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Molecular mechanisms of conjugated zinc nano-particles for nano drug delivery against hepatic cirrhosis in CCl4-induced rats model

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Rendiconti Lincei. Scienze Fisiche e Naturali Aims and scope Submit manuscript

Abstract

The study aimed to develop and analyze a conjugated zinc Nano particle formulation that would enhance its anti-cirrhosis activity by increasing its bioavailability and release. Standard characterization procedures were used to create and analyze zinc nano particles (ZNPs). Drug release and hepatic cirrhosis model testing were conducted on rats utilizing the enhanced formulation. For 30 days, ZnNPs were supplied through oral gavage. For biochemical examination of serum samples, rats were anesthetized and slaughtered after the research. The expression of genes and microRNAs (miRNAs) in liver tissues was studied; together with expression of liver specific genes and inflammatory markers. These findings were also validated by liver tissue histological and immune histochemical (IHC) studies. Measuring techniques demonstrated the practical synthesis and conjugation of ZnNPs. Nanohybrid ZnNPs showed significant anticirrhosis therapeutic activity. ZnNPs' anti-cirrhosis properties decrease TGFR1 and COL3A1 expression, because they enhance the production of miRNAs that protect against cirrhosis. Furthermore, the expression of cancer markers (AFP, p53) was down/up-regulated in ZnNPs treated groups. Similarly, the pro- and anti-inflammatory markers expressions were found normalized in ZnNPs groups compared to untreated groups. These results were further validated by histopathology and IHC analysis, which showed that ZnNPs have anti-fibrotic properties. We finally, conclude that the that we achieve loading capacity of 94%, 36.63%, respectively, in the successful synthesis of ZnNPs. Furthermore, ZnNPs exhibits in vivo hepato-protective activity by down-regulating hepatic cancer markers and upregulating hepatic functional markers which assure the use of ZnNPs for the treatment of liver cirrhosis in future studies.

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Funding

Princess Nourah bint Abdulrahman University Researchers Supporting Project number (PNURSP2023R402), Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia.

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Authors and Affiliations

  1. Department of Biology, College of Science, University of Jeddah, 21589, Jeddah, Saudi Arabia

    Fatima S. Alaryani

  2. Department of Biology, Jamoum University College, Umm Al-Qura University, 21955, Makkah, Saudi Arabia

    Ifat Alsharif & Nouf S. Al-Abbas

  3. Department of Chemistry, Al Lieth University College, Umm Al-Qura University, 21955, Makkah, Saudi Arabia

    Nehad. A. Shaer

  4. Department of Biology, College of Science, Princess Nourah bint Abdulrahman University, P.O. Box 84428, 11671, Riyadh, Saudi Arabia

    Khairiah Mubarak Alwutayd

  5. Department of Biology, Faculty of Science, University of Tabuk, 47913, Tabuk, Saudi Arabia

    Aishah E. Albalawi

  6. Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, University of Tabuk, 71491, Tabuk, Saudi Arabia

    Zuhair M. Mohammedsaleh

  7. University College of Duba, University of Tabuk, Tabuk, Saudi Arabia

    Sohad Abdulkaleg Alshareef

  8. Department of Anatomy, College of Medicine, University of Jeddah, P.O. Box 8304, 23234, Jeddah, Saudi Arabia

    Waheeb S. Aggad

Authors
  1. Fatima S. Alaryani
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  2. Ifat Alsharif
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  3. Nehad. A. Shaer
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  4. Nouf S. Al-Abbas
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  5. Khairiah Mubarak Alwutayd
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  6. Aishah E. Albalawi
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  7. Zuhair M. Mohammedsaleh
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  8. Sohad Abdulkaleg Alshareef
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  9. Waheeb S. Aggad
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Contributions

Conceptualization: FSA and KA. Methodology: FSA, IA, NAS. Software and visualization: AEA. Validation: AEA, NSA-A. Formal analysis: ZMM and KA. Investigation: WSA, resources, KA. Writing—original draft preparation: FSA and NSA-A. Editing: SAA, IA, NAS and WSA. Supervision: FSA and KA. Project administration: KA. Funding acquisition, KA. Submission, IA. All authors have read and agreed to the published version of the manuscript.

Corresponding author

Correspondence to Ifat Alsharif.

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The authors declare no conflict of interest.

Ethical approval

This study was done according to the international ethical committee from the institutional bioethics committee. All animal experiments were done by basic science labs of University of Jeddah. All study is reported in accordance guidelines.

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Alaryani, F.S., Alsharif, I., Shaer, N.A. et al. Molecular mechanisms of conjugated zinc nano-particles for nano drug delivery against hepatic cirrhosis in CCl4-induced rats model. Rend. Fis. Acc. Lincei 34, 1133–1143 (2023). https://doi.org/10.1007/s12210-023-01187-9

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  • DOI: https://doi.org/10.1007/s12210-023-01187-9

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