{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:32:29Z","timestamp":1787027549168,"version":"build-2736575974"},"reference-count":72,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,1,15]],"date-time":"2021-01-15T00:00:00Z","timestamp":1610668800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002261","name":"Russian Foundation for Basic Research","doi-asserted-by":"publisher","award":["project No. 20-04-00526"],"award-info":[{"award-number":["project No. 20-04-00526"]}],"id":[{"id":"10.13039\/501100002261","id-type":"DOI","asserted-by":"publisher"}]},{"name":"President of Russia grants for 2019\/2020","award":["No. \u041c\u041a-518.2019.3"],"award-info":[{"award-number":["No. \u041c\u041a-518.2019.3"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Inflammation and an increase in antioxidant responses mediated by oxidative stress play an important role in the pathogenesis of acute liver injury (ALI). We utilized in silico prediction of biological activity spectra for substances (PASS) analysis to estimate the potential biological activity profile of deethylated ethoxyquin (DEQ) and hypothesized that DEQ exhibits antioxidant and anti-inflammatory effects in a rat model of carbon tetrachloride (CCl4)-induced ALI. Our results demonstrate that DEQ improved liver function which was indicated by the reduction of histopathological liver changes. Treatment with DEQ reduced CCl4-induced elevation of gene expression, and the activity of antioxidant enzymes (AEs), as well as the expression of transcription factors Nfe2l2 and Nfkb2. Furthermore, DEQ treatment inhibited apoptosis, downregulated gene expression of pro-inflammatory cytokines (Tnf and Il6), cyclooxygenase 2 (Ptgs2), decreased glutathione (GSH) level and myeloperoxidase (MPO) activity in rats with ALI. Notably, DEQ treatment led to an inhibition of CCl4-induced NLRP3-inflammasome activation which was indicated by the reduced protein expression of IL-1\u03b2, caspase-1, and NLRP3 in the liver. Our data suggest that DEQ has a hepatoprotective effect mediated by redox-homeostasis regulation, NLRP3 inflammasome, and apoptosis inhibition, which makes that compound a promising candidate for future clinical studies.<\/jats:p>","DOI":"10.3390\/antiox10010122","type":"journal-article","created":{"date-parts":[[2021,1,18]],"date-time":"2021-01-18T05:17:34Z","timestamp":1610947054000},"page":"122","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Novel Antioxidant, Deethylated Ethoxyquin, Protects against Carbon Tetrachloride Induced Hepatotoxicity in Rats by Inhibiting NLRP3 Inflammasome Activation and Apoptosis"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1207-6075","authenticated-orcid":false,"given":"Igor Y.","family":"Iskusnykh","sequence":"first","affiliation":[{"name":"Department of Anatomy and Neurobiology, University of Tennessee Health Science Center, Memphis, TN 38163, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8855-5515","authenticated-orcid":false,"given":"Evgenii D.","family":"Kryl\u2019skii","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry and Microbiology, Voronezh State University, Universitetskaya sq. 1, Voronezh 394018, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darya A.","family":"Brazhnikova","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry and Microbiology, Voronezh State University, Universitetskaya sq. 1, Voronezh 394018, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9660-3054","authenticated-orcid":false,"given":"Tatyana N.","family":"Popova","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry and Microbiology, Voronezh State University, Universitetskaya sq. 1, Voronezh 394018, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khidmet S.","family":"Shikhaliev","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry, Voronezh State University, Universitetskaya sq. 1, Voronezh 394018, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantin K.","family":"Shulgin","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry and Microbiology, Voronezh State University, Universitetskaya sq. 1, Voronezh 394018, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larisa V.","family":"Matasova","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry and Microbiology, Voronezh State University, Universitetskaya sq. 1, Voronezh 394018, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4438-9201","authenticated-orcid":false,"given":"Sergey S.","family":"Popov","sequence":"additional","affiliation":[{"name":"Department of Organization of Pharmaceutical Business, Clinical Pharmacy and Pharmacognosy, Voronezh State Medical University Named after N.N. Burdenko, st. Studencheskaya 10, Voronezh 394036, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dmitry A.","family":"Zhaglin","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry and Microbiology, Voronezh State University, Universitetskaya sq. 1, Voronezh 394018, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasia A.","family":"Zakharova","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Faculty of Biomedicine, Pirogov Russian National Research Medical University, Ostrovitianov St. 1, Moscow 117997, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nelli R.","family":"Popova","sequence":"additional","affiliation":[{"name":"Laboratory of Isotope Investigations, Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Pushchino 142290, Moscow Region, Russia"},{"name":"Laboratory of Functional Materials Synthesis and Mineral Processing, Kurnakov Institute of General and Inorganic Chemistry, Russian Academy of Sciences, Moscow 119991, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolai","family":"Fattakhov","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1111\/j.1478-3231.2010.02262.x","article-title":"Acute liver failure: Mechanisms of immune-mediated liver injury","volume":"30","author":"Wu","year":"2010","journal-title":"Liver Int."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/S0140-6736(10)60274-7","article-title":"Acute liver failure","volume":"376","author":"Bernal","year":"2010","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.aquatox.2014.02.014","article-title":"Effects of carbon tetrachloride on oxidative stress, inflammatory response and hepatocyte apoptosis in common carp (Cyprinus carpio)","volume":"152","author":"Jia","year":"2014","journal-title":"Aquat. 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