Toxicology Reports最新文献_第5页

Comparative evaluation of MPTP and rotenone as inducing agents for Parkinson's disease in adult zebrafish: Behavioural and histopathological insights MPTP和鱼藤酮作为成年斑马鱼帕金森病诱导剂的比较评价：行为和组织病理学见解

Toxicology Reports Pub Date : 2025-07-12 DOI: 10.1016/j.toxrep.2025.102084

Chetan Ashok , Naveen Kumar Rajasekaran , Srikanth Jeyabalan , Gayathri Veeraraghavan , Subalakshmi Suresh , Ramya Sugumar , Sugin Lal Jabaris , Vetriselvan Subramaniyan , Ling Shing Wong

{"title":"Comparative evaluation of MPTP and rotenone as inducing agents for Parkinson's disease in adult zebrafish: Behavioural and histopathological insights","authors":"Chetan Ashok , Naveen Kumar Rajasekaran , Srikanth Jeyabalan , Gayathri Veeraraghavan , Subalakshmi Suresh , Ramya Sugumar , Sugin Lal Jabaris , Vetriselvan Subramaniyan , Ling Shing Wong","doi":"10.1016/j.toxrep.2025.102084","DOIUrl":"10.1016/j.toxrep.2025.102084","url":null,"abstract":"<div><div>Parkinson's disease (PD), a prevalent neurodegenerative disorder, is marked by dopaminergic neuron loss and motor impairments. This study aimed to establish and compare PD models in adult zebrafish using two neurotoxins, MPTP and rotenone, evaluating their impact on behaviour and histopathology. Zebrafish were exposed to MPTP via intraperitoneal injection at two different doses or to rotenone in water for 21 days. Behavioural assessments, including Novel Tank Diving Test, bradykinesia, and C-bend response, revealed progressive motor and anxiety-like impairments, with rotenone exhibiting stronger locomotor effects. Histopathological analyses confirmed dose-dependent neurodegeneration in brain regions, with MPTP showing localized damage and rotenone causing widespread but milder effects. While both neurotoxins induced PD-like phenotypes, rotenone produced more pronounced locomotor deficits, whereas MPTP triggered anxiety-like symptoms. In conclusion, our study demonstrates that MPTP induces significant locomotor dysfunction along with anxiety-like symptoms, while rotenone strongly impacts locomotion with mild anxiety effects. Both neurotoxins exhibited maximum effects at their highest doses and over a similar time frame (Day 14 to Day 22). These findings highlight the distinct neurotoxic mechanisms of MPTP and rotenone and their relevance in modelling PD pathogenesis. The zebrafish model provides a robust platform for studying neurodegenerative diseases and testing therapeutic interventions. Further studies are required to explore the molecular mechanisms underlying their neurotoxic effects and to validate these models for long-term and translational research.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"Article 102084"},"PeriodicalIF":0.0,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144653162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Acute toxicological evaluation of bone-targeted parathyroid hormone-related peptide (PTHrP) antagonist to inhibit breast cancer metastases to bone 骨靶向甲状旁腺激素相关肽（PTHrP）拮抗剂抑制乳腺癌骨转移的急性毒理学评价

Toxicology Reports Pub Date : 2025-07-12 DOI: 10.1016/j.toxrep.2025.102085

Tulasi Ponnapakkam , Muralidharan Anbalagan , Robert E. Stratford Jr. , Binghao Zou , Robert Blair , Brian G. Rowan , Robert Gensure

{"title":"Acute toxicological evaluation of bone-targeted parathyroid hormone-related peptide (PTHrP) antagonist to inhibit breast cancer metastases to bone","authors":"Tulasi Ponnapakkam , Muralidharan Anbalagan , Robert E. Stratford Jr. , Binghao Zou , Robert Blair , Brian G. Rowan , Robert Gensure","doi":"10.1016/j.toxrep.2025.102085","DOIUrl":"10.1016/j.toxrep.2025.102085","url":null,"abstract":"<div><div>The present study evaluates the <em>in vivo</em> acute toxicological profile and drug distribution of a novel bone-targeted parathyroid hormone-related peptide (PTHrP) antagonist for bone metastatic breast cancer. [W2]PTH(1−33)-CBD was created by fusing PTHrP antagonist peptide to the bacterial collagen-binding domain (CBD) of ColG collagenase from Clostridium histolyticum to target the drug to type 1 collagen in bone. Acting as an inverse agonist at the PTH/PTHrP receptor, [W2]PTH(1−33)-CBD induced apoptosis in breast cancer cells and reduced tumor burden in mouse tibia. Female C57BL/6 mice were injected with vehicle, 320 µg/kg, or 1000 µg/kg [W2]PTH(1−33)-CBD as a single injection. Animal behavior, body weight, mortality, and biochemical and organ toxicity assays showed no significant changes during 28-day study period. [W2]PTH(1−33)-CBD distribution assessed by immunohistochemistry confirmed localization to bone, skin, and kidney. No significant changes in liver enzymes or serum protein were observed. Treatment reduced serum calcium and increased creatinine, but kidney histology showed no toxicity. Histological analysis of the kidneys showed no alterations, indicating no toxicity. Histological analysis of spleen, lungs, skin, and bone showed no pathological changes. Pharmacokinetic analysis was done after a single injection of 1000 µg/kg dose (via subcutaneous and intravenous) to female Sprague Dawley rats to determine how the body metabolizes [W2]PTH(1−33)-CBD. Serum was collected at various time points, and drug analysis was performed. Exposure from both routes was similar, indicating complete absorption of [W2]PTH(1−33)-CBD following SC. No clinically significant biochemical or histopathological changes were observed at these doses, thus establishing a safety profile for treatment with novel [W2]PTH(1−33)-CBD.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"Article 102085"},"PeriodicalIF":0.0,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144631472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Modulation of the effects of a cholesterol-supplemented high-fat diet by aryl hydrocarbon receptor (AHR) activation and/or tryptophan reduction in male mice 雄性小鼠芳烃受体（AHR）激活和/或色氨酸减少对胆固醇补充高脂肪饮食影响的调节

Toxicology Reports Pub Date : 2025-07-07 DOI: 10.1016/j.toxrep.2025.102083

Avinash Bathina , Janne Hakanen , Atso Raasmaja , Jere Lindén , Laura Mairinoja , Suraj Unniappan , Lars Pettersson , Raimo Pohjanvirta

{"title":"Modulation of the effects of a cholesterol-supplemented high-fat diet by aryl hydrocarbon receptor (AHR) activation and/or tryptophan reduction in male mice","authors":"Avinash Bathina , Janne Hakanen , Atso Raasmaja , Jere Lindén , Laura Mairinoja , Suraj Unniappan , Lars Pettersson , Raimo Pohjanvirta","doi":"10.1016/j.toxrep.2025.102083","DOIUrl":"10.1016/j.toxrep.2025.102083","url":null,"abstract":"<div><div>Aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor whose role in energy metabolism is obscure. Most of its physiological ligands are derived from tryptophan (TRP). Here, fifty male C57BL/6JRccHsd mice were assigned to one of five feeding groups, control diet (CD), high-fat diet (HFD; 45 % of energy from fat), HFD with only 70 % of the regular TRP concentration (HFDtrp), HFD supplemented with a weakly toxic AHR agonist C2 (HFDc2), or HFDtrp with C2 (HFDtrp-c2). All diets contained 2 % cholesterol and were fed for 18 weeks. On weeks 14–16, the mice were tested for gas exchange and locomotor activity, and on weeks 15–17 for glucose tolerance (GTT) and insulin sensitivity (ITT). At termination, tissue samples were collected for biochemical and AI-assisted histological analyses. Body weight gain (BWG) was only 28–38 % higher in the HFD groups than in the CD group, but the HFD-fed mice accumulated 43–61 % more fat. Calorie intake was greater in the two low-TRP groups than in the two other HFD groups, while BWG remained similar. C2 induced <em>Cyp1a1</em> expression (an index of AHR activity) in all tissues examined and increased the ratio of micro-/macrosteatosis in the liver. The HFDs tended to reduce insulin sensitivity, CO<sub>2</sub> production, and the ability to respond appropriately to a low-temperature challenge. These findings suggest that the effects of AHR activity modulation on energy balance are strongly context-dependent. A sensitive response to long-term AHR activation appears to be elevated micro-/macrosteatosis ratio in the liver when exposed to HFD.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"Article 102083"},"PeriodicalIF":0.0,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144604560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Digoxin toxicity with therapeutic serum digoxin concentrations 地高辛毒性与治疗血清地高辛浓度有关

Toxicology Reports Pub Date : 2025-07-05 DOI: 10.1016/j.toxrep.2025.102079

J. Graafsma , N. Cimic , M. Dijkman , F.M.J. Gresnigt , D. Mitrovic , C. Smit

{"title":"Digoxin toxicity with therapeutic serum digoxin concentrations","authors":"J. Graafsma , N. Cimic , M. Dijkman , F.M.J. Gresnigt , D. Mitrovic , C. Smit","doi":"10.1016/j.toxrep.2025.102079","DOIUrl":"10.1016/j.toxrep.2025.102079","url":null,"abstract":"<div><h3>Introduction</h3><div>Digoxin is a cardiac glycoside used for rate control in atrial fibrillation and heart failure. Despite its efficacy, digoxin has a narrow therapeutic window and can cause severe side effects, including life-threatening arrhythmias. Literature and guidelines on management of digoxin toxicity remain inconsistent whether to include serum digoxin concentrations as a key criterium for diagnosing digoxin toxicity and determining the indication for digoxin-specific antibody fragments. This report presents a case of digoxin toxicity at therapeutic serum concentrations.</div></div><div><h3>Case report</h3><div>A 76-year-old male presented with bradycardia, hyperkalemia, and acute kidney injury following gastrointestinal bleeding. Despite serum digoxin concentrations within the therapeutic range (1.4 ng/ml), the patient exhibited symptoms consistent with severe digoxin toxicity. Initial treatments, including calcium gluconate, insulin-glucose, and sodium bicarbonate, failed to resolve hyperkalemia and/or bradycardia. Administration of 40 mg digoxin-specific antibody fragments led to rapid normalization of potassium levels, improved heart rate, and hemodynamic stabilization, indicative for severe digoxin toxicity despite therapeutic serum concentrations.</div></div><div><h3>Discussion</h3><div>This case demonstrates that digoxin toxicity can occur at serum concentrations in therapeutic range, emphasizing the importance of clinical features in diagnosing digoxin toxicity. Current guidelines vary on the role of serum digoxin concentrations in guiding the use of digoxin-specific antibody fragments, but this case underscores its efficacy in resolving symptoms related to digoxin toxicity, even at low serum concentrations.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"Article 102079"},"PeriodicalIF":0.0,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144597513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Assessment of heavy metal pollution and human health risk in the soil of selected tea plantations from southern Western Ghats, Tamil Nadu, India 印度泰米尔纳德邦西高止山脉南部选定茶园土壤重金属污染及人类健康风险评估

Toxicology Reports Pub Date : 2025-07-05 DOI: 10.1016/j.toxrep.2025.102081

Eswaran Rangasamy, Muniasamy Muniyandi

{"title":"Assessment of heavy metal pollution and human health risk in the soil of selected tea plantations from southern Western Ghats, Tamil Nadu, India","authors":"Eswaran Rangasamy, Muniasamy Muniyandi","doi":"10.1016/j.toxrep.2025.102081","DOIUrl":"10.1016/j.toxrep.2025.102081","url":null,"abstract":"<div><div>Soil pollution on agricultural land has become a significant concern in major tea-producing regions, including Tamil Nadu, a prominent tea-producing state in India. The excessive use of agrochemicals in tea plantations leads to soil contamination, which in turn pollutes tea plantation soil. Tea soil samples were collected in six different tea plantations in commercially important regions from Valparai (Coimbatore), Coonoor, Kundha, Kothagiri, Kattabettu, and Gudalur (Nilgiris), in Tamil Nadu, India. The samples were taken from depths of 0–25 cm across distances ranging from 0–250 m. These samples were digestion procedure followed AOAC method. To assess human health risks, both carcinogenic and non-carcinogenic effects will be evaluated across three primary exposure pathways: ingestion, inhalation, and dermal contact. The study conducted in six major tea-cultivated soils. Five tea plantations' soil samples are highly contaminated with cadmium and at high risk. Geoaccumulation index shows cadmium strongly contaminated in Valparai, Coonoor, and extremely contaminated in Kundha, Kothagiri, and Ooty tea soil samples. The Total Cancer Risk (TCR) in the study area mainly ingestion route values: Cd (0.0000364–0.0000583), followed by Cr (0.0000293–0.0000468), As (0.0000105–0.0000168), and Ni (0.00000269–0.00000431) All the values were higher than USEPA’s of 1 × 10<sup>6</sup>–1 × 10<sup>4</sup> (USEPA, 2004) consequently, children’s health will be severely affected compared to adults. The current study shows that due to the excess use of agrochemicals and short tea crop cultivation periods, a large amount of heavy metals accumulates in tea plantation soil. As a result, understanding toxic metals and emphasizing the reduction of agrochemicals and the extension of the tea crop cultivation period is crucial. Because soil health is key for food quality, sustainable agriculture, and increasing economic value.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"Article 102081"},"PeriodicalIF":0.0,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144588582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Targeting mitochondrial damage and ER stress to inhibit ferroptosis in cadmium-induced nephrotoxicity 靶向线粒体损伤和内质网应激抑制镉所致肾毒性铁下垂

Toxicology Reports Pub Date : 2025-07-03 DOI: 10.1016/j.toxrep.2025.102082

Saba Yousaf , Muhammad Arshad , Muhammad Raza , Anmol Fatima , Khayala Mammadova

{"title":"Targeting mitochondrial damage and ER stress to inhibit ferroptosis in cadmium-induced nephrotoxicity","authors":"Saba Yousaf , Muhammad Arshad , Muhammad Raza , Anmol Fatima , Khayala Mammadova","doi":"10.1016/j.toxrep.2025.102082","DOIUrl":"10.1016/j.toxrep.2025.102082","url":null,"abstract":"<div><div>This review highlights the pivotal roles of autophagy, ferroptosis, and endoplasmic reticulum (ER) stress in mediating cadmium (Cd)-induced nephrotoxicity. Cadmium exposure results in ER stress, which in turn activates major UPR pathways such as IRE1, ATF6, and PERK. By encouraging lipid peroxidation and suppressing cellular antioxidant defence, these mechanisms worsen ferroptosis and produce a feedback mechanism that increases cellular damage. There are two roles of autophagy in Cd-induced ferroptosis, which include its action in reducing cadmium-induced cytotoxicity by breaking down damaged components, and excessive autophagy, namely ferritinophagy, which promotes ferroptosis by iron dysregulation. The rise of mitochondrial ROS (MitoROS) caused by Cd-induced mitochondrial malfunction aids ferroptosis. This, in turn, causes ER stress and autophagy. This implies that focusing on mitochondrial health could be a useful treatment strategy. Effective treatment approaches include autophagy inhibitors like chloroquine, which have been shown to effectively reduce Cd-induced ferroptosis, and promising medicines that suppress ER stress, such as TUDCA. Desferrioxamine and other iron chelators effectively lower lipid peroxidation and iron dysregulation, therefore preventing ferroptotic cell death. Additionally, a multi-targeted treatment plan is suggested that targets iron metabolism, ER stress, and autophagy. In order to create tailored treatments for Cd-induced nephrotoxicity, this review emphasizes the need for additional study into the molecular pathways of Cd-induced ferroptosis, namely the ER stress-autophagy axis. The goal of future research should be to apply these mechanistic insights to clinical settings to enhance public health outcomes and create efficient therapies for renal failure brought on by cadmium toxicity.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"Article 102082"},"PeriodicalIF":0.0,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144549973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Sildenafil effect on testosterone-induced prostate hypertrophy and relaxation of urinary bladder neck muscles 西地那非对睾酮所致前列腺肥大及膀胱颈部肌肉松弛的影响

Toxicology Reports Pub Date : 2025-06-30 DOI: 10.1016/j.toxrep.2025.102080

Qasim A. El-Dwairi , Karem H. Alzoubi , Rania Mahafdeh

{"title":"Sildenafil effect on testosterone-induced prostate hypertrophy and relaxation of urinary bladder neck muscles","authors":"Qasim A. El-Dwairi , Karem H. Alzoubi , Rania Mahafdeh","doi":"10.1016/j.toxrep.2025.102080","DOIUrl":"10.1016/j.toxrep.2025.102080","url":null,"abstract":"<div><h3>Background</h3><div>Previous studies have demonstrated the expression of phosphodiesterase-5 receptors in prostate tissue. In this study, we investigated the efficacy of sildenafil citrate in testosterone-induced benign prostate hyperplasia (BPH) in rabbits.</div></div><div><h3>Methods</h3><div>Prostate hyperplasia was induced using testosterone propionate for 8 weeks. Rabbits were divided into two groups: control and experimental. The experimental group was further subdivided into two subgroups: one subgroup was sacrificed after testosterone induction, while the other subgroup received sildenafil (5 mg/kg/day) via intragastric intubation for 8 weeks. The weight of the prostate and relaxation of the bladder neck muscle were assessed. Organ bath experiments evaluated the effect of sildenafil on phenylephrine-precontracted bladder neck muscle strips.</div></div><div><h3>Results</h3><div>The mean prostate weight was reduced by 65.34 % after 8 weeks of treatment with sildenafil in animals with BPH. Sildenafil induced significant smooth muscle relaxation of the phenylephrine-contracted bladder neck muscle strips. The mean relaxation value was 2.11 ± 0.13, representing a 32.8 % reduction in contraction percentage. Maximal relaxation was produced at 5.0 × 10⁻⁶ M of sildenafil. Sildenafil induced significant relaxation of the phenylephrine-contracted bladder neck muscle strips. Adding the nitric oxide synthase inhibitor L-NAME inhibited relaxation, whereas sodium nitroprusside, a nitric oxide donor, increased it. Histopathological analysis showed increased papillary projections, acinar areas, and epithelial thickness in the testosterone-treated group. Sildenafil treatment reversed the hypertrophic and hyperplastic changes.</div></div><div><h3>Conclusions</h3><div>The results indicate that sildenafil may provide a dual function in the treatment of erectile dysfunction and the relief of urinary tract complications associated with prostatic hypertrophy.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"Article 102080"},"PeriodicalIF":0.0,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144524247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Toxic metals and bioelements: Combined oxidative stress effects on liver injury and thyroid hormone disruption in subjects from different areas of Erbil province 有毒金属和生物元素：埃尔比勒省不同地区受试者肝损伤和甲状腺激素紊乱的联合氧化应激效应

Toxicology Reports Pub Date : 2025-06-26 DOI: 10.1016/j.toxrep.2025.102078

Mahdi Yassin Ahmed, Kamaran Abdoulrahman

{"title":"Toxic metals and bioelements: Combined oxidative stress effects on liver injury and thyroid hormone disruption in subjects from different areas of Erbil province","authors":"Mahdi Yassin Ahmed, Kamaran Abdoulrahman","doi":"10.1016/j.toxrep.2025.102078","DOIUrl":"10.1016/j.toxrep.2025.102078","url":null,"abstract":"<div><div>In Iraq, particularly in Erbil city and Gwer road are deemed environmentally disadvantaged because of industrial pollutants and refinery activities. This study conducted 143 subjects from rural, urban, and industrial areas. The sera of subjects were taken for the analysis. The toxic metals and bioelements were assessed using ICP-MS, the oxidative stress parameters were determined via ELISA. For estimation of liver test biomarkers Kenza was used, and thyroid hormones were measured by Cobas. While their relationships were statistically analyzed. The results indicated that metals concentrations were markedly significantly increased in industrial areas, particularly for Fe 599.1 (723.9) μg/L and Mn 7.534 ± 8.793 μg/L. The median level of Cu 4082 (2824) μg/L in urban subjects is significantly lower than those of other areas. Markers for oxidative stress revealed considerably higher MDA in urban participants 1917 (1085) pg/mL, while SOD and CP exhibited significantly lower level in urban and industrial participants P-value (0.0001 and <0.0001) respectively. The liver tests revealed elevated ALT in urban and industrial participants, 29.06 ± 1.723 IU/L and 21.94 ± 1.162 IU/L, respectively. The ALP levels were significantly elevated in industrial participants (P-value <0.0001). The study found that industrial workers had significantly higher levels of TSH 2.209 ± 0.1032 μIU/L and low levels of T3 1.765 ± 0.0227 nmol/l compared to the rural individuals. Fe had positive correlations with ONOO<sup>-.</sup> and TSH (r = 0.2221, r = 0.2452). Furthermore, Cu showed positively correlated with Cp (r = 0.2967; p = 0.0068), AST (r = 0.2417; p = 0.0268) and ALB (r = 0.2187; p = 0.0457). This study shows that increased levels of hazardous metals and bioelements in industrial and urban areas cause oxidative stress, which has a significant impact on public health and causes a number of health problems, including liver injury and thyroid dysfunction.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"Article 102078"},"PeriodicalIF":0.0,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144489873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Per- and polyfluorinated substances (PFAS) promote osteoclastogenesis and bone loss through PPARα activation 全氟和多氟物质（PFAS）通过激活PPARα促进破骨细胞生成和骨质流失

Toxicology Reports Pub Date : 2025-06-20 DOI: 10.1016/j.toxrep.2025.102071

Laimar C. Garmo , Mackenzie K. Herroon , Shane Mecca , Alexis Wilson , David R. Allen , Abu Sayed Mohammed Sayam , Aaron J. Specht , Jennifer J. Schlezinger , Michael C. Petriello , Izabela Podgorski

{"title":"Per- and polyfluorinated substances (PFAS) promote osteoclastogenesis and bone loss through PPARα activation","authors":"Laimar C. Garmo , Mackenzie K. Herroon , Shane Mecca , Alexis Wilson , David R. Allen , Abu Sayed Mohammed Sayam , Aaron J. Specht , Jennifer J. Schlezinger , Michael C. Petriello , Izabela Podgorski","doi":"10.1016/j.toxrep.2025.102071","DOIUrl":"10.1016/j.toxrep.2025.102071","url":null,"abstract":"<div><div>Per- and polyfluoroalkyl substances (PFAS) are emerging as significant environmental contaminants affecting bone health, with studies linking their exposure to decreased bone mineral density (BMD), enhanced osteoclastogenesis, and disruptions in the bone marrow microenvironment. While current research highlights the effects on bone and BMD, there is a critical gap in understanding the mechanisms behind these effects. Studies presented here investigate the effects of legacy and alternative PFAS, particularly hexafluoropropylene oxide dimer acid (GenX) and perfluorohexane sulfonic acid (PFHxS), on bone health using <em>in vitro</em> and <em>in vivo</em> models. An environmentally relevant mixture of five PFAS was found to promote osteoclastic differentiation of murine bone marrow macrophages (BMMs) <em>in vitro</em>. Among the five components of the Mixture, the emerging compound, GenX, had the highest propensity to induce osteoclastogenesis. Utilizing pharmacological and genetic approaches, we identified peroxisome proliferator-activated receptor alpha (PPARα) as a potential mediator of PFAS-driven osteoclastogenesis. Furthermore, our <em>in vivo</em> mouse experiments demonstrated a decrease in trabecular and cortical bone thickness as well as altered bone mineral composition in male FVB/N mice exposed to either GenX or PFHxS (2 mg/L) for 12 weeks. Altogether, our results reveal potentially negative effects of PFAS exposure on BMD, bone mineral composition, and overall bone health and underscore the need for further research assessing the health risks associated with exposure to alternative PFAS.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"Article 102071"},"PeriodicalIF":0.0,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144481171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Determination of nitrofuran metabolites in sausage casings and crawfish using LC-Q-Orbitrap HRMS: Method development and validation LC-Q-Orbitrap液相色谱法测定香肠肠衣和小龙虾中硝基呋喃代谢物：方法建立与验证

Toxicology Reports Pub Date : 2025-06-19 DOI: 10.1016/j.toxrep.2025.102076

Omar Khaled , Lamia Ryad , Nermine Gad , Fawzy Eissa

{"title":"Determination of nitrofuran metabolites in sausage casings and crawfish using LC-Q-Orbitrap HRMS: Method development and validation","authors":"Omar Khaled , Lamia Ryad , Nermine Gad , Fawzy Eissa","doi":"10.1016/j.toxrep.2025.102076","DOIUrl":"10.1016/j.toxrep.2025.102076","url":null,"abstract":"<div><div>This study developed and validated an analytical method for determining four nitrofuran (NF) metabolites in sausage casings and crawfish matrices. The method utilizes liquid chromatography coupled with quadrupole-Orbitrap high-resolution mass spectrometry (LC-Q-Orbitrap HRMS) to analyze these metabolites. The validation of the developed method was carried out in accordance with the Commission Implementing Regulation (CIR) EU 2021/808, using three concentration levels ranging from 0.25 to 0.75 μg/kg. The recoveries ranged from 77 % to 109 %, while both repeatability and reproducibility remained consistently below 15 %. The calibration curves exhibited good linearity, with correlation coefficients (R) exceeding 0.9978. The limits of detection (LOD) ranged from 0.0218 to 0.0596 μg/kg, while the limits of quantification (LOQ) ranged from 0.0719 to 0.1966 μg/kg. The decision limit (CCα) and detection capability (CCβ) values ranged from 0.30 to 0.39 μg/kg and 0.29–0.35 μg/kg, respectively. Out of 30 crawfish samples collected from local markets in Egypt, 16.66 % contained NF metabolites residues, whereas sausage casings showed no NF metabolite residues. The reliability of the method was further demonstrated through successful participation in two proficiency testing (PT) rounds.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"Article 102076"},"PeriodicalIF":0.0,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144470002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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