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Novel Antioxidant, Deethylated Ethoxyquin, Protects against Carbon Tetrachloride Induced Hepatotoxicity in Rats by Inhibiting NLRP3 Inflammasome Activation and Apoptosis.

التفاصيل البيبلوغرافية
العنوان: Novel Antioxidant, Deethylated Ethoxyquin, Protects against Carbon Tetrachloride Induced Hepatotoxicity in Rats by Inhibiting NLRP3 Inflammasome Activation and Apoptosis.
المؤلفون: Iskusnykh IY; Department of Anatomy and Neurobiology, University of Tennessee Health Science Center, Memphis, TN 38163, USA., Kryl'skii ED; Department of Medical Biochemistry and Microbiology, Voronezh State University, Universitetskaya sq. 1, Voronezh 394018, Russia., Brazhnikova DA; Department of Medical Biochemistry and Microbiology, Voronezh State University, Universitetskaya sq. 1, Voronezh 394018, Russia., Popova TN; Department of Medical Biochemistry and Microbiology, Voronezh State University, Universitetskaya sq. 1, Voronezh 394018, Russia., Shikhaliev KS; Department of Organic Chemistry, Voronezh State University, Universitetskaya sq. 1, Voronezh 394018, Russia., Shulgin KK; Department of Medical Biochemistry and Microbiology, Voronezh State University, Universitetskaya sq. 1, Voronezh 394018, Russia., Matasova LV; Department of Medical Biochemistry and Microbiology, Voronezh State University, Universitetskaya sq. 1, Voronezh 394018, Russia., Popov SS; 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., Zhaglin DA; Department of Medical Biochemistry and Microbiology, Voronezh State University, Universitetskaya sq. 1, Voronezh 394018, Russia., Zakharova AA; Department of Medical Biochemistry, Faculty of Biomedicine, Pirogov Russian National Research Medical University, Ostrovitianov St. 1, Moscow 117997, Russia., Popova NR; Laboratory of Isotope Investigations, Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Pushchino 142290, Moscow Region, Russia.; Laboratory of Functional Materials Synthesis and Mineral Processing, Kurnakov Institute of General and Inorganic Chemistry, Russian Academy of Sciences, Moscow 119991, Russia., Fattakhov N; Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
المصدر: Antioxidants (Basel, Switzerland) [Antioxidants (Basel)] 2021 Jan 15; Vol. 10 (1). Date of Electronic Publication: 2021 Jan 15.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: MDPI AG Country of Publication: Switzerland NLM ID: 101668981 Publication Model: Electronic Cited Medium: Print ISSN: 2076-3921 (Print) Linking ISSN: 20763921 NLM ISO Abbreviation: Antioxidants (Basel) Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: Basel, Switzerland : MDPI AG, [2012]-
مستخلص: 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 (CCl 4 )-induced ALI. Our results demonstrate that DEQ improved liver function which was indicated by the reduction of histopathological liver changes. Treatment with DEQ reduced CCl 4 -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 CCl 4 -induced NLRP3-inflammasome activation which was indicated by the reduced protein expression of IL-1β, 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.
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معلومات مُعتمدة: project No. 20-04-00526 Russian Foundation for Basic Research; No. МК-518.2019.3 President of Russia grants for 2019/2020
فهرسة مساهمة: Keywords: acute liver injury; antioxidant enzymes; apoptosis; carbon tetrachloride; deethylated ethoxyquin; ethoxyquin; glutathione; inflammasome; oxidative stress
تواريخ الأحداث: Date Created: 20210120 Latest Revision: 20210218
رمز التحديث: 20240829
مُعرف محوري في PubMed: PMC7829797
DOI: 10.3390/antiox10010122
PMID: 33467773
قاعدة البيانات: MEDLINE
الوصف
تدمد:2076-3921
DOI:10.3390/antiox10010122