Immunotoxicity induced by Ivermectin is associated with NF-κB signaling pathway on macrophages

Zhang, Ping; Li, Yandi; Xu, Wenping; Cheng, Jiagao; Zhang, Cheng; Gao, Jufang; Li, Zhong; Tao, Liming; Zhang, Yang

doi:10.1016/j.chemosphere.2021.133087

Cited by 12 publications

(6 citation statements)

References 38 publications

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“…For example, Liu et al reported that avermectin damaged immune function by altering spleen tissue in the pigeon 33 . Zhang et al reported that ivermectin induced immunotoxicity by damaging the phagocytosis on macrophages 34 . Specially, several evidences on animal experiment showed the occurrence of immunotoxicity exposed to EMB, manifested as the alteration of splenic immune gene expression 35 .…”

Section: Discussionmentioning

confidence: 99%

“…33 Zhang et al reported that ivermectin induced immunotoxicity by damaging the phagocytosis on macrophages. 34 Specially, several evidences on animal experiment showed the occurrence of immunotoxicity exposed to EMB, manifested as the alteration of splenic immune gene expression. 35 However, the study on EMB immunotoxicity still warrant further investigation and the corresponding mechanism remains unknown.…”

Section: Discussionmentioning

confidence: 99%

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The potential immunotoxicity of emamectin benzoate on the human THP‐1 macrophages

Wei

Wang

et al. 2022

Environmental Toxicology

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Emamectin benzoate (EMB) as one of the typical biological pesticides has a wide range of applications in agriculture. However, the immune toxic effects of EMB in human received limited attention. In our study, THP-1 macrophage as an in vitro model was used to evaluate immune functions exposed to EMB. We observed that EMB inhibited phagocytic activity and respiratory burst capacity of macrophages without inducing cellular toxicity, implying the potential immunosuppression.Besides, EMB disturbed the cytokines balance embodied in the increase of TNF-α, IL-1β, IL-6, CCL27, CXCL8 mRNA expression and the decrease of IL-4, IL-13, IL-10 mRNA expression. EMB could exhibit pro-inflammatory responses in macrophages and promote the conversion of macrophages to M1 phenotype. Moreover, NF-κB pathway involved in regulating immune function from KEGG pathway analysis. EMB exposure could activate the NF-κB pathway in THP-1 macrophages by exploring the critical proteins. This research provided insights on immunotoxicity evaluation and clarified EMB-induced immunotoxicity was related to NF-κB pathway activation.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The potential immunotoxicity of emamectin benzoate on the human THP‐1 macrophages

Wei

Wang

et al. 2022

Environmental Toxicology

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“…It is used to treat health conditions like onchocerciasis, strongyloidiasis, lymphatic filariasis, and crusted scabies [ 10 , 21 , 22 , 23 ]. As far as the toxicity is concerned in humans, ivermectin damages the macrophages and interacts with liver cytochrome P450 enzymes, thus producing immunotoxicity and hepatotoxicity [ 24 , 25 ]. Other clinical signs observed in patients receiving ivermectin therapy may include pruritis, malaise, skin edema, hypotension, headache, and dyspnea [ 21 ].…”

Section: Introductionmentioning

confidence: 99%

Assessment of Avermectins-Induced Toxicity in Animals

et al. 2022

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Macrocyclic lactones, particularly the avermectins, have completely revolutionized the approaches aimed at control of parasites. These avermectins are the most widely used anti-parasitic drugs in veterinary field with sales exceeding one billion US dollars annually. However, before clinical usage, their safety evaluation in the animals is a major critical factor that must be considered. Many studies have reported the negative effects of avermectins like ivermectin, abamectin, doramectin, and eprinomectin on the host animals. These harmful effects arise from avermectins targeting GABA and glutamate-gated chloride channels present both in the parasites and the host animals. In this review, various modes of avermectins action along with the negative effects on the host like nephrotoxicity, hepatotoxicity, neurotoxicity, reproductive toxicity, and endocrine disruption were discussed in detail. Furthermore, other important issues like ecotoxicity, drug resistance, and drug residues in milk associated with avermectins usage were also discussed, which need special attention.

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“…Previous studies have reported that avermectin insecticides including Avermectin (AVM), Ivermectin (IVM) and EMB could cause immunotoxicity by damaging immune cells and immune organs. For example, EMB and IVM directly damaged macrophage 9,10 . Moreover, AVM induced immune toxic effects in the neutrophils of carp 11 .…”

Section: Introductionmentioning

confidence: 97%

“…For example, EMB and IVM directly damaged macrophage. 9,10 Moreover, AVM induced immune toxic effects in the neutrophils of carp. 11 AVM also exerted immunotoxicity in the spleen tissue of pigeons.…”

Section: Introductionmentioning

confidence: 99%

Studies on immunotoxicity induced by emamectin benzoate in zebrafish embryos based on metabolomics

Wei,

Wang,

et al. 2023

Environmental Toxicology

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Emamectin benzoate (EMB) is an insecticide for the control of agricultural lepidoptera pests, and also an anti‐parasiticide for the control of exoparasites in aquaculture industry. Increased studies suggest that EMB could cause toxicity to non‐targeted organisms, but its immunotoxicity to human remains unclear. In this study, zebrafish were used to investigate the immunotoxic effects induced by environmentally relevant doses of EMB. We observed that EMB exposure led to embryo mortality and delayed hatching, as well as increased malformations. Meanwhile, zebrafish exposed to EMB exhibited a significant decrease in the number of neutrophils and macrophages. In addition, untargeted metabolomics approach was developed to elucidate the mechanism of EMB‐induced immunotoxicity. We found that a total of 10 shared biomarkers were identified in response to EMB exposure. Furthermore, pathway analysis identified glycerophospholipid metabolism was the most relevant pathway. Within this pathway, it was observed abnormal increases in glycerol 3‐phosphate content, which could be attributed to the increased expression of GK5 and decreased expression of GPAT3. Our study provided novel and robust perspectives, which showed that EMB exposure to zebrafish embryos could cause metabolic disturbances that adversely affected development and immune system.

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Immunotoxicity induced by Ivermectin is associated with NF-κB signaling pathway on macrophages

Cited by 12 publications

References 38 publications

The potential immunotoxicity of emamectin benzoate on the human THP‐1 macrophages

The potential immunotoxicity of emamectin benzoate on the human THP‐1 macrophages

Assessment of Avermectins-Induced Toxicity in Animals

Studies on immunotoxicity induced by emamectin benzoate in zebrafish embryos based on metabolomics

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