Title
Targeting the NF-κB p65/Bcl-2 signaling pathway in hepatic cellular carcinoma using radiation assisted synthesis of zinc nanoparticles coated with naturally isolated gallic acid
Author
Omayma A.R. AboZaid
Department of Biochemistry, Faculty of Veterinary Medicine, Moshtohor, Benha University
Author
Mostafa A. Abdel-Maksoud
Botany and Microbiology department, College of Science, King Saud University
Author
Ibrahim A. Saleh
Faculty of Science, Zarqa University
... show all
Abstract
Purpose: Oral diethylnitrosamine (DEN) is a known hepatocarcinogen that damages the liver and causes cancer. DEN damages the liver through reactive oxygen species-mediated inflammation and biological process regulation. Materials and methods: Gallic acid-coated zinc oxide nanoparticles (Zn-GANPs) were made from zinc oxide (ZnO) synthesized by irradiation dose of 50 kGy utilizing a Co-60 γ-ray source chamber with a dose rate of 0.83 kGy/h and gallic acid from pomegranate peel. UV–visible (UV) spectrophotometry verified Zn-GANP synthesis. TEM, DLS, and FTIR were utilized to investigate ZnO-NPs' characteristics. Rats were orally exposed to DEN for 8 weeks at 20 mg/kg five times per week, followed by intraperitoneal injection of Zn-GANPs at 20 mg/kg for 5 weeks. Using oxidative stress, anti-inflammatory, liver function, histologic, apoptotic, and cell cycle parameters for evaluating Zn-GANPs treatment. Results: DEN exposure elevated inflammatory markers (AFP and NF-κB p65), transaminases (AST, ALT), γ-GT, globulin, and total bilirubin, with reduced protein and albumin levels. It also increased MDA levels, oxidative liver cell damage, and Bcl-2, while decreasing caspase-3 and antioxidants like GSH, and CAT. Zn-GANPs significantly mitigated these effects and lowered lipid peroxidation, AST, ALT, and γ-GT levels, significantly increased CAT and GSH levels (p<0.05). Zn-GANPs caused S and G2/M cell cycle arrest and G0/G1 apoptosis. These results were associated with higher caspase-3 levels and lower Bcl-2 and TGF-β1 levels. Zn-GANPs enhance and restore the histology and ultrastructure of the liver in DEN-induced rats. Conclusion: The data imply that Zn-GANPs may prevent and treat DEN-induced liver damage and carcinogenesis.
Keywords
Hepatic carcinomaPomegranate peelGallic acidRadiationZn-GANPsNF-κB p65Bcl-2G2/MTGF-β1
Object type
Language
English [eng]
Persistent identifier
https://phaidra.univie.ac.at/o:2083417
Appeared in
Title
Biomedicine & Pharmacotherapy
Volume
172
ISSN
0753-3322
Issued
2024
Publisher
Elsevier BV
Date issued
2024
Access rights
Rights statement
© 2024 The Author(s)

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