Toxins最新文献

{"title":"Differential Retention and Loss of a Mycotoxin in Fungal Evolution.","authors":"Lin Chen, Ziying Yan, Bolei Yang, Bowen Tai, Weizhao Li, Erfeng Li, Gang Wang, Fuguo Xing","doi":"10.3390/toxins17060311","DOIUrl":"10.3390/toxins17060311","url":null,"abstract":"<p><p>Ochratoxin A (OTA) is designated as a mycotoxin and is regulated worldwide due to its harmful effects on humans and animals, but the evolutionary history and ecological significance of OTA in fungi remain poorly understood. Phylogenetic analysis suggested that <i>Aspergillus</i> and <i>Metarhizium</i> obtained an ancient OT cluster, which evolved independently, followed by horizontal OT transfer from <i>Aspergillus</i> to <i>Penicillium</i>. The varying presence of functional, absent and pseudogenized OT genes across <i>Aspergillus</i> species revealed that this cluster is undergoing a degeneration process in this genus. Furthermore, the cyclase OtaY in the OTA cluster is likely derived from bacteria, which was revealed by phylogenetic analysis. This is the first attempt to investigate the ecological significance of OTA in fungi, suggesting that it may be nonfunctional in <i>Aspergillus</i> spp. and has undergone multiple forms of loss during evolution.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 6","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12197560/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144485805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular Diagnosis in Hymenoptera Allergy: Comparison of Euroline DPA-Dx and ImmunoCAP.","authors":"Lluís Marquès, Arantza Vega, Federico de la Roca, Carmen Domínguez, Víctor Soriano-Gomis, Teresa Alfaya, Laia Ferré-Ybarz, José-María Vega, Mario Tubella, Berta Ruiz-León","doi":"10.3390/toxins17060310","DOIUrl":"10.3390/toxins17060310","url":null,"abstract":"<p><p>The efficacy of Hymenoptera venom immunotherapy is contingent upon the accurate identification of the insect responsible for the allergic reaction. The techniques used to detect specific IgE suffer from difficulties due to the cross-reactivity between Hymenoptera venoms (false positives), diagnostic ability, and the limited availability of allergenic components (false negatives). In this study, we analyzed the discrepancies in the results obtained with Euroline^® DPA-Dx and ImmunoCAP^® in the diagnosis of allergic reactions due to Hymenoptera stings in 151 patients. The results (positive/negative) of ImmunoCAP^® and Euroline^® agreed in 77/151 (50.99%) cases; with 15/151 (9.93%) cases positive for the same insect, and 61/151 (40.4%) cases positive for multiple insects. When the results were used to decide which venom to use for immunotherapy, there was a statistically significant discrepancy for <i>Polistes dominula</i> (21.8% of cases with ImmunoCAP^® compared to only 8.4% with Euroline^®). The presence of <i>Polistes</i> venom phospholipase (Pol d 1) in Euroline^® did not increase its ability to differentiate double sensitization to wasps. ImmunoCAP^® and Euroline^® exhibited comparable diagnostic performance in bee venom allergy. For vespid venom allergy-particularly involving <i>Polistes</i> species-ImmunoCAP^® appeared to show a slight diagnostic advantage, although this finding should be interpreted with caution.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 6","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12197634/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144485874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative Efficacy of Ribosome-Inactivating Protein-Containing Immunotoxins in 2D and 3D Models of Sarcoma.","authors":"Giulia Calafato, Massimo Bortolotti, Letizia Polito, Andrea Bolognesi","doi":"10.3390/toxins17060308","DOIUrl":"10.3390/toxins17060308","url":null,"abstract":"<p><p>Sarcomas are very complex and clinically challenging mesenchymal tumors. Although the standard therapeutic approach has improved the 5-year survival rate, many patients experience local relapses and/or distant metastases. To improve patient outcome, new strategies need to be investigated. Immunotoxins (ITs) based on rRNA N-glycosylases (also named ribosome-inactivating proteins, RIPs) are promising tools for cancer therapy because, by combining rRNA-glycosylase's high cytotoxicity with carrier selectivity, they can specifically eliminate target neoplastic cells. In the last few years, 3D models have been extensively used in cancer research, particularly for target-specific drug screening. This study aimed to evaluate the possibility of utilizing ribosome-inactivating protein (RIP)-containing ITs to selectively target TfR1-, EGFR1- and Her2-expressing sarcoma adherent cells (ACs), spheroids (SSs) and organoids (ORs). To compare Its' efficacy and ability to induce apoptosis, we performed dose-response viability and caspase 3/7 activation assays on rhabdomyosarcoma and osteosarcoma ACs, SSs and ORs treated with Tf-IT, αEGFR1-IT and αHer2-IT. Our results indicate that, compared to the corresponding unconjugated RIPs, all ITs showed increased cytotoxicity in sarcoma ACs. Despite the increased complexity characterizing 3D models, the higher IC₅₀ differences between ITs and unconjugated RIPs were obtained in ORs, which appeared more resistant to the nonspecific killing of the RIPs than either the ACs or SSs, thus augmenting the therapeutic window between unconjugated and conjugated RIPs. IT induced a more delayed apoptosis in 3D compared to 2D models. Our results provide essential outcomes for the potential use of these RIP-based ITs as a therapeutic strategy to treat sarcoma.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 6","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12197652/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144485863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessing <i>Alternaria</i> Species and Related Mycotoxin Contamination in Wheat in Algeria: A Food Safety Risk.","authors":"Meriem Barkahoum Daichi, Mario Masiello, Miriam Haidukowski, Annalisa De Girolamo, Antonio Moretti, Amor Bencheikh, Noureddine Rouag, Stefania Somma","doi":"10.3390/toxins17060309","DOIUrl":"10.3390/toxins17060309","url":null,"abstract":"<p><p><i>Alternaria</i> species are important fungal pathogens occurring worldwide in wheat, causing both productive and qualitative losses, and posing a toxicological risk to human health due to the production of their mycotoxins in kernels. This study aimed to investigate the occurrence of <i>Alternaria</i> species and their mycotoxins in 48 wheat grain samples collected from the northeast to the southeast of Algeria. Seventy-two representative <i>Alternaria</i> strains were molecularly analyzed using a multi-locus sequence approach and evaluated for their capability to produce mycotoxins under in vitro conditions. <i>Alternaria alternata</i>, representing 42% of the strains, was the dominant species, followed to a lesser extent by species included in the <i>Infectoriae</i> section (26%). In addition, three species not previously reported in Algerian wheat, <i>A. eureka</i>, <i>A. consortialis</i> and <i>A. tellustris</i>, were identified, accounting for 5% of the total strains. Mycotoxin analyses showed high contamination of grains with alternariol monomethyl ether, alternariol and tenuazonic acid, occurring in 75, 69 and 35% of the samples, respectively. Moreover, 41 out of 48 samples showed the co-occurrence of multiple <i>Alternaria</i> mycotoxins. This study provides, for the first, time a clear picture of the occurrence and the distribution of <i>Alternaria</i> species on wheat in Algeria. Finally, the extensive monitoring activities carried out revealed the great biodiversity of <i>Alternaria</i> species able to colonize wheat grains. Moreover, findings on mycotoxin contamination raise concerns about the significant mycotoxigenic risk in Algerian wheat, emphasizing the need for strict monitoring and regulatory measures on <i>Alternaria</i> mycotoxins in food and feed.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 6","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12197503/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144485855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Growth Dynamics and Toxin Production of <i>Pseudo-nitzschia</i> Species Isolated from the Central Adriatic Sea.","authors":"Tina Tomašević, Jasna Arapov, Ivana Ujević, Tina Bonačić, Mia Bužančić, Antonija Bulić, Sanda Skejić, Romana Roje-Busatto, Živana Ninčević Gladan","doi":"10.3390/toxins17060307","DOIUrl":"10.3390/toxins17060307","url":null,"abstract":"<p><p>The marine diatoms <i>Pseudo-nitzschia</i> spp. are globally distributed primary producers, with certain species capable of producing neurotoxin domoic acid (DA), causing amnesic shellfish poisoning (ASP). This study investigates the toxicity and growth rates of <i>Pseudo-nitzschia</i> species isolated from aquaculture areas in the Central Adriatic Sea. A total of 54 strains from eight species were analysed, with strains originating from four different study sites. Growth rates and toxin production were examined across different growth phases in other species and strains. Most species, including <i>P. allochrona</i>, <i>P. calliantha</i>, <i>P. delicatissima</i>, <i>P. fraudulenta</i>, <i>P. galaxiae</i>, <i>P. mannii</i>, and <i>P. multistriata</i>, did not produce DA at any growth phase. The only species that showed toxin production, at 18 °C was <i>P. pseudodelicatissima</i> (0.0007-0.0250 pg cell^-1). Notably, the majority of <i>P. pseudodelicatissima</i> strains were toxic in the decay phase and some strains showed continuous toxin production throughout all growth phases. The highest growth rates for the analysed species were recorded in strains of <i>P. delicatissima,</i> which also exhibited the highest cell abundance (8.19 × 10⁵ cell mL^-1), followed by the species <i>P. allochrona</i>, <i>P. mannii</i> and <i>P. pseudodelicatissima.</i></p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 6","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12197538/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144485811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LL-37 Attenuates Sepsis-Induced Lung Injury by Alleviating Inflammatory Response and Epithelial Cell Oxidative Injury via ZBP1-Mediated Autophagy.","authors":"Hu Gao, Fajuan Tang, Bin Chen, Xihong Li","doi":"10.3390/toxins17060306","DOIUrl":"10.3390/toxins17060306","url":null,"abstract":"<p><p><b>Background:</b> Sepsis-induced acute lung injury (ALI) is a serious disease constituting a heavy burden on society due to high mortality and morbidity. Inflammation and oxidative stress constitute key pathological mechanisms in ALI caused by sepsis. LL-37 can improve the survival of septic mice. Nevertheless, its function and underlying mechanism in sepsis-evoked ALI is elusive. <b>Methods:</b> The human A549 alveolar epithelial cell line was treated with LL-37 or ZBP1 recombinant vector under LPS exposure. Then, the effects on cell oxidative stress injury, inflammatory response, and autophagy were analyzed. RNA-seq analysis was performed to detect the differentially expressed genes (DEGs) between the LPS and LPS/LL-37 groups. Furthermore, the effects of LL-37 on cecal ligation and the puncture (CLP)-constructed ALI model were explored. <b>Results:</b> LL-37 attenuated LPS-evoked oxidative injury in human alveolar epithelial cells by increasing cell viability and suppressing ROS, malondialdehyde, and lactate dehydrogenase levels and apoptosis. Moreover, LPS-induced releases of pro-inflammatory IL-18, TNF-α, and IL-1β were suppressed by LL-37. Furthermore, LPS's impairment of autophagy was reversed by LL-37. RNA-seq analysis substantiated 1350 differentially expressed genes between the LPS and LPS/LL-37 groups. Among them was ZBP1, a significantly down-regulated gene with the largest fold change. Moreover, LL-37 suppressed LPS-increased ZBP1 expression. Importantly, ZBP1 elevation restrained LL-37-induced autophagy in LPS-treated cells and abrogated LL-37-mediated protection against LPS-evoked oxidative injury and inflammation. LL-37 ameliorated abnormal histopathological changes, tissue edema, the lung injury score, oxygenation index (PaO2/FiO2), and glycemia contents in the CLP-constructed ALI model, which were offset through ZBP1 elevation via its activator CBL0137. Additionally, LL-37 suppressed inflammation and oxidative stress in lung tissues, concomitant with autophagy elevation and ZBP1 down-regulation. <b>Conclusions:</b> LL-37 may alleviate the progression of sepsis-evoked ALI by attenuating pulmonary epithelial cell oxidative injury and inflammatory response via ZBP1-mediated autophagy activation, indicating a promising approach for the therapy of ALI patients.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 6","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12197590/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144485872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toxicodynamic Assessment of Aqueous Neem (<i>Azadirachta indica</i> A. Juss) Seed Extract on Mortality and Carboxylesterase Activity in Key Organs of <i>Bombyx mori</i> L. Larvae.","authors":"Ajin Rattanapan, Chuthep Phannasri, Chawiwan Phannasri, Patcharawan Sujayanont, Kattinat Sagulsawasdipan","doi":"10.3390/toxins17060304","DOIUrl":"10.3390/toxins17060304","url":null,"abstract":"<p><p>Botanical insecticides derived from neem (<i>Azadirachta indica</i> A. Juss.) seeds have gained significant interest due to their sustainable characteristics and low environmental impact. However, their use in sericulture remains contentious due to the heightened sensitivity of domesticated silkworms to environmental stressors. This study systematically investigates the toxicodynamic effects of aqueous neem seed extract (ANSE) on fifth instar larvae of Thai multivoltine <i>Bombyx mori</i> L., focusing on larval mortality and carboxylesterase (CarE) enzyme activity in essential detoxification organs. Larvae were exposed to ANSE concentrations ranging from 5 to 50 mg L^-1 for up to 72 h. Key findings highlight a pronounced dose- and time-dependent increase in mortality, with an accurately determined LC₅₀ value of 17 mg L^-1 at the longest time exposure, accompanied by mortality rates reaching approximately 83% at the highest concentration tested, indicating considerable susceptibility. Additionally, notable and distinct organ-specific responses were observed, with significant inhibition of CarE activity in the midgut contrasting with elevated activities in the fat body and Malpighian tubules. These differential enzymatic responses reveal previously undocumented adaptive detoxification mechanisms. Consequently, the study advocates cautious and regulated application of neem-based insecticides in sericulture, recommending precise management of concentrations and exposure durations according to silkworm strain sensitivities to ensure optimal silk production.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 6","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12197396/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144485903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Defence Against Desiccation and Predation in Lophyohylini Casque-Headed Tree Frogs.","authors":"César Alexandre, Pedro L Mailho-Fontana, Bianca C L F Távora, Marta M Antoniazzi, Carlos Jared","doi":"10.3390/toxins17060303","DOIUrl":"10.3390/toxins17060303","url":null,"abstract":"<p><p>Casque-headed tree frogs (Lophyohylini) can have a very large and distinctive head characterised by hyperossification of their cranial skin. This type of skull was primarily associated with phragmosis, a behaviour in which the frog enters holes backwards and seals them with its head to prevent water loss in challenging environments. Further investigations revealed that hyperossification also gives rise to bony spines interspersed with skin poison glands. These peculiar anatomical features of the head make it challenging for predators to prey on the frogs in phragmosis. When bitten on the head, the bite pressure causes the spines to cross the poison glands, allowing the injection of toxins into the predator's mouth. We studied the head morphology of different Lophyohylini species along with some characteristics of their cutaneous poison, both in the field and in the laboratory. These frogs exemplify distinct chemical defence strategies, highlighting the differences between venom and poison. Notably, some species can cause self-poisoning in predators by injecting poison (in this case, venom) through their head spines, similar to the use of fangs by snakes.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 6","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12197542/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144485868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biological Mechanisms of Enterotoxigenic <i>Bacteroides fragilis</i> Toxin: Linking Inflammation, Colorectal Cancer, and Clinical Implications.","authors":"Seyedesomaye Jasemi, Paola Molicotti, Milena Fais, Ilaria Cossu, Elena Rita Simula, Leonardo A Sechi","doi":"10.3390/toxins17060305","DOIUrl":"10.3390/toxins17060305","url":null,"abstract":"<p><p>Enterotoxigenic <i>Bacteroides fragilis</i> (ETBF) has emerged as a gut microbiome pathogen that can promote intestinal inflammation and contribute to colorectal cancer (CRC). Its principal virulence factor, the <i>Bacteroides fragilis</i> toxin (BFT), is a zinc-dependent metalloprotease that disrupts epithelial barrier integrity, initiates inflammatory signaling pathways, and enhances epithelial proliferation. Although growing evidence supports a link between ETBF and CRC, some inconsistencies across studies highlight the need for further investigation into the molecular mechanisms underpinning BFT-mediated pathogenesis. This review examines the biological structure and activity of BFT, with a focus on its role in epithelial injury, inflammatory responses, and tumorigenesis. In addition, we discuss current challenges in the detection and characterization of ETBF and BFT, including technical limitations in clinical diagnostics and methodological variability across studies. Recent advances in multi-omics technologies, molecular diagnostics, nanobody-based detection platforms, and probiotic intervention are also highlighted as promising avenues for improving ETBF identification and therapeutic targeting. Future research integrating systematic molecular profiling with clinical data is essential to enhance diagnostic accuracy, elucidate pathophysiological mechanisms, and develop effective interventions against ETBF-associated diseases.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 6","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12197655/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144485857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Experimental Model of Acute Pulmonary Damage Induced by the Phospholipase A₂-Rich Venom of the Snake <i>Pseudechis papuanus</i>.","authors":"Daniela Solano, Alexandra Rucavado, Teresa Escalante, Edith Bastos Gandra Tavares, Suellen Karoline Moreira Bezerra, Clarice Rosa Olivo, Edna Aparecida Leick, Julio Alejandro Rojas Moscoso, Lourdes Dias, Iolanda de Fátima Lopes Calvo Tibério, Stephen Hyslop, José María Gutiérrez","doi":"10.3390/toxins17060302","DOIUrl":"10.3390/toxins17060302","url":null,"abstract":"<p><p>An experimental model of acute pulmonary damage was developed based on the intravenous injection of the phospholipase A₂ (PLA₂)-rich venom of <i>Pseudechis papuanus</i> (Papuan black snake) in mice. Venom caused pulmonary edema, with the accumulation of a protein-rich exudate, as observed histologically and by analysis of bronchoalveolar lavage fluid (BALF). In parallel, venom induced an increase in all of the pulmonary mechanical parameters evaluated, without causing major effects in terms of tracheal and bronchial reactivity. These effects were abrogated by incubating the venom with the PLA₂ inhibitor varespladib, indicating that this hydrolytic enzyme is responsible for these alterations. The venom was cytotoxic to endothelial cells in culture, hydrolyzed phospholipids of a pulmonary surfactant, and reduced the activity of angiotensin-converting enzyme in the lungs. The pretreatment of mice with the nitric oxide synthase inhibitor L-NAME reduced the protein concentration in the BALF, whereas no effect was observed when mice were pretreated with inhibitors of cyclooxygenase (COX), tumor necrosis factor-α (TNF-α), bradykinin, or neutrophils. Based on these findings, it is proposed that the rapid pathological effect of this venom in the lungs is mediated by (a) the direct cytotoxicity of venom PLA₂ on cells of the capillary-alveolar barrier, (b) the degradation of surfactant factor by PLA₂, (c) the deleterious action of nitric oxide in pulmonary tissue, and (d) the cytotoxic action of free hemoglobin that accumulates in the lungs as a consequence of venom-induced intravascular hemolysis. Our findings offer clues on the mechanisms of pathophysiological alterations induced by PLA₂s in a variety of pulmonary diseases, including acute respiratory distress syndrome (ARDS).</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 6","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12197351/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144485854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}