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Ivermectin
PeerJ · 2019 · IF 2.353

Environmental fate of the anti-parasitic ivermectin in an aquatic micro-ecological system after a single oral administration

Di Wang,Bing Han,Shaowu Li,Yongsheng Cao,Xue Du,Tongyan Lu

Background Ivermectin (IVM) has been widely used in the aquaculture industry since its efficacy against parasites. However, the degradation of IVM was very slow in aquatic environments and the environmental fate of IVM in a complete aquatic system was still not clear. Therefore, comparable studies in a complete aquatic system were merited and helped to elucidate the environmental fate and effects of IVM. Methods An aquatic micro-ecological system containing an aquatic environment (water and sediment) and aquatic organisms (invertebrates, aquatic plants and fish) was built to simulate the natural rearing conditions. A single dose of 0.3 mg kg −1 body weight of IVM was given to the fish by oral gavage. Water, sediment, the roots and leaves of the aquatic plants, the soft tissue of the invertebrates and the visceral mass and muscle of fish samples were collected at 0.5 hours, 1 day, 7 days, 15 days, 30 days, 45 days, 60 days and 70 days after the treatment. IVM concentration in each sample was determined using ELISA method. Results IVM was quickly and widely distributed into the whole aquatic system in one day, and then was highly accumulated in organisms resulting in long-term residues. IVM was exchanged multiple times between the different media, which caused continuous fluctuations in the concentration of IVM in the water and sediment. It was worth noting that there was a second peak value of IVM in the fish and invertebrates after 30 days. The environmental fate of the IVM in the aquatic micro-ecological system showed that the drug was transferred from the fish to aquatic plants in the first seven days, and then gathered in the water and sediment, finally accumulating in the invertebrates. Our results indicated that an effective aquatic micro-ecological system was successfully established, and it could be applied to the study the environmental fate of IVM, which will aid the scientific use of this anti-parasitic agent during aquaculture.

研究领域: 环境科学 · 水产养殖学 · 毒理学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Pharmaceutics · 2024 ·Vol. 16 ·期 5 ·601 · IF 4.9

Enhanced In Vitro Antiviral Activity of Ivermectin-Loaded Nanostructured Lipid Carriers against Porcine Epidemic Diarrhea Virus via Improved Intracellular Delivery

Xiaolin Xu,Shasha Gao,Qindan Zuo,Jiahao Gong,Xinhao Song,Yongshi Liu,Jing Xiao,Xiaofeng Zhai,Haifeng Sun,Mingzhi Zhang,Xiuge Gao,Dawei Guo

Porcine epidemic diarrhea virus (PEDV) is an acute enteric coronavirus, inducing watery diarrhea and high mortality in piglets, leading to huge economic losses in global pig industry. Ivermectin (IVM), an FDA-approved antiparasitic agent, is characterized by high efficacy and wide applicability. However, the poor bioavailability limits its application. Since the virus is parasitized inside the host cells, increasing the intracellular drug uptake can improve antiviral efficacy. Hence, we aimed to develop nanostructured lipid carriers (NLCs) to enhance the antiviral efficacy of IVM. The findings first revealed the capacity of IVM to inhibit the infectivity of PEDV by reducing viral replication with a certain direct inactivation effect. The as-prepared IVM-NLCs possessed hydrodynamic diameter of 153.5 nm with azetapotential of −31.5 mV and high encapsulation efficiency (95.72%) and drug loading (11.17%). IVM interacted with lipids and was enveloped in lipid carriers with an amorphous state. Furthermore, its encapsulation in NLCs could enhance drug internalization. Meanwhile, IVM-NLCs inhibited PEDV proliferation by up to three orders of magnitude in terms of viral RNA copies, impeding the accumulation of reactive oxygen species and mitigating the mitochondrial dysfunction caused by PEDV infection. Moreover, IVM-NLCs markedly decreased the apoptosis rate of PEDV-induced Vero cells. Hence, IVM-NLCs showed superior inhibitory effect against PEDV compared to free IVM. Together, these results implied that NLCs is an efficient delivery system for IVM to improve its antiviral efficacy against PEDV via enhanced intracellular uptake.

CAS / MDL: 9005-64-5 112-80-1
研究领域: 药学 · 病毒学 · 纳米技术 · 兽医学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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FOOD CHEMISTRY · 2023 · IF 8.8

Simultaneous quantitative determination of residues of abamectin, ivermectin, albendazole and its three metabolites in beef and chicken by HPLC-PDA

Zhaoyuan He,Xinrui Shi,Yawen Guo,Fanxun Guan,Pengfei Gao,Yayun Tang,Shuyu Liu,Yali Zhu,Kaizhou Xie,Hailan Chen

Antimicrobial drugs are frequently used in a combination or shuttle way to cope with coinfection of bacteria or parasites and prevent drug resistance, thus the accurate quantification of multiple drug residues in animal-derived foods is crucial to ensure food safety. Here, a simple and efficient high-performance liquid chromatography-photodiode array (HPLC-PDA) method was established for the simultaneous quantitative screening of six common residues of antiparasitic drugs, including abamectin (ABM), ivermectin (IVM), albendazole (ABZ) and the three metabolites of ABZ in beef and chicken. The LODs and LOQs for six target compounds in beef and chicken are determined to be 3.2 to 12.5 µg/kg and 9.0 to 30.0 µg/kg, respectively. The calibration curves show good linearity (R 2  ≥ 0.9990) between the peak area and concentration. The recoveries from the fortified blank samples are all above 85.10%. Finally, the applicability of the HPLC-PDA method is successfully demonstrated by the real sample analysis.

CAS / MDL: 76-05-1
研究领域: 分析化学 · 食品科学 · 兽医学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF MOLECULAR LIQUIDS · 2025 · IF 5.2

In silico prediction of the formation, solubilization, and stabilization of a cyclodextrin-based ternary complex of ivermectin using long-timescale molecular dynamics simulations

Wenfei Wang,Menglu Duan,Fei Li,Yanhui He,Runze Li,Qinhui He,Yuan Deng,Xiaofang Zhang,Jiao Li

Ivermectin (IVM) is one of the currently available drugs for controlling Haemonchus contortus , but its poor aqueous solubility severely limits its potential for mass prophylaxis via drinking-water administration. In this study, the cyclodextrin-based ternary supramolecular system—composed of IVM, sulfobutylether-β-cyclodextrin (SBE-β-CD), and sodium dodecyl sulfate (SDS)—was constructed to enhance its solubility and stability. This ternary inclusion complex increased IVM solubility by ~3506-fold, with an entrapment efficiency of 44.69 ± 0.64 % and a drug loading of 43.60 ± 1.67 %, while maintaining a mean particle diameter of 20.20 ± 0.39 nm (polydispersity index [PDI] = 0.17 ± 0.06). Long-timescale molecular dynamics (MD) simulations revealed that the ternary supramolecular system self-assembled into stable nanoparticles within 200 ns. The negative binding free energy (ΔG bind ) values among all three components indicated that the self-assembly process of the ternary inclusion system was thermodynamically spontaneous. Hydrogen bond analysis further identified SBE-β-CD as the core of the ternary complex, with SDS acting as a molecular bridge; together, these two components enhanced the stability and solubility of the nanoparticles. In conclusion, long-timescale MD simulations elucidated self-assembly, stabilization, and solubilization mechanisms of the cyclodextrin-based ternary complex, offering a strategy to enhance the solubility and stability of macrolide drugs.

研究领域: 药剂学 · 分子模拟 · 药物递送 · 纳米技术 · 计算化学
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Foods · 2022 ·Vol. 11 ·期 23 ·3894 · IF 5.561

Separation and Detection of Abamectin, Ivermectin, Albendazole and Three Metabolites in Eggs Using Reversed-Phase HPLC Coupled with a Photo Diode Array Detector

Yawen Guo,Zhaoyuan He,Yali Zhu,Shuyu Liu,Pengfei Gao,Kaizhou Xie,Tao Zhang,Yuhao Dong

An innovative and sensitive approach using high-performance liquid chromatography-photo diode array detection (HPLC-PDAD) was developed and optimized for the simultaneous determination of abamectin (ABM), ivermectin (IVM), albendazole (ABZ) and three metabolites in eggs. The samples were extracted with acetonitrile (MeCN)/water (90:10,v/v), and the extracts containing the targets were cleaned up and concentrated by a series of liquid–liquid extraction (LLE) steps. A reversed-phase C18 column and a mobile phase consisting of 0.1% trifluoroacetic acid (TFA) aqueous solution and methanol (MeOH) were utilized to perform optimal chromatographic separation. The developed method was validated on the basis of international guidelines. The limits of detection (LODs) and quantitation (LOQs) were 2.1–10.5 µg/kg and 7.8–28.4 µg/kg, respectively. Satisfactory linear relationships were observed for the targets in their corresponding concentration ranges. The mean recoveries ranged from 85.7% to 97.21% at 4 addition levels, with intraday and interday relative standard deviations (RSDs) in the ranges of 1.68–4.77% and 1.74–5.31%, respectively. The presented protocol was demonstrated to be applicable and reliable by being applied for the detection of target residues in locally sourced egg samples.Keywords:abamectin;ivermectin;albendazole;HPLC–PDAD;LLE

CAS / MDL: 76-05-1
研究领域: 分析化学 · 兽医学 · 食品安全
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Antioxidants · 2022 ·Vol. 11 ·期 5 ·908 · IF 7.675

Ivermectin-Induced Apoptotic Cell Death in Human SH-SY5Y Cells Involves the Activation of Oxidative Stress and Mitochondrial Pathway and Akt/mTOR-Pathway-Mediated Autophagy

Yuan Zhang,Tun Sun,Meng Li,Yanling Lin,Yue Liu,Shusheng Tang,Chongshan Dai

Ivermectin (IVM) could cause potential neurotoxicity; however, the precise molecular mechanisms remain unclear. This study explores the cytotoxicity of IVM in human neuroblastoma (SH-SY5Y) cells and the underlying molecular mechanisms. The results show that IVM treatment (2.5–15 μM) for 24 h could induce dose-dependent cell death in SH-SY5Y cells. Compared to the control, IVM treatment significantly promoted the production of ROS, mitochondrial dysfunction, and cell apoptosis. IVM treatment also promoted mitophagy and autophagy, which were charactered by the decreased expression of phosphorylation (p)-Akt and p-mTOR proteins, increased expression of LC3II, Beclin1, ATG5, PINK, and Pakin1 proteins and autophagosome formation. N-acetylcysteine treatment significantly inhibited the IVM-induced production of ROS and cell death in SH-SY5Y cells. Autophagy inhibitor (e.g., 3-methyladenine) treatment significantly inhibited IVM-induced autophagy, oxidative stress, and cell apoptosis. Taken together, our results reveal that IVM could induce autophagy and apoptotic cell death in SH-SY5Y cells, which involved the production of ROS, activation of mitochondrial pathway, and inhibition of Akt/mTOR pathway. Autophagy inhibition improved IVM-induced oxidative stress and apoptotic cell death in SH-SY5Y cells. This current study provides new insights into understanding the molecular mechanism of IVM-induced neurotoxicity and facilitates the discovery of potential neuroprotective agents.Keywords:ivermectin;neurotoxicity;oxidative stress;apoptosis;autophagy;Akt/mTOR pathway

研究领域: 神经科学 · 细胞生物学 · 药理学
✓ 已验证 DOI PubMed 高影响因子
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