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

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Abstract

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 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.

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Funding

This work was financially supported by the “PRD program for Research and innovation between the Tunisian Ministry of higher education and scientific research and the Kingdom of Morocco Ministry of National Education and Vocational Training “ PRD project number 20/PRD-10.”

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Authors and Affiliations

  1. Laboratory of Toxicology-Microbiology and Environmental Health (17ES06), Faculty of Sciences of Sfax, University of Sfax, BP1171, 3000, Sfax, Tunisia

    Bakhta Aouey, Khadija Boukholda, Brahim Gargouri & Hamadi Fetoui

  2. Institute for Tissue Engineering and Regenerative Medicine (iTERM), Helmholtz Zentrum München, 85764, Neuherberg, Germany

    Harsharan S. Bhatia

  3. Institute for Stroke and Dementia Research, Klinikum Der Universität München, Ludwig Maximilian University of Munich (LMU), 81377, Munich, Germany

    Harsharan S. Bhatia

  4. Department of Anatomy and Histology, Faculty of Veterinary Medicine, Assiut University, Assiut, Egypt

    Abdelraheim Attaai

  5. Laboratory of Cellular and Molecular Biology, University of Mohamed Seddik Ben Yahia, Jijel, Algeria

    Mohamed Kebieche

  6. Faculty of Natural and Life Sciences, LBMBPC, University of Batna 2, 05078, Fesdis, Batna2, Algeria

    Mohamed Kebieche

  7. Department of Environmental and Occupational Health, Chair in Toxicological Risk Assessment and Management, and Public Health Research Center (CReSP), University of Montreal, Roger-Gaudry Building, U424Main Station, P.O. Box 6128, Montreal, Quebec, H3C 3J7, Canada

    Michèle Bouchard

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Contributions

BA, KB, BG, and HF participated in the research design. The experiments were performed by BA, and KB. Data were analyzed by BA, KB, BG, and HF. AA contributed to histology analysis. BA, BG, and HF contributed to the writing of the manuscript. In addition, BA, KB, BG, HSB, MK, MB, and HF reviewed the data and the manuscript. All authors have read and approved the final version of the manuscript.

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Correspondence to Hamadi Fetoui.

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The experimental approach and handling of animals were performed under the experiments conducted approved by the Ethical Committee Guidelines for the Care and Use of Laboratory Animals of the Faculty of Sciences of Sfax. Tunisia. It was also carried out following guidelines as set out in the “Guide for the Care and Use of Laboratory Animals” and with the authorization of the committee.

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Aouey, B., Boukholda, K., Gargouri, B. et al. Silica Nanoparticles Induce Hepatotoxicity by Triggering Oxidative Damage, Apoptosis, and Bax-Bcl2 Signaling Pathway. Biol Trace Elem Res 200, 1688–1698 (2022). https://doi.org/10.1007/s12011-021-02774-3

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