Silica Nanoparticles Induce Hepatotoxicity by Triggering Oxidative Damage, Apoptosis, and Bax-Bcl2 Signaling Pathway

• Published in: Biological trace element research 2022-04, Vol.200 (4), p.1688-1698
• Main Authors: Aouey, Bakhta, Boukholda, Khadija, Gargouri, Brahim, Bhatia, Harsharan S., Attaai, Abdelraheim, Kebieche, Mohamed, Bouchard, Michèle, Fetoui, Hamadi
• Format: Article
• Language: English
• Subjects: Alanine; Alanine transaminase; Animals; Antioxidants; Apoptosis; Aspartate aminotransferase; Bcl-2 protein; bcl-2-Associated X Protein - genetics; Biochemistry; Biomedical and Life Sciences; Biotechnology; Body weight; Caspase-9; Chemical and Drug Induced Liver Injury; Damage; Enzymatic activity; Enzyme activity; Gene expression; Hepatocytes; Hepatotoxicity; Histopathology; Hydrogen peroxide; Hydrogen Peroxide - pharmacology; Hyperplasia; Inflammation; L-Lactate dehydrogenase; Lactate; Lactate dehydrogenase; Lactic acid; Life Sciences; Liver; Male; Markers; Nanoparticles; Nanoparticles - toxicity; Nucleotide sequence; Nutrition; Oncology; Oxidative Stress; p53 Protein; PCR; Rats; Reactive oxygen species; Serum; Side effects; Signal Transduction; Signaling; Silica; Silicon dioxide; Silicon Dioxide - toxicity; Transaminases
• ISSN: 0163-4984; 1559-0720
• DOI: 10.1007/s12011-021-02774-3

The increase in the usage of silica nanoparticles (SiNPs) in the industrial and medical fields has raised concerns about their possible adverse effects on human health. The present study aimed to investigate the potential adverse effects of SiNPs at daily doses of 25 and 100 mg/kg body weight intraperitoneally (i.p.) for 28 consecutive days on markers of liver damage in adult male rats. Results revealed that SiNPs induced a marked increase in serum markers of liver damage, including lactate dehydrogenase (LDH), alanine aminotransferase (ALAT), and aspartate aminotransferase (ASAT). SiNPs also induced an elevation of reactive oxygen species (ROS) production in liver, along with an increase in oxidative stress markers (NO, MDA, PCO, and H 2 O 2 ), and a decrease in antioxidant enzyme activities (CAT, SOD, and GPx). Quantitative real-time PCR showed that SiNPs also induced upregulation of pro-apoptotic gene expression (including Bax , p53 , Caspase-9/3 ) and downregulation of anti-apoptotic factors Bcl-2 . Moreover, histopathological analysis revealed that SiNPs induced hepatocyte alterations, which was accompanied by sinusoidal dilatation, Kupffer cell hyperplasia, and the presence of inflammatory cells in the liver. Taken together, these data showed that SiNPs trigger hepatic damage through ROS-activated caspase signaling pathway, which plays a fundamental role in SiNP-induced apoptosis in the liver.