Toxicology and applied pharmacology最新文献

{"title":"Preclinical evaluation of N-acetyl-cysteine in association with liposomes of lung surfactant's lipids for the treatment of pulmonary fibrosis and asthma","authors":"Estefanía N. Morales ,&nbsp;Constanza Confino Malecki ,&nbsp;Alejandro Maruri ,&nbsp;Vanesa R. Sánchez ,&nbsp;Agustina Portu ,&nbsp;Alejandra Goldman ,&nbsp;Nadia S. Chiaramoni ,&nbsp;Ignacio M. Fenoy","doi":"10.1016/j.taap.2025.117412","DOIUrl":"10.1016/j.taap.2025.117412","url":null,"abstract":"<div><h3>Purpose</h3><div>There is a need to generate new treatments against pulmonary diseases such as idiopathic fibrosis and asthma. <em>N</em>-acetylcysteine (NAC) has multiple clinical applications, but its unstable nature and route of administration limits its effectiveness. New pulmonary delivery strategies, such as liposomes made of lung surfactant lipids, could overcome NAC's limitations. This work aims to evaluate the efficacy of NAC combined with liposomes as a treatment for asthma and in preventing fibrotic development.</div></div><div><h3>Methods</h3><div>Unilamellar vesicles were obtained through the dehydration-rehydration method followed by multiple membrane extrusion and characterized by Dynamic Light Scattering and Transmission electron microscopy. Lung fibrosis was induced by bleomycin administration, and liposomal formulation of NAC (LipoNAC) was evaluated as a preventive treatment. LipoNAC formulation was also evaluated in a therapeutic regimen for asthma using the classic ovalbumin model. For both models, the administration of the treatment was via the intranasal route.</div></div><div><h3>Results</h3><div>NAC treatments (free NAC and LipoNAC) improved lung histopathology and decreased collagen deposition when tested in the lung fibrosis model. Only LipoNAC decreased serum levels of lactate dehydrogenase, myeloperoxidase activity in lung fluid and lung TGF-β. Although both treatments decreased Th2 cytokine and histopathological inflammation in the asthma model, only LipoNAC treatment significantly decreased mucus in asthmatic mice.</div></div><div><h3>Conclusions</h3><div>These results indicate that surfactant liposomal delivery of NAC potentiates its anti-inflammatory, mucolytic, and antioxidant activity, rendering it a promising therapy for respiratory diseases.</div></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":"502 ","pages":"Article 117412"},"PeriodicalIF":3.3,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144161130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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 oxidative stress and inflammation by lesbicoumestan (7) via the increase of Nrf2 expression in mouse Kupffer cells","authors":"Xiangying Li ,&nbsp;Lulu Yao ,&nbsp;Young-Chang Cho ,&nbsp;Da Young Lee ,&nbsp;Namki Cho ,&nbsp;Guijae Yoo ,&nbsp;Sang Yoon Choi ,&nbsp;Somy Yoon ,&nbsp;Jae Sung Lim","doi":"10.1016/j.taap.2025.117405","DOIUrl":"10.1016/j.taap.2025.117405","url":null,"abstract":"<div><div>Lesbicoumestans are a class of bioactive compounds isolated from the roots of <em>Lespedeza bicolor</em> (<em>L. bicolor</em>). These compounds have been reported to exhibit anticancer and antiproliferative activities. In this study, our primary focus was to examine the antioxidant capabilities of lesbicoumestan (7) (LC-7), a newly isolated coumestan from roots of L. <em>bicolor</em>, using lipopolysaccharide (LPS)-stimulated immortalized mouse Kupffer cells (ImKCs) as the experimental model. The investigation revealed that LC-7 played a pivotal role in inhibiting the production of reactive oxygen species (ROS). Additionally, LC-7 effectively restored the imbalanced glutathione(GSH)/glutathione disulfide ratio and enhanced the activity of glutathione peroxidase (GPx) following cellular exposure to LPS. Moreover, our investigation revealed that LC-7 exhibited the capacity to enhance the expression of heme oxygenase-1 (HO-1), leading to inhibition of nitric oxide (NO) and proinflammatory cytokines production induced by LPS. Notably, LC-7 did not significantly impact the nuclear factor kappa B cells (NF-κB) and mitogen-activated protein kinase (MAPK) pathways. Intriguingly, LC-7 modulated the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway by direct interaction with Kelch-like-ECH-associated protein 1 (Keap1). These findings suggest that LC-7 possesses antioxidant and anti-inflammatory properties in LPS-stimulated ImKCs by upregulating Nrf2 expression.</div></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":"501 ","pages":"Article 117405"},"PeriodicalIF":3.3,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144139196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Curcumin induces apoptosis via downregulation of SKP2 and induction of GADD45A/CDKN1A expression through generation of ROS in cutaneous T-cell lymphoma cells","authors":"Shilpa Kuttikrishnan ,&nbsp;Muhammad Suleman ,&nbsp;Fareed Ahmad ,&nbsp;Zahwa Mariyam ,&nbsp;Ummu Habeeba ,&nbsp;Kirti S. Prabhu ,&nbsp;Joerg Buddenkotte ,&nbsp;Martin Steinhoff ,&nbsp;Shahab Uddin","doi":"10.1016/j.taap.2025.117403","DOIUrl":"10.1016/j.taap.2025.117403","url":null,"abstract":"<div><div>Curcumin, a plant derived natural product isolated from <em>Curcuma longa</em>. The aim of this study is to investigate the anti-proliferative effects and the underlying mechanisms of curcumin in Cutaneous T cell lymphoma (CTCL), a type of non-Hodgkin lymphoma that primarily affects the skin. The study found that curcumin induced apoptosis in CTCL cells by activating mitochondrial signaling pathways and caspases leading to growth inhibition. Furthermore, Curcumin treatment downregulated the expression of S-phase kinase protein (SKP2) with concomitant upregulation of GADD45A, CDKN1A and CDKN1B. Curcumin also suppresses the expression of anti-apoptotic molecules including XIAP and cIAPs. Curcumin treatment of CTCL cells generates reactive oxygen species (ROS) and depletion of glutathione. Pretreatment of CTCL with <em>N</em>-acetyl cysteine prevented curcumin-mediated generation of ROS and prevention caspase activity. Co-treatment of CTCL with subtoxic doses of curcumin and bortezomib potentiated the anticancer action.</div><div>Co-treatment of CTCL with subtoxic doses of curcumin and bortezomib potentiated the anticancer action. Molecular docking studies revealed a strong binding affinity of curcumin to the active site of SKP2, primarily involving key residues crucial for its activity.</div><div>Altogether, our results suggest that targeting SKP2 and GADD45A signaling by curcumin could be an attractive strategy for the treatment of CTCL.</div></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":"501 ","pages":"Article 117403"},"PeriodicalIF":3.3,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144133246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spermidine exerts cardiometabolic protection in estrogen-deprived rats via mitigating cardiac mitochondrial dysfunction and apoptosis","authors":"Wichida Kaorop ,&nbsp;Chayodom Maneechote ,&nbsp;Wasana Pratchayasakul ,&nbsp;Sirinart Kumfu ,&nbsp;Busarin Arunsak ,&nbsp;Apisek Kongkaew ,&nbsp;Siriporn C. Chattipakorn ,&nbsp;Nipon Chattipakorn","doi":"10.1016/j.taap.2025.117399","DOIUrl":"10.1016/j.taap.2025.117399","url":null,"abstract":"<div><div>Postmenopausal conditions are linked to elevated risks of various complications, particularly cardiovascular diseases (CVDs). While estrogen supplementation is a standard intervention, it increase adverse effects of CVDs and breast cancer prevalence in postmenopausal women. Spermidine, a naturally occurring polyamine, has recently emerged attention for its protective effects in heart pathologies. However, the cardioprotective effects of spermidine against estrogen deprivation-related cardiac dysfunctions remain unclear. We hypothesized that spermidine exerted cardiometabolic protection by mitigating mitochondrial dysfunction, mitochondrial dynamics alterations, oxidative stress, inflammation, and cardiac cell death in female rats with ovariectomy (OVX)-induced estrogen deprivation. Fifty female Wistar rats were divided into a sham group (n = 10) and a 12-week-OVX-operated group (n = 40). The OVX rats were randomly assigned to receive either vehicle treatment, spermidine (OS, 20 mg/kg/day, p.o., n = 10), or estradiol (OE, 50 mg/kg/day, s.c., n = 10) for 8 weeks. Echocardiography and heart rate variability (HRV) were assessed, followed by euthanasia for cardiac tissue collection and blood sampling. OVX rats exhibited impaired metabolic, mitochondrial, and autophagic functions, along with elevated oxidative stress, inflammation, and apoptosis, leading to LV dysfunction. Spermidine and estrogen equally ameliorated all cardiometabolic adverse effects in OVX-induced estrogen-deprived female rats, suggesting spermidine as a promising alternative therapy for preventing cardiometabolic dysfunction in postmenopausal women.</div></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":"501 ","pages":"Article 117399"},"PeriodicalIF":3.3,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144133175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dual therapy for amanita phalloides-induced acute liver failure in mice: A combination of etanercept and alpha-1 antitrypsin","authors":"Nils Jedicke ,&nbsp;Nataliia Petriv ,&nbsp;Huizhen Suo ,&nbsp;Inga Hochnadel ,&nbsp;Danny Jonigk ,&nbsp;Ralf Lichtinghagen ,&nbsp;Julia Held ,&nbsp;Paco Pino ,&nbsp;Divor Kiseljak ,&nbsp;Florian M. Wurm ,&nbsp;Maria J. Wurm ,&nbsp;Michael Peter Manns ,&nbsp;Hans Heinrich Wedemeyer ,&nbsp;Sabina Janciauskiene ,&nbsp;Tetyana Yevsa","doi":"10.1016/j.taap.2025.117400","DOIUrl":"10.1016/j.taap.2025.117400","url":null,"abstract":"<div><h3>Background</h3><div>The toxin α-amanitin from <em>Amanita phalloides</em> induces hepatocyte death and disrupts local and systemic immune responses, key drivers of acute liver failure (ALF). Although TNF-α plays a central role in ALF, TNF-α-targeted therapies alone have shown limited efficacy.</div></div><div><h3>Methods</h3><div>Serum alpha1-globulin levels were measured retrospectively in a cohort of patients with amanita-induced ALF. Additionally, a murine interventional study was conducted, incorporating flow cytometry (FACS)-based immunophenotyping to analyze immune cell populations in the liver and lung to assess systemic versus liver-specific immune effects.</div></div><div><h3>Results</h3><div>We observed a correlation between lower serum alpha1-globulin levels—primarily comprising α1-antitrypsin (AAT)—and increased disease severity in patients with amanita-induced ALF. In a murine interventional study aiming to evaluate the therapeutic potential of alpha1-antitrypsin and TNF-α inhibition—alone and in combination—, the combined administration of etanercept (Enbrel®), a TNF-α scavenger, and recombinant AAT (recAAT) produced in CHO cells significantly improved survival rates in mice with amanita-induced ALF. Reduced liver damage markers, including lower cleaved caspase-3 levels, and decreased activation of liver CD4+ T cells and natural killer (NK) cells, accompanied this protective effect. Additionally, there was an increase in liver dendritic cells and IL-6+ TNF-α + macrophages, suggesting their potential role in mitigating liver injury. Immune changes in the lung were less pronounced and showed only modest reductions in CD4⁺ and NK1.1⁺ cells, with no significant shifts in innate immune populations.</div></div><div><h3>Conclusions</h3><div>Our findings from the mouse model suggest a promising approach for treating ALF caused by α-amanitin from <em>Amanita phalloides</em>: the combined use of AAT (broad-spectrum protease inhibitor) and a TNF-α inhibitor. This dual therapy offers a novel and potentially effective treatment strategy for ALF patients.</div></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":"500 ","pages":"Article 117400"},"PeriodicalIF":3.3,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144108208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating N-acetylcysteine for mitigating cisplatin-induced oxidative stress and ionocyte damage in a zebrafish model","authors":"Szu-Jung Chen ,&nbsp;Ciao-Ling Wu ,&nbsp;Li-Yih Lin ,&nbsp;Jiun-Lin Horng","doi":"10.1016/j.taap.2025.117401","DOIUrl":"10.1016/j.taap.2025.117401","url":null,"abstract":"<div><div>In this study, we examined the protective effects of <em>N</em>-acetylcysteine (NAC) against cisplatin-induced toxicity in zebrafish embryos. Cisplatin (<em>cis</em>-diamminedichloroplatinum II), a widely used anticancer drug, is associated with significant cytotoxic effects toward non-target tissues, including renal and ototoxic damage. Using zebrafish embryos exposed to cisplatin, we evaluated survival rates, hatching rates, ionocyte densities, oxidative stress, and platinum accumulation. NAC co-treatment significantly enhanced survival and hatching rates, preserved ionocyte density, mitigated oxidative stress, and reduced platinum accumulation. These findings highlight ionocytes as an effective model for assessing non-renal toxicity due to their high metabolic activity and mitochondrial abundance. The results suggest that NAC might serve as a co-therapeutic agent to alleviate cisplatin-induced toxicity during chemotherapy.</div></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":"501 ","pages":"Article 117401"},"PeriodicalIF":3.3,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144120927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated transcriptomics and metabolomics unravel the key metabolic pathways involved in the therapeutic mechanism of Salvianic acid A against hepatic fibrosis","authors":"Yunan Zhang ,&nbsp;Yan Zhang ,&nbsp;Jianan Zhang ,&nbsp;Wenfang Lai ,&nbsp;Guiqing He ,&nbsp;Jichan Shi ,&nbsp;Chuan Zhang ,&nbsp;Liyan Xiong ,&nbsp;Tingfang Wang ,&nbsp;Fei Ye ,&nbsp;Xiangao Jiang","doi":"10.1016/j.taap.2025.117398","DOIUrl":"10.1016/j.taap.2025.117398","url":null,"abstract":"<div><div>Effective drugs for the clinical treatment of hepatic fibrosis have not yet been identified. Salvianic acid A (SAA) protective mechanisms primarily include anti-inflammation, anti-oxidative stress, and modulation of immune system function. Metabolic dysfunction is well recognized as the driver for hepatic fibrosis. However, the precise action mode and underlying mechanism of SAA in modulating hepatic metabolism to combat hepatic fibrosis remain incompletely understood. This study aimed to investigate the metabolic mechanism by which SAA improves hepatic fibrosis based on metabolomics and transcriptomics profiling. A mouse model of carbon tetrachloride (CCl₄)-induced hepatic fibrosis mouse model was established, and protective effects of SAA were evaluated through pathological characteristics. Integrated metabolomics and transcriptomics analysis revealed three key altered metabolic pathways: bile secretion, carbohydrate digestion and absorption, and regulation of lipolysis in adipocytes. SAA modulated the bile secretion pathway, dependent on reducing water channel protein <em>Aqp1</em>, cholesterol synthesis enzyme <em>Hmgcr</em> and Na⁺/K⁺-ATPase enzyme <em>Atp1a3</em>, accompanied by up-regulating metabolites glutathione and glucose levels. SAA also regulated carbohydrate digestion and absorption by decreasing the glucose homeostasis-related <em>Akt3</em>, essential enzyme <em>G6pc</em> for gluconeogenesis/glycogenolysis and glucose transporter <em>Atp1a3</em> with a concomitant increase of metabolites D-galactose, maltose, and sucrose levels. Moreover, SAA improved lipolysis in adipocytes in liver fibrosis through inhibiting lipolysis related <em>Prkg1,</em> lipid transporter <em>Fabp4,</em> lipolysis-associated <em>Akt3</em> and increasing lipolysis mediator <em>Adrb3</em>, along with upregulated levels of metabolites adenosine monophosphate and norepinephrine. In conclusion, SAA alleviates hepatic fibrosis through modulating metabolic disorders, mainly relying on the metabolic improvements of bile secretion, carbohydrate digestion and absorption and adipocyte lipolysis.</div></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":"500 ","pages":"Article 117398"},"PeriodicalIF":3.3,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144102666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fluvoxamine, an inhibitor of CYP1A2, improves CS-induced pulmonary inflammation through estrogen deficiency","authors":"Siyu-Yang ,&nbsp;Ruibing-Sun ,&nbsp;Liqing-Wang ,&nbsp;Mingzhe-Cao","doi":"10.1016/j.taap.2025.117395","DOIUrl":"10.1016/j.taap.2025.117395","url":null,"abstract":"<div><div>Chronic obstructive pulmonary disease (COPD), one of the most prevalent respiratory diseases worldwide, exhibits marked gender disparities, with women disproportionately affected. Current therapeutic modalities for COPD are relatively ineffective as the available drugs cannot considerably delay disease progression or substantially affect inflammation. Therefore, the suppression of inflammatory responses is considered an essential management strategy for COPD. Fluvoxamine, a CYP1A2 inhibitor with anti-inflammatory effects, and CYP1A2 affects estrogen metabolism. However, its potential as a COPD treatment and interaction with estrogen in women are unclear. This study explored fluvoxamine's efficacy in female mice with cigarette smoke (CS)-induced COPD. Administering 8 mg/kg fluvoxamine intraperitoneally markedly reduced CS-induced lung damage, lowering histopathological injury and pro-inflammatory cytokines in bronchoalveolar lavage fluid and serum. RNA-seq analysis revealed that fluvoxamine significantly suppressed the upregulation of inflammation-related genes. Furthermore, the KEGG and GSEA analysis of differentially expressed genes in lung transcriptomics revealed that the metabolism of xenobiotics by cytochrome P450 and JAK-STAT signaling pathway were regulated after fluvoxamine treatment. WB and ELISA assay also demonstrated a significant decrease in CYP1A2 and estrogen levels following treatment with fluvoxamine or tamoxifen. Crucially, fluvoxamine matched tamoxifen (an estrogen inhibitor) in improving lung structural parameters (mean linear intercept, destructive index). These results suggest fluvoxamine mitigates COPD by inhibiting CYP1A2, reducing inflammatory mediators and estrogen. The proposed mechanism combines estrogen metabolism modulation and anti-inflammatory action, offering dual therapeutic benefits. This study positions fluvoxamine as a novel COPD treatment candidate, particularly for women, targeting hormonal and inflammatory pathways. Further research is needed to validate clinical translation.</div></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":"501 ","pages":"Article 117395"},"PeriodicalIF":3.3,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lung microbiota metabolite L-malic acid attenuates the airway inflammation in asthma by inhibiting ferroptosis","authors":"Lishan Lin ,&nbsp;Danhui Huang ,&nbsp;Haohua Huang ,&nbsp;Lingyan Xie ,&nbsp;Yi Huang ,&nbsp;Cuiping Ye ,&nbsp;Lanhe Chu ,&nbsp;Yujie Qiao ,&nbsp;Xiaojing Meng ,&nbsp;Shaoxi Cai ,&nbsp;Hangming Dong","doi":"10.1016/j.taap.2025.117396","DOIUrl":"10.1016/j.taap.2025.117396","url":null,"abstract":"<div><div>Inhaled environmental allergens, such as house dust mites (HDM), have been shown to induce an inflammatory reaction, tissue injury, and increased airway sensitivity in the lungs, ultimately leading to the development of allergic asthma. The imbalance of respiratory microbiota and metabolites plays a crucial role in the progression of allergic asthma. However, there is limited knowledge available regarding the alterations in respiratory microbiota and metabolites and their impact on the host in the context of asthma. The aim of this study was to investigate the potential pathways involved in the development of asthma through the analysis of lung flora and metabolites. A mouse model of house dust mite (HDM)-induced asthma was established, and alveolar lavage samples were collected for microbiome 16S rRNA sequencing and untargeted metabolic analysis. Microbiological analyses indicated a significant alteration in the microbiota after 4 and 6 weeks of HDM nebulisation stimulation. This was characterized by a decrease in microbial diversity, as well as reductions in the relative proportion of <em>Gallionella</em> and <em>Lactobacillus</em>. Conversely, the abundance of <em>Flavobacterium</em> and <em>Ralstonia</em> increased in the HDM4W and HDM6W groups, respectively. Metabolomic analyses revealed seven distinct metabolites, among them L-malic acid, which were linked to signaling pathways in a mouse model of HDM-induced asthma. The correlation analysis demonstrated a positive association between L-malic acid and <em>Rhodanobacter</em> and <em>Nocardioides</em>. L-malic acid was discovered to be efficacious in reducing airway inflammation in mice with house dust mite-induced asthma. Further analysis revealed that this change was linked to lipid peroxidation and changes in ferroptosis markers, namely GPX4 and FTH. These findings suggest that L-malate inhibits ferroptosis. However, the introduction of ferroptosis inducers, such as Erastin, was observed to negate the beneficial effect of butyrate. In summary, this research implies that the respiratory microbiota metabolite L-malic acid lessens airway inflammation in asthma by inhibiting ferroptosis, offering a potential approach for managing asthma.</div></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":"500 ","pages":"Article 117396"},"PeriodicalIF":3.3,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144089733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to \"FOXO3a reactivation mediates the synergistic cytotoxic effects of rapamycin and cisplatin in oral squamous cell carcinoma cells\" [Toxicology and Applied Pharmacology 251 (2011) 8-15].","authors":"Liang Fang, Huiming Wang, Lin Zhou, Da Yu","doi":"10.1016/j.taap.2025.117397","DOIUrl":"10.1016/j.taap.2025.117397","url":null,"abstract":"","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":" ","pages":"117397"},"PeriodicalIF":3.3,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144085737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}