{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T06:30:05Z","timestamp":1768717805012,"version":"3.49.0"},"reference-count":70,"publisher":"The Endocrine Society","issue":"12","license":[{"start":{"date-parts":[[2022,9,21]],"date-time":"2022-09-21T00:00:00Z","timestamp":1663718400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Illinois Toxicology and Environmental Health Interdisciplinary Environmental Toxicology Program"},{"name":"UIUC startup funds"},{"DOI":"10.13039\/100005302","name":"University of Illinois, Urbana-Champaign","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100005302","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,10,26]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Imidacloprid (IMI) is the most frequently detected neonicotinoid pesticide in the environment. Despite typically low toxicity in vertebrates, 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, such as the 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\u2212\/\u2212 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 \u03b1-diversity in Car\u2212\/\u2212 mice while decreased \u03b1-diversity in WT mice. We observed Car\u2212\/\u2212 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 villi structure and Cyp gene expression in the intestine.<\/jats:p>","DOI":"10.1210\/jendso\/bvac145","type":"journal-article","created":{"date-parts":[[2022,9,21]],"date-time":"2022-09-21T21:31:18Z","timestamp":1663795878000},"source":"Crossref","is-referenced-by-count":7,"title":["Deletion of Constitutive Androstane Receptor Led to Intestinal Alterations and Increased Imidacloprid in Murine Liver"],"prefix":"10.1210","volume":"6","author":[{"given":"Anushna","family":"Sen","sequence":"first","affiliation":[{"name":"Department of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign , Urbana, IL 61801 , USA"},{"name":"Toxicology Training Program, University of Illinois at Urbana-Champaign , Urbana, IL 61801 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Madison","family":"Goforth","sequence":"additional","affiliation":[{"name":"Toxicology Training Program, University of Illinois at Urbana-Champaign , Urbana, IL 61801 , USA"},{"name":"School of Animal and Comparative Biomedical Sciences, University of Arizona , Tucson, AZ 85721 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kerry K","family":"Cooper","sequence":"additional","affiliation":[{"name":"School of Animal and Comparative Biomedical Sciences, University of Arizona , Tucson, AZ 85721 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2819-695X","authenticated-orcid":false,"given":"Sayeepriyadarshini","family":"Anakk","sequence":"additional","affiliation":[{"name":"Department of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign , Urbana, IL 61801 , USA"},{"name":"Toxicology Training Program, University of Illinois at Urbana-Champaign , Urbana, IL 61801 , USA"},{"name":"Cancer Center at Illinois, University of Illinois at Urbana-Champaign , Urbana, IL 61801 , USA"},{"name":"Division of Nutritional Sciences, University of Illinois at Urbana-Champaign , Urbana, IL 61801 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","published-online":{"date-parts":[[2022,9,21]]},"reference":[{"issue":"6","key":"2022102713172706300_bvac145-B1","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1039\/C9EM00586B","article-title":"A critical review on the potential impacts of neonicotinoid insecticide use: current knowledge of environmental fate, toxicity, and implications for human health","volume":"22","author":"Thompson","year":"2020","journal-title":"Environ Sci Process Impacts"},{"key":"2022102713172706300_bvac145-B2","author":"U.S. Geological 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