Silica nanoparticles induce hepatotoxicity by triggering oxidative damage, apoptosis, and bax-Bcl2 signaling pathway
| Autor: | Harsharan S. Bhatia, Mohamed Kebieche, Michèle Bouchard, Khadija Boukholda, Brahim Gargouri, Bakhta Aouey, Abdelraheim Attaai, Hamadi Fetoui |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
Endocrinology Diabetes and Metabolism Clinical Biochemistry Apoptosis Caspase Hepatotoxicity Ros Silica Nanoparticles 010501 environmental sciences Pharmacology medicine.disease_cause 01 natural sciences Biochemistry Inorganic Chemistry 03 medical and health sciences chemistry.chemical_compound Downregulation and upregulation Lactate dehydrogenase medicine Animals bcl-2-Associated X Protein 0105 earth and related environmental sciences chemistry.chemical_classification 0303 health sciences Reactive oxygen species biology 030302 biochemistry & molecular biology Biochemistry (medical) Kupffer cell Hydrogen Peroxide General Medicine Silicon Dioxide Rats Oxidative Stress medicine.anatomical_structure chemistry Hepatocyte biology.protein Nanoparticles Chemical and Drug Induced Liver Injury Oxidative stress Signal Transduction |
| Zdroj: | Biol. Trace Elem. Res. 200, 1688-1698 (2021) |
| Popis: | 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 100mg/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 H2O2), 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. |
| Databáze: | OpenAIRE |
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