دورية أكاديمية

Naringenin Against Cadmium Toxicity in Fibroblast Cells: An Integrated Network Pharmacology and In Vitro Metabolomics Approach.

التفاصيل البيبلوغرافية
العنوان: Naringenin Against Cadmium Toxicity in Fibroblast Cells: An Integrated Network Pharmacology and In Vitro Metabolomics Approach.
المؤلفون: Priya K; Biochemistry and Environmental Toxicology Laboratory, Lab. #103, School of Environmental Sciences, Jawaharlal Nehru University, New Delhi, India., Roy AC; Biochemistry and Environmental Toxicology Laboratory, Lab. #103, School of Environmental Sciences, Jawaharlal Nehru University, New Delhi, India., Prasad A; Biochemistry and Environmental Toxicology Laboratory, Lab. #103, School of Environmental Sciences, Jawaharlal Nehru University, New Delhi, India., Kumar P; Biochemistry and Environmental Toxicology Laboratory, Lab. #103, School of Environmental Sciences, Jawaharlal Nehru University, New Delhi, India., Ghosh I; Biochemistry and Environmental Toxicology Laboratory, Lab. #103, School of Environmental Sciences, Jawaharlal Nehru University, New Delhi, India.
المصدر: Environmental toxicology [Environ Toxicol] 2024 Aug 06. Date of Electronic Publication: 2024 Aug 06.
Publication Model: Ahead of Print
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: John Wiley & Sons Country of Publication: United States NLM ID: 100885357 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1522-7278 (Electronic) Linking ISSN: 15204081 NLM ISO Abbreviation: Environ Toxicol Subsets: MEDLINE
أسماء مطبوعة: Original Publication: New York, NY : John Wiley & Sons, c1999-
مستخلص: Cadmium, a heavy metal, disrupts cellular homeostasis and is highly toxic, with no effective treatments currently available against its toxicity. According to studies, phytochemicals provide a promising strategy for mitigating cadmium toxicity. Naringenin (NG), a potent antioxidant found primarily in citrus fruits, showed protective properties against cadmium toxicity in rats. Nonetheless, the precise mechanism of cadmium cytotoxicity in fibroblasts remains unknown. This study evaluated NG against cadmium (CdCl 2 ) toxicity utilizing network pharmacology and in silico molecular docking, and was further validated experimentally in rat fibroblast F111 cells. Using network pharmacology, 25 possible targets, including the top 10 targets of NG against cadmium, were identified. Molecular docking of interleukin 6 (IL6), the top potential target with NG, showed robust binding with an inhibition constant (Ki) of 58.76 μM, supporting its potential therapeutic potential. Pathway enrichment analysis suggested that "response to reactive oxygen species" and "negative regulation of small molecules metabolic process" were the topmost pathways targeted by NG against cadmium. In vitro analysis showed that NG (10 μM) attenuated CdCl 2 -induced oxidative stress by reducing altered intracellular ROS, mitochondrial mass, and membrane potential. Also, NG reversed CdCl 2 -mediated nuclear damage, G2/M phase arrest, and apoptosis. GC/MS-based metabolomics of F111 cells revealed CdCl 2 reduced cholesterol levels, which led to alterations in primary bile acid, steroid and steroid hormone biosynthesis pathways, whereas, NG restored these alterations. In summary, combined in silico and in vitro analysis suggested that NG protected cells from CdCl 2 toxicity by mitigating oxidative stress and metabolic pathway alterations, providing a comprehensive understanding of its protective mechanisms against cadmium-induced toxicity.
(© 2024 Wiley Periodicals LLC.)
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معلومات مُعتمدة: DST-PURSE; UGC UPE-II
فهرسة مساهمة: Keywords: cadmium; metabolomics; naringenin; network pharmacology; oxidative stress
تواريخ الأحداث: Date Created: 20240806 Latest Revision: 20240806
رمز التحديث: 20240806
DOI: 10.1002/tox.24388
PMID: 39105392
قاعدة البيانات: MEDLINE
الوصف
تدمد:1522-7278
DOI:10.1002/tox.24388