The apoptotic, oxidative and histological changes induced by different diameters of sphere gold nanoparticles (GNPs) with special emphasis on the hepatoprotective role of Quercetin

Abstract

Purpose: Gold nanoparticles (GNPs) as pharmaceutical and drug delivery tools exhibited harmful effects on human health and other living species. Quercetin 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 quercetin in mitigating the toxicological effects of GNPs. Methods: Groups of rats were treated with or without sphere GNPs (10, 20 and 50 nm) and quercetin (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; AST, ALT, ALP and bilirubin. These 10 nm GNPs were associated with oxidative stress and markedly decreased antioxidant enzymes: GPX, CAT and 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 quercetin decreased all tested hepatic enzymes and increased serum level of antioxidant enzymes compared to 10 nm GNPs. Quercetin 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. Quercetin 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, quercetin demonstrated a significant prophylactic role against hepatotoxicity of GNPs.