenomation from snakebites. This study provides an ethnobotanical inventory of medicinal plants used by local communities in the Oued Righ region for snakebite treatment and evaluates their therapeutic potential. Ethnobotanical data were collected through structured surveys of 200 local residents, herbalists, and healers. Data were analyzed using ethnobotanical indices, including relative citation frequency (RFC), use value (UV), and family importance value (FIV). A total of 41 plant species from 23 families were identified, and their uses for snake envenomation were documented. The most frequently used plants were <em>Citrullus colocynthis</em> (14.95%) and <em>Nigella sativa</em> (10.74%), with Asteraceae being the most represented family. The remedies are predominantly prepared using aerial parts and seeds in various forms, such as poultices and decoctions. The ethnobotanical indices highlight the cultural importance and pharmacological potential of these plants. This study documents traditional knowledge on snakebite treatments, creating a foundational database for future pharmacological studies. The identified plant species hold significant potential for developing new antivenom therapies.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"255 ","pages":"Article 108259"},"PeriodicalIF":2.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143024666","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 : 2025-02-01DOI: 10.1016/j.toxicon.2025.108254
Mehdi Ait Laaradia , Jawad Laadraoui , Amina Ettitaou , Fatimzahra Agouram , Khadija Oubella , Soad Moubtakir , Rachida Aboufatima , Abderrahman Chait
Scorpion venom research aims to develop treatments for dangerous species and identify candidates for new drugs. The extraction of high-quality venom, which is essential, requires mastery of the extraction and maintenance of scorpions. It is in this perspective that we have undertaken this present work which aims to contribute to scientifically mastering venom yields and the factors that influence them in scorpions.
Two experiments were conducted. In the first, the volume yield and protein concentration of venom from 121 Buthus lienhardi scorpions were examined according to their size, sex, mass and place of origin. In the second experiment, the quality and quantity of venom regenerated over 30 days after extraction were measured on 80 scorpions, with samples collected at different time points (8 H, 16 H, 24 H, 32 H, 48 H, 3 days (D), 7 D, 11 D, 15 D and 30 D). In addition, the toxicity of venom samples collected from mice at different stages was evaluated.
The volume of venom extracted by electrical stimulation was linearly related to body length. Body length and protein concentration were not correlated. When considering the multiple influences on production volume in Buthus lienhardi, the most important factor was body length, but volume was also positively associated with mesosome length and relative body mass. Male scorpions produced a greater volume of venom with a higher protein concentration than females.
For venom regeneration, the volume of venom extracted after depletion showed a significant increase over the days, reaching a complete recovery by day 11. In contrast, protein regeneration and toxicity were slower than that of volume, with a complete recovery observed by day 15.
This study should lead to the design of better venom extraction protocols for several studies such as treatment development, basic research and especially for drug development.
{"title":"Variation in venom yield, protein concentration and regeneration toxicity in the scorpion Buthus lienhardi","authors":"Mehdi Ait Laaradia , Jawad Laadraoui , Amina Ettitaou , Fatimzahra Agouram , Khadija Oubella , Soad Moubtakir , Rachida Aboufatima , Abderrahman Chait","doi":"10.1016/j.toxicon.2025.108254","DOIUrl":"10.1016/j.toxicon.2025.108254","url":null,"abstract":"<div><div>Scorpion venom research aims to develop treatments for dangerous species and identify candidates for new drugs. The extraction of high-quality venom, which is essential, requires mastery of the extraction and maintenance of scorpions. It is in this perspective that we have undertaken this present work which aims to contribute to scientifically mastering venom yields and the factors that influence them in scorpions.</div><div>Two experiments were conducted. In the first, the volume yield and protein concentration of venom from 121 <em>Buthus lienhardi</em> scorpions were examined according to their size, sex, mass and place of origin. In the second experiment, the quality and quantity of venom regenerated over 30 days after extraction were measured on 80 scorpions, with samples collected at different time points (8 H, 16 H, 24 H, 32 H, 48 H, 3 days (D), 7 D, 11 D, 15 D and 30 D). In addition, the toxicity of venom samples collected from mice at different stages was evaluated.</div><div>The volume of venom extracted by electrical stimulation was linearly related to body length. Body length and protein concentration were not correlated. When considering the multiple influences on production volume in <em>Buthus lienhardi</em>, the most important factor was body length, but volume was also positively associated with mesosome length and relative body mass. Male scorpions produced a greater volume of venom with a higher protein concentration than females.</div><div>For venom regeneration, the volume of venom extracted after depletion showed a significant increase over the days, reaching a complete recovery by day 11. In contrast, protein regeneration and toxicity were slower than that of volume, with a complete recovery observed by day 15.</div><div>This study should lead to the design of better venom extraction protocols for several studies such as treatment development, basic research and especially for drug development.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"255 ","pages":"Article 108254"},"PeriodicalIF":2.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143042271","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 : 2025-02-01DOI: 10.1016/j.toxicon.2025.108263
Rahisa Scussel , Mírian Ívens Fagundes , Gabriel Paulino Luiz , Nathalia Coral Galvani , Fernanda F. Gava , Ellen De-Pieri , Lariani Tamires Witt Tietbohl , Taise Possamai-Della , Jorge M. Aguiar-Geraldo , Samira S. Valvassori , Vanessa Moraes de Andrade , Carlos Chávez-Olórtegui , Ricardo Andrez Machado-de-Ávila
Tityus serrulatus accident promote vast symptomatology related to toxins of the venom, which leads to a massive release of neurotransmitters, notably dopamine, affecting behavior and neurochemistry. The recommended treatment for envenomation is the antiscorpionic serum (SAEsc) administration. Related to this complexity of the Tityus serrulatus envenomation, this study aimed to assess organism responses to the venom, its impact on behavior, oxidative stress, neurochemistry, and genetic impacts, as well as the efficacy of SAEsc, especially concerning dopamine levels and genetic interactions. Swiss mice were divided into groups and administered different venom concentrations intracerebroventricularly to assess behavioral impacts and brain oxidative stress. Oxidative stress was evaluated through reactive oxygen species (ROS) analysis and antioxidant assays, including dichloro-dihydro-fluorescein diacetate (DCF), thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD), and glutathione (GSH) measurements. Swiss mice were divided into four groups to evaluate genomic modulation, micronucleus enhancement, and dopamine levels. Additionally, SAEsc's neutralizing effect on dopamine was also investigated. Results showed that venom doses (100–300 ng/μL) increased lipid peroxidation in the brain, with SAEsc maintaining dopamine balance and neutralizing venom up to 24 h post-envenomation. After 24 h, cellular repair became less efficient, leading to mutagenic damage in both treated and untreated animals. The results highlight the importance of considering genomic and neurotransmitter function modulation in the treatment of Tityus serrulatus envenomation.
{"title":"Behavior and oxidative stress evaluation of scorpion Tityus serrulatus (Lutz & Mello,1922) envenomation with genomic modulation and dopaminergic neutralization by antiscorpionic serum treatment","authors":"Rahisa Scussel , Mírian Ívens Fagundes , Gabriel Paulino Luiz , Nathalia Coral Galvani , Fernanda F. Gava , Ellen De-Pieri , Lariani Tamires Witt Tietbohl , Taise Possamai-Della , Jorge M. Aguiar-Geraldo , Samira S. Valvassori , Vanessa Moraes de Andrade , Carlos Chávez-Olórtegui , Ricardo Andrez Machado-de-Ávila","doi":"10.1016/j.toxicon.2025.108263","DOIUrl":"10.1016/j.toxicon.2025.108263","url":null,"abstract":"<div><div><em>Tityus serrulatus</em> accident promote vast symptomatology related to toxins of the venom, which leads to a massive release of neurotransmitters, notably dopamine, affecting behavior and neurochemistry. The recommended treatment for envenomation is the antiscorpionic serum (SAEsc) administration. Related to this complexity of the <em>Tityus serrulatus</em> envenomation, this study aimed to assess organism responses to the venom, its impact on behavior, oxidative stress, neurochemistry, and genetic impacts, as well as the efficacy of SAEsc, especially concerning dopamine levels and genetic interactions. Swiss mice were divided into groups and administered different venom concentrations intracerebroventricularly to assess behavioral impacts and brain oxidative stress. Oxidative stress was evaluated through reactive oxygen species (ROS) analysis and antioxidant assays, including dichloro-dihydro-fluorescein diacetate (DCF), thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD), and glutathione (GSH) measurements. Swiss mice were divided into four groups to evaluate genomic modulation, micronucleus enhancement, and dopamine levels. Additionally, SAEsc's neutralizing effect on dopamine was also investigated. Results showed that venom doses (100–300 ng/μL) increased lipid peroxidation in the brain, with SAEsc maintaining dopamine balance and neutralizing venom up to 24 h post-envenomation. After 24 h, cellular repair became less efficient, leading to mutagenic damage in both treated and untreated animals. The results highlight the importance of considering genomic and neurotransmitter function modulation in the treatment of <em>Tityus serrulatus</em> envenomation.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"255 ","pages":"Article 108263"},"PeriodicalIF":2.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143047887","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}
The immune response is increasingly being linked to the pathogenic processes underlying neurological disorders including potassium channel malfunction. Few investigations, meanwhile, have shown how cyclooxygenase-2 (COX-2) is involved in the neuroimmunopathology linked to potassium channel failure. Thus, using an animal model of neuropathology caused by kaliotoxin, an exclusive blocker of voltage-gated potassium channels from the scorpion venom of Androctonus australis hector, we examined the immunomodulatory impact of celecoxib (selective inhibitor of COX-2). The neural and systemic pathogenic effects of KTX can be considerably reduced by celecoxib-mediated COX-2 inhibition, according to the results. It most certainly works via controlling the immunoinflammatory exposure by raising IL-10 levels; decreasing proinflammatory cytokine levels including mostly TNFα and IL-6, and balancing oxidative status. Along with that, by significantly promoting tissue healing, COX-2 inhibitor also enhances cellular metabolism. One potential treatment approach for immunoinflammatory exacerbations linked to neurodegenerative is the COX-2 inhibitor.
{"title":"Immunomodulatory effect of selective COX-2 inhibitor celecoxib on the neuropathological disorders and immunoinflammatory response induced by Kaliotoxin from Androctonus australis venom","authors":"Amina Ladjel-Mendil , Nesrine Ahras-Sifi , Hadjila Moussaoui , Fatah Chérifi , Fatima Laraba-Djebari","doi":"10.1016/j.toxicon.2025.108265","DOIUrl":"10.1016/j.toxicon.2025.108265","url":null,"abstract":"<div><div>The immune response is increasingly being linked to the pathogenic processes underlying neurological disorders including potassium channel malfunction. Few investigations, meanwhile, have shown how cyclooxygenase-2 (COX-2) is involved in the neuroimmunopathology linked to potassium channel failure. Thus, using an animal model of neuropathology caused by kaliotoxin, an exclusive blocker of voltage-gated potassium channels from the scorpion venom of <em>Androctonus australis hector</em>, we examined the immunomodulatory impact of celecoxib (selective inhibitor of COX-2). The neural and systemic pathogenic effects of KTX can be considerably reduced by celecoxib-mediated COX-2 inhibition, according to the results. It most certainly works via controlling the immunoinflammatory exposure by raising IL-10 levels; decreasing proinflammatory cytokine levels including mostly TNFα and IL-6, and balancing oxidative status. Along with that, by significantly promoting tissue healing, COX-2 inhibitor also enhances cellular metabolism. One potential treatment approach for immunoinflammatory exacerbations linked to neurodegenerative is the COX-2 inhibitor.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"255 ","pages":"Article 108265"},"PeriodicalIF":2.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143068220","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}
Scorpion envenomation, especially from Hemiscorpius lepturus, poses a significant health risk, leading to considerable morbidity and mortality. The venom's major toxin, which includes phospholipase D (PLD), is responsible for various systemic complications. In prior studies, we identified a native phospholipase D (PLD) toxin as a key lethal factor in the venom of H. lepturus. A recombinant PLD that retained its toxicity was developed and designated as PLD1. Additionally, a non-toxic and devoid of lethal effects mutant form of the recombinant PLD1 protein, was produced and named as mPLD1. Building on this knowledge, we aimed to produce a novel antivenom using recombinant mPLD1-based immunogen and commercial antisera were included for comparison. Two horses were immunized separately with either recombinant or mutant PLD1, resulting in high titer antisera with no significant difference between the two immunogens. Purified F(ab')2 fragments derived from horse antisera demonstrated a markedly enhanced specificity in the detection of PLD1 and crude venom when compared to commercial alternatives. Furthermore, in vivo neutralization assays revealed that the antisera generated from mPLD1 protein was 89 and 36 times more potent than those of commercial ones. Horses produced highly neutralizing antibodies against PLD1 than the two local commercial antisera. These findings underscore the promise of the developed anti-mPLD1 as a highly effective therapeutic molecule for H. lepturus envenomation. Given that the production process for the recombinant immunogen is straightforward and utilizes cost-effective technologies, focusing on the manufacture of this highly efficient antisera could lead to significant advancements in horse antisera production platforms.
{"title":"Innovative production of highly potent equine neutralizing antibody against Hemiscorpius lepturus scorpion venom using recombinant mPLD1 protein","authors":"Amir Amirkhani , Somayyeh Karami-Mohajeri , Mahmoud Reza Heidari , Bagher Amirheidari , Ali Mandegary , Mohammad Hosseininejad-Chafi , Maryam Khalili-Salmasi , Shabnam Tavangarroosta , Kamran Pooshang Bagheri , Delavar Shahbazzadeh","doi":"10.1016/j.toxicon.2025.108260","DOIUrl":"10.1016/j.toxicon.2025.108260","url":null,"abstract":"<div><div>Scorpion envenomation, especially from <em>Hemiscorpius lepturus</em>, poses a significant health risk, leading to considerable morbidity and mortality. The venom's major toxin, which includes phospholipase D (PLD), is responsible for various systemic complications. In prior studies, we identified a native phospholipase D (PLD) toxin as a key lethal factor in the venom of <em>H. lepturus</em>. A recombinant PLD that retained its toxicity was developed and designated as PLD1. Additionally, a non-toxic and devoid of lethal effects mutant form of the recombinant PLD1 protein, was produced and named as mPLD1. Building on this knowledge, we aimed to produce a novel antivenom using recombinant mPLD1-based immunogen and commercial antisera were included for comparison. Two horses were immunized separately with either recombinant or mutant PLD1, resulting in high titer antisera with no significant difference between the two immunogens. Purified F(ab')2 fragments derived from horse antisera demonstrated a markedly enhanced specificity in the detection of PLD1 and crude venom when compared to commercial alternatives. Furthermore, <em>in vivo</em> neutralization assays revealed that the antisera generated from mPLD1 protein was 89 and 36 times more potent than those of commercial ones. Horses produced highly neutralizing antibodies against PLD1 than the two local commercial antisera. These findings underscore the promise of the developed anti-mPLD1 as a highly effective therapeutic molecule for <em>H. lepturus</em> envenomation. Given that the production process for the recombinant immunogen is straightforward and utilizes cost-effective technologies, focusing on the manufacture of this highly efficient antisera could lead to significant advancements in horse antisera production platforms.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"255 ","pages":"Article 108260"},"PeriodicalIF":2.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143024712","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 : 2025-02-01DOI: 10.1016/j.toxicon.2025.108258
Juliana Sartorelo Almeida , Cecilia Gomez Ravetti , Vandack Alencar Nobre , Paula Frizera Vassallo , Marcus Vinícius Melo de Andrade
Scorpion stings have a fatality rate of 0.16%, with the majority of deaths occurring in children. The resources currently available for diagnosing cardiac dysfunction caused by scorpion stings, the most common cause of death, are echocardiograms and laboratory tests, such as troponin, creatine phosphokinase-MB (CKMB), and Brain natriuretic peptide (BNP). The present study aims to evaluate the accuracy of the biomarkers soluble Supression tumorigenicity 2 (sST2) and Heart-type fatty-acid-binding protein (FABP3) in detecting cardiac dysfunction in patients stung by scorpions. This work is a prospective cross-sectional study, carried out between December 2020 and May 2022, with patients, aged 0–19 years, stung by a scorpion. Serum or plasma samples from all patients with signs of severity upon hospital admission were collected and tested with standardized cardiac damage biomarker kits. The results were compared with cardiac dysfunction detected by cardiac ultrasound. This study included 49 patients, the majority female (51%), with a median age of 3.6 years. Left ventricular dysfunction was identified in 13 patients (26.5%), with 7 cases classified as severe. The biomarkers of sST2 and FABP-3 showed an association with left ventricular dysfunction, presenting AUCs of 0.77 and 0.81, respectively. The cut-off values determined for both biomarkers showed a sensitivity of 92.3%. Ultrasensitive troponin presented an AUC of 0.89, with a sensitivity of 84.6%. The study showed an association between sST2 and FABP-3, as well as the presence of acute cardiac dysfunction, identified by cardiac ultrasound. Both biomarkers demonstrated sensitivity in identifying patients with signs of cardiac damage, similar to troponin. The results related to cardiac dysfunction may be linked to the early detection of cardiac lesions and subclinical dysfunctions, enabling faster and more effective interventions. Limitations of this study include the small sample size, data collection in a single center, and the lack of serial measurements of biomarkers.
{"title":"New biomarkers in scorpion stings","authors":"Juliana Sartorelo Almeida , Cecilia Gomez Ravetti , Vandack Alencar Nobre , Paula Frizera Vassallo , Marcus Vinícius Melo de Andrade","doi":"10.1016/j.toxicon.2025.108258","DOIUrl":"10.1016/j.toxicon.2025.108258","url":null,"abstract":"<div><div>Scorpion stings have a fatality rate of 0.16%, with the majority of deaths occurring in children. The resources currently available for diagnosing cardiac dysfunction caused by scorpion stings, the most common cause of death, are echocardiograms and laboratory tests, such as troponin, creatine phosphokinase-MB (CKMB), and Brain natriuretic peptide (BNP). The present study aims to evaluate the accuracy of the biomarkers soluble Supression tumorigenicity 2 (sST2) and Heart-type fatty-acid-binding protein (FABP3) in detecting cardiac dysfunction in patients stung by scorpions. This work is a prospective cross-sectional study, carried out between December 2020 and May 2022, with patients, aged 0–19 years, stung by a scorpion. Serum or plasma samples from all patients with signs of severity upon hospital admission were collected and tested with standardized cardiac damage biomarker kits. The results were compared with cardiac dysfunction detected by cardiac ultrasound. This study included 49 patients, the majority female (51%), with a median age of 3.6 years. Left ventricular dysfunction was identified in 13 patients (26.5%), with 7 cases classified as severe. The biomarkers of sST2 and FABP-3 showed an association with left ventricular dysfunction, presenting AUCs of 0.77 and 0.81, respectively. The cut-off values determined for both biomarkers showed a sensitivity of 92.3%. Ultrasensitive troponin presented an AUC of 0.89, with a sensitivity of 84.6%. The study showed an association between sST2 and FABP-3, as well as the presence of acute cardiac dysfunction, identified by cardiac ultrasound. Both biomarkers demonstrated sensitivity in identifying patients with signs of cardiac damage, similar to troponin. The results related to cardiac dysfunction may be linked to the early detection of cardiac lesions and subclinical dysfunctions, enabling faster and more effective interventions. Limitations of this study include the small sample size, data collection in a single center, and the lack of serial measurements of biomarkers.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"255 ","pages":"Article 108258"},"PeriodicalIF":2.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143024717","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 : 2025-02-01DOI: 10.1016/j.toxicon.2025.108262
Tianyang Wang, Runzi Cui, Hai-Fan Yu, Dian Yang, Shuting Zhang, Yuzhe Nie, Chun-Bo Teng
Aflatoxin (AF) is a toxic metabolite produced by the fungus Aspergillus. The various subtypes of AFs include B1, B2, G1, G2, M1, and M2, with Aflatoxin B1 (AFB1) being the most toxic. These AFs are widespread in the environment, particularly in soil and food crops. The World Health Organization (WHO) has classified AFB1 as a highly potent natural Class 1A carcinogen. Excessive exposure to AFB1 can lead to poisoning in both humans and animals, posing substantial risks to food safety and livestock breeding industries. This review provides an overview of the metabolic processes, detection methods, and the detrimental impacts of AFB1 on animal reproduction, immunity, nerves, intestines, and metabolism. Furthermore, it explores the preventive and control capacities of natural active substances, trace elements, and microorganisms against AFB1. Ultimately, this paper serves as a reference for further research on the pathogenic mechanism of AFB1, the development of preventive drugs, and the selection of effective detoxification measures for AFB1 in animal feed.
{"title":"The impact of aflatoxin B1 on animal health: Metabolic processes, detection methods, and preventive measures","authors":"Tianyang Wang, Runzi Cui, Hai-Fan Yu, Dian Yang, Shuting Zhang, Yuzhe Nie, Chun-Bo Teng","doi":"10.1016/j.toxicon.2025.108262","DOIUrl":"10.1016/j.toxicon.2025.108262","url":null,"abstract":"<div><div>Aflatoxin (AF) is a toxic metabolite produced by the fungus Aspergillus. The various subtypes of AFs include B1, B2, G1, G2, M1, and M2, with Aflatoxin B1 (AFB1) being the most toxic. These AFs are widespread in the environment, particularly in soil and food crops. The World Health Organization (WHO) has classified AFB1 as a highly potent natural Class 1A carcinogen. Excessive exposure to AFB1 can lead to poisoning in both humans and animals, posing substantial risks to food safety and livestock breeding industries. This review provides an overview of the metabolic processes, detection methods, and the detrimental impacts of AFB1 on animal reproduction, immunity, nerves, intestines, and metabolism. Furthermore, it explores the preventive and control capacities of natural active substances, trace elements, and microorganisms against AFB1. Ultimately, this paper serves as a reference for further research on the pathogenic mechanism of AFB1, the development of preventive drugs, and the selection of effective detoxification measures for AFB1 in animal feed.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"255 ","pages":"Article 108262"},"PeriodicalIF":2.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143042269","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 : 2025-02-01DOI: 10.1016/j.toxicon.2025.108267
Libo Yuan , Lei Lei , Yu Zhang , Yuan Fang , Kui Lu
The Bee venom peptide Anoplin (GLLKRIKTLL) was synthesized and modified by using antibiotics at its N-terminus, resulting in three peptide derivatives: Ano1, Ano2 and Ano3. The synthetic yields were 92.3%, 75.1% and 95.4%, respectively. Multi-spectroscopy methods were employed to investigate the interaction between these peptides and ct-DNA. The experimental results revealed that Anoplin, Ano1 and Ano2 interacted with ct-DNA in a groove-binding mode, whereas Ano3 exhibited a mosaic-binding mode. Moreover, circular dichroism revealed that these peptides have ability to unfold parallel G-quadruplex structures, indicating that they can interact with secondary nucleic acid structure. Notably, antimicrobial activity results indicated that all three derived peptides exhibited excellent antimicrobial activity against both gram-positive and gram-negative bacteria. The synthesized peptide conjugate Ano3 exhibited a MIC value of 1.4 μM to S. flexneri. Scanning electron microscopy results distinctly showed that Ano3 could rupture the cell wall of bacteria. These results provide novel methods to create effective antibacterial agents for both Gram-positive and Gram-negative bacteria by utilizing natural toxic molecules.
{"title":"Bee venom peptide Anoplin conjugates as antibacterial agents for both Gram-positive and Gram-negative bacteria","authors":"Libo Yuan , Lei Lei , Yu Zhang , Yuan Fang , Kui Lu","doi":"10.1016/j.toxicon.2025.108267","DOIUrl":"10.1016/j.toxicon.2025.108267","url":null,"abstract":"<div><div>The Bee venom peptide Anoplin (GLLKRIKTLL) was synthesized and modified by using antibiotics at its N-terminus, resulting in three peptide derivatives: Ano1, Ano2 and Ano3. The synthetic yields were 92.3%, 75.1% and 95.4%, respectively. Multi-spectroscopy methods were employed to investigate the interaction between these peptides and ct-DNA. The experimental results revealed that Anoplin, Ano1 and Ano2 interacted with ct-DNA in a groove-binding mode, whereas Ano3 exhibited a mosaic-binding mode. Moreover, circular dichroism revealed that these peptides have ability to unfold parallel G-quadruplex structures, indicating that they can interact with secondary nucleic acid structure. Notably, antimicrobial activity results indicated that all three derived peptides exhibited excellent antimicrobial activity against both gram-positive and gram-negative bacteria. The synthesized peptide conjugate Ano3 exhibited a MIC value of 1.4 μM to <em>S. flexneri</em>. Scanning electron microscopy results distinctly showed that Ano3 could rupture the cell wall of bacteria. These results provide novel methods to create effective antibacterial agents for both Gram-positive and Gram-negative bacteria by utilizing natural toxic molecules.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"255 ","pages":"Article 108267"},"PeriodicalIF":2.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143075577","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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