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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.
AboZaid, Omayma A R; Abdel-Maksoud, Mostafa A; Saleh, Ibrahim A; El-Tayeb, Mohamed A; El-Sonbaty, Sawsan M; Shoker, Faten E; Salem, Maha A; Emad, Ayat M; Mani, Samson; Deva Magendhra Rao, Arunagiri Kuha; Mamdouh, Mohamed A; Kotob, Mohamed H; Aufy, Mohammed; Kodous, Ahmad S.
Afiliación
  • AboZaid OAR; Department of Biochemistry, Faculty of Veterinary Medicine, Moshtohor, Benha University, Egypt.
  • Abdel-Maksoud MA; Botany and Microbiology department- College of Science- King Saud University, Saudi Arabia.
  • Saleh IA; Faculty of Science, Zarqa University, Zarqa 13110, Jordan.
  • El-Tayeb MA; Botany and Microbiology department- College of Science- King Saud University, Saudi Arabia.
  • El-Sonbaty SM; Radiation Microbiology Department, National Center for Radiation Research & Technology (NCRRT), Egyptian Atomic-Energy Authority (EAEA), Egypt.
  • Shoker FE; Department of Biochemistry, Faculty of Veterinary Medicine, Moshtohor, Benha University, Egypt.
  • Salem MA; Pharmacology and Toxicology Department, Faculty of Pharmacy, Modern University for Technology and Information, Egypt.
  • Emad AM; Pharmacognosy Department, Faculty of Pharmacy, October 6 University, Sixth of October City, Giza 12585, Egypt.
  • Mani S; Department of Research, Rajiv Gandhi Cancer Institute, and Research Centre, Sector 5, Rohini, Delhi 110085, India; Department of Molecular Oncology, Cancer Institute (WIA), 38, Sardar Patel Road, P.O. Box 600036, Chennai, Tamilnadu, India.
  • Deva Magendhra Rao AK; Department of Molecular Oncology, Cancer Institute (WIA), 38, Sardar Patel Road, P.O. Box 600036, Chennai, Tamilnadu, India.
  • Mamdouh MA; Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, October 6 University, 6th of October City, Giza 12585, Egypt.
  • Kotob MH; Department of Pharmaceutical Sciences, Division of Pharmacology and Toxicology, University of Vienna, Vienna, Austria; Department of Pathology, Faculty of Veterinary Medicine, Assiut University, Assiut, Egypt.
  • Aufy M; Department of Pharmaceutical Sciences, Division of Pharmacology and Toxicology, University of Vienna, Vienna, Austria. Electronic address: Mohammed.aufy@univie.ac.at.
  • Kodous AS; Department of Molecular Oncology, Cancer Institute (WIA), 38, Sardar Patel Road, P.O. Box 600036, Chennai, Tamilnadu, India; Radiation Biology department, National Center for Radiation Research & Technology (NCRRT), Egyptian Atomic-Energy Authority (EAEA), Egypt. Electronic address: ahmadkmp11@g
Biomed Pharmacother ; 172: 116274, 2024 Mar.
Article en En | MEDLINE | ID: mdl-38364738
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-ß1 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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Óxido de Zinc / Carcinoma Hepatocelular / Nanopartículas del Metal / Neoplasias Hepáticas Límite: Animals Idioma: En Revista: Biomed Pharmacother Año: 2024 Tipo del documento: Article Pais de publicación: Francia

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Óxido de Zinc / Carcinoma Hepatocelular / Nanopartículas del Metal / Neoplasias Hepáticas Límite: Animals Idioma: En Revista: Biomed Pharmacother Año: 2024 Tipo del documento: Article Pais de publicación: Francia