Toxicology Reports最新文献_第9页

A case report of a 79-year-old female with aluminum toxicity presenting with altered mental status in Eldoret, Kenya 肯尼亚埃尔多雷特一名79岁女性铝中毒病例报告，表现为精神状态改变

Q1 Environmental Science

Toxicology Reports

Pub Date : 2025-09-15 DOI: 10.1016/j.toxrep.2025.102128

Ann Mutugi , Eduardo Cadore Guzzo , Matthew Koech , Maritim Koech , Jie Tang

Introduction

Aluminum is renally excreted and can cause toxicity in patients with end-stage renal disease (ESRD). In low- and middle-income countries (LMICs), potential sources of aluminum toxicity include the use of aluminum cookware and clay pots, well water, and contaminated dialysis water.

Patient concerns

We report a case of an elderly East African woman from a rural area with ESRD who was undergoing twice-weekly hemodialysis and who presented with altered mental status. Acute cardiac and neurological events were ruled out. A head CT scan was normal. Both the infectious and metabolic workups were unremarkable. Since the patient came from a rural home where her family used clay pots, aluminum utensils, and well water for drinking, a decision was made to rule out aluminum toxicity. Serum aluminum levels were significantly elevated at 534 micrograms/L.

Diagnosis

Aluminum toxicity based on the clinical presentation and elevated serum aluminum levels

Interventions

Daily hemodialysis with a high-flux dialyzer. Deferoxamine was not administered because of concerns about life-threatening neurotoxicity.

Outcomes

Her mental status started to improve within a week of initiating intensified hemodialysis. After nine months, her serum aluminum level decreased by more than 50 %, and the patient’s cognition returned to her baseline.

Take-home lessons

ESRD patients in LMICs are at greater risk for potential aluminum toxicity than are those in developed countries. Regular testing of serum aluminum levels is necessary in these patients since the initial presentation of aluminum toxicity can be nonspecific.

铝通过肾脏排出，可对终末期肾病（ESRD）患者造成毒性。在低收入和中等收入国家，铝毒性的潜在来源包括使用铝制炊具和陶罐、井水和受污染的透析水。我们报告一位来自东非农村地区患有ESRD的老年妇女，她每周接受两次血液透析，并表现出精神状态改变。排除了急性心脏和神经系统事件。头部CT扫描正常。感染和代谢检查均无显著差异。由于患者来自农村家庭，她的家人使用陶罐，铝制餐具和井水饮用，因此决定排除铝毒性。血清铝水平显著升高至534微克/升。诊断：基于临床表现和血清铝水平升高的铝毒性。方法：每日高通量透析器血液透析。由于担心危及生命的神经毒性，没有给予去铁胺。结果：她的精神状态在开始强化血液透析的一周内开始改善。9个月后，她的血清铝水平下降了50%以上 %，患者的认知能力恢复到基线。与发达国家相比，中低收入国家的重度肾病患者潜在铝中毒的风险更大。定期检测血清铝水平对这些患者是必要的，因为铝毒性的最初表现可能是非特异性的。

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引用次数: 0

Extracellular RNA in iron-induced hepatic injury: Beyond TLR3 toward an integrated inflammatory axis. 铁诱导的肝损伤中的细胞外RNA：超越TLR3走向综合炎症轴。

Q1 Environmental Science

Toxicology Reports

Pub Date : 2025-09-11 eCollection Date: 2025-12-01 DOI: 10.1016/j.toxrep.2025.102126

Hector A Cabrera-Fuentes, Klaus T Preissner

引用次数: 0

Surviving cyanide poisoning: A case report highlighting the role of early antidote use 幸存的氰化物中毒：一个病例报告强调早期使用解毒剂的作用

Q1 Environmental Science

Toxicology Reports

Pub Date : 2025-09-10 DOI: 10.1016/j.toxrep.2025.102127

Berber C. Hospes , Elise M.A. Slob , Tom K. Brinkman , Sharif M. Pasha , Erik B. Wilms , Hans W.P.M. Overdiek

Survival after high-dose oral cyanide ingestion is rare, and when untreated cases often result in death within an hour. Immediate treatment however, can be lifesaving. We describe a patient who fully recovered after prompt intervention. He arrived at the emergency department unconscious, with red skin and a Glasgow Coma Scale of 3 and was suspected of an intentional intoxication with an unknown white crystalline powder. He rapidly suffered a cardiac arrest. Blood gas analysis showed severe metabolic acidosis, high lactate, and slightly elevated methemoglobin. In suspect of cyanide poisoning, hydroxocobalamin (2 doses of 5 g intravenous) and sodium thiosulfate (12.5 g intravenous) were administered. Thereafter spontaneous circulation returned. The patient was intubated and sedated in the intensive care unit for four days. After extubation, he was transferred to a general ward. A magnetic resonance imaging scan showed no post-anoxic or toxic damage. During his 14-day stay, he fully recovered. The white powder was identified in the pharmaceutical laboratory by infrared spectrometry, confirming the presence of cyanide. Subsequently, the patient admitted to ingesting potassium cyanide. He obtained the potassium cyanide from his workplace, a chemical laboratory.

大剂量口服氰化物摄入后存活的情况非常罕见，如果不治疗，通常会在一小时内死亡。然而，立即治疗可以挽救生命。我们描述一个病人谁完全恢复后及时干预。他被送到急诊室时已经失去知觉，皮肤发红，格拉斯哥昏迷等级为3级，怀疑是故意服用一种未知的白色结晶粉末。他很快心脏骤停。血气分析显示严重的代谢性酸中毒，高乳酸，高铁血红蛋白轻微升高。疑似氰化物中毒患者给予羟钴胺素（5 g静脉注射2剂）和硫代硫酸钠（12.5 g静脉注射）。此后，自然循环又恢复了。病人在加护病房插管并注射镇静剂4天。拔管后，他被转到普通病房。磁共振成像扫描显示无缺氧后或毒性损伤。在14天的住院治疗中，他完全康复了。在药物学实验室用红外光谱法鉴定出白色粉末，证实了氰化物的存在。随后，病人承认摄入氰化钾。他从他工作的化学实验室获得了氰化钾。

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引用次数: 0

Safety evaluation of a fungal beta-glucanase 真菌β -葡聚糖酶的安全性评价

Q1 Environmental Science

Toxicology Reports

Pub Date : 2025-09-09 DOI: 10.1016/j.toxrep.2025.102125

Dnyaneshwar Jondhale , Corrine Harris , Gregory S. Ladics

Pig and poultry feed are often included with beta-glucanase to alleviate the anti-nutritional impacts of beta-glucans found in many cereal grains. Safety studies were conducted on beta-glucanase, including skin and eye irritation, dermal sensitization, a 90-day rat oral subchronic study, and genotoxicity, to evaluate the safety of a beta-glucanase for use as an animal feed additive. Beta-glucanase is produced by fermentation with a fungal (Trichoderma reesei) production strain expressing a wild-type fungal endoglucanase (egl2) gene to overexpress the endoglucanase (referred to as beta-glucanase throughout the paper) enzyme. Beta-glucanase was predicted to be non-irritant (No Category) to the skin or eyes in reconstructed human epidermis tissues (RhE) and reconstructed human cornea-like epithelium (RhCE), respectively. Beta-glucanase was tested in vitro in the direct peptide reactivity assay (DPRA), the KeratinoSens™ assay and the human cell line activation test (h-CLAT). Using the 2 out of 3 approach, beta-glucanase was not a dermal sensitizer based on the negative KeratinoSens™ and h-CLAT assays. In vitro genotoxicity testing confirmed beta-glucanase to be non-genotoxic. In the 90-day subchronic study, rats were administered beta-glucanase daily via oral gavage at dose-levels of 0 (Milli-Q® water), 250, 500 or 1000 mg total organic solids (TOS)/kg bodyweight (bw)/day (equivalent to 0; 42,102; 84,205 and 168,410 units (U)/kg bw/day, respectively). No test item-related adverse effects were observed. A no-observed-adverse-effect level (NOAEL) for beta-glucanase was established at 1000 mg TOS/kg body weight/day, the highest test concentration. Based on this NOAEL and an estimate of consumption determined from the proposed inclusion of the beta-glucanase in feed at the maximum recommended level (426 U/kg), a margin of safety value of 5681 was calculated based on highest expected daily feed intake in broilers, the target species with highest feed intake relative to body weight. The findings support the safe use of beta-glucanase as an animal feed additive.

猪和家禽饲料中通常含有-葡聚糖酶，以减轻许多谷物中发现的-葡聚糖的抗营养影响。对β -葡聚糖酶进行了安全性研究，包括皮肤和眼睛刺激、皮肤致敏、90天大鼠口服亚慢性研究和遗传毒性，以评估β -葡聚糖酶作为动物饲料添加剂的安全性。β -葡聚糖酶是通过真菌（里氏木霉）生产菌株发酵产生的，该菌株表达野生型真菌内切葡聚糖酶（egl2）基因，以过表达内切葡聚糖酶（在本文中称为β -葡聚糖酶）酶。预测β -葡聚糖酶在重建的人表皮组织（RhE）和重建的人角膜样上皮（RhCE）中分别对皮肤或眼睛无刺激性（No Category）。β -葡聚糖酶在体外通过直接肽反应性试验（DPRA）、KeratinoSens™试验和人细胞系激活试验（h-CLAT）进行检测。使用2 / 3的方法，基于阴性KeratinoSens™和h-CLAT检测，β -葡聚糖酶不是皮肤增敏剂。体外遗传毒性试验证实-葡聚糖酶无遗传毒性。在为期90天的亚慢性研究中，大鼠每天以0 （milliq®水）、250、500或1000 mg总有机固体(TOS)/kg体重(bw)/天的剂量水平（分别相当于0,42,102、84,205和168,410单位(U)/kg体重/天）灌胃给予β -葡聚糖酶。没有观察到与测试项目相关的不良反应。β -葡聚糖酶的无观察到不良反应水平（NOAEL）为最高试验浓度1000 mg TOS/kg体重/天。根据该NOAEL和根据建议在饲料中添加最大推荐水平（426 U/kg）确定的消耗量估计，根据肉仔鸡（相对体重而言采食量最高的目标品种）的最高预期日采食量计算出5681的安全边际值。该研究结果支持β -葡聚糖酶作为动物饲料添加剂的安全使用。

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引用次数: 0

The Caenorhabditis elegans worm Development and Activity Test (wDAT) can be used to differentiate between reversible and irreversible developmental effects 秀丽隐杆线虫的发育和活动测试（wDAT）可用于区分可逆和不可逆的发育效应

Q1 Environmental Science

Toxicology Reports

Pub Date : 2025-09-05 DOI: 10.1016/j.toxrep.2025.102124

Piper Reid Hunt, Nicholas Olejnik, Jeffrey Yourick, Robert L. Sprando

Developmental delay and spontaneous locomotor activity changes, as well as the reversibility of these adverse effects are apical endpoints used in chemical safety evaluations. These endpoints were assessed at sublethal concentrations in C. elegans using 5-fluorouracil (5FU), hydroxyurea (HU), or ribavirin (RV), teratogens that are associated with reduced fetal growth in mammals. C. elegans develop from egg to egg-laying adult in about three days. Synchronized cohorts were exposed either continuously, or for 24 h (early-only) from first-feeding after hatching. Developmental delays were dose-responsive for all three chemicals in both exposure schemes. For 5FU and HU, developmental delays and hypoactivity levels were similar in continuous and early-only exposure groups, consistent with irreversible developmental effects. The observed hypoactivity in developing C. elegans may be related to reported 5FU-induced muscle impairment and HU-induced post-exposure effects on locomotion parameters in mammals. In contrast to 5FU- and HU-induced hypoactivity, RV was associated with a non-significant trend to slight hyperactivity in both exposure schemes. Continuous RV exposures induced delays to sequential developmental milestones that increased with exposure duration. RV-induced delays were significantly reduced but not eliminated in early-only exposure cohorts, consistent with cumulative RV effects on developmental progress. These findings suggest that C. elegans may be a useful model for detecting chemicals with irreversible, reversible, and/or cumulative effects on organismal development.

发育迟缓和自发运动活动的改变，以及这些不良反应的可逆性是用于化学品安全性评价的主要终点。使用5-氟尿嘧啶（5FU）、羟基脲（HU）或利巴韦林（RV）在秀丽隐杆线虫中的亚致死浓度对这些终点进行了评估，这些致畸物与哺乳动物胎儿生长降低有关。秀丽隐杆线虫由卵发育为产卵成虫约需三天。同步队列要么连续暴露，要么从孵化后第一次喂食开始暴露24 h（仅早期）。在两种暴露方案中，所有三种化学物质的发育迟缓都是剂量反应性的。对于5FU和HU，持续暴露组和早期暴露组的发育迟缓和低活动水平相似，与不可逆的发育影响一致。在发育中的秀丽隐杆线虫中观察到的低活性可能与报道的5fu诱导的肌肉损伤和hu诱导的暴露后对哺乳动物运动参数的影响有关。与5FU-和hu诱导的低活动性相反，RV在两种暴露方案中都与轻度多动的非显著趋势相关。随着暴露时间的延长，连续的RV暴露会导致顺序发育里程碑的延迟。在早期暴露组中，RV诱导的延迟显著减少，但并未消除，这与RV对发育进展的累积影响一致。这些发现表明秀丽隐杆线虫可能是检测对生物体发育具有不可逆、可逆和/或累积效应的化学物质的有用模型。

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引用次数: 0

Assessment of heavy metal exposure and cancer risk in Addis Ababa: Trends, risk factors and demographic variations in urinary cadmium, lead and chromium levels 亚的斯亚贝巴重金属接触和癌症风险评估：尿中镉、铅和铬水平的趋势、风险因素和人口变化

Q1 Environmental Science

Toxicology Reports

Pub Date : 2025-09-02 DOI: 10.1016/j.toxrep.2025.102122

Tsigereda Assefa Alemayehu , Andualem Mekonnen Hiruy , Mehari Meles , Belay Tefera , Tadesse Alemu Terfie

This study aims to assess the exposure levels of Pb, Cd, and Cr and evaluate trends in heavy metal exposure among the population of Addis Ababa. A cross-sectional study was conducted involving 417 participants randomly selected from the population. Spot urine and water samples, socio-demographic characteristics, and food consumption frequency were collected. Heavy metals were analyzed using microwave plasma-atomic emission spectroscopy. Metal exposure risk from drinking water was assessed. The median concentrations of urinary Pb, Cr, and Cd were 19.4865 µg/g creatinine, 55.65 µg/g creatinine, and below the detection limit (Bd), respectively. Female participants and individuals who consumed meat daily had the highest median concentration of Pb (p < 0.005). Those who drank two or more cups of water daily had lower Pb (P < 0.01). Females who consumed eggs daily and drank two or more cups of water had the highest concentration of Cd, ranking in the 75th percentile. The median Cr concentration was higher in underweight participants (BMI < 18.5 kg/m²) at 88.41 µg/g creatinine and in overweight participants (BMI ≥ 25 kg/m²) at 66.49 µg/g creatinine compared to normal-weight participants, who had a median concentration of 48.44 µg/g creatinine (P < 0.01). Three metals were detected in 14.4 % and two metals in 52.8 %, and their levels showed an increasing trend over 12 years. Health risk analysis revealed that the highest Cumulative Incremental Life Cancer Risk (CILCR) values were found in Kirkos (KR-10–1.9 ×10⁻³), Lideta (LI-10–2.33 ×10⁻³), and Nifas Silk (NS-11–2.46 ×10⁻³) districts, indicating a significant cancer risk associated with cumulative exposure.

本研究旨在评估亚的斯亚贝巴人口中铅、镉和铬的暴露水平，并评估重金属暴露的趋势。一项横断面研究从人群中随机选择了417名参与者。收集尿样和水样、社会人口统计学特征和食物消费频率。采用微波等离子体原子发射光谱对重金属进行了分析。对饮用水中的金属暴露风险进行了评估。尿Pb、Cr、Cd中位浓度分别为19.4865 µg/g肌酐、55.65 µg/g肌酐，均低于检出限（Bd）。女性参与者和每天吃肉的个体的铅中位数浓度最高（p <； 0.005）。每天喝两杯或两杯以上水的人铅含量较低（P <； 0.01）。每天吃鸡蛋并喝两杯或两杯以上水的女性Cd浓度最高，排名在第75个百分位数。与正常体重的参与者相比，体重不足的参与者（BMI < 18.5 kg/m²）的Cr浓度中位数为88.41 µg/g肌酐，超重参与者（BMI≥25 kg/m²）的Cr浓度中位数为66.49 µg/g肌酐，正常体重的参与者的Cr浓度中位数为48.44 µg/g肌酐（P <； 0.01）。3种金属含量为14.4% %，2种金属含量为52.8% %，在12年内呈上升趋势。健康风险分析显示，Kirkos （KR-10-1.9 ×10−3）、Lideta （LI-10-2.33 ×10−3）和Nifas Silk （NS-11-2.46 ×10−3）地区的累积累积终身癌症风险（CILCR）值最高，表明累积暴露与显著的癌症风险相关。

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引用次数: 0

The protective role of nicardipine in dextran sulfate sodium-induced colitis in mice: Modulating inflammation and apoptosis 尼卡地平对硫酸葡聚糖钠诱导小鼠结肠炎的保护作用：调节炎症和细胞凋亡

Q1 Environmental Science

Toxicology Reports

Pub Date : 2025-09-02 DOI: 10.1016/j.toxrep.2025.102123

Ali M. Al-Joda , Munaf H. Zalzala

Ulcerative colitis (UC) is a chronic inflammatory bowel disease associated with persistent inflammation, oxidative stress, and epithelial apoptosis. Nicardipine, a dihydropyridine calcium channel blocker, exhibits anti-inflammatory and anti-apoptotic properties, but its therapeutic potential in UC remains unclear. This study evaluated the effects of nicardipine on dextran sulfate sodium (DSS)-induced colitis in mice, focusing on inflammatory, oxidative, and apoptotic pathways. Fifty BALB/c mice were assigned to five groups (n = 10): control, DSS, nicardipine 12 mg/kg, nicardipine 24 mg/kg, and 5-aminosalicylate (ASA) 75 mg/kg. Treatments were administered for 3 days before and 10 days during DSS exposure. Disease severity was assessed by body weight, disease activity index (DAI), and colon length. Colonic mRNA levels of Nlrp3, TNF-α, IL-17, and TNFSF10 were quantified by RT-PCR; protein expression of caspase-3, caspase-8, BAX, and BCL-2 was analyzed by Western blot. Serum malondialdehyde (MDA), myeloperoxidase (MPO), glutathione peroxidase-1 (GPX-1), occludin, and prostaglandin E₂ (PGE-2) were measured by ELISA. Histological scoring assessed epithelial integrity and inflammation. Nicardipine dose-dependently reduced DSS-induced weight loss, DAI, and colon shortening. Both doses significantly downregulated Nlrp3, TNF-α, IL-17, and TNFSF10 (p < 0.05), decreased caspase-3 and BAX, and increased BCL-2. Nicardipine restored GPX-1, lowered MDA and MPO, preserved occludin, and reduced PGE-2. Histology confirmed reduced mucosal injury and preserved epithelial architecture. Nicardipine attenuates DSS-induced colitis by suppressing pro-inflammatory cytokines, reducing oxidative stress, and inhibiting apoptosis, supporting its potential as a therapeutic candidate for UC. Further studies are warranted to clarify its molecular mechanisms and clinical relevance.

溃疡性结肠炎（UC）是一种慢性炎症性肠病，与持续炎症、氧化应激和上皮细胞凋亡有关。尼卡地平是一种二氢吡啶钙通道阻滞剂，具有抗炎和抗凋亡的特性，但其在UC中的治疗潜力尚不清楚。本研究评估尼卡地平对小鼠右旋糖酐硫酸钠（DSS）诱导结肠炎的影响，重点关注炎症、氧化和凋亡途径。50只BALB/c小鼠分为5组（n = 10）：对照组、DSS组、尼卡地平12 mg/kg组、尼卡地平24 mg/kg组和5-氨基水杨酸酯（ASA） 75 mg/kg组。分别于DSS暴露前3天和暴露后10天进行处理。通过体重、疾病活动指数（DAI）和结肠长度评估疾病严重程度。RT-PCR法检测Nlrp3、TNF-α、IL-17、TNFSF10 mRNA水平；Western blot检测caspase-3、caspase-8、BAX、BCL-2蛋白的表达。ELISA法检测血清丙二醛（MDA）、髓过氧化物酶（MPO）、谷胱甘肽过氧化物酶-1 （GPX-1）、occludin、前列腺素e2 （PGE-2）水平。组织学评分评估上皮完整性和炎症。尼卡地平剂量依赖性降低dss诱导的体重减轻、DAI和结肠缩短。两种剂量均显著下调Nlrp3、TNF-α、IL-17和TNFSF10 (p < 0.05)，降低caspase-3和BAX，升高BCL-2。尼卡地平恢复GPX-1，降低MDA和MPO，保留occludin，降低PGE-2。组织学证实粘膜损伤减轻，上皮结构保留。尼卡地平通过抑制促炎细胞因子、减少氧化应激和抑制细胞凋亡来减轻dss诱导的结肠炎，支持其作为UC治疗候选药物的潜力。需要进一步的研究来阐明其分子机制和临床意义。

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引用次数: 0

Holistic approach to assess human health risks, integrating physicochemical quality attributes and heavy metal levels in tap water 全面评估人类健康风险的方法，整合自来水的物理化学质量属性和重金属含量

Q1 Environmental Science

Toxicology Reports

Pub Date : 2025-08-30 DOI: 10.1016/j.toxrep.2025.102121

Molla Tefera , Habtamu Aderajew , Dessie Ezez , Mamo Dikamu , Worku Lakew

Heavy metal contamination is a serious concern affecting the safety of tap water sources. Hence, this study evaluated physicochemical quality indices, carcinogenic and non-carcinogenic health hazard derived from the level of toxic metals in tap water in Gondar city, Ethiopia. The results revealed that except dissolved oxygen, salinity and nitrite, all quality attributes were below the allowable quality standards. The average concentrations for iron (Fe), copper (Cu), lead (Pb), chromium (Cr) and cadmium (Cd) were ranged from 0.003 mg/L to 5 mg/L, 0.475 mg/L to 0.752 mg/L, 0.14 mg/L to 0.703 mg/L, 0.261 mg/L to 2.182 mg/L, and 0.035 mg/L to 4.286 mg/L, respectively. The mean levels of metals in different areas decreased in the order: AR > AZ1 > PS1 > AZ3 > PS2 > MR > PS3 > SHD > AZ2 > CL. Except for Cu, the concentration of Fe, Pb, Cr, and Cd exceeded the safe limits described by WHO/FAO. According to principal component analysis and cluster analysis, anthropogenic activities were found to be the major source of metals. Chronic daily intake (CDI), target hazard quotient (THQ), hazard index (HI), and incremental lifetime cancer risk assessment (ILCR) were employed to evaluate human health risks. Except for Pb in AZ1, PS3, and AR, the values of THQ for both ingestion and dermal pathways from the analysed metals for adults were within the safety limits (THQ

<

1). However, the distribution pattern of HI values were presented in the decreasing order: PS1 > PS2 > AZ3 > MR > PS3 > AR > AZ2 > AZ1 > SHD > CL. Except, the HI values in CL, all values were greater than one (HI > 1), indicating that tap water in these areas may pose non-carcinogenic health risk. The analysis of carcinogenic health risks indicated that the lifetime cancer risk (ingestion and dermal exposure pathways) of heavy metals were in accordance with the acceptable range for tap water (10^–6 – 10^–4). This finding provides valuable input for the development of precise action plans aimed at elevating water quality standards in the studied areas.

重金属污染是影响自来水水源安全的一个严重问题。因此，本研究评估了埃塞俄比亚贡达尔市自来水中有毒金属含量的理化质量指标、致癌和非致癌健康危害。结果表明，除溶解氧、盐度和亚硝酸盐外，其余质量指标均低于允许质量标准。铁(Fe)的平均浓度、铜(铜)、铅(Pb)、铬(Cr)和镉(Cd) 范围从0.003 mg / L - 5 mg / L, 0.475 mg / L 0.752 mg / L, 0.14 mg / L 0.703 mg / L, 0.261 2.182 mg / L mg / L和0.035 4.286 mg / L mg / L,分别。金属在不同地区的平均水平降低的顺序:基于“增大化现实”技术的祝辞 AZ1 祝辞 PS1 祝辞 AZ3 祝辞 PS2 祝辞 先生在 PS3 祝辞 梅毒性心脏病祝辞 AZ2 祝辞 CL。除Cu外，Fe、Pb、Cr、Cd均超过WHO/FAO规定的安全限值。主成分分析和聚类分析表明，人为活动是重金属的主要来源。采用慢性每日摄入量（CDI）、目标危害商（THQ）、危害指数（HI）和增量终生癌症风险评估（ILCR）评价人体健康风险。除AZ1、PS3和AR中的Pb外，所分析的成人金属的摄入和皮肤途径的THQ值均在安全范围内（THQ <1）。但HI值的分布格局为PS1 >； PS2 > AZ3 > MR > PS3 > AR > AZ2 > AZ1 > SHD >； CL。除CL中的HI值外，其余均大于1 (HI > 1)，表明这些地区的自来水可能存在非致癌性健康风险。致癌性健康风险分析表明，重金属终生致癌风险（摄入途径和皮肤接触途径）符合自来水可接受范围（10-6 - 10-4）。这一发现为制定旨在提高所研究地区水质标准的精确行动计划提供了宝贵的投入。

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引用次数: 0

Corrigendum to: "Delayed-onset status epilepticus without cholinergic features in organophosphate poisoning: A case report" [Toxicol. Rep. 15 (2025) 102106]. 《有机磷中毒中无胆碱能特征的迟发性癫痫持续状态：一例报告》的勘误[毒物杂志]。众议员15(2025)102106]。

Q1 Environmental Science

Toxicology Reports

Pub Date : 2025-08-29 eCollection Date: 2025-12-01 DOI: 10.1016/j.toxrep.2025.102118

Shayani Vimalanathan, Pramith Ruwanpathirana, Thashi Chang

[This corrects the article DOI: 10.1016/j.toxrep.2025.102106.].

[这更正了文章DOI: 10.1016/j.toxrep.2025.102106.]。

引用次数: 0

Butein mitigates 5-FU-triggered hepatotoxicity via antioxidant, anti-inflammatory, and anti-apoptotic pathways 丁蛋白通过抗氧化、抗炎和抗凋亡途径减轻5- fu引发的肝毒性

Q1 Environmental Science

Toxicology Reports

Pub Date : 2025-08-26 DOI: 10.1016/j.toxrep.2025.102120

Ruaa Adnan Mohammed , Nada N. Al-Shawi

5-Fluorouracil (5-FU) is a widely used chemotherapeutic agent, but its hepatotoxic potential poses clinical challenges, as it induces oxidative stress, inflammation, and apoptosis in liver tissue. Butein, a natural chalcone flavonoid that possesses varied biological activity, such as anticancer, anti-inflammatory, and antiplatelet effects. This study aimed to evaluate the possible protective effects of Butein against 5-FU-induced hepatotoxicity in rats. Male albino rats were divided into 4 Groups (of 7 animals each): control, 5-FU, and two Butein-pretreated Groups (50 and 100 mg/kg/day, orally for 14 days) each before a single intraperitoneal dose of 150 mg/kg 5-FU, which was injected on day 14. Serum liver enzymes (ALT and AST), cytokines (IL-6, IL-10, and NF-κB), oxidative stress markers (MDA and GSH), TNF-α gene expression, and protein levels of caspase-3 and NRF2 were evaluated. Histological assessments were also conducted. 5-FU significantly elevated serum ALT and AST levels, increased NF-κB, IL-6, MDA, and TNF-α expression, and decreased IL-10, GSH, and NRF2 levels (p < 0.05). Histological changes included sinusoidal dilation, congestion, and hepatocyte degeneration. Pre-treatment with Butein markedly attenuated these alterations, where both doses of Butein significantly reduced transaminases, pro-inflammatory cytokines, and oxidative stress markers while enhancing antioxidant defenses and anti-inflammatory IL-10 levels. Notably, the high dose of Butein restored NRF2 expression and reduced caspase-3 protein levels more effectively than the lower dose. Histologically, the high dose of Butein preserved normal hepatic architecture with minimal pathological changes. In conclusoin, Butein offers dose-dependent hepatoprotection against 5-FU-induced liver injury through the attenuation of oxidative stress, suppression of pro-inflammatory and apoptotic markers, and upregulation of antioxidant defenses; moreover, the histopathological evaluation further supported the biochemical and molecular findings, particularly at the 100 mg/kg/day, which preserved normal hepatic architecture and minimized cellular damage; and, thus support the prophylactic potentialof Butein in managing chemotherapeutic liver toxicity.

5-氟尿嘧啶（5-FU）是一种广泛使用的化疗药物，但其潜在的肝毒性给临床带来了挑战，因为它会引起肝组织的氧化应激、炎症和细胞凋亡。丁酮，一种天然查尔酮类黄酮，具有多种生物活性，如抗癌、抗炎和抗血小板作用。本研究旨在探讨丁胺素对5- fu诱导的大鼠肝毒性的保护作用。雄性白化病大鼠分为4组（每组7只）：对照组、5-FU组和2个butein预处理组（50和100 mg/kg/天，口服14 d），第14天腹腔注射单次剂量150 mg/kg 5-FU。检测血清肝酶（ALT、AST）、细胞因子（IL-6、IL-10、NF-κB）、氧化应激标志物（MDA、GSH）、TNF-α基因表达及caspase-3、NRF2蛋白水平。同时进行组织学评估。5-FU显著提高血清ALT、AST水平，提高NF-κB、IL-6、MDA、TNF-α表达，降低IL-10、GSH、NRF2水平（p <； 0.05）。组织学改变包括窦状窦扩张、充血和肝细胞变性。Butein预处理显著减弱了这些改变，其中两种剂量的Butein都显著降低了转氨酶、促炎细胞因子和氧化应激标志物，同时增强了抗氧化防御和抗炎IL-10水平。值得注意的是，高剂量Butein比低剂量更有效地恢复NRF2表达并降低caspase-3蛋白水平。组织学上，高剂量的丁胺素保留了正常的肝脏结构，病理改变很小。综上所述，通过抑制氧化应激、抑制促炎和凋亡标志物以及上调抗氧化防御，丁蛋白对5- fu诱导的肝损伤具有剂量依赖性的肝保护作用；此外，组织病理学评估进一步支持了生化和分子的发现，特别是在100 mg/kg/天的剂量下，保留了正常的肝脏结构并最大限度地减少了细胞损伤；因此，支持丁胺素在管理化疗肝毒性方面的预防潜力。

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