دورية أكاديمية
أعرض في EDS

Isobavachalcone induces hepatotoxicity in zebrafish embryos and HepG2 cells via the System Xc - -GSH-GPX4 signaling pathway in ferroptosis response.

التفاصيل البيبلوغرافية
العنوان: Isobavachalcone induces hepatotoxicity in zebrafish embryos and HepG2 cells via the System Xc - -GSH-GPX4 signaling pathway in ferroptosis response.
المؤلفون: Ni X; College of Veterinary Medicine, Xinjiang Agricultural University, Urumqi, China.; Innovation Center for Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, China Agricultural University, Beijing, China., Gao C; Innovation Center for Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, China Agricultural University, Beijing, China., Zhu X; Innovation Center for Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, China Agricultural University, Beijing, China., Zhang X; Innovation Center for Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, China Agricultural University, Beijing, China., Fang Y; Innovation Center for Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, China Agricultural University, Beijing, China., Hao Z; College of Veterinary Medicine, Xinjiang Agricultural University, Urumqi, China.; Innovation Center for Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, China Agricultural University, Beijing, China.
المصدر: Journal of applied toxicology : JAT [J Appl Toxicol] 2024 Aug; Vol. 44 (8), pp. 1139-1152. Date of Electronic Publication: 2024 Apr 06.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: John Wiley And Sons Country of Publication: England NLM ID: 8109495 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1099-1263 (Electronic) Linking ISSN: 0260437X NLM ISO Abbreviation: J Appl Toxicol Subsets: MEDLINE
أسماء مطبوعة: Publication: : Chichester : John Wiley And Sons
Original Publication: [Philadelphia, Pa. : Heyden & Son, c1981-
مواضيع طبية MeSH: Zebrafish*/embryology , Chalcones*/toxicity , Chalcones*/pharmacology , Ferroptosis*/drug effects , Signal Transduction*/drug effects , Phospholipid Hydroperoxide Glutathione Peroxidase*/metabolism , Phospholipid Hydroperoxide Glutathione Peroxidase*/genetics, Animals ; Humans ; Hep G2 Cells ; Embryo, Nonmammalian/drug effects ; Glutathione/metabolism ; Chemical and Drug Induced Liver Injury/metabolism ; Chemical and Drug Induced Liver Injury/etiology ; Oxidative Stress/drug effects ; Membrane Potential, Mitochondrial/drug effects
مستخلص: Isobavachalcone (IBC) is a flavonoid component of the traditional Chinese medicine Psoraleae Fructus, with a range of pharmacological properties. However, IBC causes some hepatotoxicity, and the mechanism of toxicity is unclear. The purpose of this paper was to investigate the possible mechanism of toxicity of IBC on HepG2 cells and zebrafish embryos. The results showed that exposure to IBC increased zebrafish embryo mortality and decreased hatchability. Meanwhile, IBC induced liver injury and increased expression of ALT and AST activity. Further studies showed that IBC caused the increase of ROS and MDA the decrease of CAT, GSH, and GSH-Px; the increase of Fe 2+ content; and the changes of ferroptosis related genes (acsl4, gpx4, and xct) and iron storage related genes (tf, fth, and fpn) in zebrafish embryos. Through in vitro verification, it was found that IBC also caused oxidative stress and increased Fe 2+ content in HepG2 cells. IBC caused depolarization of mitochondrial membrane potential (MMP) and reduction of mitochondrial ATP, as well as altered expression of ACSl4, SLC7A11, GPX4, and FTH1 proteins. Treatment of HepG2 cells with ferrostatin-1 could reverse the effect of IBC. Targeting the System Xc - -GSH-GPX4 pathway of ferroptosis and preventing oxidative stress damage might offer a theoretical foundation for practical therapy and prevention of IBC-induced hepatotoxicity.
(© 2024 John Wiley & Sons Ltd.)
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معلومات مُعتمدة: 2060302 Key Project at Central Government Level; 2022YFD1801105 State Key Research and Development Plan, China; 2023KFKT001 Key Laboratory of Animal Disease Prevention Control and Food Safety of Sichuan Province
فهرسة مساهمة: Keywords: HepG2 cell; ferroptosis; hepatotoxicity; isobavachalcone; zebrafish embryo
المشرفين على المادة: 0 (Chalcones)
EC 1.11.1.12 (Phospholipid Hydroperoxide Glutathione Peroxidase)
20784-50-3 (isobavachalcone)
GAN16C9B8O (Glutathione)
تواريخ الأحداث: Date Created: 20240406 Date Completed: 20240715 Latest Revision: 20240715
رمز التحديث: 20240715
DOI: 10.1002/jat.4607
PMID: 38581191
قاعدة البيانات: MEDLINE
الوصف
تدمد:1099-1263
DOI:10.1002/jat.4607