Toxicology最新文献

{"title":"Embryonic ethanol exposure induces oxidative stress and inflammation in zebrafish model: A dose-dependent study","authors":"Sampath Raghul Kannan ,&nbsp;Indrani Paramasivan Latha Laxmi ,&nbsp;Sheikh F. Ahmad ,&nbsp;Ramasamy Tamizhselvi","doi":"10.1016/j.tox.2024.153876","DOIUrl":"10.1016/j.tox.2024.153876","url":null,"abstract":"<div><p>Alcohol, or ethanol, is a major contributor to detrimental diseases and comorbidities worldwide. Alcohol use during pregnancy intervenes the developing embryos leading to morphological changes, neurocognitive defects, and behavioral changes known as fetal alcohol spectrum disorder (FASD). Zebrafish have been used as a model to study FASD; however, the mechanism and the impact of ethanol on oxidative stress and inflammation in the zebrafish FASD model remain unexplored. Hence, we exposed zebrafish embryos to different concentrations of ethanol (0 %, 0.5 %, 1.0 %, 1.25 %, and 1.5 % ethanol (v/v)) at 4–96 hours post-fertilization (hpf) to study and characterize the ethanol concentration for the FASD model to induce oxidative stress and inflammation. Here, we studied the survival rate and developmental toxicity parameters at different time points and measured oxidative stress, reactive oxygen species (ROS) generation, apoptosis, and pro-inflammatory gene expression in zebrafish larvae. Our findings indicate that ethanol causes various developmental abnormalities, including decreased survival rate, spontaneous tail coiling, hatching rate, heart rate, and body length, associated with increased malformation. Further, ethanol exposure induced oxidative stress by increasing lipid peroxidation and nitric oxide production and decreasing glutathione levels. Subsequently, ethanol increased ROS generation, apoptosis, and pro-inflammatory gene (TNF-α and IL-1β) expression in ethanol exposed larvae. 1.25 % and 1.5 % ethanol had significant impacts on zebrafish larvae in all studied parameters. However, 1.5 % ethanol showed decreased survival rate and increased malformations. Overall, 1.25 % ethanol is the ideal concentration to study the oxidative stress and inflammation in the zebrafish FASD model.</p></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141470940","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":"Biphasic effects of ethanol consumption on N,N-dimethylformamide-induced liver injury in mice","authors":"Qing-Xiang Zheng ,&nbsp;Qing-Lin Liu ,&nbsp;Wen-Na Sun ,&nbsp;Xin-Yu Jiang ,&nbsp;Tao Zeng","doi":"10.1016/j.tox.2024.153872","DOIUrl":"10.1016/j.tox.2024.153872","url":null,"abstract":"<div><p><em>N,N-</em>Dimethylformamide (DMF) is a well-documented occupational hazardous material, which can induce occupational liver injury. The current study was designed to investigate whether ethanol consumption can affect DMF-induced hepatotoxicity and the potential underlying mechanisms involved. We found that a single dose of ethanol (1.25, 2.5, or 5 g/kg bw by gavage) significantly repressed the increase in serum alanine transaminase (ALT) and aspartate transaminase (AST) activities and alleviated the liver histopathological changes in mice challenged with 3 g/kg DMF. In contrast, long-term moderate drinking (2.5 g/kg bw) significantly aggravated the repeated DMF (0.7 g/kg bw) exposure-induced increase in the serum ALT and AST activities. Mechanistically, acute ethanol consumption suppressed DMF-induced activation of the NLR family pyrin domain-containing protein 3 (NLRP3) inflammasome, while long-term moderate ethanol consumption promoted hepatocyte apoptosis in the mouse liver. Notably, cytochrome P4502E1 (CYP2E1) protein level and activity in mouse livers were not significantly affected by ethanol per se in the two models. These results confirm that regular drinking can increase the risk of DMF-induced hepatotoxicity, and suggest that DMF-handling workers should avoid consuming ethanol to reduce the risk of DMF-indued liver injury.</p></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141459437","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":"Nanoplastics trigger the aging and inflammation of porcine kidney cells","authors":"Guanglin Lu,&nbsp;Shuqin Wei","doi":"10.1016/j.tox.2024.153870","DOIUrl":"10.1016/j.tox.2024.153870","url":null,"abstract":"<div><p>Nanoplastics have now become a pervasive contaminant, being detected in various environmental media. However, our understanding of the specific toxicological effects of nanoplastics (NPs) on the kidneys remains unclear, which is a scientific problem that needs to be solved. To address this question, we employed two kidney cell lines as in vitro models to study the toxicological effects of NPs on porcine kidney cells. Firstly, we observed that NPs can be internalized into the cytoplasm in a time- and dose-dependent manner by using a laser confocal microscope. We further discovered that NPs can trigger inflammatory responses and lead to porcine kidney cell senescence by detection of senescence marker molecules. Furthermore, the potential molecular mechanism(s) by which NPs induce porcine kidney cell senescence were explored, we found that NPs induce oxidative stress in the porcine kidney cells, leading to the accumulation of reactive oxygen species (ROS) within mitochondria, ultimately triggering inflammatory responses and senescence in the kidney cells. In summary, our experimental results not only provide new evidence for the toxicity of NPs but also offer new ideas and directions for future research. This discovery will aid in our deeper understanding of the potential health impacts of NPs on domestic pigs.</p></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141459436","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":"Exploring microbiota-gut-brain axis biomarkers linked to autism spectrum disorder in prenatally chlorpyrifos-exposed Fmr1 knock-out and wild-type male rats","authors":"Ana M. Salmerón ,&nbsp;Cristian Pérez-Fernández ,&nbsp;Ana C. Abreu ,&nbsp;Silvia Fernández ,&nbsp;Ana I. Tristán ,&nbsp;Diego Ruiz-Sobremazas ,&nbsp;María Cabré ,&nbsp;Laia Guardia-Escote ,&nbsp;Ignacio Fernández ,&nbsp;Fernando Sánchez-Santed","doi":"10.1016/j.tox.2024.153871","DOIUrl":"10.1016/j.tox.2024.153871","url":null,"abstract":"<div><p><em>Fmr1</em> (fragile X messenger ribonucleoprotein 1)<em>-</em>knockout (KO) rats, modeling the human Fragile X Syndrome (FXS), are of particular interest for exploring the ASD-like phenotype in preclinical studies<em>.</em> Gestational exposure to chlorpyrifos (CPF) has been associated with ASD diagnosis in humans and ASD-like behaviors in rodents and linked to the microbiota-gut-brain axis. In this study, we have used both <em>Fmr1</em>-KO and wild-type male rats (F2 generation) at postnatal days (PND) 7 and 40 obtained after F1 pregnant females were randomly exposed to 1 mg/kg/mL/day of CPF or vehicle. A nuclear magnetic resonance (NMR) metabolomics approach together with gene expression profiles of these F2 generation rats were employed to analyze different brain regions (such as prefrontal cortex, hippocampus, and cerebellum), whole large intestine (at PND7) and gut content (PND40). The statistical comparison of each matrix spectral profile unveiled tissue-specific metabolic fingerprints. Significant variations in some biomarker levels were detected among brain tissues of different genotypes, including taurine, myo-inositol, and 3-hydroxybutyric acid, and exposure to CPF induced distinct metabolic alterations, particularly in serine and myo-inositol. Additionally, this study provides a set of metabolites associated with gastrointestinal dysfunction in ASD, encompassing several amino acids, choline-derived compounds, bile acids, and sterol molecules. In terms of gene expression, genotype and gestational exposure to CPF had only minimal effects on decarboxylase 2 (<em>gad2</em>) and cholinergic receptor muscarinic 2 (<em>chrm2</em>) genes.</p></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0300483X24001525/pdfft?md5=432e9b7a63cce3501a5e69b031ed8e6c&pid=1-s2.0-S0300483X24001525-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141459435","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":"Pulmonary damage induction upon Acrylic amide exposure via activating miRNA-223–3p and miRNA-325–3p inflammasome/pyroptosis and fibrosis signaling pathway: New mechanistic approaches of A green-synthesized extract","authors":"Amirah Albaqami ,&nbsp;Manal E. Alosaimi ,&nbsp;Ibrahim Jafri ,&nbsp;Amany Abdel-Rahman Mohamed ,&nbsp;Yasmina M. Abd El-Hakim ,&nbsp;Tarek Khamis ,&nbsp;Sara T. Elazab ,&nbsp;Ahmed E. Noreldin ,&nbsp;Moustafa Elhamouly ,&nbsp;Ali H. El-Far ,&nbsp;Areej A. Eskandrani ,&nbsp;Badriyah S. Alotaibi ,&nbsp;Hanim M.abdelnour ,&nbsp;Ayman A. Saleh","doi":"10.1016/j.tox.2024.153869","DOIUrl":"https://doi.org/10.1016/j.tox.2024.153869","url":null,"abstract":"<div><p>Exposure to acrylic amide (AD) has garnered worldwide attention due to its potential adverse health effects, prompting calls from the World Health Organization for intensified research into associated risks. Despite this, the relationship between oral acrylic amide (acrylamide) (AD) exposure and pulmonary dysfunction remains poorly understood. Our study aimed to investigate the correlation between internal oral exposure to AD and the decline in lung function, while exploring potential mediating factors such as tissue inflammation, oxidative stress, pyroptosis, and apoptosis. Additionally, we aimed to evaluate the potential protective effect of zinc oxide nanoparticles green-synthesized moringa extract (ZNO-MONPs) (10 mg/kg b.wt) against ACR toxicity and conducted comprehensive miRNA expression profiling to uncover novel targets and mechanisms of AD toxicity (miRNA 223–3 P and miRNA 325–3 P). Furthermore, we employed computational techniques to predict the interactions between acrylic amide and/or MO-extract components and tissue proteins. Using a rat model, we exposed animals to oral acrylamide (20 mg/kg b.wt for 2 months). Our findings revealed that AD significantly downregulated the expression of miRNA 223–3 P and miRNA 325–3 P, targeting NLRP-3 &amp; GSDMD, respectively, indicating the induction of pyroptosis in pulmonary tissue via an inflammasome activating pathway. Moreover, AD exposure resulted in lipid peroxidative damage and reduced levels of GPX, CAT, GSH, and GSSG. Notably, AD exposure upregulated apoptotic, pyroptotic, and inflammatory genes, accompanied by histopathological damage in lung tissue. Immunohistochemical and immunofluorescence techniques detected elevated levels of indicative harmful proteins including vimentin and 4HNE. Conversely, concurrent administration of ZNO-MONPs with AD significantly elevated the expression of miRNA 223–3 P and miRNA 325–3 P, protecting against oxidative stress, apoptosis, pyroptosis, inflammation, and fibrosis in rat lungs. In conclusion, our study highlights the efficacy of ZNO-MONPs NPs in protecting pulmonary tissue against the detrimental impacts of foodborne toxin AD.</p></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141438618","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":"Tetrabromobisphenol S (TBBPS) exposure causes gastric cell senescence and inflammation by inducing iron overload","authors":"Lei Zhang,&nbsp;Deshuai Kong,&nbsp;Xiulei Zhao,&nbsp;Yu Meng,&nbsp;Jinchao Li,&nbsp;Zhenyong Wang,&nbsp;Wei Chai","doi":"10.1016/j.tox.2024.153866","DOIUrl":"10.1016/j.tox.2024.153866","url":null,"abstract":"<div><p>Tetrabromobisphenol S (TBBPS) is a brominated flame retardants (BFRs). TBBPS is widely used as a new type of BFR to replace TBBPA. Here, we used gastric cells as a model for evaluating the effect of TBBPS on the toxicology of gastric cells. Biochemical assays such as indirect immunofluorescence, cell proliferation assay were performed to analyze the toxicological effects of TBBPS on gastric cells. Cell proliferation analysis showed that TBBPS caused inhibition of gastric cell proliferation, and TBBPS induced gastric cell death. Further analysis showed that TBBPS led to ferroptosis and senescence of gastric cells by detecting ferroptosis-related marker molecules. Further work showed that TBBPS treatment resulted in lowered ferritin expression alongside heightened transferrin levels, which may be a potential molecular mechanism for TBBPS-induced ferroptosis and senescence in gastric cells. Here, our team investigates the effects of TBBPS on gastric cells in an in vitro model, and found that TBBPS caused toxicological damage to gastric cells. This study indicates potential toxic effects of TBBPS on the gastric cells, thereby providing a basis for further research into the toxicology of TBBPS.</p></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141443372","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":"Oleanolic acid-3-glucoside, a synthetic oleanane-type saponin, ameliorates methylmercury-induced dysfunction of synaptic transmission in mice","authors":"Ryosuke Nakamura ,&nbsp;Takashi Iwai ,&nbsp;Yasukazu Takanezawa ,&nbsp;Tatsuya Shirahata ,&nbsp;Naruki Konishi ,&nbsp;Yuka Ohshiro ,&nbsp;Shimpei Uraguchi ,&nbsp;Mitsuo Tanabe ,&nbsp;Yoshinori Kobayashi ,&nbsp;Kenji Sakamoto ,&nbsp;Tsutomu Nakahara ,&nbsp;Megumi Yamamoto ,&nbsp;Masako Kiyono","doi":"10.1016/j.tox.2024.153867","DOIUrl":"10.1016/j.tox.2024.153867","url":null,"abstract":"<div><p>Methylmercury (MeHg) is widely distributed in nature and is known to cause neurotoxic effects. This study aimed to examine the anti-MeHg activity of oleanolic acid-3-glucoside (OA3Glu), a synthetic oleanane-type saponin derivative, by evaluating its effects on motor function, pathology, and electrophysiological properties in a mouse model of MeHg poisoning. Mice were orally administered 2 or 4 mg·kg⁻¹·d⁻¹ MeHg with or without 100 µg·kg⁻¹·d⁻¹ OA3Glu 5x/week for four weeks. Motor function was evaluated using beam-walking and dynamic weight-bearing (DWB) tests. High-dose MeHg exposure significantly increased the frequency of stepping off the hind leg while crossing the beam in the beam-walking test, and increased weight on forelegs when moving freely in the DWB test. OA3Glu treatment alleviated motor abnormality caused by high-dose MeHg exposure in both motor function tests. Additionally, OA3Glu treatment reduced the number of contracted Purkinje cells frequently observed in the cerebellum of MeHg-treated groups, although cerebrum histology was similar in all experimental groups. The synaptic potential amplitude in the cerebellum decreased as MeHg exposure increased, which was restored by OA3Glu treatment. Even in the cerebrum, where the effects of MeHg were not observed, the amplitude of the field potential was suppressed with increasing MeHg exposure but was restored with OA3Glu treatment. Taken together, the study findings suggest that OA3Glu improves neurotransmission and movement disorders associated with MeHg exposure via protection of Purkinje cells in the cerebellum while ameliorating pre/post-synaptic deficits in the cerebral cortex in which no changes were observed at the tissue level, potentially providing a treatment to mitigate MeHg toxicity.</p></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141437589","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":"Deoxynivalenol induces cell senescence in RAW264.7 macrophages via HIF-1α-mediated activation of the p53/p21 pathway","authors":"Jiefeng Li ,&nbsp;Xu Wang ,&nbsp;Eugenie Nepovimova ,&nbsp;Qinghua Wu ,&nbsp;Kamil Kuca","doi":"10.1016/j.tox.2024.153868","DOIUrl":"10.1016/j.tox.2024.153868","url":null,"abstract":"<div><p>Deoxynivalenol (DON), a potent mycotoxin, exhibits strong immunotoxicity and poses a significant threat to human and animal health. Cell senescence has been implicated in the immunomodulatory effects of DON; however, the potential of DON to induce cell senescence remains inadequately explored. Emerging evidence suggests that hypoxia-inducible factor-1α (HIF-1α) serves as a crucial target of mycotoxins and is closely involved in cell senescence. To investigate this potential, we employed the RAW264.7 macrophage model and treated the cells with varying concentrations of DON (2–8 μM) for 24 h. Transcriptome analysis revealed that 2365 genes were significantly upregulation while 2405 genes were significantly decreased after exposure to DON. KEGG pathway enrichment analysis demonstrated substantial enrichment in pathways associated with cellular senescence and hypoxia. Remarkably, we observed a rapid and sustained increase in HIF-1α expression following DON treatment. DON induced cell senescence through the activation of the p53/p21^WAF1/CIP1 (p21) and p16^INK4A (p16) pathways, while also upregulating the expression of nuclear factor-κB, leading to the secretion of senescence-associated secretory phenotype (SASP) factors, including IL-6, IL-8, and CCL2. Crucially, HIF-1α positively regulated the expression of p53, p21, and p16, as well as the secretion of SASP factors. Additionally, DON induced cell cycle arrest at the S phase, enhanced the activity of the senescence biomarker senescence-associated β-galactosidase, and disrupted cell morphology, characterized by mitochondrial damage. Our study elucidates that DON induces cell senescence in RAW264.7 macrophages by modulating the HIF-1α/p53/p21 pathway. These findings provide valuable insights for the accurate prevention of DON-induced immunotoxicity and associated diseases.</p></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141437588","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":"In vitro toxicity and chemical analysis of e-cigarette aerosol produced amid dry hitting","authors":"Jonathan M. Beard ,&nbsp;Clancy Collom ,&nbsp;James Y. Liu ,&nbsp;Precious Obiako ,&nbsp;Robert M. Strongin ,&nbsp;Jose Zavala ,&nbsp;Christie M. Sayes","doi":"10.1016/j.tox.2024.153865","DOIUrl":"10.1016/j.tox.2024.153865","url":null,"abstract":"<div><p>Dry hitting, a phenomenon produced by e-cigarettes with refillable cartridges when the liquid in the coil is low, is a common occurrence among regular vapers despite being an unintended consequence of the device. This phenomenon's hazard to public health is still unknown and needs further investigation. Lung cells cultured at the air-liquid interface were exposed to vaped aerosol consisting of 3 % w/v ethyl maltol in propylene glycol for three-second puffs every 30 seconds for 80 total puffs with either dry hit or saturated conditions. Cytotoxicity was measured colorimetrically. The thermal degradation of the heating coils and wicks was visualized using scanning electron microscopy. The chemical byproducts in the aerosol were analyzed using proton nuclear magnetic resonance and inductively coupled plasma mass spectrometry. The results revealed a highly significant increase in cytotoxicity from dry hit treatments. Imaging showed thermal decomposition of the cotton wick after dry hitting, which was confirmed by energy dispersive x-ray spectroscopy with less oxygen in the dry hit cotton. Chemical byproducts were found via unique peaks in the dry hit condensate in the aromatic and alkene regions. Saturated condensate showed higher concentrations of detected metal species than dry-hit condensate. E-cigarette users should avoid dry hitting by refilling tanks or cartridges preemptively or by using disposable coils to avoid increased toxicity during vaping.</p></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141321706","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 inhibits PAT-induced renal ferroptosis via the p62/Keap1/Nrf2 signalling pathway","authors":"Jianan Zhai ,&nbsp;Zhengguo Chen ,&nbsp;Qi zhu ,&nbsp;Zhifang Guo ,&nbsp;Xiance Sun ,&nbsp;Liping Jiang ,&nbsp;Jing Li ,&nbsp;Ningning Wang ,&nbsp;Xiaofeng Yao ,&nbsp;Cong Zhang ,&nbsp;Haoyuan Deng ,&nbsp;Shaopeng Wang ,&nbsp;Guang Yang","doi":"10.1016/j.tox.2024.153863","DOIUrl":"10.1016/j.tox.2024.153863","url":null,"abstract":"<div><p>Patulin (PAT), the most common mycotoxin, is widespread in foods and beverages which poses a serious food safety issue to human health. Our previous research confirmed that exposure to PAT can lead to acute kidney injury (AKI). Curcumin is the most abundant active ingredient in turmeric rhizome with various biological activities. The aim of this study is to investigate whether curcumin can prevent the renal injury caused by PAT, and to explore potential mechanisms. <em>In vivo</em>, supplementation with curcumin attenuated PAT-induced ferroptosis. Mechanically, curcumin inhibited autophagy, led to the accumulation of p62 and its interaction with Keap1, promoted the nuclear translocation of nuclear factor E2 related factor 2 (Nrf2), and increased the expression of antioxidant stress factors in the process of ferroptosis. These results have also been confirmed in HKC cell experiments. Furthermore, knockdown of Nrf2 in HKC cells abrogated the protective effect of curcumin on ferroptosis. In conclusion, we confirmed that curcumin mitigated PAT-induced AKI by inhibiting ferroptosis via activation of the p62/Keap1/Nrf2 pathway. This study provides new potential targets and ideas for the prevention and treatment of PAT.</p></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141327830","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}