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Protective Effects of Liriodendrin Against Oxidative Stress and Ferroptosis in a Mouse Model of Lipopolysaccharide-Induced Acute Respiratory Distress Syndrome 鹅掌楸素对脂多糖诱导急性呼吸窘迫综合征小鼠模型氧化应激和铁中毒的保护作用
IF 3.2 3区 医学 Q2 ENVIRONMENTAL SCIENCES Pub Date : 2025-08-27 DOI: 10.1002/tox.24565
Frank Cheau-Feng Lin, Sheng-Wen Wu, Shih-Pin Chen, Chun-Hung Su, Stella Chin-Shaw Tsai, Yu-Hsiang Kuan

Liriodendrin, a bioactive lignan diglucoside derived from several medicinal plants, has been demonstrated to exhibit pharmacological activities, such as antioxidative and anti-inflammatory activities. Up to now, no evidence has shown that acute respiratory distress syndrome (ARDS) is improved by liriodendrin. This study was conducted to investigate the protective effects of liriodendrin against oxidative stress and ferroptosis, key mechanisms underlying the pathogenesis of ARDS, in a mouse model of lipopolysaccharide (LPS)-induced ARDS. To investigate the potential of liriodendrin to mitigate oxidative stress and inhibit ferroptosis, adult BALB/c male mice with LPS-induced ARDS were treated with varying concentrations of liriodendrin. Mice received liriodendrin or dexamethasone before LPS administration. The effects of liriodendrin were evaluated by measuring changes in pulmonary histopathology, levels of lipid peroxidation, activities of antioxidative enzymes (superoxide dismutase, catalase, glutathione peroxidase), and expression of ferroptosis-related proteins (heme oxygenase-1, cystine/glutamate antiporter SLC7A11, glutathione peroxidase-4). In addition, we measured the phosphorylation of nuclear factor erythroid 2-related factor 2 (Nrf-2), a critical regulator of cellular defense mechanisms against oxidative damage. The results indicated that liriodendrin substantially suppressed histopathological damage, reduced lipid peroxidation, and restored antioxidative enzyme activity in a dose-dependent manner. Furthermore, this compound markedly upregulated the expression of ferroptosis-related proteins and promoted the phosphorylation of Nrf-2. Our findings suggest that liriodendrin protects against LPS-induced ARDS by regulating oxidative stress and ferroptosis. The ability of liriodendrin to modulate both antioxidative responses and ferroptosis markers through Nrf-2 phosphorylation highlights its potential as a therapeutic agent in the treatment of ARDS.

Liriodendrin是一种从几种药用植物中提取的生物活性木脂素二葡糖苷,已被证明具有抗氧化和抗炎等药理活性。到目前为止,还没有证据表明利碘树精对急性呼吸窘迫综合征(ARDS)有改善作用。本研究在脂多糖(LPS)诱导的ARDS小鼠模型中,探讨liriodendrin对氧化应激和铁下沉的保护作用,这是ARDS发病机制的关键机制。为了研究liriodendrin减轻氧化应激和抑制铁下沉的潜力,我们用不同浓度的liriodendrin治疗LPS诱导的ARDS成年BALB/c雄性小鼠。小鼠在LPS给药前分别给予利碘树精或地塞米松。通过测量肺组织病理学、脂质过氧化水平、抗氧化酶(超氧化物歧化酶、过氧化氢酶、谷胱甘肽过氧化物酶)活性和铁中毒相关蛋白(血红素加氧酶‐1、胱氨酸/谷氨酸反转运蛋白SLC7A11、谷胱甘肽过氧化物酶‐4)表达的变化来评估liriodendrin的作用。此外,我们测量了核因子红细胞2相关因子2 (Nrf - 2)的磷酸化,Nrf - 2是细胞防御氧化损伤机制的关键调节因子。结果表明,liriodendrin显著抑制组织病理损伤,减少脂质过氧化,恢复抗氧化酶活性,并呈剂量依赖性。此外,该化合物显著上调铁下垂相关蛋白的表达,并促进Nrf - 2的磷酸化。我们的研究结果表明,鹅掌楸素通过调节氧化应激和铁下垂来预防LPS诱导的ARDS。liriodendrin通过Nrf‐2磷酸化调节抗氧化反应和铁吊标志物的能力突出了其作为治疗ARDS的治疗药物的潜力。
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引用次数: 0
A Multibiomarker Approach to Delineate the Toxicity of Methoxyfenozide on Oncorhynchus mykiss 多生物标志物方法研究甲氧虫酰肼对夜蛾的毒性
IF 3.2 3区 医学 Q2 ENVIRONMENTAL SCIENCES Pub Date : 2025-08-22 DOI: 10.1002/tox.24562
Tarek Fakhereddin, Demet Dogan

Methoxyfenozide is a diacylhydrazine-class insect growth regulator functioning as an ecdysone receptor agonist and inducing premature and lethal molt in susceptible larvae. This investigation was conducted to evaluate the impact of methoxyfenozide-based commercial insecticide BYPASS on multiple end points in tissues of juvenile Oncorhynchus mykiss following 7, 14, and 21 days of exposure to sublethal concentrations of 0.042, 0.21, and 0.42 mg/L. There was not any significant change in CF and/or HSI. The treatment resulted in diminished AChE activity in brain and muscle together with a significant decline in Na+, K+-ATPase in gill and kidney tissues. The increase in the activities of antioxidant enzymes was followed by elevated levels of TBARS and PC throughout the experiment in all tissues, proving the status of oxidative stress. It is supported by the observed increase in 8-OHdG level following 21 days of exposure. Caspase-3 activity rose in a tissue-specific manner indicating the initiation of apoptosis via the mitochondrial pathway. Multi-biomarker responses showed concentration-dependent effects in calculated indexes as well as higher biomarker scores for antioxidant enzymes. Overall, the neurotoxic potential and pro-oxidant activity of BYPASS, along with its potency to cause DNA damage, apoptosis, and to disrupt osmoregulation, were revealed. The outcomes manifest the first experimental sublethal effects caused by methoxyfenozide in tissues of O. mykiss , increasing our understanding of the risk insecticides represent and the need for strict regulatory scrutiny to mitigate the risk for non-target organisms.

甲氧虫酰肼是一种二酰基肼类昆虫生长调节剂,作为蜕皮激素受体激动剂,可诱导易感幼虫过早和致死性蜕皮。本研究旨在评估以甲氧虫酰肼为基础的商业杀虫剂BYPASS在暴露于0.042、0.21和0.42 mg/L亚致死浓度7天、14天和21天后对绿吻Oncorhynchus mykiss幼鱼组织多个终点的影响。CF和/或HSI没有明显变化。治疗导致脑和肌肉中乙酰胆碱酯酶活性降低,同时鳃和肾脏组织中Na+、K+‐atp酶显著下降。在整个实验过程中,各组织中抗氧化酶活性的升高伴随着TBARS和PC水平的升高,证明了氧化应激状态。暴露21天后8‐OHdG水平的升高也证实了这一点。Caspase‐3活性以组织特异性的方式上升,表明凋亡通过线粒体途径开始。多生物标志物反应在计算指标中显示出浓度依赖效应,抗氧化酶的生物标志物得分也较高。总的来说,我们揭示了BYPASS的神经毒性和促氧化活性,以及它引起DNA损伤、细胞凋亡和破坏渗透调节的能力。研究结果首次证实了甲氧虫酰肼对麦吻蝽组织的亚致死效应,增加了我们对杀虫剂所代表的风险的理解,以及对降低非目标生物风险的严格监管审查的必要性。
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引用次数: 0
Intravenous Administration of Liposomes Encapsulating Oleanolic Acid Ameliorates Lung Injury Caused by Air Pollutants 静脉注射齐墩果酸脂质体可改善空气污染物引起的肺损伤
IF 3.2 3区 医学 Q2 ENVIRONMENTAL SCIENCES Pub Date : 2025-08-22 DOI: 10.1002/tox.24564
Rioko Funayama, Aeri Toratani, Yui Uehara, Reno Kinoshita, Moeka Shimada, Rion Imai, Mikako Shimoda, Masahiro Kawahara, Susumu Hama, Ken-ichiro Tanaka

Health problems caused by air pollutants, such as fine particulate matter, are becoming more prevalent worldwide, and there is an urgent need to develop prevention and treatment strategies to combat this increase. A main mechanism by which air pollutants cause health problems is by entering the respiratory system and increasing oxidative stress. Oleanolic acid (OA) is a natural pentacyclic triterpenoid compound found in various plants that exhibits many physiological effects, including antioxidant, anticancer, and anti-inflammatory effects. However, the effect of OA on lung injury caused by air pollutants has not been reported. We therefore analyzed the effect of OA using a mouse model of particulate matter (PM)-induced lung injury. Oral administration of OA (5–80 mg/kg) to male ICR mice suppressed PM-induced increases in inflammatory cell counts, protein levels, and dsDNA levels in bronchoalveolar lavage fluid; however, the effects were not significant. We therefore analyzed the efficacy of intravenous administration using OA encapsulated in polyethylene glycol-modified liposomes (OA-Lipo). Intravenous administration of OA-Lipo (20–100 μg/kg) was more effective against PM-induced lung injury at lower doses than oral administration. OA-Lipo also significantly suppressed increased expression of inflammatory cytokines and chemokines and ROS production in PM-exposed mice. Furthermore, intravenous administration of OA-Lipo increased the expression of various antioxidant factors in the lungs of mice. Based on these results, we believe that OA-Lipo exerts an antioxidant effect by increasing the expression of various antioxidant factors, thereby preventing the development of lung injury caused by air pollutants.

空气污染物(如细颗粒物)造成的健康问题在世界范围内日益普遍,迫切需要制定预防和治疗战略,以遏制这种增加。空气污染物引起健康问题的主要机制是通过进入呼吸系统并增加氧化应激。齐墩果酸(OA)是一种天然的五环三萜化合物,存在于多种植物中,具有多种生理作用,包括抗氧化、抗癌和抗炎作用。然而,OA对空气污染物所致肺损伤的影响尚未见报道。因此,我们使用颗粒物质(PM)诱导的肺损伤小鼠模型分析OA的作用。雄性ICR小鼠口服OA (5-80 mg/kg)可抑制PM诱导的支气管肺泡灌洗液中炎症细胞计数、蛋白水平和dsDNA水平的增加;然而,效果并不显著。因此,我们分析了用聚乙二醇修饰脂质体(OA‐Lipo)包裹OA静脉给药的疗效。低剂量静脉给药OA - Lipo (20-100 μg/kg)比口服给药对PM诱导的肺损伤更有效。OA‐Lipo还显著抑制PM暴露小鼠炎症细胞因子和趋化因子的表达以及ROS的产生。此外,静脉给药OA‐Lipo增加了小鼠肺部各种抗氧化因子的表达。基于这些结果,我们认为OA‐Lipo通过增加各种抗氧化因子的表达来发挥抗氧化作用,从而防止空气污染物引起的肺损伤的发展。
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引用次数: 0
Toxicity Assessment of Environmental Concentrations of Ciprofloxacin in the Gills and Kidney of a Neotropical Catfish 新热带鲶鱼鳃和肾中环丙沙星环境浓度的毒性评价。
IF 3.2 3区 医学 Q2 ENVIRONMENTAL SCIENCES Pub Date : 2025-08-19 DOI: 10.1002/tox.24560
Lucicleide Ângelo Silva Jungles de Carvalho, Maiara Vicentini, Laís Fernanda Oya-Silva, Maritana Mela Prodocimo, Julio Cesar Moreira Brito, Tarcio Teodoro Braga, Marta Margarete Cestari, Helena Cristina Silva de Assis

Antibiotics are frequently detected in aquatic environments, yet their effects on aquatic biota remain poorly understood. This study evaluated the toxic effects of long-term (28 days) exposure of Rhamdia quelen to environmentally relevant concentrations of ciprofloxacin (1, 10, and 100 μg L−1), focusing on the gills and posterior kidney. After the exposure period, the fish were anesthetized and euthanized. Gills were collected for biochemical and histopathological biomarker analysis. The posterior kidney was sampled for biochemical, genotoxic, and histopathological biomarkers, as well as for the evaluation of apoptosis, cell necrosis, and the incidence of melanomacrophage centers (MMC). Results showed oxidative stress in the gills of both male and female fish. Exposure to 10 and 100 μg L−1 CIP induced epithelial alterations in the gills in a concentration-dependent manner in both sexes. In the kidney, CIP exposure caused DNA damage and necrosis in females. At 10 μg L−1, CIP disrupted the normal histoarchitecture of the renal parenchyma, and at 100 μg L−1, necrosis was observed in both sexes. Exposure to 10 and 100 μg L−1 also led to an increase in MMC. These findings indicate that contamination of aquatic habitats with antibiotics such as CIP is an environmental concern. In addition to affecting target organisms, such contaminants may have sublethal effects on fish that could extend to higher ecological levels.

在水生环境中经常检测到抗生素,但对其对水生生物群的影响仍知之甚少。本研究评估了长期(28天)暴露于环境相关浓度的环丙沙星(1、10和100 μg L-1)对鼠黄的毒性作用,重点是鳃和后肾。暴露期后,鱼被麻醉并实施安乐死。收集鳃进行生化和组织病理学生物标志物分析。采集后肾的生化、基因毒性和组织病理学生物标志物,以及评估细胞凋亡、细胞坏死和黑色素巨噬细胞中心(MMC)的发生率。结果表明,雄鱼和雌鱼的鳃都存在氧化应激。暴露于10和100 μg L-1的CIP中,两性鱼鳃上皮呈浓度依赖性改变。在肾脏中,CIP暴露导致女性DNA损伤和坏死。10 μg L-1时,CIP破坏肾实质的正常组织结构,100 μg L-1时,两性均出现坏死。暴露于10和100 μg L-1也导致MMC增加。这些发现表明,CIP等抗生素污染水生栖息地是一个环境问题。除了影响目标生物外,这些污染物还可能对鱼类产生亚致死效应,并可能扩展到更高的生态水平。
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引用次数: 0
Toxicity of Commonly Used Plasticizers to the Freshwater Organisms Tilapia sparrmanii (Fish) and Caridina nilotica (Shrimp): Lethal and Sublethal Effects 常用增塑剂对淡水生物罗非鱼和虾的毒性:致死性和亚致死性作用。
IF 3.2 3区 医学 Q2 ENVIRONMENTAL SCIENCES Pub Date : 2025-08-19 DOI: 10.1002/tox.24563
Paul Kojo Mensah, Neil John Griffin, Ntombekhaya Mgaba, Margaret Fafa Awushie Akwetey, Oghenekaro Nelson Odume

The toxicity of microplastics in aquatic environments is usually due to plasticizers, the chemical additives that keep the plastic polymers together. Thus, the current study reports on the toxicity of three common plasticizers found in freshwater ecosystems and their impacts on two South African freshwater organisms at the organismal and biochemical levels. Tilapia sparrmanii (fish) and Caridina nilotica (shrimp) were exposed to varying concentrations of the test plasticizers, including bisphenol-A (BPA), calcium stearate (CAS), and dibutyl phthalate (DBP). The impacts of these plasticizers on mortality and biomarkers (acetylcholinesterase activity and lipid peroxidation) were investigated using 96-h short-term static nonrenewal and 21-day long-term static renewal exposure methods, respectively. All experiments were conducted in temperature-controlled rooms. Mortality was determined after 96 h, while biochemical effects were measured after 21 days. The results revealed that all three plasticizers significantly affected the mortality of both organisms. Also, acetylcholinesterase activity per unit protein in shrimp decreased significantly at all levels of exposure, while lipid peroxidation increased significantly at all levels of exposure. This study has shown that short-term and long-term exposures to the tested plasticizers could adversely impact populations of the tested organisms at both the organismal and biochemical levels.

微塑料在水生环境中的毒性通常是由于增塑剂,一种使塑料聚合物保持在一起的化学添加剂。因此,目前的研究报告了在淡水生态系统中发现的三种常见增塑剂的毒性及其在生物和生物化学水平上对两种南非淡水生物的影响。罗非鱼(鱼)和尼罗提卡鱼(虾)暴露在不同浓度的测试增塑剂中,包括双酚a (BPA)、硬脂酸钙(CAS)和邻苯二甲酸二丁酯(DBP)。分别采用96 h短期静态不更新和21 d长期静态更新暴露方法,研究了这些增塑剂对死亡率和生物标志物(乙酰胆碱酯酶活性和脂质过氧化)的影响。所有实验均在温控室内进行。96 h后测定死亡率,21 d后测定生化效应。结果显示,这三种增塑剂对两种生物的死亡率都有显著影响。各暴露水平下,对虾单位蛋白乙酰胆碱酯酶活性显著降低,脂质过氧化水平显著升高。这项研究表明,短期和长期暴露于所测试的增塑剂可能在生物和生化水平上对被测试生物种群产生不利影响。
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引用次数: 0
Integrated Use of Oxidative Stress and Histological Biomarkers of T. tinca as Indicators of 17-Alpha-Ethynylestradiol Exposure 结合氧化应激和组织学生物标志物作为17- α -乙炔雌醇暴露的指标。
IF 3.2 3区 医学 Q2 ENVIRONMENTAL SCIENCES Pub Date : 2025-08-15 DOI: 10.1002/tox.24557
Ana L. Oropesa, Alfonso Ramos, Cesar Fallola, Luis J. Gomez

The potential adverse effects of 17-alpha-ethynylestradiol (50, 100, and 500 μg EE2/kg b.w., for 30 days) on tench ( Tinca tinca ) were evaluated by integrating biomarkers including physiological (hepato-somatic index, spleen-somatic index, and hematocrit), oxidative stress (catalase, glutathione peroxidase, and glutathione reductase activities; total glutathione level, and lipid peroxidation), metabolic (glutathione S-transferase activity), as well as histopathological (descriptive and analytical studies) responses. The general health status of the EE2-exposed tench was disturbed based on the increase of somatic indices at high tested doses, and the development of anemia in all exposed individuals. Effective control of reactive oxygen species by the antioxidant defense system of the tench exposed to EE2 should have occurred because the lipid peroxidation process was irrelevant. Histopathological study revealed the presence of regressive changes in the liver (vacuolar degeneration, and deposits of eosinophilic material), regressive (deposits of eosinophilic material), and progressive (hyperplasia of reticuloendothelial cells) changes in the spleens of exposed fish. The severity of some lesions was dose dependent. The identified injuries did not compromise the functions of these organs. Finally, a common pattern of correlation between parameters of oxidative stress and morphological changes was not detected in the current study.

采用生理指标(肝体指数、脾体指数、红细胞压积)、氧化应激(过氧化氢酶、谷胱甘肽过氧化物酶和谷胱甘肽还原酶活性)评价17- α -乙炔雌二醇(50、100和500 μg EE2/kg b.w,连续30 d)对田鼠(Tinca Tinca)的潜在不良影响;总谷胱甘肽水平和脂质过氧化),代谢(谷胱甘肽s -转移酶活性)以及组织病理学(描述性和分析性研究)反应。在高剂量下,ee2暴露个体的躯体指标增加,并出现贫血,从而影响了暴露个体的总体健康状况。由于脂质过氧化过程不相关,暴露于EE2的海胆的抗氧化防御系统对活性氧的有效控制应该已经发生。组织病理学研究显示,暴露的鱼肝脏出现退行性变化(空泡变性和嗜酸性物质沉积),脾脏出现退行性变化(嗜酸性物质沉积)和进行性变化(网状内皮细胞增生)。一些病变的严重程度是剂量依赖性的。发现的损伤并没有损害这些器官的功能。最后,在目前的研究中,氧化应激参数和形态学变化之间没有发现共同的相关模式。
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引用次数: 0
Sublethal Exposure to a Chlorpyrifos-Cypermethrin Mixture Disrupts Limb Development and Causes Severe Skeletal Abnormalities in Domestic Chick Embryos 亚致死暴露于毒死蜱-氯氰菊酯混合物会破坏家禽胚胎的肢体发育并导致严重的骨骼异常。
IF 3.2 3区 医学 Q2 ENVIRONMENTAL SCIENCES Pub Date : 2025-08-05 DOI: 10.1002/tox.24558
Shashikant Sharma, Juhi Vaishnav, Pooja Raval, Suresh Balakrishnan

This study examines the teratogenic effects of a sublethal dose (0.1 ppm) of a combination insecticide containing 50% chlorpyrifos (CP) and 5% cypermethrin (CM) on chick embryo limb development, revealing severe skeletal abnormalities and disruptions in key molecular pathways. Early-stage defects, including reduced somite numbers and abnormal somite patterning, were observed by day 2, with prominent limb deformities, such as limb shortening and twisted digits, emerging by days 10 and 21. X-ray analysis confirmed skeletal anomalies, while Alcian blue-Alizarin red staining revealed malformed cartilage and bone structures. Gene and protein expression analyses showed significant downregulation of Sonic hedgehog (SHH), Fibroblast Growth Factors (FGF10, FGF8), and WNT7A, leading to impaired digit formation and limb elongation. HOX genes (HOXA11, HOXD11) were initially upregulated but later downregulated, disrupting limb segment identity. Additionally, downregulation of Tbx4 and Pitx1 contributed to hindlimb malformations. Dysregulation of CASPASE3 impaired apoptosis, resulting in defective digit separation. Molecular docking studies indicated strong binding affinities of CP and CM to SHH, FGF10, WNT7A, and HOX proteins, suggesting interference with these signaling pathways. Notably, the disruption of the SHH-FGF-WNT axis, essential for limb patterning, was a key driver of these defects. Biochemical assays further revealed reduced hydroxyproline content, indicating impaired collagen synthesis. These findings highlight severe disruptions in SHH, FGF, WNT, HOX, Tbx4, and Pitx1 pathways, emphasizing the need for stricter pesticide regulations to prevent congenital limb malformations.

本研究考察了含有50%毒死蜱(CP)和5%氯氰菊酯(CM)的亚致死剂量(0.1 ppm)的组合杀虫剂对鸡胚胎肢体发育的致畸作用,揭示了严重的骨骼异常和关键分子途径的中断。第2天观察到早期缺陷,包括体体数量减少和体体图案异常,第10天和第21天出现明显的肢体畸形,如肢体缩短和手指扭曲。x射线分析证实骨骼异常,而阿利新蓝-茜素红染色显示软骨和骨结构畸形。基因和蛋白表达分析显示,Sonic hedgehog基因(SHH)、成纤维细胞生长因子(FGF10、FGF8)和WNT7A显著下调,导致手指形成和肢体伸长受损。HOX基因(HOXA11, HOXD11)最初上调,但随后下调,破坏肢体节段识别。此外,Tbx4和Pitx1的下调导致后肢畸形。CASPASE3的失调会损害细胞凋亡,导致手指分离缺陷。分子对接研究表明,CP和CM与SHH、FGF10、WNT7A和HOX蛋白具有很强的结合亲和性,表明它们可能干扰这些信号通路。值得注意的是,对肢体形成至关重要的SHH-FGF-WNT轴的破坏是这些缺陷的关键驱动因素。生化分析进一步显示羟基脯氨酸含量降低,表明胶原合成受损。这些发现强调了SHH、FGF、WNT、HOX、Tbx4和Pitx1通路的严重破坏,强调了需要更严格的农药法规来预防先天性肢体畸形。
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引用次数: 0
Cadmium-Induced Mitochondrial and MAMs Dysregulation in Rat Testis: The Protective Role of D-Aspartate 镉诱导大鼠睾丸线粒体和MAMs失调:d -天冬氨酸的保护作用。
IF 3.2 3区 医学 Q2 ENVIRONMENTAL SCIENCES Pub Date : 2025-08-04 DOI: 10.1002/tox.24559
Debora Latino, Sara Falvo, Massimo Venditti, Alessandra Santillo, Giulia Grillo, Gabriella Chieffi Baccari, Imed Messaoudi, Maria Maddalena Di Fiore

Cadmium (Cd), a heavy metal, disrupts the structure of seminiferous tubules and induces cell death at multiple stages of sperm development. Cd also impairs Leydig cells (LCs), resulting in reduced serum testosterone (T) levels. This study primarily examined the impact of Cd on the mitochondrial compartment and mitochondrial-associated endoplasmic reticulum membranes (MAMs) in rat testis. Additionally, the potential of D-aspartate (D-Asp) to mitigate Cd-induced effects on steroidogenesis and spermatogenesis was assessed by administering D-Asp simultaneously or preventively with Cd. The findings demonstrated that Cd exerts reprotoxicity by affecting the mitochondrial compartment and MAMs, evidenced by an imbalance in mitochondrial dynamics, impaired mitophagy pathway, and downregulated mitochondrial biogenesis. Cd exposure also reduced lipid transfer-related factor expression and increased ER stress. Moreover, elevated levels of Ca2+ transfer-related proteins, indicative of perturbed Ca2+ homeostasis, may be associated with enhanced oxidative stress and apoptosis, which are known effects of Cd. Immunofluorescent analysis revealed that the Cd-induced mitochondrial and MAMs damage was prominent in LCs, spermatocytes, and spermatids, confirming the metal's adverse effects on steroidogenesis and spermatogenesis. Conversely, co-administration or preventive administration of D-Asp with Cd preserved mitochondrial homeostasis and functional ER-mitochondria interactions. In conclusion, the study offers novel insights into the cellular mechanisms underlying Cd-induced reprotoxicity. Importantly, it highlights the efficacy of D-Asp in preventing or counteracting testicular damage caused by Cd by enhancing mitochondrial and MAMs functionality.

镉(Cd)是一种重金属,会破坏精小管的结构,并在精子发育的多个阶段诱发细胞死亡。Cd也损害间质细胞(LCs),导致血清睾酮(T)水平降低。本研究主要研究了镉对大鼠睾丸线粒体室和线粒体相关内质网膜(MAMs)的影响。此外,d-天冬氨酸(D-Asp)通过与Cd同时或预防性给药来评估其减轻Cd诱导的甾体生成和精子发生效应的潜力。研究结果表明,Cd通过影响线粒体室和MAMs来发挥生殖毒性,这可以通过线粒体动力学失衡、线粒体自噬途径受损和线粒体生物发生下调来证明。Cd暴露也降低了脂质转移相关因子的表达,增加了内质网应激。此外,Ca2+转移相关蛋白水平的升高,表明Ca2+稳态受到干扰,可能与氧化应激和细胞凋亡的增强有关,这是已知的镉的影响。免疫荧光分析显示,镉诱导的线粒体和MAMs损伤在lc、精母细胞和精子细胞中很突出,证实了金属对类固醇形成和精子发生的不利影响。相反,D-Asp与Cd的共同给药或预防性给药可保持线粒体稳态和er -线粒体功能相互作用。总之,该研究为cd诱导生殖毒性的细胞机制提供了新的见解。重要的是,它强调了D-Asp通过增强线粒体和MAMs功能来预防或抵消Cd引起的睾丸损伤的功效。
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引用次数: 0
Determination of the Elemental Impurity Levels in Different Mushroom Species and Probabilistic Risk Assessment 不同菌种中元素杂质含量测定及概率风险评估。
IF 3.2 3区 医学 Q2 ENVIRONMENTAL SCIENCES Pub Date : 2025-08-01 DOI: 10.1002/tox.24556
İsmail Acar, Fadime Canbolat, Faruk Ayata

Mushroom cultivation and traditional mushroom procurement are widespread worldwide. Therefore, it is important to determine the extent of the risk of heavy metal exposure by consuming wild edible mushrooms. The aim of this study was to determine the levels of four elemental impurities (Cd, Pb, As, and Hg) in edible mushroom species (Macrolepiota mastoidea, Bovista aestivalis, Tricholoma fracticum, Helvella sp., and Rhizopogon roseolus) collected from Çanakkale and Van regions of Türkiye and to investigate potential health risks. For elemental impurity analysis, 0.3 g dry samples of mushrooms collected in Çanakkale and Van provinces between 2022 and 2023 were weighed and analyzed by inductively coupled plasma-mass spectrometry (ICP-MS). Target hazard quotient (THQ) was calculated for non-carcinogenic risk assessment in children and adults, followed by hazard index (HI) for each mushroom. Carcinogenic risk (CR) was determined. Probabilistic total THQ and total CR in children and adults were calculated using the Monte Carlo simulation method. Cd levels in five mushroom species ranged between 11.19–4838.71 μg/kg, Pb levels between 495.43 and 2836.81 μg/kg, As levels between 3267.52 and 25823.07 μg/kg, and Hg levels between 0.00 and 1594.50 μg/kg. The non-carcinogenic risk potential of As level was observed in all mushroom samples. THQ value was found to be greater than 1. These values also affected the HI value in all mushrooms; the latter was also greater than 1. Since As was detected in all mushrooms in the study and the CR value of this risk element was at a level that may pose a potential carcinogenic hazard, a potential health risk in adults and children can be noted. Furthermore, the Monte Carlo simulation showed that the health risks due to elemental impurity accumulation in mushrooms may increase significantly in children and adults, causing serious health problems. Children are more severely affected by elemental impurity concentrations than adults, especially considering their body weight, which makes it necessary to take protective measures.

蘑菇种植和传统的蘑菇采购在世界各地都很普遍。因此,确定食用野生食用菌的重金属暴露风险程度是很重要的。本研究的目的是测定从 rkiye Çanakkale和Van地区采集的食用菌种(Macrolepiota mastoidea、Bovista aestivalis、Tricholoma fracticum、Helvella sp.和Rhizopogon roseolus)中的四种元素杂质(Cd、Pb、As和Hg)的含量,并调查其潜在的健康风险。为了进行元素杂质分析,对2022年至2023年间在Çanakkale和Van省采集的0.3 g干蘑菇样品进行称重,并通过电感耦合等离子质谱(ICP-MS)进行分析。计算儿童和成人非致癌性风险评估的目标危害商(THQ),然后计算每种蘑菇的危害指数(HI)。测定致癌风险(CR)。采用蒙特卡罗模拟法计算儿童和成人的概率总THQ和总CR。5种蘑菇Cd含量在11.19 ~ 4838.71 μg/kg之间,Pb含量在495.43 ~ 2836.81 μg/kg之间,As含量在3267.52 ~ 25823.07 μg/kg之间,Hg含量在0.00 ~ 1594.50 μg/kg之间。在所有蘑菇样品中均观察到砷含量的非致癌风险潜力。发现THQ值大于1。这些数值也影响了所有蘑菇的HI值;后者也大于1。由于在研究中所有蘑菇中都检测到As,并且该风险因素的CR值处于可能构成潜在致癌危害的水平,因此可以注意到成人和儿童的潜在健康风险。此外,蒙特卡罗模拟表明,蘑菇中元素杂质积累对儿童和成人的健康风险可能显著增加,造成严重的健康问题。儿童受元素杂质浓度的影响比成人更严重,特别是考虑到他们的体重,因此有必要采取保护措施。
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引用次数: 0
RETRACTION: Machine Learning Analysis of Oxidative Stress‐Related Phenotypes for Specific Gene Screening in Ovarian Cancer 摘自:氧化应激相关表型的机器学习分析用于卵巢癌的特定基因筛选
IF 4.5 3区 医学 Q2 ENVIRONMENTAL SCIENCES Pub Date : 2025-07-15 DOI: 10.1002/tox.24555
RETRACTION: C. Pan, C. Pan, L. Chen, and A. Lin, “,” Environmental Toxicology 39, no. (2024): 47634775, https://doi.org/10.1002/tox.24321.The above article, published online on 20 August 2024 in Wiley Online Library (http://onlinelibrary.wiley.com/), has been retracted by agreement between the authors; the journal Editor‐in‐Chief, April Rodd; and John Wiley & Sons, Inc. Following an investigation by the publisher, the parties have concluded that the true authorship of the article has come under question. Therefore, upon request of the authors, the article has been retracted.
引用本文:潘志明,陈丽丽,林爱玲,“环境毒理学”,第39期。(2024): 4763-4775, https://doi.org/10.1002/tox.24321.The上述文章于2024年8月20日在线发表于Wiley online Library (http://onlinelibrary.wiley.com/),经作者同意撤回;杂志主编,April Rodd;约翰·威利&;儿子,Inc。在出版商进行调查后,双方得出结论,这篇文章的真实作者身份受到质疑。因此,应作者的要求,这篇文章已被撤回。
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引用次数: 0
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Environmental Toxicology
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