Toxicology and applied pharmacology最新文献

{"title":"Evaluation of the effects of Tempol on oxidative stress and angiotensin-II induced hypertension in mice exposed to nicotine from electronic and tobacco cigarettes","authors":"Wael A. Alanazi ,&nbsp;Yazeed Alqudayri ,&nbsp;Faleh Alqahtani ,&nbsp;Fawaz Alasmari ,&nbsp;Doaa M. El-Nagar","doi":"10.1016/j.taap.2025.117386","DOIUrl":"10.1016/j.taap.2025.117386","url":null,"abstract":"<div><div>Electronic cigarette (<em>E</em>-Cig) is commonly used as an alternative to tobacco cigarette (T-Cig), as it lacks many of the toxicants present in T-Cigs. However, the toxicological mechanisms underlying <em>E</em>-Cig-induced hypertension are not yet well understood. The goal of this research was to explore the effects of Tempol in reducing hypertension caused by T-Cig and <em>E</em>-Cig exposure by mitigating oxidative stress and regulating angiotensin-II production in mouse models subjected to T-Cig and <em>E</em>-Cig smoke. Male C57BL/6 J mice were assigned to eight distinct groups: Air, Air + Tempol, T-Cig, T-Cig + Tempol, NIC-free <em>E</em>-Cig, NIC-free E-Cig + Tempol, E-Cig, and E-Cig + Tempol. Mice exposed to smoking for 12 min per hour, 6 cycles/day, 7 days/week for 4 weeks. Blood pressure was monitored, and Angiotensin-II and cGMP levels were measured using ELISA. Oxidative stress markers (GPx, GSTA1, SOD, MDA, nitrite) were assessed by RT-PCR and biochemical assays. The collected data showed a weight loss with high blood pressure and vasoconstriction in the T-Cig and <em>E</em>-Cig groups. Results showed an induction of angiotensin-II, GPx, GSTA1, SOD, and MDA. In contrast, cGMP and nitrite levels were reduced in the T-Cig and <em>E</em>-Cig groups. Tempol treatment regulated oxidative stress markers, angiotensin-II and cGMP levels, leading to a significant reduction in blood pressure. The results indicate that Tempol is essential in reducing oxidative stress and the effects of angiotensin-II caused by T-Cig and <em>E</em>-Cig exposure, thereby contributing to the regulation of systemic hemodynamic function.</div></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":"500 ","pages":"Article 117386"},"PeriodicalIF":3.3,"publicationDate":"2025-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143948148","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":"Flavor-induced inflammation and cytotoxicity in human aortic smooth muscle cells: Potential implications for E-cigarette safety","authors":"Mariam Bitar ,&nbsp;Clément Mercier ,&nbsp;Laurent Bertoletti ,&nbsp;Jérémie Pourchez ,&nbsp;Valérie Forest","doi":"10.1016/j.taap.2025.117388","DOIUrl":"10.1016/j.taap.2025.117388","url":null,"abstract":"<div><div>Electronic nicotine delivery systems (ENDS), commonly known as e-cigarettes, are considered safer alternatives to tobacco smoking, yet their long-term health effects, particularly on cardiovascular health, remain unclear. The aim of this study was to investigate the cytotoxic and pro-inflammatory effects of device power, nicotine content and flavor molecules on human aortic smooth muscle cells. AoSMCs cells were exposed to e-liquids and e-cigarette aerosol condensates containing different ratios of propylene glycol (PG) and vegetable glycerin (VG), nicotine (0, 10, 20 mg/mL), and flavors (cinnamon, menthol, tobacco), with the devices operated at different power levels (10 W, 15 W, 25 W). After a 24 h incubation, cytotoxicity was evaluated using lactate dehydrogenase (LDH) release, while pro-inflammatory effects were measured by interleukin-8 (IL-8) production. The results showed no significant cytotoxicity or inflammation in cells exposed to PG/VG base or nicotine-containing e-liquids. However, e-liquids as well as aerosol condensates containing flavors induced significant increases in IL-8 production compared to controls without flavor. Moreover, the pro-inflammatory response was more pronounced in response to aerosol condensates than to the corresponding e-liquids. Cinnamon, in particular, produced the highest inflammatory response, and the effect was enhanced at higher power settings (25 W), which also induced cytotoxicity, particularly at high concentrations. These findings demonstrate that flavors, especially cinnamon, and device power levels are key factors influencing the inflammatory potential and cytotoxicity of e-cigarette aerosols. Further studies are needed to explore the long-term cardiovascular risks associated with ENDS use and the role of flavor molecules and of their thermal degradation products.</div></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":"500 ","pages":"Article 117388"},"PeriodicalIF":3.3,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143935529","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":"Potent and highly selective inhibition of selpercatinib towards UDP-glucuronosyltransferase 1A4 (UGT1A4) isoform","authors":"Yueyi Liu ,&nbsp;Xin Lv ,&nbsp;Hang Yin ,&nbsp;Lili Jiang","doi":"10.1016/j.taap.2025.117393","DOIUrl":"10.1016/j.taap.2025.117393","url":null,"abstract":"<div><div>Selpercatinib is a potent and highly selective Rearranged during Transfection (RET) kinase inhibitor for patients with RET fusion-positive thyroid cancer and non-small-cell lung cancer. The present study aims to investigate the inhibitory effects of selpercatinib towards human UDP-glucuronosyltransferases (UGTs), and assess its risk for drug-drug interactions (DDIs) via UGT inhibition. The inhibition of selpercatinib towards 12 recombinant human UGT isoforms were measured. Our data demonstrated that selpercatinib exhibited highly selective inhibition towards UGT1A4. Enzyme kinetic study indicated that selpercatinib competitively inhibited the activity of UGT1A4, with a <em>K</em>_i value of 1.57 ± 0.14 μM. The quantitative prediction of DDIs risk indicated that the co-administration of selpercatinib with UGT1A4 substrate might trigger clinically significant DDIs. Additional caution should be taken to avoid unexpected DDIs when selpercatinib and other UGT1A4 substrates are combined.</div></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":"500 ","pages":"Article 117393"},"PeriodicalIF":3.3,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143935530","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":"Protective effect of empagliflozin against paracetamol-induced acute kidney injury through modulation of AMPK/SIRT1/PGC-1α pathway in experimental mice","authors":"Esraa M. Mosalam ,&nbsp;Hind S. AboShabaan ,&nbsp;Marwa M. Mahfouz ,&nbsp;Amany Said Sallam ,&nbsp;Enas Elhosary ,&nbsp;Albatoul Allam ,&nbsp;Ebtehal M. Metwally ,&nbsp;Moataz A. Shaldam ,&nbsp;Mai El-Sayed Ghoneim","doi":"10.1016/j.taap.2025.117382","DOIUrl":"10.1016/j.taap.2025.117382","url":null,"abstract":"<div><div>Emerging evidences about paracetamol-induced kidney injury in clinical settings are concerning, especially when administered at high doses. Empagliflozin, an oral SGLT2 inhibitor, employed in the management of diabetes mellitus, exhibits antioxidant, anti-inflammatory, and anti-apoptotic attributes. Thus, the objective of this study is to investigate whether empagliflozin may alleviate paracetamol-triggered nephrotoxicity and unravel the mechanistic insights responsible for its protective impact. In this regard, male mice were assigned to four groups: normal, paracetamol, empagliflozin 10, and empagliflozin 20. Kidney function tests, histopathological examination, immunohistochemistry, oxidative stress biomarkers, inflammatory cytokines, and other molecular targets were detected. Our results showed that paracetamol administration impaired kidney functions along with causing aberrations in renal histoarchitecture. Additionally, paracetamol triggered oxidative stress, inflammation, and apoptosis <em>via</em> hindering the AMPK/SIRT1/PGC-1α cascade and Nrf2/HO-1 while activating the NF-κB hub. Nevertheless, pretreatment with empagliflozin markedly enhanced the kidney function tests and mitigated histopathological alterations caused by paracetamol. Additionally, empagliflozin suppressed the oxidative stress as confirmed by an upregulation of Nrf2, which subsequently increased HO-1, SOD, and GSH, while reducing the MDA level. Moreover, it inhibited the NF-κB-mediated inflammatory process by dampening NF-κB, IL-1β, and TNF-α expressions as well as lowering Bax expression-induced apoptosis. The observed safeguards effects were facilitated <em>via</em> boosting AMPK/SIRT1/PGC-1α signaling trajectory. Collectively, our study verified the enduring reno-protective potential of empagliflozin, particularly at high dose, in the context of paracetamol-induced renal injury by instigating the AMPK/SIRT1/PGC-1α hinge.</div></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":"500 ","pages":"Article 117382"},"PeriodicalIF":3.3,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143936900","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":"Repurposing of cabergoline to improve cognitive decline in D-galactose-injected ovariectomized rats: Modulation of AKT/mTOR, GLT-1/P38-MAPK, and ERK1/2 signaling pathways","authors":"Sheer A. Joodi ,&nbsp;Mahmoud M. Khattab,&nbsp;Weam W. Ibrahim","doi":"10.1016/j.taap.2025.117391","DOIUrl":"10.1016/j.taap.2025.117391","url":null,"abstract":"<div><div>Dopamine is involved in many physiological functions including reward phenomenon, motor, learning, and memory functions. Dopamine receptor agonists have been shown to reduce amyloid (Aβ) deposition, enhance memory, and improve cortical plasticity in experimental studies and Alzheimer's disease (AD) patients; however, the molecular mechanisms involved haven't been investigated yet. The target of this investigation was to elucidate the modulatory effects of cabergoline (CAB), a dopamine receptor agonist, against AD. Ovariectomized rats were injected with D-galactose (150 mg/kg/day, i.p) for ten weeks to exacerbate AD. CAB administration (1 mg/kg/day, i.p) for 28 days, beginning from the 7th week of D-galactose administration, attenuated the associated histopathological alterations and enhanced the spatial and recognition memory in Morris water maze and Novel object recognition tests, respectively. CAB decreased the hippocampal concentrations of Aβ42, p-tau, and β-secretase, while upregulating α-secretase. Moreover, CAB diminished nuclear factor-kappa β (NF-κβ), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and myeloperoxidase, while elevating brain-derived neurotrophic factor and phospho-cAMP response element binding protein. Further, CAB reduced the hippocampal phosphorylated forms of protein kinase B (AKT) and mammalian target of rapamycin (mTOR) contrary to elevating Beclin-1, resulting in autophagy induction, which participates in accelerating Aβ42 and p-tau aggregates clearance. Moreover, CAB increased the hippocampal glutamate transporter-1 (GLT-1) protein expression, promoting glutamate uptake that possibly reduced Ca²⁺ overload and consequently decreased the phosphorylated forms of P38-MAPK and ERK1/2. In conclusion, CAB improved cognitive decline of D-gal/OVX animals, restored hippocampal architecture, exerted neuroprotection, and enhanced autophagic machinery via modulating AKT/mTOR, GLT-1/P38-MAPK, and ERK1/2 pathways.</div></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":"500 ","pages":"Article 117391"},"PeriodicalIF":3.3,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143935528","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":"Metformin alleviates cadmium-induced reproductive toxicity by enhancing mitochondrial biosynthesis and epigenetic modifications in female mice","authors":"Jiaqiao Zhu ,&nbsp;Min Zhu ,&nbsp;Hangbin Zhao ,&nbsp;Yifan Lin ,&nbsp;Xiaoxue Han ,&nbsp;Ankai Tan ,&nbsp;Yixian Wang ,&nbsp;Yonggang Ma ,&nbsp;Junwei Li ,&nbsp;Zongping Liu","doi":"10.1016/j.taap.2025.117390","DOIUrl":"10.1016/j.taap.2025.117390","url":null,"abstract":"<div><div>Cadmium, a pervasive environmental pollutant, exerts detrimental effects on various tissues and cells, particularly targeting the reproductive system, thereby posing significant risks to both animal food safety and human health. Despite its widespread impact, research on substances capable of mitigating cadmium-induced reproductive toxicity remains scarce, especially concerning female reproductive health. Metformin, a widely used oral antihyperglycemic drug, has demonstrated a range of beneficial effects, including anti-aging and antioxidant properties. This study aims to investigate the potential and underlying mechanisms of metformin in alleviating cadmium-induced reproductive toxicity in females. Over a period of 35 consecutive days, mice were exposed to cadmium-contaminated water (32 mg/l) and orally administered 10 mg metformin dissolved in 0.2 ml normal saline. Our findings reveal that metformin effectively mitigates cadmium-induced disruptions in the estrous cycle, follicular development, and oocyte meiotic maturation. Specifically, metformin enhances ATP production in oocytes by boosting mitochondrial mass and biosynthesis, thereby counteracting cadmium-induced oxidative stress and spindle morphology defects during meiosis. Additionally, metformin restores the DNA repair capacity of oocytes, alleviating cadmium-induced DNA damage. This restorative effect is partially mediated by metformin's ability to improve key epigenetic modifications, such as histone acetylation, histone methylation, and DNA methylation in oocytes. These results underscore metformin's potential as a protective or therapeutic agent against cadmium reproductive toxicity, primarily by maintaining cellular homeostasis to bolster oocyte resilience against cadmium toxicity and preserving normal epigenetic modifications to ensure oocyte quality.</div></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":"500 ","pages":"Article 117390"},"PeriodicalIF":3.3,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143932209","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":"Epigallocatechin gallate with nobiletin as a novel combination therapy to induce autophagy and apoptosis in oral cancer","authors":"Siyu Zhu ,&nbsp;Byunggook Kim ,&nbsp;Ok-Su Kim ,&nbsp;Guowu Ma ,&nbsp;Sunhun Kim ,&nbsp;Young Kim ,&nbsp;Jaeseok Kang ,&nbsp;Weiyi Wang ,&nbsp;Okjoon Kim","doi":"10.1016/j.taap.2025.117380","DOIUrl":"10.1016/j.taap.2025.117380","url":null,"abstract":"<div><div>Oral cancer (OC) represents a serious health and economic problem and the global prevalence of OC is still increasing. Epigallocatechin gallate (EGCG) is the most abundant polyphenol in green tea, and nobiletin (NOB) is a bioactive polyethoxylated flavone isolated from the peels of citrus fruits. Both have been proven to exert an anti-cancer effect in OC. Integrated stress response (ISR) is a key translation signaling network activated by oncogenic stress, modulating ISR activity is an innovative drug target in cancer therapy. Herein, we investigated combined EGCG and NOB in a ratio at 125 <span><math><mi>μ</mi></math></span>M:25 <span><math><mi>μ</mi></math></span>M additively decreased cell viability of OC cells most. Combination treatment with 125 <span><math><mi>μ</mi></math></span>M EGCG and 25 <span><math><mi>μ</mi></math></span>M NOB increased LC3 expression and autophagosome formation, and induced autophagic cell death. In addition, this combination increased cleaved caspase-3, cleaved caspase-9, and cleaved PARP levels, induced apoptotic cell death. Furthermore, we explored the effect of the EGCG and NOB combination in regulating ISR activity. Our results showed that this combination inhibited the GCN2/eIF2α axis and activated the PERK/ATF4/CHOP pathway. Results further demonstrated that silencing either GCN2 or PERK reversed EGCG+NOB-induced cell proliferation inhibition, autophagy and apoptosis. In this combined system, GCN2 and PERK are targets of EGCG-induced autophagy and NOB-induced apoptosis, EGCG and NOB produce additive effects to induce OC cell death. In summary, our study identified that EGCG combined with NOB, as a potent ISR mediator, cooperates to induce autophagy and apoptosis, further supporting the combination of EGCG and NOB as a promising strategy for OC treatment.</div></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":"500 ","pages":"Article 117380"},"PeriodicalIF":3.3,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143935527","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":"Palmitic acid and lipopolysaccharide induce macrophage TNFα secretion, suppressing browning regulators and mitochondrial respiration in adipocytes","authors":"Tsui-Chun Tsou,&nbsp;Szu-Ching Yeh,&nbsp;Feng-Yuan Tsai,&nbsp;Pei-Yu Chen","doi":"10.1016/j.taap.2025.117389","DOIUrl":"10.1016/j.taap.2025.117389","url":null,"abstract":"<div><div>Obesity and its associated pro-inflammatory activity contribute significantly to metabolic dysfunction. In contrast, browning of white adipose tissue (WAT) generally improves metabolic health. Our prior research suggested that macrophage-derived pro-inflammatory cytokines suppress key regulators of browning—adrenergic receptor β3 (<em>Adrb3</em>) and peroxisome proliferator-activated receptor γ (<em>Pparg</em>)—as well as energy metabolism mediators—insulin receptor substrate 1 (<em>Irs1</em>) and hormone-sensitive lipase (<em>Lipe</em>)—in diet-induced obese mice. To explore this mechanism, we developed an in vitro model using RAW264.7 macrophages and 3T3-L1 adipocytes exposed to palmitic acid (PA) and/or lipopolysaccharide (LPS). PA (200 μM) and LPS (1.0 μg/ml) synergistically promoted M1 polarization of macrophages and secretion of pro-inflammatory cytokines, with tumor necrosis factor-α (TNFα), C-C motif chemokine ligand 2 (CCL2), CCL5, and interleukin-6 (IL-6) being predominant. Conditioned media from both control and PA-treated macrophages, when exposed to LPS ≥0.01 μg/ml, significantly downregulated <em>Adrb3</em>, <em>Pparg</em>, <em>Irs1</em>, and <em>Lipe</em> in adipocytes. At physiologically relevant LPS levels (≤0.001 μg/ml), PA-treated macrophage media exerted greater suppression of these genes than controls. Among the cytokines, TNFα emerged as the primary mediator, significantly reducing expression of the four key regulators. Furthermore, adipocytes treated with TNFα exhibited significant reductions in both uncoupling protein 1 (<em>Ucp1</em>) expression and mitochondrial respiration. These findings demonstrate that exposure to obesity-associated factors (PA and LPS) induces macrophage-derived TNFα, which suppresses browning and mitochondrial function in adipocytes. This mechanism may inform new therapeutic strategies targeting TNFα to alleviate obesity-related metabolic disorders.</div></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":"500 ","pages":"Article 117389"},"PeriodicalIF":3.3,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143936898","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":"Luteolin-7-O-glucuronide alleviates doxorubicin-induced cardiotoxicity by inhibiting PPAR-mediated ferroptosis","authors":"Lishuang Cui ,&nbsp;Qing Xia ,&nbsp;Yongcheng Wang ,&nbsp;Cong Han ,&nbsp;Xiaohan Zang ,&nbsp;Lijuan Zhang ,&nbsp;Jianguo Xing ,&nbsp;Ruifang Zheng ,&nbsp;Yun Zhang","doi":"10.1016/j.taap.2025.117381","DOIUrl":"10.1016/j.taap.2025.117381","url":null,"abstract":"<div><div>Inhibiting ferroptosis has been proposed to rescue myocardial cell death in Doxorubicin (DOX)-induced cardiotoxicity (DIC). Here, we aimed to investigate whether luteolin-7-O-glucuronide (LOG) alleviates DIC via ferroptosis suppression in zebrafish and H9C2 cardiomyocytes, as well as the potential mechanism. We found that LOG improved zebrafish cardiac function and mitigated the upregulation of CK-MB, cTnT, nppa, and nppb caused by DOX. Moreover, LOG suppressed the high levels of ROS, GSSG, and MDA in response to DOX and increased GSH activity and gpx4 levels in zebrafish. Additionally, LOG increased cell viability and the GSH/GSSG ratio, reduced oxidative damage and the accumulation of ferrous ions, and maintained mitochondrial function in H9C2 cells. Mechanistically, LOG improved the abnormal expression of key genes in the PPAR signaling pathway and ferroptosis induced by DOX. In conclusion, our study emphasized that LOG attenuates DIC by mitigating oxidative stress-triggered lipid peroxidation related to the inhibition of PPAR-mediated ferroptosis.</div></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":"500 ","pages":"Article 117381"},"PeriodicalIF":3.3,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143928317","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":"Brain functional activity and connectivity alterations induced by acute carbon monoxide poisoning contribute to delayed neuropsychiatric sequelae","authors":"Yanli Zhang ,&nbsp;Tianhong Wang ,&nbsp;Lubin Gou ,&nbsp;Mei Shi ,&nbsp;Le Song ,&nbsp;Shaofeng Zhao ,&nbsp;Shuaiwen Wang ,&nbsp;Shunlin Guo ,&nbsp;Junqiang Lei","doi":"10.1016/j.taap.2025.117384","DOIUrl":"10.1016/j.taap.2025.117384","url":null,"abstract":"<div><div>The brain functional activity and connectivity alterations induced by acute carbon monoxide (CO) poisoning may contribute to delayed neurological sequelae (DNS) and be associate with the poisoning severities, although comprehensive evidence remains limited. Seventy-four subjects were prospectively recruited for this study, comprising eighteen DNS patients, twenty-six non-DNS patients, and thirty healthy controls. The study employed analysis methods such as the amplitude of low-frequency fluctuation, regional homogeneity, weighted degree centrality, secondary seed-based functional connectivity (FC), and Granger causality analysis to assess functional activity and connectivity. Partial correlation analyses between extracted abnormal functional indices and clinical variables including duration of CO exposure and Glasgow Coma Scale scores were further explored. The results showed that DNS patients exhibited altered functional activity in specific nodes of the visual network (VN), sensorimotor network (SMN), and executive control network (ECN) (Gaussian random field [GRF]-corrected, <em>P</em> &lt; 0.05). Additionally, altered FC values were detected in the nodes of the VN, default mode network (DMN), ECN, SMN, and the cerebello-cortical motor loop nodes (GRF-corrected, <em>P</em> &lt; 0.05). VN hyperactivity exerted inhibitory effects on the DMN and SMN, as well as self-inhibition within DMN nodes. Conversely, DMN nodes showed hypoactivity and received excitatory influences from the anterior cerebellar and ECN nodes. Connectivity changes of above networks and loop nodes were associated with the clinical severities (Bonferroni-corrected, <em>P</em> &lt; 0.05). These findings highlight significant changes in neural functional activity and connectivity across cognitive and motor-related network nodes, potentially contributing to DNS development and associating with the poisoning severities.</div></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":"500 ","pages":"Article 117384"},"PeriodicalIF":3.3,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143942421","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}