Toxicon最新文献

{"title":"Podocarpusflavone A Inhibits Multiple Myeloma Cells by Targeting the PI3K/AKT Pathway to Mediate c-Myc Downregulation and Activate the Intrinsic Apoptosis Pathway.","authors":"Jian Gao, Guanghui Cheng, Haimei Jiang, Jiawen Chu, Mengyuan Zhang","doi":"10.1016/j.toxicon.2026.109143","DOIUrl":"https://doi.org/10.1016/j.toxicon.2026.109143","url":null,"abstract":"<p><p>Multiple myeloma (MM) is an incurable blood cancer driven by uncontrolled growth of malignant plasma cells. Current treatments rarely yield durable remissions. Podocarpusflavone A-a natural biflavonoid from Podocarpus plants-shows broad antitumor activity, yet its effects on MM are unknown. This study used an integrative approach combining in vitro functional assays with bioinformatic profiling to investigate the anti-myeloma activity of Podocarpusflavone A. CCK-8 assays showed that the compound potently inhibited U266 and RPMI-8226 MM cell viability, with IC₅₀ values of 8.87 μM and 17.49 μM, respectively. Flow cytometry and Western blot analyses showed that Podocarpusflavone A induces apoptosis in a dose-dependent manner, increasing Cleaved-Caspase3 and BAX while decreasing Bcl-2-revealing a key molecular mechanism for its therapeutic potential. Further bioinformatic analyses combined with rigorous Western blot validation showed that Podocarpusflavone A effectively targets and suppresses the PI3K/AKT pathway, thereby promoting the downregulation of the oncogenic effector c-Myc. Immunofluorescence assays revealed that this compound significantly increases intracellular ROS, induces DNA damage, and disrupts mitochondrial membrane potential. These findings reveal that Podocarpusflavone A induces apoptosis in MM cells by simultaneously inhibiting pro-survival signaling and activating the intrinsic, mitochondria-dependent apoptotic pathway. This is the first study to comprehensively identify its specific molecular targets in MM-offering a promising new strategy to overcome drug resistance and current clinical limitations.</p>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":" ","pages":"109143"},"PeriodicalIF":2.4,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147864580","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":"Inter-individual variability in equine antibody responses to African snake venoms follows heavy-tailed distributions with implications for antivenom production.","authors":"Adriana Sánchez, Paola Sánchez, Andrés Sánchez, Gina Durán, Gabriela Solano, Mauren Villalta, Aarón Gómez, José María Gutiérrez, Guillermo León","doi":"10.1016/j.toxicon.2026.109145","DOIUrl":"https://doi.org/10.1016/j.toxicon.2026.109145","url":null,"abstract":"<p><p>Variability in the antibody response of horses used for snake antivenom manufacture is well recognized, yet its statistical structure and implications for industrial productivity remain poorly characterized. In this study, we quantified antivenom antibody titers by ELISA in a cohort of 14 horses immunized with venoms from the clinically most important snakes in sub-Saharan Africa. To integrate antibody levels with plasma availability, we calculated the Cumulative Plasma Productivity (CPP) by converting individual plasma volumes into titer-corrected equivalents and sequentially pooling these volumes according to their corrected contribution. Distributional analysis revealed right-skewed, heavy-tailed patterns better approximated by a log-normal model than by a strict Pareto (power-law) form, with approximately 20-30% of horses accounting for nearly half of total cohort productivity. Excluding plasma from the lowest-productivity horses did not significantly improve the venom-neutralizing potency of the plasma pool in the mouse model but substantially reduced the total plasma volume. While the exact quantitative contributions may vary across cohorts, the qualitative conclusions are likely to be generalizable under similar experimental conditions.</p>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":" ","pages":"109145"},"PeriodicalIF":2.4,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147857355","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":"Astragaloside IV attenuates cisplatin-induced acute kidney injury by suppressing KAT5-mediated NLRP3 acetylation and inflammasome activation.","authors":"Yi Qian, Panpan Hong, Yijian Ying, Shuai Xie, Yumei Zheng","doi":"10.1016/j.toxicon.2026.109128","DOIUrl":"https://doi.org/10.1016/j.toxicon.2026.109128","url":null,"abstract":"<p><p>Cisplatin, a highly effective chemotherapeutic agent, is subject to significant clinical limitations due to its dose-limiting nephrotoxicity, which can result in acute kidney injury (AKI) and chronic kidney disease. The present study investigates the renoprotective potential of Astragaloside IV (AS-IV), a primary bioactive component of Astragalus membranaceus, against cisplatin-induced nephrotoxicity (CIAKI) and elucidates its underlying molecular mechanism. In a murine model, AS-IV treatment was demonstrated to significantly ameliorate cisplatin-induced renal dysfunction, histopathological damage, and the upregulation of markers associated with inflammation and fibrosis. Utilising network pharmacology and molecular docking methodologies, we have identified the pyroptosis pathway as a pivotal target of AS-IV. Subsequent mechanistic studies revealed that AS-IV specifically inhibits NLRP3 inflammasome-mediated pyroptosis. This inhibition occurs via potential binding of AS-IV to the lysine acetyltransferase KAT5 (Tip60), thereby suppressing KAT5 expression and its catalytic activity. Consequently, AS-IV has been demonstrated to impede KAT5-mediated acetylation of NLRP3 at the K24 residue, a critical step for inflammasome assembly and activation. The present study elucidates a hitherto unobserved mechanism by which AS-IV mitigates CIAKI, through the potential targeting of the KAT5/NLRP3 acetylation axis to inhibit pyroptosis. This work provides novel insights into the pathogenesis of cisplatin-induced nephrotoxicity and positions AS-IV as a promising therapeutic candidate for preventing and treating this serious side effect.</p>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":" ","pages":"109128"},"PeriodicalIF":2.4,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147857394","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":"Deferoxamine alleviates T-2 toxin-induced articular chondrocyte ferroptosis via the Nrf2/xCT/GPX4 axis: Implications for Kashin-Beck Disease pathology.","authors":"Yi-Ming Ren, Wei-Yu Hou, Yuan Pan, Chimey Rigzin, Champa Tutob, Khe Drup, Yuan-Hui Duan, Yun-Bo Sun, Tao Yang, Han-Ji Zhang, Yuan-Hong Hao, Xue-Qiang Wang, Tian-Wei Sun, Meng-Qiang Tian","doi":"10.1016/j.toxicon.2026.109146","DOIUrl":"https://doi.org/10.1016/j.toxicon.2026.109146","url":null,"abstract":"<p><p>Kashin-Beck disease (KBD) is a debilitating endemic osteochondropathy. Environmental toxins, particularly T-2 toxin, and selenium deficiency are established etiological factors. This study aimed to investigate whether T-2 toxin induces ferroptosis in articular chondrocytes and explore the therapeutic potential and mechanism of the iron chelator, Deferoxamine (DFO). A total of 32 three-week-old male Sprague-Dawley rats were randomly allocated into four groups: Control, T-2 toxin (100 ng/g·BW/d), T-2 toxin + low DFO (10 mg/kg), and T-2 toxin + high DFO (100 mg/kg). After a 4-week intervention, knee joints were analyzed using micro-CT, micro-MRI, and histopathological staining (HE and Safranin O). Chondrocyte ferroptosis was assessed via mitochondrial ultrastructure observation, iron content measurement, GSH and MDA levels, and expression analysis of key ferroptosis-related markers (Nrf2, xCT, GPX4) using RT-qPCR and Western blot. T-2 toxin exposure induced severe articular cartilage degradation, accompanied by intracellular iron overload lipid peroxidation, oxidative stress and distinctive mitochondrial damage characteristic of ferroptosis. At the molecular level, T-2 toxin significantly reduced the expression of components within the Nrf2/xCT/GPX4 signaling axis. DFO co-treatment, especially at the high dose, effectively alleviated cartilage damage, normalized iron levels, and preserved mitochondrial integrity. Mechanistically, DFO dose-dependently reversed the T-2 toxin-induced downregulation of the Nrf2/xCT/GPX4 pathway, upregulating the protein and mRNA expression of these key anti-ferroptosis markers. Our findings demonstrate that T-2 toxin induces ferroptosis in articular chondrocytes, at least partially, through the suppression of the Nrf2/xCT/GPX4 axis. DFO exerts a potent chondroprotective effect by chelating iron and promoting the expression and nuclear accumulation of these signaling proteins . This study not only elucidates a novel mechanism for T-2 toxin-induced cartilage injury-a hallmark of KBD-but also identifies ferroptosis as a promising therapeutic target, with DFO representing a potential therapeutic agent.</p>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":" ","pages":"109146"},"PeriodicalIF":2.4,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147857327","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":"Mechanism of GCN2/eIF2α signaling pathway in MC-LR-induced hepatocyte oxidative damage and alpha-lipoic acid intervention","authors":"Ailin Tan ,&nbsp;Yu Huang ,&nbsp;Hanyun Shen ,&nbsp;Chaoyun Chen ,&nbsp;Qingbi Zhang ,&nbsp;Jun Bai ,&nbsp;Liangping Luo ,&nbsp;Xuelian Jiang ,&nbsp;Shuai Li ,&nbsp;Zhixia Han","doi":"10.1016/j.toxicon.2026.109020","DOIUrl":"10.1016/j.toxicon.2026.109020","url":null,"abstract":"<div><div>Prior research indicates that α-lipoic acid (α-LA) confers protection against the hepatotoxic effects of microcystin-LR (MC-LR), although the precise mechanisms remain to be fully defined. This investigation aims to elucidate how the reactive oxygen species (ROS)-mediated GCN2/eIF2α pathway enables α-LA to mitigate oxidative damage in hepatocytes caused by MC-LR, thus providing a robust scientific foundation for elucidating the mechanisms of MC-LR-induced cellular damage and identifying novel preventive and therapeutic approaches. For this purpose, human normal hepatocytes (L02 cells) and mouse normal hepatocytes (AML12 cells) were categorized into ten experimental groups: a blank control group, a 1 μM MC-LR exposure group, a 50 μg/mL α-LA group, combined MC-LR and α-LA groups, an siGCN2 group, a GCN2 inhibitor (GCN2iB) group, and groups treated with 1 μM MC-LR in conjunction with siGCN2 or GCN2iB. The investigation revealed that MC-LR diminishes SOD activity, elevates MDA levels, reduces mitochondrial membrane potential, and stimulates ROS generation, culminating in oxidative cellular damage. MC-LR activates the GCN2/eIF2α pathway by promoting ROS, resulting in oxidative damage to cells. Furthermore, application of inhibitors or silencing of GCN2 activity can reduce ROS generation, thereby attenuating MC-LR-induced oxidative damage in hepatocytes. α-LA pretreatment enhances the antioxidant capacity of AML12 cells and L02 cells and alleviates MC-LR-induced oxidative stress (OS). It is suggested that α-LA can protect AML12 cells and L02 cells from oxidative damage caused by MC-LR to a certain extent. α-LA can alleviate MC-LR-induced oxidative damage in AML12 and L02 cells to a certain extent by inhibiting the GCN2/eIF2α pathway.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"274 ","pages":"Article 109020"},"PeriodicalIF":2.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146182619","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":"Severe venom-induced consumption coagulopathy, snakebite-associated thrombotic microangiopathy, and local necrosis following Western bush viper (Atheris chlorechis) envenoming in France","authors":"Sébastien Larréché ,&nbsp;Gael Le Roux ,&nbsp;Jean-Philippe Chippaux ,&nbsp;Jérémy Hardy ,&nbsp;Anne-Laure Fédou ,&nbsp;Magali Labadie","doi":"10.1016/j.toxicon.2026.109021","DOIUrl":"10.1016/j.toxicon.2026.109021","url":null,"abstract":"<div><h3>Background</h3><div><em>Atheris</em> spp. are small African vipers whose bites are rarely reported but can result in significant envenoming. There is no specific antivenom available. We describe a case of systemic <em>A. chlorechis</em> envenoming presenting with venom-induced consumption coagulopathy (VICC), snakebite-associated thrombotic microangiopathy (TMA), and local necrosis.</div></div><div><h3>Case presentation</h3><div>A 33-year-old man was bitten on the index finger by a captive <em>A. chlorechis</em>. Within 6 hours, early laboratory abnormalities progressed to VICC with markedly prolonged PT/aPTT, undetectable fibrinogen, elevated fibrin monomers, and factor V deficiency. Despite the administration of four vials of Inoserp™ Pan-Africa and repeated transfusions of fibrinogen and fresh frozen plasma, the patient continued to exhibit signs of coagulopathy for 48 hours. Thrombocytopenia, anaemia, schistocytes, and hyperbilirubinemia indicated snakebite-associated TMA, which resolved spontaneously without renal involvement. Progressive local necrosis developed on the finger and dorsal hand, ultimately requiring amputation of the proximal phalanx and surgical debridement.</div></div><div><h3>Conclusion</h3><div>This case demonstrates that <em>A. chlorechis</em> envenoming can produce both local and systemic toxicity. The absence of clinical improvement after Inoserp™ Pan-Africa is consistent with preclinical data showing limited cross-neutralization against <em>Atheris</em> venoms. Administration of clotting factors in the presence of unneutralized procoagulant toxins may have contributed to the development of TMA. Therefore, fresh frozen plasma and fibrinogen should be reserved for cases of coagulopathy with active bleeding or when an invasive procedure is being considered, particulary in the absence of a concomitant effective antivenom. The local necrosis highlights the potential for significant local sequelae, necessitating cautious but timely surgical intervention.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"274 ","pages":"Article 109021"},"PeriodicalIF":2.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146143536","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":"Integrating epidemiological evidence and immunodiagnostic development for early diagnosis of Bothrops spp. envenomation in Brazil","authors":"Mariana Fernandes Fonseca ,&nbsp;Alessandra Becker-Finco ,&nbsp;Bianca Prado-Costa ,&nbsp;Guilherme Rabelo Coelho ,&nbsp;Michele Marta Weber-Lima ,&nbsp;João Carlos Degraf Muzzi ,&nbsp;Isabella Gizzi Jiacomini ,&nbsp;Martina Beltramino ,&nbsp;Luciana Aparecida Freitas-de-Sousa ,&nbsp;Patrícia Bianca Clissa ,&nbsp;Juliana Ferreira de Moura ,&nbsp;Larissa Magalhães Alvarenga","doi":"10.1016/j.toxicon.2026.109022","DOIUrl":"10.1016/j.toxicon.2026.109022","url":null,"abstract":"<div><div>Snakebite envenoming remains a major public health issue in Brazil, with <em>Bothrops</em> genus responsible for most cases. To support public health planning, we analyzed epidemiological data from Paraná State and reported, for the first time, a species-level identification of snakes responsible for accidents in this region. The results revealed that <em>Bothrops jararaca</em> accounted for over 85% of cases, followed by <em>Bothrops jararacussu</em>, reinforcing their epidemiological and clinical relevance. Based on this evidence, two monoclonal antibodies were produced by hybridoma technology for application in a diagnostic tool for early identification of <em>Bothrops</em> spp. envenomation. The antibodies were sequenced and immunochemically characterized, and both specifically recognized bothropic metalloproteinases. When applied in a competitive ELISA, the assay detected venom concentrations as low as 60 ng/mL in sera spiked with <em>B. jararaca</em> and <em>Bothrops alternatus</em> and showed no reactivity with other medically relevant genera. Although detection of <em>B. jararacussu</em>, <em>Bothrops moojeni</em> and <em>Bothrops neuwiedi</em> required higher concentrations, these venoms remained detectable, indicating potential for broader application. Further optimization could enhance its sensitivity, enabling more effective detection across a wider spectrum of species. Together, these findings provide novel epidemiological and immunodiagnostic insights, that can guide the development of improved diagnostic platforms for <em>Bothrops</em> spp. envenoming.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"274 ","pages":"Article 109022"},"PeriodicalIF":2.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146143508","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":"Therapeutic potentials of Cerastes cerastes venom: A comprehensive review of bioactive molecules and biomedical applications","authors":"Abderrezak Khelfi","doi":"10.1016/j.toxicon.2026.109023","DOIUrl":"10.1016/j.toxicon.2026.109023","url":null,"abstract":"<div><div>Snake venoms represent a vast reservoir of bioactive molecules with both toxic and therapeutic potential. The Saharan horned viper (<em>Cerastes cerastes</em>), distributed across North Africa and the Middle East, produces a venom rich in proteins and peptides that modulate key physiological processes. This review synthesizes current knowledge on the pharmacological activities of <em>Cerastes cerastes</em> venom and its purified components, emphasizing their potential applications in medicine. Enzymes such as phospholipases A₂, serine proteinases, metalloproteinases, L-amino acid oxidases, and disintegrins have been isolated and characterized, displaying diverse biological effects. These include pro- and anticoagulant activities relevant to hemostasis, cytotoxic and anti-angiogenic properties with implications in cancer therapy, and antiparasitic effects against <em>Leishmania</em> and <em>Schistosoma</em> species. Furthermore, venom-derived L-amino acid oxidases exhibit strong antibacterial activity, particularly against resistant pathogens such as MRSA, while emerging evidence highlights immunomodulatory and radioprotective roles. Despite their promise, challenges related to toxicity, stability, delivery, and potential immunogenicity must be addressed for successful clinical translation. Collectively, <em>Cerastes cerastes</em> venom exemplifies the therapeutic versatility of natural toxins and offers a valuable platform for the discovery and development of novel agents targeting cancer, infectious diseases, hemostatic disorders, and immune-mediated conditions.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"274 ","pages":"Article 109023"},"PeriodicalIF":2.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146137825","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":"Tetrodotoxin in diet items of highly toxic ribbon worm Cephalothrix cf. simula (Palaeonemertea, Nemertea)","authors":"G.V. Malykin,&nbsp;M.S. Puzanov,&nbsp;P.V. Velansky,&nbsp;V.G. Kuznetsov,&nbsp;T. Yu Magarlamov","doi":"10.1016/j.toxicon.2026.109012","DOIUrl":"10.1016/j.toxicon.2026.109012","url":null,"abstract":"<div><div>We, for the first time, have carried out a search for tetrodotoxin and its analogues (TTXs) in extracts of various animals being potential diet items for highly toxic nemerteans <em>Cephalothrix</em> cf. <em>simula</em> using high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS). We have screened TTXs in a total of 57 specimens from 2 classes. Рresence of TTX from five polychaetes species belonging to three families was shown. We here discuss the role of diet items as a source of TTXs for carnivorous TTX-bearing animals.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"273 ","pages":"Article 109012"},"PeriodicalIF":2.4,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146053996","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":"Purification and Characterization of Two Neurotoxins BmKNT1 and BmKNT2 from the Scorpion Buthus martensii karsch venom","authors":"Yusuf Ali ,&nbsp;Shamsiddin Fazliddinov ,&nbsp;Ailin Hu ,&nbsp;Naziermu Dongmulati ,&nbsp;Han He ,&nbsp;Zi Yang ,&nbsp;Yanhua Gao ,&nbsp;Ahmidin Wali ,&nbsp;Haji Akber Aisa ,&nbsp;Sharafitdin Mirzaakhmedov ,&nbsp;Akmal Asrorov ,&nbsp;Abulimiti Yili","doi":"10.1016/j.toxicon.2026.109014","DOIUrl":"10.1016/j.toxicon.2026.109014","url":null,"abstract":"<div><div>Scorpion venom is a heterogeneous mixture of proteins and peptides, many of which have multiple bioactivities, including antitumor activity, modulation of ion channels, analgesia, and anti-inflammatory effects. This study, two peptides named BmKNT1 and BmKNT2 were isolated and purified from the <em>Buthus martensii</em> Karsch (BmK) venom by gel filtration chromatography (GFC), ion-exchange chromatography (IEC) and Reverse phase high-performance liquid chromatography (RP-HPLC), respectively. The primary structure of BmKNT1 (69 amino acid residues, theoretical pI/Mw: 7.66/7660.5 Da) and BmKNT2 (64 amino acid residues, theoretical pI/Mw: May 6, 7270.33) were determined by a combination of Edman degradation and MALDI-TOF-MS/MS sequencing analysis. It showed a high similarity to that of other scorpion neurotoxins. The Effects of both neurotoxins on Na⁺-channel, K⁺-channel and Ca²⁺-channel in rat dorsal root ganglion (DRG) were determined at 100 μg/ml. The results showed BmKNT2 had inhibitory activity on K⁺-channels expressed on DRG cells, which is a typical characteristic of voltage-gated potassium channel pore area inhibitors. On the contrary, BmKNT1 has activation activity on the K⁺-channel in rat DRG, and both toxins have inhibitory activity on Ca²⁺-channels in rat DRG.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"273 ","pages":"Article 109014"},"PeriodicalIF":2.4,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146053903","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}