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Ameliorative potential of manganese nanoparticles with low-level ionizing radiation against experimentally induced hepatocarcinogenesis

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Nanotechnology is a rich field with infinite possibilities of drug designs for cancer treatment. We aimed to biosynthesize manganese nanoparticles (Mn NPs) using Lactobacillus helveticus to investigate its anticancer synergistic effect with low-dose gamma radiation on HCC-induced rats. Diethylnitrosamine (DEN) (20 mg/kg BW, 5 times a week for 6 weeks) induced HCC in rats. Rats received Mn NPs (5 mg/kg BW/day) by gastric gavage over 4 weeks concomitant with single dose of gamma radiation (γ-R) (0.25 Gy). Characterization, cytotoxicity, and anticancer activity of Mn NPs were evaluated. DEN-induced significant liver dysfunction (alanine transaminase activity ALT, total proteins, and albumin levels) associated with significant increase in lipid peroxidation levels with reduction in super oxide dismutase activity. Furthermore, DEN intoxication is sponsored for remarkable increase in levels of Alfa-fetoprotein, tumor necrosis factor α, vascular endothelial growth factor, and transforming growth factor beta with remarkable decrease in caspase 3 and cytochrome c. Treatment with Mn NPs (4.98–11.58 nm) and single dose gamma radiation evoked significant repair in ALT, total protein, and albumin accompanied with balanced oxidative status, diminished inflammatory biomarkers, angiogenic factor, and growth factor with restoration in apoptotic factors. Mn NPs revealed obvious in vitro cytotoxic activity against HepG2 cell line in a dose-dependent manner. Our findings were well appreciated with the histopathological study. In conclusion, a new approach of the single or combined use of Mn NPs with low-dose γ-radiation regimens as promising paradigm for HCC treatment is recommended.

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Data availability

The datasets generated during the current study are available from the corresponding author on reasonable request.


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This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations



NA participated in the design of the study, practical work, and statistical analysis. SE participated in the design of the study, practical work, and statistical analysis. MH participated in practical work, statistical analysis, and drafting the manuscript. All authors revised the manuscript and have given final approval of the version to be published and they are aware of the responsibilities connected to the authorship.

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Correspondence to Marwa G. A. Hegazy.

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All Animal procedures were performed according to the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments and are in accordance with the recommendations for the proper care and use of laboratory animals approved by the Animal Care Committee of NCRRT, Egyptian Atomic Energy Authority (approval number 31A/20).

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Not applicable.

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The authors declare no competing interests.

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Responsible Editor: Mohamed M. Abdel-Daim

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Supplementary information

Supplementary Fig. 1

DLS analysis of the biosynthesized MnNPs (DOCX 21 kb)

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Abdel-Aziz, N., El-Sonbaty, S.M. & Hegazy, M.G.A. Ameliorative potential of manganese nanoparticles with low-level ionizing radiation against experimentally induced hepatocarcinogenesis. Environ Sci Pollut Res 28, 65474–65486 (2021).

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