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MICROCHEMICAL JOURNAL · 2020 · IF 3.594

Determination and generating study on monoiodoacetic acid and diiodoacetic acid in water by liquid chromatography-inductively coupled plasma mass spectrometry

Deye Liu,Shi Cheng,Wenliang Ji,Hui Shen,Jinghua Yuan,Jing Wang,Wenting Zhang,Hong Liu,Yonglin Zhou

In this study, we have developed a method to directly detect monoiodoacetic acid (MIAA) and diiodoacetic acid (DIAA) in drinking water using liquid chromatography-inductively coupled plasma mass spectrometry (LC-ICP-MS). MIAA and DIAA were qualitatively analyzed based on the retention time and quantitatively measured using the peak area integral. The figures of merit from five independent labs reveal that the LODs of the method were 0.06 ~ 0.22 μg/L for MIAA and 0.04 ~ 0.18 μg/L for DIAA, and the recovery rates were 95% ~ 107% and 94% ~ 103% for MIAA and DIAA, respectively. Concomitant anions such as 200 mg/L of SO 4 2− , NO 3 − , BrO 3 − , and F − , 300 mg/L of Cl − and 2.0 mg/L of chlorine or bromine based haloacetic acids (HAAs) could not interfere with this method. Additionally, the results for the quality control samples from five labs were consistent with one another. The verification data from five independent labs proved that the method is accurate and adaptable. Since the method does not use pretreatments or toxic organic reagents, the greenness of the method is guaranteed compared to that of conventional methods. Hence, the method used to detect MIAA and DIAA in drinking water is qualified as a standard method for wide application. Furthermore, the generation study of iodoacetic acids (IAAs) in Cl 2 and UV 275 -Cl 2 disinfection systems was performed. The results showed that the amount of IAAs was significantly higher when UV 275 -Cl 2 was used to disinfect the high-iodium water than when only Cl 2 was applied, especially in weak acid conditions. This conclusion is of great importance in suggesting how to reduce the potential risk of IAAs when producing drinking water when chlorine or a UV 275 -Cl 2 disinfection process is applied.

研究领域: 环境科学 · 分析化学 · 公共卫生
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MICROCHEMICAL JOURNAL · 2024 · IF 4.9

Rapid and simultaneous analysis of monoiodoacetic acid and inorganic iodine in drinking water by capillary electrophoresis-inductively coupled plasma mass spectrometry

Yuke Wu,Xi Wang,Zhengqin Pang,Jinyi Zhang,Chengbin Zheng

Monoiodoacetic acid (MIAA) is a disinfection by-product formed during water disinfection through the oxidation of iodide, followed by a reaction with natural organic matter. It exhibits high toxicity and strong mutagenicity and is potentially carcinogenic to humans. Therefore, the simultaneous detection of MIAA and inorganic iodine can enable the safety assessment of drinking water and expand the study of the dynamic transformation process between the two forms. Currently, there is a lack of efficient and rapid universal screening methods for MIAA and inorganic iodine. In this work, a simple and efficient method was developed to combine capillary electrophoresis with inductively coupled plasma mass spectrometry using a spray-efficient nebulizer interface for the speciation analysis of I −  , IO 3 −  , and MIAA. The method is based on qualitative analysis of retention time and quantitative determination using peak area. The detection limits of the three iodine forms were 0.16 μg L − 1 , 0.40 μg L − 1 , and 1.22 μg L − 1 , respectively. By coupling two instruments, the method combines the advantages of rapidity and accuracy with high injection efficiency. It is also more environmentally friendly as it does not require complex pre-treatment and avoids the use of toxic organic compounds. The accuracy of this method has been validated through the incorporation of authentic samples, paving the way for its deployment in the risk assessment of substantial volumes of drinking water and the expansion of the novel approach for further investigation into the genesis and transformation of MIAA.

CAS / MDL: 64-69-7
研究领域: 环境科学 · 分析化学
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JOURNAL OF ORTHOPAEDIC RESEARCH · 2012 ·Vol. 31 ·期 3 ·364-369 · IF 2.811

Monosodium iodoacetate induces apoptosis via the mitochondrial pathway involving ROS production and caspase activation in rat chondrocytes in vitro

Liping Jiang,Longjie Li,Chengyan Geng,Dezheng Gong,Lijie Jiang,Nobuyuki Ishikawa,Koji Kajima,Laifu Zhong

Monosodium iodoacetate (MIA) is an inhibitor of glyceraldehyde-3-phosphate dehydrogenase activity, and causes dose-dependent cartilage degradation resembling the pathological changes of human osteoarthritis (OA). In this study, we assessed the apoptosis induced by MIA and clarified the underlying mechanisms using the primary rat chondrocytes. The apoptosis of primary rat chondrocytes was analyzed by flow cytometry. The levels of mitochondrial membrane potential (ΔΨm) were evaluated using fluorescence spectrophotometer. The production of reactive oxygen species (ROS) was determined by fluorescence spectrophotometer. Apoptosis-related protein cytochrome c and procaspase-3 expressions were examined by Western blotting. We found that MIA treatment induces apoptosis in chondrocytes, as confirmed by increases in the percent of apoptotic cells, up-regulation of cytochrome c and caspase-3 protein levels. Treatment with MIA increases ROS production and decreases the levels of ΔΨm. The antioxidant, N -acetylcysteine (NAC), significantly prevented the production of ROS, the reduction of ΔΨm, the release of cytochrome c and the activation of caspase-3. Further, NAC completely protected the cells from MIA-induced apoptosis. Together these observations suggest that the mechanisms of MIA-induced apoptosis are primarily via ROS production and mitochondria-mediated caspase-3 activation in primary rat chondrocytes. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31: 364–369, 2013

研究领域: 医学 · 生物学
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SEPARATION AND PURIFICATION TECHNOLOGY · 2021 · IF 7.312

Formation of toxic iodinated by-products during the oxidation process of iohexol by catalytic ozonation in water

Pengwei Yan,Zhonglin Chen,Shuyu Wang,Yanchi Zhou,Jimin Shen,Shengxin Zhao,Lei Yuan,Weiqiang Wang,Xiaotong Xu,Xinwei Zhu,Jing Kang

The formation of iodinated by-products during the chemical oxidation process for organic compounds contaminated water has gained increasing attention. Iodinated by-products are more genotoxic, cytotoxic and mutagenic than those of chlorine and bromine analogs. It was reported that the oxidation process of iodinated X-ray contrast media (ICM) could generate iodinated by-products. This study investigated the generation of iodinated by-products during catalytic ozonation of iohexol (one of wide detected ICM). The formation of iodoform (IF) and monoiodoacetic acid (MIAA), and the degradation kinetics of iohexol were compared in different oxidation systems. The effect of various factors, including the iohexol concentration, ozone concentration, HA concentration and solution pH on iodinated by-products generation was evaluated. Additionally, the fate of iodine was investigated by the mass balance calculation. The generated concentrations of I-THMs species with one iodide atom were far higher than those of species with more iodine atoms in the catalytic system at the coexistence of Cl − and Br − . The generation of I-THMs in actual water was relatively low and the normalized value of I-THMs/DOC (μg/mg) had no significant difference. The formation mechanism of high molecular weight iodine-containing by-products included cleavage of the side chain, H-abstraction, substitution iodine for chlorine or bromine and amide oxidation.

研究领域: 环境科学 · 毒理学
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CHEMOSPHERE · 2019 · IF 5.108

Superoxide dismutase response and the underlying molecular mechanism induced by iodoacetic acid

Jing Wang,Rui Jia,Xiaolin Zheng,Rutao Liu,Wansong Zong

Given the ubiquity of iodinated disinfection by-products (I-DBPs) in drinking water and their prominent toxicity, it is of vital significance to evaluate I-DBPs toxicity and explore the underlying mechanism. The toxicity of iodoacetic acid (IAA), a typical type of I-DBPs, might be linked with oxidative stress . However, it remains unknown for the response of antioxidant enzyme superoxide dismutase (SOD) in the mouse primary hepatocytes when exposed to IAA and the underlying mechanism. This study explored SOD response to IAA and the underlying mechanisms at the molecular and cellular levels. Under IAA exposure, the observed increase of SOD activity in the hepatocytes was caused by the increase of SOD production via ROS stimulation and the increase of SOD molecular activity. Molecular experiments showed that IAA binds to SOD molecule mainly via electrostatic forces with one binding site around the active site and six binding sites in the surface of protein. The binding interaction leads to the conformational changes of SOD and the disruption of protein aggregates. This work could offer basic data for the comprehensive understanding of the adverse effects of IAA and references for assessing the harmful effects of DBPs.

CAS / MDL: 87-51-4
研究领域: 毒理学 · 分子生物学 · 环境科学
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JOURNAL OF HAZARDOUS MATERIALS · 2024 · IF 12.2

GRP78/IRE1 and cGAS/STING pathway crosstalk through CHOP facilitates iodoacetic acid-mediated testosterone decline

Li Mou,Daguang Sun,Jiayuan Qu,Xiaoyin Tan,Suli Wang,Qiang Zeng,Changjiang Liu

Iodoacetic acid (IAA) is an emerging unregulated iodinated disinfection byproduct with high toxicity and widespread exposure. IAA has potential reproductive toxicity and could damage male reproduction. However, the underlying mechanisms and toxicological targets of IAA on male reproductive impairment are still unclear, and thus Sprague-Dawley rats and Leydig cells were used in this work to decode these pending concerns. Results showed that after IAA exposure, the histomorphology and ultrastructure of rat testes were abnormally changed, numbers of Leydig cells were reduced, the hypothalamic-pituitary-testis (HPT) axis was disordered, and testosterone biosynthesis was inhibited. Proteomics analyses displayed that oxidative stress, endoplasmic reticulum stress, and steroid hormone biosynthesis were involved in IAA-caused reproductive injury. Antioxidant enzymes were depleted, while levels of ROS, MDA, 8-OHdG, and γ-H2A.X were increased by IAA. IAA triggered oxidative stress and DNA damage, and then activated the GRP78/IRE1/XBP1s and cGAS/STING/NF-κB pathways in Leydig cells. The two signaling pathways constructed an interactive network by synergistically regulating the downstream transcription factor CHOP, which in turn directly bound to and negatively modulated steroidogenic StAR, finally refraining testosterone biosynthesis in Leydig cells. Collectively, IAA as a reproductive toxicant has anti-androgenic effects, and the GRP78/IRE1 and cGAS/STING pathway crosstalk through CHOP facilitates IAA-mediated testosterone decline.

CAS / MDL: 91085-56-2
研究领域: 生殖毒理学 · 分子生物学 · 内分泌学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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SCIENCE OF THE TOTAL ENVIRONMENT · 2023 · IF 9.8

Novel evidence on iodoacetic acid-induced immune protein functional and conformational changes: Focusing on cellular and molecular aspects

Shuqi Guo,Falin He,Shaoyang Hu,Wansong Zong,Rutao Liu

Elevated levels of iodide occur in raw water in certain regions, where iodination disinfection byproducts are formed during chloramine-assisted disinfection of naturally iodide-containing water. Iodoacetic acid (IAA) is one of the typical harmful products. The mechanisms underlying IAA-induced immunotoxicity and its direct effects on biomolecules remained unclear in the past. Cellular, biochemical, and molecular methods were used to investigate the mechanism of IAA-induced immunotoxicity and its binding to lysozyme . In the presence of IAA, the cell viability of coelomocytes was significantly reduced to 70.8 %, as was the intracellular lysozyme activity. Upon binding to IAA, lysozyme underwent structural and conformational changes, causing elongation and unfolding of the protein due to loosening of the backbone and polypeptide chains. IAA effectively quenched the fluorescence of lysozyme and induced a reduction in particle sizes. Molecular docking revealed that the catalytic residue, Glu 35, which is crucial for lysozyme activity, resided within the docking range, suggesting the preferential binding of IAA to the active site of lysozyme. Moreover, electrostatic interaction emerged as the primary driving force behind the interaction between IAA and lysozyme. In conclusion, the structural and conformational changes induced by IAA in lysozyme resulted in impaired immune protein function in coelomocytes, leading to cellular dysfunction.

研究领域: 环境科学 · 毒理学 · 生物化学 · 分子生物学 · 免疫学
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JOURNAL OF HAZARDOUS MATERIALS · 2024 · IF 12.2

Enhanced detection of monoiodoacetic acid at ng/L level by ion chromatography with novel derivatization-free pretreatment

Wenyu Li,Wei Ma,Yang Yang,Huan He,Baiyang Chen

Concerns have recently arisen regarding the formation of carcinogenic and genotoxic iodinated haloacetic acids (HAAs), such as monoiodoacetic acid (MIAA), during the disinfection of iodine-containing water with chloramine. Existing detection methods for MIAA rely on either labor-intensive derivatization operations or expensive instruments, making analysis challenging. To bypass these issues, this study proposed a novel two-step liquid-liquid extraction strategy to enrich MIAA and then pioneered the integration of common ion chromatography (IC) with an ultraviolet detector to measure trace MIAA precisely. This novel approach achieved a remarkable 155.6-fold enrichment of MIAA and significantly reduced the need for water and chemicals, hence enhancing its efficiency and environmental friendliness. Besides, this method effectively removed coexisting anions and separated MIAA from other interferents by adjusting IC column and eluent conditions. The method detection limit of MIAA is an impressive 21.44 ng/L, and the recoveries in synthetic and real water samples ranged from 85 to 113%, with maximum deviations of 7.59%. We validated the reliability of our approach by comparing it with the USEPA 552.3 method. In conclusion, this IC-based method proves to be a robust and environment-benign solution for detecting trace MIAA in complex water components.

研究领域: 环境化学 · 分析化学 · 水处理技术
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Oxidative Medicine and Cellular Longevity · 2015 · IF 3.516

Protective Effect of Edaravone in Primary Cerebellar Granule Neurons against Iodoacetic Acid-Induced Cell Injury

Xinhua Zhou,Longjun Zhu,Liang Wang,Baojian Guo,Gaoxiao Zhang,Yewei Sun,Zaijun Zhang,Simon Ming-Yuen Lee,Pei Yu,Yuqiang Wang

Edaravone (EDA) is clinically used for treatment of acute ischemic stroke in Japan and China due to its potent free radical-scavenging effect. However, it has yet to be determined whether EDA can attenuate iodoacetic acid- (IAA-) induced neuronal death in vitro. In the present study, we investigated the effect of EDA on damage of IAA-induced primary cerebellar granule neurons (CGNs) and its possible underlying mechanisms. We found that EDA attenuated IAA-induced cell injury in CGNs. Moreover, EDA significantly reduced intracellular reactive oxidative stress production, loss of mitochondrial membrane potential, and caspase 3 activity induced by IAA. Taken together, EDA protected CGNs against IAA-induced neuronal damage, which may be attributed to its antiapoptotic and antioxidative activities.

CAS / MDL: 107-15-3
研究领域: 神经科学 · 药理学 · 细胞生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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MOLECULAR PHARMACEUTICS · 2023 · IF 4.9

Microgel Encapsulated Nanoparticles for Intra-articular Disulfiram Delivery to Treat Osteoarthritis

Yisi Liu,Jun Yao,Guotao Deng,Gang Zhong,Jianping Zhao,Qiumei Lan,Jinzhi Meng,Yin Yu,Fei Chen

Osteoarthritis (OA) affects numerous patients worldwide, and there are no approved disease-modifying drugs. Repurposing FDA-approved small molecular drugs could be a promising alternative strategy to treat OA. Disulfiram (DSF), a clinically approved drug for treatment of alcoholism, inhibits inflammasome activation and exhibits a protective role in interleukin-1β-induced cardiac injury. However, its efficacy in treating OA remains to be explored due to its poor water solubility and stability, which limit its use in OA treatment. Here, the anti-inflammatory effect of DSF is evaluated in vitro, and a double-layer encapsulation approach is developed for intra-articular delivery of DSF for OA treatment in vivo. DSF is loaded into poly(lactic-co-glycolic acid)-based nanoparticles and encapsulated in gelatin methacrylate microgels through a microfluidic device. Results show that DSF effectively inhibits the expression of key inflammatory cytokines in OA chondrocytes, and the double-layer encapsulation approach reduces the burst release of DSF and prolongs its retention time in the in vitro study. Sustained release of DSF from microgels mitigates cartilage inflammation and subchondral bone erosion in a monoiodoacetate-induced rat OA model. This work demonstrates the potential of repurposing FDA-approved drugs for OA treatment and provides a promising platform for intra-articular delivery of small molecules for superior therapeutic effect.

研究领域: 药学 · 生物医学工程 · 骨科 · 药物递送系统 · 炎症研究
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ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY · 2024 · IF 6.2

Role of iron homeostasis in the mutagenicity of disinfection by-products in mammalian cells

Yemian Zhou,Yun Liu,Tong Wang,Han Li,Jing He,An Xu

Disinfection by-products (DBPs) generated from water treatment have serious adverse effects on human health and natural ecosystems. However, research on the mutagenicity of DBPs with different chemical structures is still limited. In the present study, we compared the mutagenicity of 8 typical DBPs in human-hamster hybrid (A L ) cells and clarified the mechanisms involved. Our data displayed that the rank order for mutagenicity was as follows: iodoacetamide (IAcAm) > iodoacetonitrile (IAN) > iodoacetic acid (IAA) > bromoacetamide (BAcAm) ≈ bromoacetonitrile (BAN) > bromoacetic acid (BAA), which was confirmed by DNA double strand breaks and oxidative DNA damage. In contrast, bromoform (TBM) and iodoform (TIM) had minimal mutagenicity. The mutation spectrum analysis further revealed that IAN, IAcAm, and IAA could induce multilocus deletions in mammalian cells. Interestingly, nitrogenous DBPs (N-DBPs) and IAA were found to cause varying degrees of iron overload and lipid peroxidation, which was mediated by the activation of the Nrf2/HO-1 signaling pathway. Moreover, the presence of deferoxamine (DFO), an iron ion inhibitor, effectively reduced γ-H2AX and 8-OHdG induced by N-DBPs and IAA. These results indicated that the variations in genotoxicity among DBPs with different structures were associated with their ability to disrupt iron homeostasis. This study provided new insights into the mechanisms underlying the structure-dependent toxicity of DBPs and established a foundation for a more comprehensive understanding and intervention of the health risks associated with DBPs.

CAS / MDL: 7705-08-0 144-48-9
研究领域: 环境科学 · 毒理学 · 分子生物学 · 细胞生物学
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SAUDI PHARMACEUTICAL JOURNAL · 2020 · IF 2.879

Fraxetin inhibits interleukin-1β-induced apoptosis, inflammation, and matrix degradation in chondrocytes and protects rat cartilage in vivo

Qing Wang,Di Zhuang,Wenchang Feng,Bitao Ma,Liping Qin,Lilun Jin

Osteoarthritis (OA) is a disease characterized by degeneration of the joint complex due to cartilage destruction. Fraxetin, a widely used and studied coumarin compound extracted from a traditional Chinese herb (Qin Pi), has shown anti-inflammatory and antioxidant properties, but its effects on OA have not been studied. In the present study, western blotting, immunofluorescence, and terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL) were used to evaluate the effects of fraxetin on IL-1β-induced apoptotic activity, inflammatory responses, and catabolism in rat chondrocytes. The results showed that fraxetin prevented IL-1β-induced apoptosis of chondrocytes and inhibited inflammatory mediator release by regulating the Toll-like receptor 4 (TLR4)/myeloid differentiation primary response 88 (MyD88)/nuclear factor (NF)-κB pathway in chondrocytes. Additionally, fraxetin suppressed the upregulation of matrix metalloproteinase 13 (MMP13) and degradation of collagen II in the extracellular matrix (ECM). Moreover, the effects of fraxetin in vivo were assessed in a monosodium iodoacetate (MIA)-induced rat model of OA using hematoxylin and eosin (H&E) and Safranin O-fast green staining and magnetic resonance imaging (MRI). The results showed that fraxetin protected the cartilage against destruction. In conclusion, fraxetin could be a potential therapeutic for OA.

CAS / MDL: 574-84-5
研究领域: 药理学 · 风湿病学 · 骨科
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