Mechanism of Neonicotinoid Toxicity: Impact on Oxidative Stress and Metabolism

Wang, Xu; Anadón, Arturo; Wu, Qinghua; Qiao, Fang; Arés, Irma; Martínez-Larrañaga, María-Rosa; Zhang, Yuan; Martínez, María-Aránzazu

doi:10.1146/annurev-pharmtox-010617-052429

Cited by 215 publications

(109 citation statements)

References 139 publications

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“…THC may induce oxidative stress leading to ROS generation and related toxic effects . Oxidative stress induced by THC could inhibit the antioxidant defense system and lead to the damage of cellular macromolecules, such as DNA, lipids, and proteins . In fact, free radicals can attack the renal cell membrane and initiate lipid peroxide chain reactions.…”

Section: Discussionmentioning

confidence: 99%

Potential benefits of polysaccharides derived from marine alga Ulva lactuca against hepatotoxicity and nephrotoxicity induced by thiacloprid, an insecticide pollutant

Kammoun

Sellem

Saad

et al. 2019

Environmental Toxicology

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The present study aimed to evaluate the potential protective and antioxidant effect of polysaccharides (PS) extracted from Ulva lactuca against thiacloprid (THC) induced nephrotoxicity and hepatotoxicity. The antioxidant capacity of PS was tested in vitro using ABTS radical scavenging activity and plasmid DNA cleavage assays andin vivo on adult male rats treated for 30 days. Animals were allocated into four groups: control; THC (22.5 mg/kg); THC (22.5 mg/kg) + PS1 (100 mg/kg diet); and THC (22.5 mg/kg) + PS2 (200 mg/kg diet). The structural features of PS were determined by Fourier transformed infrared (FT‐IR), UV absorption peak detection, high performance liquid chromatography (HPLC) and gel permeation chromatography, and also functional properties were investigated. Overall, results indicated that THC increased significantly malondialdehyde, advanced oxidation protein products, glutathione levels, which is correlated with severe histological and plasmatic biochemical injuries in both liver and kidney tissues. However, cotreatment PS induced a significant protective and healing affects against the nephrotoxicity and hepatotoxcity induced by THC.

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Section: Discussionmentioning

confidence: 99%

Potential benefits of polysaccharides derived from marine alga Ulva lactuca against hepatotoxicity and nephrotoxicity induced by thiacloprid, an insecticide pollutant

Kammoun

Sellem

Saad

et al. 2019

Environmental Toxicology

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“…Since HSA is the major xenobiotic carrier in human plasma, binding of neonicotinoids to HSA may substantially reduce their free levels in plasma and may affect the binding of endogenous (e.g., heme) and exogenous (e.g., drugs) compounds to the FA1 site of HSA. Moreover, since HSA has antioxidant properties, it may help to counteract the oxidative stress by reactive nitrogen and oxygen species, which play a key role in neonicotinoid toxicity …”

Section: Resultsmentioning

confidence: 99%

“…Moreover, since HSA has antioxidant properties, 42 it may help to counteract the oxidative stress by reactive nitrogen and oxygen species, which play a key role in neonicotinoid toxicity. 9…”

Section: Discussionmentioning

confidence: 99%

“…Imidaclothiz, thiamethoxam, and clothianidin belong to the second‐generation chlorothiazoles. Dinotefuran belongs to the third‐generation furanyls, and sulfoxaflor belongs to the fourth‐generation sulfoximines …”

Section: Introductionmentioning

confidence: 99%

“…Dinotefuran belongs to the third-generation furanyls, and sulfoxaflor belongs to the fourth-generation sulfoximines. [5][6][7][8][9] The selectivity of neonicotinoids for insects rather than vertebrates is due to the fact that they have little or no effect on binding activity of vertebrate nAChRs. Rather, neonicotinoids interact with a proposed unique subsite consisting of cationic amino acid residues in the insect nAChR.…”

Section: Introductionmentioning

confidence: 99%

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Neonicotinoid trapping by the FA1 site of human serum albumin

et al. 2019

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Neonicotinoids are a widely used class of insecticides that target the acetylcholine recognition site of the nicotinic acetylcholine receptors in the central nervous system of insects. Although neonicotinoids display a high specificity for insects, their use has been recently debated since several studies led to the hypothesis that they may have adverse ecological effects and potential risks to mammals and even humans. Due to their hydrophobic nature, neonicotinoids need specific carriers to allow their distribution in body fluids. Human serum albumin (HSA), the most abundant plasma protein, is a key carrier of endogenous and exogenous compounds. The in silico docking and ligand binding properties of acetamiprid, clothianidin, dinotefuran, imidacloprid, nitenpyram, thiacloprid, and thiamethoxam to HSA are here reported. Neonicotinoids bind to multiple fatty acid (FA) binding sites, preferentially to the FA1 pocket, with high affinity. Values of the dissociation equilibrium constant for neonicotinoid binding FA1 of HSA (i.e., calcKn) derived from in silico docking simulations (ranging between 3.9 × 10−5 and 6.3 × 10−4 M) agree with those determined experimentally from competitive inhibition of heme‐Fe(III) binding (i.e., expKn; ranging between 2.1 × 10−5 and 6.9 × 10−5 M). Accounting for the HSA concentration in vivo (~7.5 10−4 M), values of Kn here determined suggest that the formation of the HSA:neonicotinoid complexes may occur in vivo. Therefore, HSA appears to be an important determinant for neonicotinoid transport and distribution to tissues and organs, particularly to the liver where they are metabolized.

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Profiling and Identification of Biocatalyzed Transformation of Sulfoxaflor In Vivo

Guo

Wang

et al. 2020

Angewandte Chemie

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In the present study, we investigated the biotransformation of the neonicotinoid pesticide sulfoxaflor and the metabolic responses in Sprague‐Dawley rats. Sulfoxaflor transformation was catalyzed by cytochrome P450 while five phase I and four phase II metabolites were identified for the first time in vivo. The experimental results demonstrated that sulfoxaflor brought about the metabolic profiling disturbances in liver and bile. Exposure to sulfoxaflor caused dysregulation of bile acid synthesis and reabsorption by the expression of farnesoid X receptor (FXR). Our data provided insights into biotransformation of chemicals while enabling the implementation of a new toolbox for the design of sulfoximine compounds.

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Mechanism of Neonicotinoid Toxicity: Impact on Oxidative Stress and Metabolism

Cited by 215 publications

References 139 publications

Potential benefits of polysaccharides derived from marine alga Ulva lactuca against hepatotoxicity and nephrotoxicity induced by thiacloprid, an insecticide pollutant

Potential benefits of polysaccharides derived from marine alga Ulva lactuca against hepatotoxicity and nephrotoxicity induced by thiacloprid, an insecticide pollutant

Neonicotinoid trapping by the FA1 site of human serum albumin

Profiling and Identification of Biocatalyzed Transformation of Sulfoxaflor In Vivo

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