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Zinc oxide nanoparticles regulate NF-kB expression and restrict inflammation response in doxorubicin-induced kidney injury in rats

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Abstract

Object

Doxorubicin (DOX) is an anthracycline drug used for cancer treatment. However, its treatment is contiguous with renal toxic effects. This study aims to investigate the therapeutic effects of zinc oxide nanoparticles (ZnONPs) on doxorubicin-induced nephrotoxicity.

Methods

ZnONPs were prepared by the hydrothermal microwave method and characterized by XRD, SEM (combined with EDX) and HRTEM. To explore the possible nephrotoxicity and antioxidant effect of ZnONPs, rats were grouped as follows: control group, ZnONPs-treated group, doxorubicin group, and ZnONPs-Doxorubicin-treated group.

Results

DOX treatment increases renal tissue oxidative stress markers, while lowering antioxidant enzymes in tissue along with degenerative alterations in the renal tissue compared to control rats. Upon treatment with ZnONPs, a significant alteration was observed in the activities of superoxide dismutase, glutathione peroxidase, malondialdehyde, catalase, and the levels of kidney function, albumin, albuminuria, immune nuclear factor kappa B (NF-kB), and interleukin-6 (IL-6) compared to the doxorubicin group and control group. ZnONPs' administration to the doxorubicin group showed eminent renal injury control and restoration of the biochemical profile. This increases their active role in controlling kidney functions in order to improve nephrotoxicity and inflammatory responses. Histopathological and immunohistochemical observations provided context for these findings. In addition, ZnONPs alone did not show any undesirable effects on the renal parameters. However, its administration improves the renal functions.

Conclusion

We concluded that the administration of ZnONPs ameliorated nephrotoxicity in rats caused by doxorubicin through its antioxidant and anti-inflammatory and antiapoptotic properties. This shows the therapeutic application of ZnONPs as a safe anti-inflammatory and might serve as a potential adjuvant that avoids DOX-induced nephrotoxicity.

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Data availability

The data that supports this work are available upon reasonable request.

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Acknowledgements

The authors would like to thank the Chemistry Department, Faculty of Science, Mansoura University, Egypt, for providing some of the facilities required during this study. They are also thankful for the faculty of Science, Suez Canal University, Egypt, for providing facilities required for the study.

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Authors and Affiliations

  1. Department of Chemistry, Faculty of Science, Suez Canal University, Ismailia, Egypt

    Ahlam Elgohary, Faten Metwalli & Nasser Y. Mostafa

  2. Biochemistry Division, Chemistry Department, Faculty of Science, Mansoura University, Mansoura, 35516, Egypt

    Manar reffat & Omali Y. El-Khawaga

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  1. Ahlam Elgohary
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  2. Faten Metwalli
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  3. Nasser Y. Mostafa
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Contributions

The study's inception and design were contributed by all authors.

Corresponding author

Correspondence to Omali Y. El-Khawaga.

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Conflict of interest

Ahlam Elgohary, Faten Metwalli, Nasser Y. Mostafa, Manar reffat and Omali Y. El-Khawaga declare that we have no conflict of interest.

Ethical approval

This study was approved by Research Ethical Committee of the Suez Canal University, Ismailia, Egypt. Number (REC25/2022).

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Elgohary, A., Metwalli, F., Mostafa, N.Y. et al. Zinc oxide nanoparticles regulate NF-kB expression and restrict inflammation response in doxorubicin-induced kidney injury in rats. Toxicol. Environ. Health Sci. 15, 437–448 (2023). https://doi.org/10.1007/s13530-023-00194-5

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