The Apoptotic, Oxidative and Histological Changes Induced by Different Diameters of Sphere Gold Nanoparticles (GNPs) with Special Emphasis on the Hepatoprotective Role of Quercetin

Wael A M Ghonimi; Foll Alnada A F Abdelrahman; Gamal A Salem; Naief Dahran; Shafika A El Sayed

doi:10.34172/apb.2024.014

The Apoptotic, Oxidative and Histological Changes Induced by Different Diameters of Sphere Gold Nanoparticles (GNPs) with Special Emphasis on the Hepatoprotective Role of Quercetin

Adv Pharm Bull. 2024 Mar;14(1):208-223. doi: 10.34172/apb.2024.014. Epub 2023 Oct 14.

Authors

Wael A M Ghonimi¹, Foll Alnada A F Abdelrahman¹, Gamal A Salem², Naief Dahran³, Shafika A El Sayed¹

Affiliations

¹ Department of Histology and Cytology, Faculty of Veterinary Medicine, Zagazig University, 44519 Zagazig, Egypt.
² Department of Pharmacology, Faculty of Veterinary Medicine, Zagazig University, 44519 Zagazig, Egypt.
³ Department of Anatomy, Faculty of Medicine, University of Jeddah, Jeddah, Saudi Arabia.

Abstract

Purpose: Gold nanoparticles (GNPs) as pharmaceutical and drug delivery tools exhibited harmful effects on human health and other living species. Quercetin (Qur) reveals various pharmacological effects specially antioxidant, anti-inflammatory and antiapoptotic. This study is directed to investigate hepatotoxicity of GNPs, in addition, to assess the impact of Qur in mitigating the toxicological effects of GNPs.

Methods: Groups of rats were treated with or without sphere GNPs (10, 20 and 50 nm) and Qur (200 mg/kg b.wt.). Blood and liver samples from euthanized rats were subjected to biochemical, hematological, histopathological, and immunohistochemical investigations.

Results: In comparison with 20 and 50 nm treated groups, the 10 nm GNPs significantly increased serum hepatic enzymes, aspartate aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP) and bilirubin. These 10 nm GNPs were associated with oxidative stress and markedly decreased antioxidant enzymes: catalase (CAT), glutathione peroxidase (GPX) and superoxide dismutase (SOD). Immunohistochemically, 10 nm GNPs expressed intense positive signals in nuclei of hepatocytes when stained with anti-caspase-3 antibody confirming extensive apoptosis. Pre-cotreatment with Qur decreased all tested hepatic enzymes and increased serum level of antioxidant enzymes compared to 10 nm GNPs. Qur treatment strongly exhibited anti-Ki67 antibody (proliferative marker) indicating high proliferation of hepatic parenchyma. Histopathologically, 10 nm GNPs revealed diffuse hydropic degenerations, severe sinusoidal congestion, coagulative necrosis, sever steatosis and diffuse hemosiderosis within the hepatic parenchyma. Qur treatment ameliorated most of these pathological effects.

Conclusion: The smaller diameters of GNPs induce potential oxidative stress, cytotoxic, and apoptotic effects in hepatic tissues rather than larger ones. In addition, Qur demonstrated a significant prophylactic role against hepatotoxicity of GNPs.

Keywords: Apoptosis; GNPs; Gold nanoparticle; Nanoparticles; Oxidative stress; Quercetin; Toxicity.