Toxicon最新文献

{"title":"Changes in regulatory requirements for potency testing of snake antivenom in Korea","authors":"Wonjong Lee ,&nbsp;Hyun Jeong Kim ,&nbsp;Yu Jeong Oh ,&nbsp;Su Kyoung Seong ,&nbsp;Young Hoon Kim ,&nbsp;Youngju Choi ,&nbsp;Sang-Mi Park ,&nbsp;Kiwon Han ,&nbsp;Chan Woong Choi","doi":"10.1016/j.toxicon.2025.108337","DOIUrl":"10.1016/j.toxicon.2025.108337","url":null,"abstract":"<div><div>Snake antivenoms are manufactured under Good Manufacturing Practice, with quality controlled according to Korean regulations. Potency results for anti-lethal and anti-hemorrhagic titers collected since 2017 showed ranges of 6280–15,120 and 6080–10,160 U/vial, respectively. A strong correlation (r = 0.8356–0.9216) was observed between the two tests. These findings support the removal of the anti-hemorrhagic test from Korean regulations, aligning with global efforts to reduce animal testing while ensuring the efficacy of biological products.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"258 ","pages":"Article 108337"},"PeriodicalIF":2.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143761041","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":"Baicalin alleviates lipid accumulation in adipocytes via inducing metabolic reprogramming and targeting Adenosine A1 receptor","authors":"Zaikuan Zhang ,&nbsp;Runzhi Wang ,&nbsp;Jin Cai ,&nbsp;Xinyi Li ,&nbsp;Xiaosong Feng ,&nbsp;Shengming Xu ,&nbsp;Zhihong Jiang ,&nbsp;Peiyi Lin ,&nbsp;Zengyi Huang ,&nbsp;Yajun Xie","doi":"10.1016/j.toxicon.2025.108339","DOIUrl":"10.1016/j.toxicon.2025.108339","url":null,"abstract":"<div><div>Excessive lipid accumulation can lead to obesity, metabolic-associated fatty liver disease, and type 2 diabetes. However, there are currently few drugs that could effectively and safely inhibit the accumulation of intracellular lipids. In this study, we observed that baicalin significantly altered cellular respiration by reducing mitochondrial oxygen consumption while enhancing glycolytic flux, accompanied by increased phosphorylation of AMPK and ACC, suggesting an adaptation to altered energy availability. Baicalin effectively reduced lipid droplet formation and intracellular triglyceride levels in adipocytes, as marked by downregulating genes and proteins associated with lipid storage, including <em>Cd36</em>, <em>Fabp4</em>, and FASN. Transcriptomic analysis identified 2150 differentially expressed genes in baicalin-treated adipocytes, with significant enrichment in metabolic pathways such as glycolysis, gluconeogenesis, and lipid metabolism. Further analysis revealed that baicalin upregulated glycolytic and fatty acid β-oxidation (FAO) pathways while downregulating pyruvate dehydrogenase, inducing a shift toward glycolysis and FAO for energy production. Molecular docking analysis revealed that Adenosine A1 receptor (ADORA1) was the target of baicalin, which inhibited the maturation of sterol regulatory element binding protein 1 (SREBP1) and finally alleviated lipid deposition. These results demonstrate that baicalin induces metabolic reprogramming of adipocytes by inhibiting glucose aerobic metabolism while enhancing anaerobic glycolysis and FAO. Meanwhile, baicalin targets ADORA1, which subsequently influences the processing of SREBP1 and downregulates lipid biosynthesis, positioning baicalin as a potential therapeutic agent against obesity and related metabolic disorders.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"258 ","pages":"Article 108339"},"PeriodicalIF":2.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143796462","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":"Lutein and Zeaxanthin abated neurobehavioral, neurochemical and oxido-inflammatory derangement in rats intoxicated with Aflatoxin B1","authors":"Solomon Owumi ,&nbsp;Joseph Chimezie ,&nbsp;Marvellous O. Salami ,&nbsp;Japheth A. Ishaya ,&nbsp;Chidindu Vine Onyemuwa ,&nbsp;Mark Nnamdi ,&nbsp;Olatunde Owoeye","doi":"10.1016/j.toxicon.2025.108345","DOIUrl":"10.1016/j.toxicon.2025.108345","url":null,"abstract":"<div><div>Aflatoxin B₁ (AFB₁), a mycotoxin commonly present in feed, has several toxic effects. AFB₁ seems to have a neurotoxic effect that leads to neurobehavioral impairment. On the other hand, Lutein and Zeaxanthin (LUT/ZEA) have antioxidant and anti-inflammatory effects. Here, we aimed to compare the effects of AFB₁ and the co-treatment with LUT/ZEA on neurobehavioural and biochemical changes <em>viz-a-viz</em> oxido-inflammatory response in male rats' hippocampal and pre-frontal cortexes. Experimental rats of the Wistar strain (n = 40) were randomly grouped into treatment cohorts: Control (corn oil 2 mL/kg), AFB₁ (75 μg/kg), LUT/ZEA only (100 mg/kg), AFB₁ + LUT/ZEA (75 μg/kg + 100 mg/kg), and AFB₁ + LUT/ZEA (75 μg/kg + 200 mg/kg). All groups were administered their respective treatment orally for 28 days, while behavioural tests were conducted using open field tests (OFT), Y-maze, novel object tests (NORT), and forced swim tests (FST) 1 h after treatment on day 26–28. The animals were euthanized on day 29. In the hippocampal and pre-frontal cortex, antioxidant indicators (SOD, CAT, GSH, GST, GPx, TSH), inflammatory mediators (XO, NO, MPO), and acetylcholinesterase activity were measured. Our finding presents the anti-oxidant effect of lutein/Zeaxanthin in the brains of AFB₁-intoxicated rats, indicating better cognitive and spatial memory capacity in Y-maze and NORT, an improvement in locomotive and explorative behaviour in OFT and reduction in anxio-depressive-like behaviour in LUT/ZEA co-treated rats. Acetylcholinesterase activity was enhanced in LUT/ZEA co-treated rats. LUT/ZEA co-treatment dampened oxido-inflammatory mediators by decreasing XO, NO, and MPO levels and increasing antioxidant activities (SOD, CAT, GSH, GST, GPx, TSH) in the prefrontal and hippocampal cortices. We surmise that mechanistically, co-treatment with LUT/ZEA effectively lessened AFB₁ neurotoxicity through anti-inflammatory and antioxidant pathways and essentially improved the experimental rats' neurobehavioural outcomes.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"258 ","pages":"Article 108345"},"PeriodicalIF":2.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143800501","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":"Alleviation of LPS-induced acute lung injury by propolis-based nanocomposites through the TLR4/NFKB and P2X7/AKT pathways: Randomized-controlled experimental study","authors":"Hilal Üstündağ ,&nbsp;Adem Kara ,&nbsp;Necip Gökhan Taş ,&nbsp;Ferdane Danişman Kalindemi̇rtaş ,&nbsp;Nezahat Kurt ,&nbsp;Elif Erbaş ,&nbsp;Mehmet Tahir Huyut ,&nbsp;Mustafa Gül ,&nbsp;İshak Afşin Kari̇per","doi":"10.1016/j.toxicon.2025.108330","DOIUrl":"10.1016/j.toxicon.2025.108330","url":null,"abstract":"<div><div>Sepsis-associated acute lung injury continues to pose a significant medical challenge with substantial morbidity and mortality rates. In this study, we investigated the therapeutic potential of propolis-based treatments and their nanocomposites in modulating inflammation and apoptosis using a lipopolysaccharide (LPS)-induced rat model of sepsis. Forty-two Sprague-Dawley rats were divided into seven groups (n = 6): control, LPS (5 mg/kg, i.p.), LPS + Propolis (100 mg/kg, i.p.), LPS + NanoPropolis (100 mg/kg, i.p.), LPS + silver nanoparticles propolis (AgNPsPro) (50 mg/kg), and a negative propolis group (100 mg/kg, i.p.). The rats were assessed for inflammatory, oxidative stress, and apoptotic markers through Western blot, histopathological analyses, and biochemical measurements. The LPS group exhibited significantly higher levels of pro-inflammatory cytokines (IL-1β, TNF-α) and the systemic infection marker presepsin (PRSN) in blood, as well as the oxidative stress marker malondialdehyde (MDA) in lung tissue. The treatment groups, particularly LPS + AgNPsPro, showed significant reductions in these markers, with decreased levels of MDA, IL-1β, TNF-α, NF-κB, and TLR4, and increased GSH content in lung tissue (p &lt; 0.05). The anti-apoptotic protein BCL-2 was upregulated, while pro-apoptotic BAX expression was reduced, indicating enhanced cell survival. The P2X7 receptor, a key inflammation regulator, and the AKT signaling pathway, involved in cell survival, were positively modulated by the treatments. Histopathological findings corroborated these results, showing less lung tissue damage. In conclusion<strong>,</strong> propolis-based treatments, especially in combination with nanoparticles, demonstrate therapeutic potential in reducing inflammation, oxidative stress, and apoptosis in sepsis-induced lung injury.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"258 ","pages":"Article 108330"},"PeriodicalIF":2.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143731168","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":"Tityus paraguayensis, a scorpion from the Brazilian Cerrado: First assessment of venom and hemolymph composition and biological activity","authors":"Henrique Ranieri Covali-Pontes ,&nbsp;Mila Marluce Lima Fernandes ,&nbsp;Laís Corrêa de Lima ,&nbsp;Maria Ligia Rodrigues Macedo ,&nbsp;Giovana Cristina Giannesi ,&nbsp;Maria Antônia Bastos de Oliveira ,&nbsp;Alda Maria Teixeira Ferreira ,&nbsp;Breno Emanuel Farias Frihling ,&nbsp;Ludovico Migliolo ,&nbsp;Natália Gabrielly Pereira dos Santos ,&nbsp;Monica Viviana Abreu Falla ,&nbsp;Guilherme Rabelo Coelho ,&nbsp;Malson Neilson de Lucena","doi":"10.1016/j.toxicon.2025.108332","DOIUrl":"10.1016/j.toxicon.2025.108332","url":null,"abstract":"<div><div>Scorpionism is a serious public health problem in Brazil, where scorpion stings are the most frequent accidents caused by venomous animals. Scorpion venoms comprise a complex mixture of different classes of molecules, some of which may possess pharmacological properties. This study aimed to investigate the biological activity and composition of the venom and hemolymph of <em>Tityus paraguayensis</em>, an endemic species found in Mato Grosso do Sul State. The hemolymph showed proteolytic and lipase activities associated with innate immunity and digestive processes, respectively. Although these activities are not believed to be involved in the manifestations of envenomation, they might prove valuable in the prospection of compounds with antimicrobial activity. The venom exhibited phospholipase and lipase activities and stimulated (Na⁺,K⁺)-ATPase activity. The venom was also analyzed for activity against epimastigote forms of <em>Trypanosoma cruzi</em>. In this assay, <em>T. paraguayensis</em> venom inhibited parasite growth. The venom did not cause cytotoxicity to Vero cells. SDS-PAGE analysis revealed proteins ranging from 10 to 140 kDa, as well as bands with molecular mass &lt;10 kDa, possibly corresponding to neurotoxic peptides. HPLC analysis of <em>T. paraguayensis</em> venom revealed that the highest number of peaks had retention times of 1–20 min (0–35 % acetonitrile). The partial sequence of peak 10 was determined by Q-TOF analysis and was partially identified as a peptide (Tp10) that possible act as a K⁺ channel ligand (KTx). Additionally, 5 toxins related to potassium channel toxins, 3 toxins related to sodium channel toxins and a metalloproteinase were identified by shotgun proteomic of <em>T. paraguayensis</em> venom. This is the first report of the biological activities, HPLC profile, electrophoretic pattern and proteomic analysis of <em>T. paraguayensis</em> venom. These findings suggest that <em>T. paraguayensis</em> venom may be a valuable source for the identification of molecules with pharmacological applications.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"258 ","pages":"Article 108332"},"PeriodicalIF":2.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143744043","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":"Why do antivenoms still terrify Brazilian doctors? Lessons from the penicillin treatment decentralization","authors":"Wuelton Monteiro ,&nbsp;Adele Schwartz Benzaken ,&nbsp;Fan Hui Wen","doi":"10.1016/j.toxicon.2025.108329","DOIUrl":"10.1016/j.toxicon.2025.108329","url":null,"abstract":"<div><div>Penicillin and antivenom treatments may cause early adverse reactions. Given the low incidence of hypersensitivity reactions attributed to penicillin, the Brazilian Ministry of Health determined the decentralization of the use of this medicine to community health centers, especially to treat syphilis and prophylaxis of congenital syphilis. Regarding antivenoms, the establishment of modern purification technologies in the manufacturing process ensured the increasing efficacy and safety in the country. However, lack of training and the use of outdated evidence on the frequency of adverse reactions and the overdiagnosis of hypersensitivity reactions to antivenoms generates resistance from health professionals to administer these products in non-hospital settings. Also, robust studies on the safety of concomitant medications are lacking in this field. This results in delays in treatment leading to poor clinical outcomes.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"258 ","pages":"Article 108329"},"PeriodicalIF":2.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143731550","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":"Melittin: A promising therapeutic agent for rheumatoid arthritis treatment","authors":"Rong Huang ,&nbsp;Xiying He ,&nbsp;Qingxin Meng ,&nbsp;Guangyu Yan ,&nbsp;Kun Dong ,&nbsp;Yakai Tian","doi":"10.1016/j.toxicon.2025.108335","DOIUrl":"10.1016/j.toxicon.2025.108335","url":null,"abstract":"<div><div>Rheumatoid Arthritis (RA) is a globally prevalent chronic disease that presents significant challenges in terms of curability. The etiology and onset of RA are not readily identifiable, and as the disease advances, it is characterized by joint pain, swelling, and damage, potentially resulting in paralysis. The adverse effects associated with existing pharmacological treatments are considerable, and prolonged use may pose significant health risks. Melittin, a naturally occurring anti-rheumatic compound, has garnered increasing scholarly interest. Melittin has demonstrated the potential to significantly augment the therapeutic efficacy of certain first-line pharmacological agents while minimizing adverse effects, thereby rendering it appropriate for prolonged use. Melittin's mechanisms of action in treating RA encompass anti-inflammatory effects, immunomodulatory effects, analgesic effects, reduction of cardiovascular disease risk, and organ-protective effects, targeting multiple aspects of RA to alleviate symptoms. Clarifying the biological functions of melittin and its mechanisms in treating RA can provide valuable insights for the application of melittin in the intervention of RA disease progression. However, melittin can cause allergic reactions, hemolysis, and cytotoxicity in the body, which limit its application. Research has shown that strategies including melittin-based nanomodification, immunoconjugation, and structural regulation can improve the specificity of melittin, decrease cytotoxicity, and mitigate the lytic effects on non-target cells of bee venom. These findings suggest that melittin holds promise for clinical applications. This article provides a comprehensive overview of the disease progression associated with RA, examines the biological properties of Mmelittin, and discusses therapeutic strategies for utilizing melittin in the treatment of rheumatoid arthritis. The objective is to mitigate the toxic side effects of melittin while enhancing its targeted anti-inflammatory effects, thereby investigating its potential clinical value in the prevention of rheumatoid arthritis.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"258 ","pages":"Article 108335"},"PeriodicalIF":2.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143731355","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":"Using corn cob powder to induce AFB1-degrading enzyme production in Cladosporium uredinicola HSK8 for detoxification purposes","authors":"Mengxiong Xiang ,&nbsp;Ernuo Tian ,&nbsp;Shuting Wang ,&nbsp;Siyao Wang ,&nbsp;Runmei Zhang ,&nbsp;Jianyi Guo ,&nbsp;Ming Liu ,&nbsp;Qiang Ding ,&nbsp;Jun Cai","doi":"10.1016/j.toxicon.2025.108333","DOIUrl":"10.1016/j.toxicon.2025.108333","url":null,"abstract":"<div><div>Aflatoxin B₁ (AFB₁) is a highly toxic mycotoxin that contaminates food sources and poses serious health risks. This study examines <em>Cladosporium uredinicola</em> HSK8's ability to degrade AFB₁. It was demonstrated that the hydrolysis of corn cob powder, following high-temperature treatment, generates derivatives such as furfural and vanillin, which stimulate the production of various AFB₁-degrading enzymes by <em>C. uredinicola</em> HSK8. The total enzymatic activity reached a peak of 3750 U/mL in fermentation broth with 3 % corn cob powder. Two AFB₁-degrading enzymes were further isolated, purified and analyzed. The results showed that enzymes can disrupt both the furan and benzene rings, exhibiting strong catalytic activity. The results suggested corn cob powder as a complex carbon source not only promotes the growth of <em>C. uredinicola</em> but also induces the production of AFB₁-degrading enzymes. Therefore, the fermentation broth of <em>C. uredinicola</em> HSK8 cultured with corn cob powder holds great potential for the detoxification of AFB₁ in food and feed.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"258 ","pages":"Article 108333"},"PeriodicalIF":2.6,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143725493","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":"Production and characterization of pertussis toxin specific monoclonal and polyclonal antibodies: Implication for toxin purification and detection","authors":"Danyal Imani ,&nbsp;Tannaz Bahadori ,&nbsp;Maryam Mobini ,&nbsp;Mohammad Ali Judaki ,&nbsp;Mahmood Jeddi-Tehrani ,&nbsp;Mohammad Mehdi Amiri ,&nbsp;Fazel Shokri","doi":"10.1016/j.toxicon.2025.108334","DOIUrl":"10.1016/j.toxicon.2025.108334","url":null,"abstract":"<div><h3>Background</h3><div>Pertussis is a pulmonary disease caused by the gram-negative bacteria Bordetella pertussis (<em>BP</em>) with a high fatality rate among newborns and young children. Pertussis toxin (PT) is essential for pertussis pathogenesis as well as production of acellular pertussis vaccines (aPV). Traditional PT purification procedures are laborious and yield low purity and recovery rates. Also, due to the low production levels of PT by <em>BP</em> and the difficulties of purification, an appropriate immunoassay is needed to monitor PT concentrations upstream and downstream of the production process. This study investigates production and application of monoclonal and polyclonal antibodies for efficient PT purification and quantification.</div></div><div><h3>Methods</h3><div>Rabbits and mice were immunized with native PT to produce polyclonal and monoclonal antibodies (MAbs). The MAbs were selected based on affinity, isotype and specificity, as determined by enzyme-linked immunosorbent assay (ELISA) and immunoblotting. The native PT antigen was purified using an immunoaffinity column. The purity and recovery rates of native PT were analyzed by ELISA, SDS-PAGE, and immunoblotting. Additionally, monoclonal and polyclonal antibodies were used to establish an ELISA assay for measurement of PT concentration.</div></div><div><h3>Results</h3><div>A highly pure PT with recovery rates of around 74 ± 4.9 % was obtained following purification by immunoaffinity column, using polyclonal antibodies. Furthermore, the designed ELISA demonstrated suitable reactivity for measurement of the PT antigen.</div></div><div><h3>Conclusion</h3><div>Our results indicate suitability of the produced monoclonal and polyclonal anti-PT antibodies for purification and monitoring of PT by immunoaffinity chromatography and ELISA, respectively. The immunoaffinity method offers an efficient replacement for PT purification in the context of developing aPV.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"258 ","pages":"Article 108334"},"PeriodicalIF":2.6,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143731280","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":"Antitumor and antiproliferative potential of crotoxin in triple negative breast tumors","authors":"De Andrade Camila Marques ,&nbsp;Machado Cleni Mara Marzocchi ,&nbsp;De Castro Fabíola Attié ,&nbsp;Teixeira Natércia ,&nbsp;Amaral Cristina ,&nbsp;Campos Felipe ,&nbsp;Canicoba Nathália Cristina ,&nbsp;Torqueti Maria Regina","doi":"10.1016/j.toxicon.2025.108322","DOIUrl":"10.1016/j.toxicon.2025.108322","url":null,"abstract":"<div><div>Triple negative breast carcinoma represents around 15 % of breast cancer cases. Is a type of breast cancer with poor prognosis, because it has a high rate of recurrence, metastasis and death and can be resistant to therapy. The recommended treatment is the use of anthracyclines with taxanes, however, these medications have several side effects. Thus, there is a need for new therapeutic approaches. Crotoxin, the main toxin found in the venom of the South American rattlesnake <em>Crotalus durissus terrificus</em>, is a potent β-neurotoxin that has phospholipase A2 (PLA2) activity. It exhibits preferential cytotoxic activity against several types of tumor cells and is most cytotoxic to cell lines that express high levels of epidermal growth factor receptors. Considering this, in this study, we evaluated the biological mechanisms that trigger the antitumor effects of crotoxin in a cell line representing triple negative breast carcinoma (MDA-MB-231 tumor cells). Results demonstrated that crotoxin had anti-apoptotic, anti-autophagic and pro-necrotic actions. The pro-necrotic effect occurred through mechanisms of apoptosis evasion, autophagy inhibition and DNA damage. Therefore, this study represents an important milestone to better understand the effects and mechanisms of action of crotoxin in triple negative breast cancer.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"258 ","pages":"Article 108322"},"PeriodicalIF":2.6,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143693415","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}