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Metabolomics approach to evaluate diclazuril-induced developmental toxicity in zebrafish embryo 用代谢组学方法评价双唑利对斑马鱼胚胎的发育毒性
IF 4.1 2区 环境科学与生态学 Q1 MARINE & FRESHWATER BIOLOGY Pub Date : 2025-02-01 DOI: 10.1016/j.aquatox.2025.107238
Veena Jain , Ved Prakash , Garima Sagar , Alok Kumar , Pankaj Ramji Jagdale , Anjaneya Ayanur , Sadasivam Anbumani , Somendu Kumar Roy
Anticoccidials, commonly used in veterinary medicine to treat coccidiosis in food-producing animals, particularly in poultry farming, are associated with potential environmental risks due to their excretion in manure and subsequent land-spreading. Diclazuril, a widely used anticoccidial, has been detected in groundwater, raising concerns about its impact on non-target species. This study investigates the developmental toxicity of diclazuril in zebrafish embryos over a 96-hour exposure period, utilizing biomarkers such as oxidative stress indicators and metabolomic profiles. The acute toxicity assessment determined an LC50 of 255 µg/L for diclazuril. Observed sublethal effects included pericardial edema, curved spine, and yolk sac edema, which worsened with increasing concentrations from 106 µg/L to 515 µg/L. Based on the Lowest Observed Adverse Effect Level (LOAEL), further experiments were conducted at concentrations of 50 µg/L, 100 µg/L, and 200 µg/L. Significant increases in reactive oxygen species (ROS) were noted at 100 µg/L and 200 µg/L, alongside notable reduction in superoxide dismutase (SOD) and glutathione S-transferase (GST) activities at concentrations ≥100 µg/L, while no significant changes observed in catalase (CAT) activity. Metabolomic analysis using GC–MS/MS revealed significant disturbances in pathways such as pyruvate metabolism, the citric acid cycle, and amino acid metabolism, indicating potential mitochondrial dysfunction in groups exposed to concentrations ≥100 µg/L. Furthermore, alterations in histological lesions in brain region and altered neurotransmitter activity suggests possible neurobehavioral disorders. Increased oxidative stress, along with decreased ATP and NADH levels, points to mitochondrial dysfunction, which is further supported by ultrastructural analysis and locomotor behavior confirming mitochondrial disruption. The disruption of cellular energetics is likely a key factor contributing to the neurotoxic effects observed in zebrafish embryos exposed to ≥100 µg/L of diclazuril.
抗球虫药通常在兽药中用于治疗食用动物(特别是家禽养殖)的球虫病,由于它们在粪便中排泄并随后在土地上扩散,因此与潜在的环境风险有关。在地下水中发现了广泛使用的抗球虫药迪拉齐利,这引起了人们对其对非目标物种影响的担忧。本研究利用氧化应激指标和代谢组学特征等生物标志物,研究了双硫珠在斑马鱼胚胎中暴露96小时的发育毒性。急性毒性评价结果表明,双唑利的LC50为255µg/L。观察到的亚致死效应包括心包水肿、脊柱弯曲和卵黄囊水肿,随着浓度从106µg/L增加到515µg/L而恶化。根据最低观察到的不良影响水平(LOAEL),在50µg/L、100µg/L和200µg/L的浓度下进行进一步的实验。在100µg/L和200µg/L浓度下,活性氧(ROS)显著增加,超氧化物歧化酶(SOD)和谷胱甘肽s -转移酶(GST)活性显著降低,过氧化氢酶(CAT)活性无显著变化。使用GC-MS /MS进行的代谢组学分析显示,丙酮酸代谢、柠檬酸循环和氨基酸代谢等途径存在显著紊乱,表明暴露于浓度≥100 μ g/L的组可能存在线粒体功能障碍。此外,脑组织病变的改变和神经递质活性的改变提示可能存在神经行为障碍。氧化应激增加,ATP和NADH水平下降,表明线粒体功能障碍,超微结构分析和运动行为进一步证实了线粒体破坏。对细胞能量的破坏可能是斑马鱼胚胎暴露于≥100µg/L的地祖里所观察到的神经毒性效应的关键因素。
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引用次数: 0
Ingestion of polyethylene microplastics impacts cichlid behaviour despite having low retention time
IF 4.1 2区 环境科学与生态学 Q1 MARINE & FRESHWATER BIOLOGY Pub Date : 2025-02-01 DOI: 10.1016/j.aquatox.2025.107248
Miguel Eduardo L. Felismino, Ségolène Chevallier Rufigny, Samuel Evan Gonzalez-Fleurant, Grant E. Brown
Microplastics, particles between 0.001 and 5 mm in diameter, are ubiquitous in the environment and their consumption by aquatic organisms is known to lead to a variety of adverse effects. However, studies on the effects of microplastics on prey fish have not shown consistent trends, with results varying across species and plastic type used. Here, we manipulated the levels of microplastic (MP) exposure among juvenile convict cichlids (Archocentrus nigrofasciatus) by feeding them brine shrimp (Artemia spp.) exposed to 0, 10, or 100 MP ml-1 of virgin polyethylene microspheres (10–20 μm) for a 10-day period. We then tested groups of 3 cichlids in a 2-day maze trial, in which we measured the latency to explore and time to complete a novel maze. We found no impacts of microplastic exposure on foraging rate, growth, or competitive aggression. However, our results demonstrate that microplastics exposure shaped exploratory behaviour and maze performance. Despite these effects, we found very little microplastics remaining in the fish's bodies after the experiment. A companion experiment demonstrates that most plastic particles were egested within 24 h. Our current results show that pristine microplastics at non-lethal levels have consequences on cichlid behaviour and decision-making but not growth.
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引用次数: 0
Size-specific mediation of the physiological responses and degradation ability of microalgae to sulfamerazine by microplastics
IF 4.1 2区 环境科学与生态学 Q1 MARINE & FRESHWATER BIOLOGY Pub Date : 2025-02-01 DOI: 10.1016/j.aquatox.2025.107257
Xinlei Wang , Min Lv , Jin Liu , Mingtao Ba , Mingsan Man , Kun Yin , Jing Ding , Xianbo Chang , Lingxin Chen
Antibiotics and microplastics (MPs) are two classes of emerging contaminants that are commonly found in various water environments. However, how different sized MPs affect the toxicity and biodegradation of antibiotics remains poorly understood. We investigated the effects of polystyrene (PS) MPs with different particle sizes (100 nm and 30 μm) on the physiological responses and degradation behavior of Phaeodactylum tricornutum to sulfamerazine (SMR). Results showed that microalgae growth was inhibited by SMR, and MPs especially those of smaller size exacerbated the inhibitory effects of SMR on microalgae, including decreasing the content of chlorophyll a, carotenoids, malondiadehyde and superoxide dismutase activity. MPs exhibited low adsorption towards SMR, and MPs especially 30 μm MPs strengthened SMR photodegradation through leaching more organic chemicals. In comparison, 100 nm MPs obstructed the light, resulting in insignificant effects on photodegradation. Apart from photodegradation, SMR could be bioaccumulated and biodegraded by microalgae, and biodegradation was the main removal mechanism. The overall influence of MPs on SMR degradation by microalgae was a balance of the promotion on photodegradation and negative effects on microalgae growth, with the degradation efficiency and rate of SMR significantly lower in treatment of 100 nm MPs (0.0128 ± 0.0012 day−1, 30.13 ± 0.36 %) than treatments without MPs (0.0155 ± 0.0011 day−1, 32.90 ± 3.11 %) or with 30 μm MPs (0.0165 ± 0.0013 day−1, 34.46 ± 2.52 %). Overall, this study reveals the size-specific effects of MPs on the toxicity and degradation behavior of SMR, providing novel insights into the combined effects of SMR and MPs.
{"title":"Size-specific mediation of the physiological responses and degradation ability of microalgae to sulfamerazine by microplastics","authors":"Xinlei Wang ,&nbsp;Min Lv ,&nbsp;Jin Liu ,&nbsp;Mingtao Ba ,&nbsp;Mingsan Man ,&nbsp;Kun Yin ,&nbsp;Jing Ding ,&nbsp;Xianbo Chang ,&nbsp;Lingxin Chen","doi":"10.1016/j.aquatox.2025.107257","DOIUrl":"10.1016/j.aquatox.2025.107257","url":null,"abstract":"<div><div>Antibiotics and microplastics (MPs) are two classes of emerging contaminants that are commonly found in various water environments. However, how different sized MPs affect the toxicity and biodegradation of antibiotics remains poorly understood. We investigated the effects of polystyrene (PS) MPs with different particle sizes (100 nm and 30 μm) on the physiological responses and degradation behavior of <em>Phaeodactylum tricornutum</em> to sulfamerazine (SMR). Results showed that microalgae growth was inhibited by SMR, and MPs especially those of smaller size exacerbated the inhibitory effects of SMR on microalgae, including decreasing the content of chlorophyll a, carotenoids, malondiadehyde and superoxide dismutase activity. MPs exhibited low adsorption towards SMR, and MPs especially 30 μm MPs strengthened SMR photodegradation through leaching more organic chemicals. In comparison, 100 nm MPs obstructed the light, resulting in insignificant effects on photodegradation. Apart from photodegradation, SMR could be bioaccumulated and biodegraded by microalgae, and biodegradation was the main removal mechanism. The overall influence of MPs on SMR degradation by microalgae was a balance of the promotion on photodegradation and negative effects on microalgae growth, with the degradation efficiency and rate of SMR significantly lower in treatment of 100 nm MPs (0.0128 ± 0.0012 day<sup>−1</sup>, 30.13 ± 0.36 %) than treatments without MPs (0.0155 ± 0.0011 day<sup>−1</sup>, 32.90 ± 3.11 %) or with 30 μm MPs (0.0165 ± 0.0013 day<sup>−1</sup>, 34.46 ± 2.52 %). Overall, this study reveals the size-specific effects of MPs on the toxicity and degradation behavior of SMR, providing novel insights into the combined effects of SMR and MPs.</div></div>","PeriodicalId":248,"journal":{"name":"Aquatic Toxicology","volume":"279 ","pages":"Article 107257"},"PeriodicalIF":4.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143035193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Multigenerational effects of virgin and sampled plastics on the benthic macroinvertebrate Chironomus riparius 原始塑料和取样塑料对底栖大型无脊椎动物摇蚊(Chironomus riparius)的多代影响。
IF 4.1 2区 环境科学与生态学 Q1 MARINE & FRESHWATER BIOLOGY Pub Date : 2025-02-01 DOI: 10.1016/j.aquatox.2024.107205
Riccardo Sbarberi , Stefano Magni , Benedetta Ponti , Erica Tediosi , Maria Chiara Neri , Andrea Binelli
Although sediments are important reservoirs of plastics, most of the ecotoxicological studies on these contaminants are focused on the organisms living in the water column, while only a smaller number of evidence concerns the plastic impact on benthic species. Therefore, this study compared the multigenerational effects on the sediment-dwelling midge Chironomus riparius exposed to both virgin polystyrene microbeads (22,400–224,000 plastics/kg sediments dry weight), and plastic mixtures (40–420 plastics/kg dry weight) collected from four of the main tributaries of Po River (Ticino, Adda, Oglio and Mincio Rivers, Northern Italy) to evaluate the role played by other characteristics related to these physical contaminants in determining their toxicity as opposed to concentration alone. The modified Chironomid Life-Cycle Toxicity Test (OECD 233) was used to evaluate the multigenerational effects on the Emergence and Development Rates, Fecundity and Fertility. In addition, a biomarkers’ suite of cellular stress, neurotoxicity, and energetic metabolism was applied in the 2nd generation (2nd/3rd instar of larvae) to investigate the potential mechanisms associated to the apical effects. Our results showed no significant (p > 0.05) multigenerational effect for any of the endpoints tested for the virgin plastics’ exposures. Coherently, no significant effects on biomarkers were measured. Concerning the sampled plastics, the particles collected in Adda River instead induced a significant decrease (p < 0.05) of the Emergence Rate in the 2nd generation, suggesting that this parameter was the most susceptible among those measured. These results highlight that the different plethora of polymers, sizes and shapes of plastics sampled in natural ecosystems, compared to homogeneous characteristics of virgin polystyrene microbeads, appears to have considerable importance over concentration alone in determining the toxicity of these emerging contaminants.
尽管沉积物是塑料的重要储存库,但有关这些污染物的生态毒理学研究大多集中在水体生物上,只有较少的证据涉及塑料对底栖生物的影响。因此,本研究比较了从波河的四条主要支流(意大利北部的提契诺河、阿达河、奥廖河和明乔河)收集的原生聚苯乙烯微珠(22,400-224,000 个塑料/千克沉积物干重)和塑料混合物(40-420 个塑料/千克沉积物干重)对沉积物栖息蠓的多代影响,以评估与这些物理污染物相关的其他特征在决定其毒性方面所起的作用,而不仅仅是浓度。经修改的摇蚊生命周期毒性试验(OECD 233)被用来评估对新陈代谢率、生殖力和繁殖力的多代影响。此外,还在第二代幼虫(第二/三龄幼虫)中应用了一套细胞应激、神经毒性和能量代谢生物标志物,以研究与顶端效应相关的潜在机制。我们的研究结果表明,在接触原始塑料的情况下,对任何一个测试终点都没有明显的多代效应(p > 0.05)。同样,我们也没有测得对生物标志物的明显影响。关于取样塑料,在 Adda 河收集的颗粒反而导致第二代出现率显著下降(p < 0.05),这表明该参数是所测参数中最易受影响的。这些结果突出表明,与原始聚苯乙烯微珠的同质特性相比,在自然生态系统中采样的塑料具有不同的聚合物、尺寸和形状,这在确定这些新出现污染物的毒性方面似乎比浓度本身更重要。
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引用次数: 0
Tetrachlorantraniliprole induces neurodevelopmental toxicity through oxidative stress-mediated apoptosis and dysregulation of Wnt signaling pathway 四氯虫腈通过氧化应激介导的细胞凋亡和Wnt信号通路失调诱导神经发育毒性。
IF 4.1 2区 环境科学与生态学 Q1 MARINE & FRESHWATER BIOLOGY Pub Date : 2025-02-01 DOI: 10.1016/j.aquatox.2024.107229
Ru Guo , Youjuan Wu , Tingting Yu , Chen Guo , Zijia Yin , Guannan Zhao , Meifeng Li , Huiling Mao , Chengyu Hu , Xiaowen Xu
Tetrachlorantraniliprole (TCTP) is a novel bisamide insecticide and widely used to protect against lepidopteran insect species. However, the application of TCTP in rice fields often leads to water pollution, posing threats to aquatic organisms and potentially to human health. Few studies have assessed the toxic effects of TCTP on aquatic animals. In this study, we used zebrafish as a model organism to evaluate the toxicity of TCTP. Our findings indicated that TCTP adversely affected the development of zebrafish larvae, impacting parameters such as heart rate, body length, and pericardial edema. Exposure to TCTP resulted in the increased embryo mortality along with higher concentrations of the compound. The expression of neurodevelopment-related genes was inhibited in embryos exposed to TCTP. Hematoxylin and eosin (HE) staining revealed that TCTP caused damage to the brain cells of the embryos. Behavioral analysis showed a reduction in activity of the larvaes, which aligned with a decrease in acetylcholinesterase (AChE) activity. Additionally, RNA sequencing (RNA-seq) was employed to elucidate the mechanisms of toxicity. GO and KEGG analysis identified that the pathways were related to oxidative stress, apoptosis and Wnt signaling. We observed an increase of reactive oxygen species (ROS) and Ca²/Mg²-ATPase activity, while antioxidant enzyme activities (SOD, MDA, CAT, Na/K-ATPase and T-ATPase) were significantly decreased in TCTP-exposed groups. Furthermore, TCTP induced brain cells apoptosis, as evidenced by the upregulation of pro-apoptotic genes (bax, p53, TNFα, caspase3 and caspase9) and the downregulation of anti-apoptotic gene (bcl2). Moreover, TCTP increased the expression of genes involved in Wnt signaling pathway. Notably, oxidative stress and neuronal damage induced by TCTP could be mitigated by astaxanthin, an antioxidant. Additionally, IWR-1, an inhibitor of Wnt signaling pathway, effectively alleviated the upregulation of genes associated with TCTP treatment and inhibited oxidative stress-induced apoptosis. In conclusion, this study demonstrated TCTP-induced defects of neurodevelopment and the brain cells in zebrafish larvae which were primarily driven by oxidative stress-induced apoptosis and dysregulation of Wnt signaling pathway. Importantly, these toxic phenotypes can be rescued by treatment with astaxanthin or IWR-1.
四氯虫腈(TCTP)是一种新型双酰胺类杀虫剂,广泛用于鳞翅目昆虫的防治。然而,TCTP在稻田中的应用往往会导致水污染,对水生生物造成威胁,并对人体健康造成潜在威胁。很少有研究评估TCTP对水生动物的毒性作用。在本研究中,我们以斑马鱼为模型生物来评价TCTP的毒性。我们的研究结果表明,TCTP对斑马鱼幼虫的发育有不利影响,影响心率、体长和心包水肿等参数。暴露于TCTP导致胚胎死亡率随着化合物浓度的增加而增加。暴露于TCTP的胚胎中,神经发育相关基因的表达受到抑制。苏木精和伊红(HE)染色显示TCTP对胚胎脑细胞造成损伤。行为分析表明,幼虫活性降低,这与乙酰胆碱酯酶(AChE)活性降低一致。此外,RNA测序(RNA-seq)被用于阐明毒性机制。GO和KEGG分析发现这些通路与氧化应激、细胞凋亡和Wnt信号通路有关。我们观察到,tctp暴露组活性氧(ROS)和Ca²/Mg²- atp酶活性升高,而抗氧化酶(SOD、MDA、CAT、Na/ k - atp酶和t - atp酶)活性显著降低。此外,TCTP诱导脑细胞凋亡,其表现为促凋亡基因(bax、p53、TNFα、caspase3和caspase9)上调,抗凋亡基因(bcl2)下调。此外,TCTP增加了Wnt信号通路相关基因的表达。值得注意的是,虾青素可以减轻TCTP引起的氧化应激和神经元损伤。此外,Wnt信号通路抑制剂IWR-1可有效缓解TCTP治疗相关基因的上调,抑制氧化应激诱导的细胞凋亡。综上所述,本研究证明tctp诱导斑马鱼幼体神经发育和脑细胞缺陷主要由氧化应激诱导的细胞凋亡和Wnt信号通路失调驱动。重要的是,这些毒性表型可以通过虾青素或IWR-1治疗来挽救。
{"title":"Tetrachlorantraniliprole induces neurodevelopmental toxicity through oxidative stress-mediated apoptosis and dysregulation of Wnt signaling pathway","authors":"Ru Guo ,&nbsp;Youjuan Wu ,&nbsp;Tingting Yu ,&nbsp;Chen Guo ,&nbsp;Zijia Yin ,&nbsp;Guannan Zhao ,&nbsp;Meifeng Li ,&nbsp;Huiling Mao ,&nbsp;Chengyu Hu ,&nbsp;Xiaowen Xu","doi":"10.1016/j.aquatox.2024.107229","DOIUrl":"10.1016/j.aquatox.2024.107229","url":null,"abstract":"<div><div>Tetrachlorantraniliprole (TCTP) is a novel bisamide insecticide and widely used to protect against lepidopteran insect species. However, the application of TCTP in rice fields often leads to water pollution, posing threats to aquatic organisms and potentially to human health. Few studies have assessed the toxic effects of TCTP on aquatic animals. In this study, we used zebrafish as a model organism to evaluate the toxicity of TCTP. Our findings indicated that TCTP adversely affected the development of zebrafish larvae, impacting parameters such as heart rate, body length, and pericardial edema. Exposure to TCTP resulted in the increased embryo mortality along with higher concentrations of the compound. The expression of neurodevelopment-related genes was inhibited in embryos exposed to TCTP. Hematoxylin and eosin (HE) staining revealed that TCTP caused damage to the brain cells of the embryos. Behavioral analysis showed a reduction in activity of the larvaes, which aligned with a decrease in acetylcholinesterase (AChE) activity. Additionally, RNA sequencing (RNA-seq) was employed to elucidate the mechanisms of toxicity. GO and KEGG analysis identified that the pathways were related to oxidative stress, apoptosis and Wnt signaling. We observed an increase of reactive oxygen species (ROS) and Ca²/Mg²-ATPase activity, while antioxidant enzyme activities (SOD, MDA, CAT, Na/K-ATPase and T-ATPase) were significantly decreased in TCTP-exposed groups. Furthermore, TCTP induced brain cells apoptosis, as evidenced by the upregulation of pro-apoptotic genes (<em>bax, p53, TNFα, caspase3</em> and <em>caspase9</em>) and the downregulation of anti-apoptotic gene (<em>bcl2</em>). Moreover, TCTP increased the expression of genes involved in Wnt signaling pathway. Notably, oxidative stress and neuronal damage induced by TCTP could be mitigated by astaxanthin, an antioxidant. Additionally, IWR-1, an inhibitor of Wnt signaling pathway, effectively alleviated the upregulation of genes associated with TCTP treatment and inhibited oxidative stress-induced apoptosis. In conclusion, this study demonstrated TCTP-induced defects of neurodevelopment and the brain cells in zebrafish larvae which were primarily driven by oxidative stress-induced apoptosis and dysregulation of Wnt signaling pathway. Importantly, these toxic phenotypes can be rescued by treatment with astaxanthin or IWR-1.</div></div>","PeriodicalId":248,"journal":{"name":"Aquatic Toxicology","volume":"279 ","pages":"Article 107229"},"PeriodicalIF":4.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142913419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Arsenite-induced liver apoptosis via oxidative stress and the MAPK signaling pathway in marine medaka 亚砷酸盐通过氧化应激和MAPK信号通路诱导海洋medaka肝脏凋亡
IF 4.1 2区 环境科学与生态学 Q1 MARINE & FRESHWATER BIOLOGY Pub Date : 2025-02-01 DOI: 10.1016/j.aquatox.2024.107226
Jiangtian Lin , Ting Zhang , Li Zhang
Arsenic (As) is widely recognized for its hazards to aquatic organisms; however, its toxicological impacts on apoptosis in marine fish remain inadequately explored. This study investigated the effects of in vivo dietary exposure to 50 or 500 mg/kg AsIII (as NaAsO2) over 28 days in marine medaka, alongside in vitro exposure to 50–750 μg/L AsIII for 48 h in a hepatic cell line derived from marine medaka, to elucidate the toxicity and underlying molecular mechanisms. In vivo, As significantly accumulated in liver tissue (1.79-fold compared to the control), causing hepatic lesions and increased apoptosis (4.85 ± 0.56 % and 9.29 ± 1.82 %, respectively). Gene expression analysis showed downregulation of bcl2l1 and upregulation of bax, caspase-3 and caspase-9, indicating mitochondrial pathway-mediated apoptosis. In vitro, As exposure induced hepatocyte morphological changes, reactive oxygen species (ROS) production, and apoptosis. Additionally, mapk1 and mapk3 (ERK pathway) were downregulated both in vivo and in vitro, while mapk14a (P38 pathway), mapk8b and mapk9 (JNK pathway) were upregulated exclusively in hepatocytes. Furthermore, n-acetyl cysteine (NAC) attenuated As-induced apoptosis and modulated the expression of MAPK signaling pathway genes, including mapk3 and mapk8b, suggesting that As-induced oxidative stress regulates apoptosis via the MAPK signaling pathway. In contrast, phenylbutyric acid (PBA) was ineffective in preventing apoptosis. Overall, these results demonstrate that As induces endogenous apoptosis through oxidative stress and the MAPK signaling pathway in marine medaka.
砷(As)对水生生物的危害已被广泛认识;然而,其对海鱼细胞凋亡的毒理学影响尚未得到充分探讨。本研究通过对海洋medaka肝脏细胞系在体内暴露于50或500 mg/kg AsIII(以NaAsO2形式)超过28天,以及在体外暴露于50 - 750 μg/L AsIII 48小时的影响进行研究,以阐明其毒性及其潜在的分子机制。在体内,As在肝组织中显著积累(为对照组的1.79倍),引起肝脏病变和细胞凋亡增加(分别为4.85±0.56%和9.29±1.82%)。基因表达分析显示bcl2l1下调,bax、caspase-3和caspase-9上调,提示线粒体途径介导的细胞凋亡。在体外,砷暴露诱导肝细胞形态改变、活性氧(ROS)产生和细胞凋亡。此外,mapk1和mapk3 (ERK通路)在体内和体外均下调,而mapk14a (P38通路)、mapk8b和mapk9 (JNK通路)仅在肝细胞中上调。此外,n-乙酰半胱氨酸(NAC)可减弱砷诱导的细胞凋亡,并调节MAPK信号通路基因mapk3和mapk8b的表达,表明砷诱导的氧化应激通过MAPK信号通路调控细胞凋亡。而苯基丁酸(PBA)对细胞凋亡无抑制作用。综上所述,这些结果表明,As通过氧化应激和MAPK信号通路诱导海洋medaka内源性细胞凋亡。
{"title":"Arsenite-induced liver apoptosis via oxidative stress and the MAPK signaling pathway in marine medaka","authors":"Jiangtian Lin ,&nbsp;Ting Zhang ,&nbsp;Li Zhang","doi":"10.1016/j.aquatox.2024.107226","DOIUrl":"10.1016/j.aquatox.2024.107226","url":null,"abstract":"<div><div>Arsenic (As) is widely recognized for its hazards to aquatic organisms; however, its toxicological impacts on apoptosis in marine fish remain inadequately explored. This study investigated the effects of <em>in vivo</em> dietary exposure to 50 or 500 mg/kg AsIII (as NaAsO<sub>2</sub>) over 28 days in marine medaka, alongside <em>in vitro</em> exposure to 50–750 μg/L AsIII for 48 h in a hepatic cell line derived from marine medaka, to elucidate the toxicity and underlying molecular mechanisms. <em>In vivo</em>, As significantly accumulated in liver tissue (1.79-fold compared to the control), causing hepatic lesions and increased apoptosis (4.85 ± 0.56 % and 9.29 ± 1.82 %, respectively). Gene expression analysis showed downregulation of <em>bcl2l1</em> and upregulation of <em>bax, caspase-3</em> and <em>caspase-9</em>, indicating mitochondrial pathway-mediated apoptosis. <em>In vitro</em>, As exposure induced hepatocyte morphological changes, reactive oxygen species (ROS) production, and apoptosis. Additionally, <em>mapk1</em> and <em>mapk3</em> (ERK pathway) were downregulated both <em>in vivo</em> and <em>in vitro</em>, while <em>mapk14a</em> (P38 pathway), <em>mapk8b</em> and <em>mapk9</em> (JNK pathway) were upregulated exclusively in hepatocytes. Furthermore, n-acetyl cysteine (NAC) attenuated As-induced apoptosis and modulated the expression of MAPK signaling pathway genes, including <em>mapk3</em> and <em>mapk8b</em>, suggesting that As-induced oxidative stress regulates apoptosis via the MAPK signaling pathway. In contrast, phenylbutyric acid (PBA) was ineffective in preventing apoptosis. Overall, these results demonstrate that As induces endogenous apoptosis through oxidative stress and the MAPK signaling pathway in marine medaka.</div></div>","PeriodicalId":248,"journal":{"name":"Aquatic Toxicology","volume":"279 ","pages":"Article 107226"},"PeriodicalIF":4.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142925335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Evidence for low bioavailability of dietary nanoparticulate cerium in a freshwater food chain 淡水食物链中膳食纳米粒铈生物利用度低的证据
IF 4.1 2区 环境科学与生态学 Q1 MARINE & FRESHWATER BIOLOGY Pub Date : 2025-02-01 DOI: 10.1016/j.aquatox.2024.107228
Lisa A. Golding , Paul Callaghan , Brad M. Angel , Graeme E. Batley , Grant Griffiths , An Nguyen , Tom Cresswell
Radioactive 141Ce in ionic (I-Ce), nano (N-Ce, 11 ± 9 nm mean primary particle size ± standard deviation) and micron-sized (M-Ce, 530 ± 440 µm) forms associated with natural and artificial diets in natural river water and synthetic freshwater were used to measure the real-time biokinetics of dietary 141Ce assimilation in a freshwater food chain. The model food chain consisted of microalgae (Raphidocelis subcapitata), snails (Potamopyrgus antipodarum) and prawns (Macrobrachium australiense). Pulse-chase experiments showed that 91–100 % of all forms of cerium associated with all diets and water types were eliminated from the digestive system of the snail and prawn within 24 h, with no detectable cerium assimilation. The prawn and snail median elimination times (ET50) and elimination rates (Ke) for all cerium forms ranged from 0.05 to 1.7 d, and 30 to >100 % per d, respectively. The pulse-chase results were supported by the autoradiographic evidence for N-Ce and M-Ce that confirmed no detectable assimilation and translocation within the tissue of the prawn over time. In contrast, the more soluble I-Ce was found to be associated in low quantities with the hepatopancreas in the prawn confirming that the lack of dissolution by N-Ce and M-Ce in the digestive environment of these organisms makes these forms less bioavailable. In addition, hetero-agglomeration of N-Ce and M-Ce resulted in particles that did not dissociate in digestive fluids and were too large to be assimilated thereby making them non-bioavailable. Based on the results from this study and from the literature review, the risk of N-Ce biomagnification and chronic dietary toxicity in freshwater ecosystems is no greater than the risk associated with M-Ce or I-Ce.
采用天然河水和合成淡水中与天然和人工饲料相关的离子(I-Ce)、纳米(N-Ce,平均初级粒径为11±9 nm±标准差)和微米(m - ce, 530±440µm)形式的放射性141Ce,测量了淡水食物链中饲料中141Ce同化的实时生物动力学。模型食物链由微藻(Raphidocelis subcapitata)、蜗牛(Potamopyrgus antipodarum)和对虾(Macrobrachium australiense)组成。脉冲追踪实验表明,在24 h内,与所有饲料和水类型相关的91 - 100%的各种形式的铈从蜗牛和对虾的消化系统中被消除,没有检测到铈的同化。对虾和蜗牛对所有形式铈的中位消除时间(ET50)和消除率(Ke)分别为0.05 ~ 1.7 d和30 ~ 100% / d。脉冲追踪结果得到了N-Ce和M-Ce的放射自显影证据的支持,这些证据证实,随着时间的推移,对虾的组织内没有可检测到的同化和移位。相比之下,在对虾的肝胰脏中发现了较易溶解的低量I-Ce,这证实了在这些生物体的消化环境中缺乏N-Ce和M-Ce的溶解使得这些形式的生物利用度较低。此外,N-Ce和M-Ce的异团聚导致颗粒不能在消化液中解离,并且太大而无法被吸收,从而使它们不能被生物利用。根据本研究结果和文献综述,淡水生态系统中N-Ce生物放大和慢性膳食毒性的风险并不大于与M-Ce或I-Ce相关的风险。
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引用次数: 0
Gender effects of nanoplastics and emerging contaminants mixtures in Mytilus galloprovincialis 纳米塑料和新出现的污染物混合物在紫贻贝中的性别效应
IF 4.1 2区 环境科学与生态学 Q1 MARINE & FRESHWATER BIOLOGY Pub Date : 2025-02-01 DOI: 10.1016/j.aquatox.2024.107219
J.M. Gonçalves , M. Benedetti , G. d'Errico , F. Regoli , M.J. Bebianno
The reproduction of mussels occurs within the water column, and if gametogenesis is successful, gametes are exposed to the surrounding contaminants. Nanoplastics and other emerging contaminants have been gaining vast attention; however, their effects on the reproductive tissues of mussels with sex differentiation are scarce. Here, the effects of polystyrene nanoparticles (50 nm; 10 µg/L), the cytotoxic drug 5-fluorouracil (10 ng/L), and a mixture of the two were evaluated in the gonads of Mytilus galloprovincialis after a 21-day exposure for a multi-biomarker assessment, and after 28 days for the accumulation of nanoplastics. The effects on the activity of superoxide dismutase, catalase, glutathione-S-transferase, and lipid peroxidation were evaluated. Moreover, synergistic and antagonistic interactions in the mixture were calculated. A weight of evidence model was also used to elaborate on the hazardous level of biomarker results relative to polystyrene nanoparticles alone and in the mixture. The accumulation of nanoplastics appeared gender and time-specific, with females mostly compromised. According to the data set, a synergistic interaction between the cytotoxic drug and the nanoplastics makes the combination far more dangerous than individual stressors. The Weight Of Evidence model also confirms that females are more compromised at chronic exposure times than males. This study shows that the uptake, fate, and impact of emerging contaminants of concern can be significantly influenced by sex.
贻贝的繁殖发生在水柱中,如果配子发生成功,配子就会暴露在周围的污染物中。纳米塑料和其他新兴污染物已经引起了广泛的关注;然而,它们对具有性别分化的贻贝生殖组织的影响很少。在这里,聚苯乙烯纳米颗粒(50 nm;10µg/L),细胞毒性药物5-氟尿嘧啶(10 ng/L),以及两者的混合物,在暴露21天后进行多生物标志物评估,并在28天后进行纳米塑料积累评估。评价了其对超氧化物歧化酶、过氧化氢酶、谷胱甘肽- s -转移酶和脂质过氧化活性的影响。此外,还计算了混合物中的协同和拮抗相互作用。证据权重模型还用于详细说明相对于单独的聚苯乙烯纳米颗粒和混合物中的生物标志物结果的危险水平。纳米塑料的积累具有性别和时间特异性,以雌性为主。根据数据集,细胞毒性药物和纳米塑料之间的协同相互作用使得这种组合比单个压力源要危险得多。证据权重模型还证实,女性在长期暴露时间下比男性更容易受到损害。这项研究表明,新出现的污染物的吸收、命运和影响可能受到性别的显著影响。
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引用次数: 0
Developing predictive models for assessing LC50 of organic contaminants in Gammarus species using interpretable structural parameters 利用可解释的结构参数建立预测模型来评估Gammarus物种中有机污染物的LC50
IF 4.1 2区 环境科学与生态学 Q1 MARINE & FRESHWATER BIOLOGY Pub Date : 2025-02-01 DOI: 10.1016/j.aquatox.2025.107235
Mehran Karimi , Eskandar Kolvari , Mohammad Hossein Keshavarz , Nadiya Koukabi
Gammarus species are crucial indicators of environmental health, making them important for ecological studies and water quality assessments. They offer a wide range of specific responses regarding the median lethal concentration (LC50) of organic compounds. This research presents four predictive models to determine the LC50 of chemicals impacting selected gammarid amphipods: Gammarus lacustris, Gammarus fasciatus, Gammarus pulex, and Gammarus pseudolimnaeus. These species are recognized for their sensitivity to various pollutants and are among the most sensitive aquatic invertebrates. The new models provide straightforward methods for estimating the pLC50 (−log LC50/molecular weight) of various organic compounds based on interpretable structural parameters including the number of effective functional groups, the types of atoms present, and various structural characteristics of organic molecules. This study aims to leverage the largest available experimental dataset compared to prior quantitative structure–activity relationship (QSAR) models for these gammarid amphipods. The dataset contained toxicity data for 91 compounds affecting Gammarus fasciatus, 50 for Gammarus lacustris, and 48 each for Gammarus pseudolimnaeus and Gammarus pulex, aligning with comparative QSAR models. External datasets included 13 compounds for Gammarus fasciatus, 2 for Gammarus lacustris, and 6 for Gammarus pseudolimnaeus. Efforts focus on using interpretable structural parameters of organic compounds rather than computer-based descriptors, as outlined in the existing QSAR models. For the species G. fasciatus, G. lacustris, G. pseudolimnaeus, and G. pulex, the R² ratios for the new models versus the best QSAR models are 0.915/0.728, 0.955/0.747, 0.976/0.769, and 0.970/0.768, respectively. The higher R² values in the new models demonstrate greater reliability and robustness in capturing the data's underlying relationships.
该物种是环境健康的重要指标,对生态研究和水质评价具有重要意义。它们对有机化合物的中位致死浓度(LC50)提供了广泛的特定响应。本研究提出了四种预测模型,以确定影响Gammarus lacustris, Gammarus fasciatus, Gammarus pulex和Gammarus pseudolimnaeus的化学物质的LC50。这些物种因其对各种污染物的敏感性而被认为是最敏感的水生无脊椎动物之一。新模型提供了基于可解释的结构参数(包括有效官能团的数量、存在的原子类型和有机分子的各种结构特征)来估计各种有机化合物的pLC50(−log LC50/分子量)的直接方法。本研究的目的是利用最大的可用实验数据集,与之前的定量结构-活性关系(QSAR)模型相比,这些双足类动物。该数据集包含91种影响筋膜Gammarus fasciatus的化合物的毒性数据,50种影响湖泊Gammarus, 48种影响伪滨Gammarus和细尾Gammarus pulex,与比较QSAR模型一致。外部数据集包括13个fasciatus Gammarus化合物,2个湖泊Gammarus化合物和6个伪滨虾Gammarus化合物。努力的重点是使用有机化合物的可解释结构参数,而不是现有QSAR模型中概述的基于计算机的描述符。新模型与最佳QSAR模型的R²比分别为0.915/0.728、0.955/0.747、0.976/0.769和0.970/0.768。新模型中较高的R²值表明,在捕捉数据的潜在关系方面具有更高的可靠性和鲁棒性。
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引用次数: 0
Tributyl phosphate inhibits neurogenesis and motor functions during embryonic development in zebrafish 磷酸三丁酯抑制斑马鱼胚胎发育过程中的神经发生和运动功能。
IF 4.1 2区 环境科学与生态学 Q1 MARINE & FRESHWATER BIOLOGY Pub Date : 2025-02-01 DOI: 10.1016/j.aquatox.2024.107203
Gourav Chakraborty , Bhagyashri Joshi , Kedar Ahire , Chinmoy Patra
Tributyl phosphate (TBP), an organophosphate ester (OPE), is heavily used as a solvent in chemical industries, a plasticizer, and to extract radioactive molecules. Thus, widespread uses of TBP in industrialized countries led to the release of TBP and its metabolites, dibutyl phosphate (DBP) and monobutyl phosphate (MBP), in the environment and were detected in human samples. Accumulating these OPEs over time in humans and aquatic animals may develop toxicological effects. The reports also say TBP passes through the mother-fetal transmission route and may affect embryonic development. However, the impact of TBP and its metabolites on vertebrate development has been poorly studied. Ex-utero development, high fecundity, and optical transparency make the zebrafish a preferred model for toxicological evaluation. Thus, we aim to explore the toxic effects of TBP and its metabolites on aquatic animals using zebrafish as a model organism. Embryos in the chorion were incubated in 10–60 µM test chemicals from 6 to 48 h post fertilization (hpf), and analyzed the adverse effects on embryos. Our study found that 10–20 µM TBP inhibits neural growth, resulting in decreased spontaneous movement frequency and locomotive behavior without altering the overall embryonic growth and muscle functions. In contrast, DBP-treated embryos showed increased spontaneous movement frequency without changing the motor neuron growth and locomotive behavior. Further, in higher concentrations, TBP is teratogenic, and DBP is lethal to the embryos. Altogether, we found that TBP inhibits neurogenesis and motor behavior; however, its metabolite DBP is neuroexcitatory in zebrafish embryos.
磷酸三丁酯(TBP)是一种有机磷酸酯(OPE),在化学工业中被广泛用作溶剂、增塑剂和提取放射性分子。因此,工业化国家对TBP的广泛使用导致TBP及其代谢物磷酸二丁酯(DBP)和磷酸一丁酯(MBP)在环境中释放,并在人类样本中检测到。在人类和水生动物体内长期积累这些OPEs可能会产生毒理学效应。报告还说,TBP通过母婴传播途径,可能影响胚胎发育。然而,TBP及其代谢物对脊椎动物发育的影响研究甚少。体外发育,高繁殖力和光学透明性使斑马鱼成为毒理学评估的首选模型。因此,我们的目的是探讨TBP及其代谢物对水生动物的毒性作用,以斑马鱼为模式生物。受精后6 ~ 48 h,绒毛膜内胚胎在10 ~ 60µM的试验化学品中孵育,分析其对胚胎的不良影响。我们的研究发现,10-20µM TBP抑制神经生长,导致自发运动频率和运动行为降低,但不改变整体胚胎生长和肌肉功能。相比之下,dbp处理的胚胎在不改变运动神经元生长和运动行为的情况下,自发运动频率增加。此外,在较高浓度下,TBP会致畸,DBP对胚胎是致命的。总之,我们发现TBP抑制神经发生和运动行为;然而,其代谢物DBP在斑马鱼胚胎中具有神经兴奋性。
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引用次数: 0
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Aquatic Toxicology
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