Imidacloprid increases intestinal permeability by disrupting tight junctions

Zhao, Gang; Wang, Xiaoyu; Li, Jin-Wang; Wang, Ran; Ren, Fazheng; Pang, Guo‐Fang; Li, Yixuan

doi:10.1016/j.ecoenv.2021.112476

Cited by 34 publications

(12 citation statements)

References 55 publications

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“…Absorption in the gut is important for orally ingested pesticides to exert potential toxicity. IMI is rapidly taken up by intestinal transporters [ 33 ] and can also disrupt the colon's tight junctions, resulting in increased intestinal permeability and decreased ileal bile acid transporter gene expression [ 8 , 34 ]. Thus, to assess the role of CAR in IMI-mediated intestinal toxicity, both the small and large intestine (along with luminal contents) were collected from WT and Car −/− mice.…”

Section: Resultsmentioning

confidence: 99%

Deletion of Constitutive Androstane Receptor Led to Intestinal Alterations and Increased Imidacloprid in Murine Liver

Sen

Goforth

Cooper

et al. 2022

Journal of the Endocrine Society

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Imidacloprid (IMI) is the most frequently detected neonicotinoid pesticide in the environment. Despite typically low vertebrate toxicity, IMI exposure is associated with liver and gastrointestinal toxicity. The mechanism underlying IMI toxicity in mammals is unclear. Pesticide exposure frequently activates xenobiotic nuclear receptors, like constitutive androstane receptor (CAR), to induce detoxification phase I and phase II genes. This study examined the role of CAR in mediating IMI off-target toxicity. Female Car-/- and wild-type (WT) mice were orally administered imidacloprid (50 mg/kg, twice daily) for 21 days, following which serum, liver, and intestinal tissues were collected. Liver tissue analysis indicated mild inflammation and induction of detoxification gene Cyp2b10 in IMI-exposed WT mice. The absence of CAR increased hepatic IMI accumulation. Microbiome analysis of ileal samples revealed IMI altered microbial diversity in a genotype-specific manner, with increased α-diversity in Car-/- mice while decreased α-diversity in WT mice. We observed Car-/- mice exhibit intestinal alterations with decreased CYP-P450 expression, blunted villi height, and increased small intestine length and weight independent of IMI-exposure. Our results suggest that IMI is not overtly toxic. However, the absence of xenobiotic nuclear receptor CAR allows increased accumulation of IMI in the liver and disrupts the structure and Cyp gene expression in the intestine.

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Section: Resultsmentioning

confidence: 99%

Deletion of Constitutive Androstane Receptor Led to Intestinal Alterations and Increased Imidacloprid in Murine Liver

Sen

Goforth

Cooper

et al. 2022

Journal of the Endocrine Society

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“…CHN also induced oxidative stress by decreasing reduced glutathione and increasing lipid peroxidation. Zhao et al [ 67 ] investigated the impact of the neonicotinoid pesticide imidacloprid (IMI), detected in the environment and in foods, which is absorbed and metabolized by the intestine. They found that IMI exposure significantly increased intestinal permeability of male Wistar rats exposed to an oral dose of 0.06 mg/kg body weight/day for 90 days, followed by elevated serum levels of endotoxin and inflammatory biomarkers (TNF-α, IL-1β) without any variation in body weight.…”

Section: Pesticides Disrupt the Integrity Of The Epithelial Barriersmentioning

confidence: 99%

Pesticides and Their Impairing Effects on Epithelial Barrier Integrity, Dysbiosis, Disruption of the AhR Signaling Pathway and Development of Immune-Mediated Inflammatory Diseases

Lima

Falcão

Rosa

et al. 2022

IJMS

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The environmental and occupational risk we confront from agricultural chemicals increases as their presence in natural habitats rises to hazardous levels, building a major part of the exposome. This is of particular concern in low- and middle-income countries, such as Brazil, known as a leading producer of agricultural commodities and consumer of pesticides. As long as public policies continue to encourage the indiscriminate use of pesticides and governments continue to support this strategy instead of endorsing sustainable agricultural alternatives, the environmental burden that damages epithelial barriers will continue to grow. Chronic exposure to environmental contaminants in early life can affect crucial barrier tissue, such as skin epithelium, airways, and intestine, causing increased permeability, leaking, dysbiosis, and inflammation, with serious implications for metabolism and homeostasis. This vicious cycle of exposure to environmental factors and the consequent damage to the epithelial barrier has been associated with an increase in immune-mediated chronic inflammatory diseases. Understanding how the harmful effects of pesticides on the epithelial barrier impact cellular interactions mediated by endogenous sensors that coordinate a successful immune system represents a crucial challenge. In line with the epithelial barrier hypothesis, this narrative review reports the available evidence on the effects of pesticides on epithelial barrier integrity, dysbiosis, AhR signaling, and the consequent development of immune-mediated inflammatory diseases.

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“…When domestic chickens are exposed to actual doses of IMI in the field, they show neurological signs of diminished response to external stimuli 8 . In addition, the level of tight junction proteins can be decreased by IMI, which can disrupt the intestinal epithelial barrier 9 . Another study found that IMI exposure increases oxidative stress by inhibiting the Nrf2 gene in quail livers and activates transforming growth factor‐β1（ TGF‐β1 ）/ Smad signaling pathway to promote liver fibrosis 10 .…”

Section: Introductionmentioning

confidence: 99%

“…8 In addition, the level of tight junction proteins can be decreased by IMI, which can disrupt the intestinal epithelial barrier. 9 Another study found that IMI exposure increases oxidative stress by inhibiting the Nrf2 gene in quail livers and activates transforming growth factor-β1(TGF-β1)/Smad signaling pathway to promote liver fibrosis. 10 The immune system is also one of the target organs of IMI.…”

mentioning

confidence: 99%

Resveratrol alleviates imidacloprid‐induced mitochondrial apoptosis, necroptosis, and immune dysfunction in chicken lymphocyte lines by inhibiting the ROS/MAPK signaling pathway

Wang,

Sun,

et al. 2023

Environmental Toxicology

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Imidacloprid (IMI) is a neonicotinoid insecticide with the highest global market share, and IMI exposure in the environment can negatively affect many nontarget organisms (a general term for organisms affected by drugs other than target organisms). Resveratrol (RSV), a non‐flavonoid polyphenolic organic compound derived from peanuts, grapes, and other plants, has anti‐inflammatory and antioxidant effects. It is currently unclear how RSV protects against cell damage caused by IMI. Therefore, we established an experimental model of chicken lymphocyte lines exposed to 110 μg/mL IMI and/or 0.5 μM RSV for 24 h. According to the experimental results, IMI markedly raised intracellular reactive oxygen species levels and diminished the activity of the cellular antioxidant enzymes (CAT, SOD, and GPx), leading to MDA accumulation and decreased T‐AOC. JNK, ERK, and P38, the essential components of the mitogen‐activated protein kinase (MAPK) signaling pathway, were also expressed more when IMI was present. Additionally, IMI resulted in upregulation of mitochondrial apoptosis (Caspase 3, Caspase 9, Bax, and Cyt‐c) and necroptosis (Caspase 8, RIPK1, RIPK3, and MLKL) related factors expression, downregulation of Bcl‐2 expression, induction of upregulation of cytokine IL‐6 and TNF‐α expression, and downregulation of IFN‐γ expression. The combined treatment of RSV and IMI significantly reduced cellular oxidative stress levels, inhibited the MAPK signaling pathway, and alleviated IMI‐induced mitochondrial apoptosis, necroptosis, and immune dysfunction. To summarize, RSV antagonized IMI‐induced mitochondrial apoptosis, necroptosis, and immune dysfunction in chicken lymphocyte lines by inhibiting the ROS/MAPK signaling pathway.

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Imidacloprid increases intestinal permeability by disrupting tight junctions

Cited by 34 publications

References 55 publications

Deletion of Constitutive Androstane Receptor Led to Intestinal Alterations and Increased Imidacloprid in Murine Liver

Deletion of Constitutive Androstane Receptor Led to Intestinal Alterations and Increased Imidacloprid in Murine Liver

Pesticides and Their Impairing Effects on Epithelial Barrier Integrity, Dysbiosis, Disruption of the AhR Signaling Pathway and Development of Immune-Mediated Inflammatory Diseases

Resveratrol alleviates imidacloprid‐induced mitochondrial apoptosis, necroptosis, and immune dysfunction in chicken lymphocyte lines by inhibiting the ROS/MAPK signaling pathway

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