Identification of hepatotoxicity of untreated and UV-irradiated GdYVO₄:Eu³⁺ nanoparticles
DOI:
https://doi.org/10.15584/ejcem.2026.1.16Keywords:
gadolinium-yttrium orthovanadate nanoparticles, hepatotoxicity, oxidative stress, UV-irradiationAbstract
Introduction and aim. Gadolinium–yttrium orthovanadate GdYVO4:Eu3+ nanoparticles (NPs) display dual redox activity, acting as pro-oxidants or antioxidants depending on the surrounding environment, concentration, and pretreatment conditions, a property that can be harnessed for potential oncological therapies. This study aims to evaluate the effect of untreated and UV-irradiated NPs administered orally on blood biochemical parameters, liver tissue, and histological condition of liver tissue in an experiment on laboratory rats.
Material and methods. Male rats of the WAG population received oral colloidal NPs solutions (in untreated and UV-irradiated forms) at different doses: (50, 100, 200) μg/kg of body weight for 14 days. The content of medium-weight molecules, alanine aminotransferase activity, direct and indirect bilirubin content, and von Willebrand factor content were determined in blood serum. The content of reduced glutathione, superoxide dismutase, diene conjugates, and TBK-active products was determined in liver homogenates. Liver tissue samples were examined using morphological and morphometric methods.
Results. The formation of oxidative stress, intoxication, damage to endothelial cells, impaired membrane permeability, destruction of hepatocytes, and destruction of sinusoidal endothelial cells were detected.
Conclusion. It has been established that the introduction of GdYVO4: Eu3+ NP, both in untreated and UV-irradiated forms, induces dose-dependent effects, including oxidative stress, endothelial dysfunction, intoxication, damage to hepatocyte membranes, functional and histological damage to the liver, with more pronounced effects observed for UV-irradiated NPs.
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References
Raj S, Khurana S, Choudhari R, et al. Specific targeting cancer cells with nanoparticles and drug delivery in cancer therapy. Semin Cancer Biol. 2021;69:166-177. doi:10.1016/j.semcancer.2019.11.002
Yetisgin AA, Cetinel S, Zuvin M, Kosar A, Kutlu O. Therapeutic Nanoparticles and Their Targeted Delivery Applications. Molecules. 2020;25(9):2193. doi:10.3390/molecules25092193
Thakur N, Thakur S, Chatterjee S, Das J, Sil PC. Nanoparticles as Smart Carriers for Enhanced Cancer Immunotherapy. Front Chem. 2020;8:597806. doi:10.3389/fchem.2020.597806
Pavelić K, Kraljević Pavelić S, Bulog A, et al. Nanoparticles in Medicine: Current Status in Cancer Treatment. Int J Mol Sci. 2023;24(16):12827. doi:10.3390/ijms241612827
Abdesselem M, Schoeffel M, Maurin I, et al. Multifunctional rare-earth vanadate nanoparticles: luminescent labels, oxidant sensors, and MRI contrast agents. ACS Nano. 2017;8(11):11126-11137. doi:10.1021/nn504170x
Howard D, Sebastian S, Le QV-C, Thierry B, Kempson I. Chemical Mechanisms of Nanoparticle Radiosensitization and Radioprotection: A Review of Structure-Function Relationships Influencing Reactive Oxygen Species. Int J Mol Sci. 2020;21(2):579. doi:10.3390/ijms21020579
Liu Y, Zhang P, Li F, et al. Metal-based NanoEnhancers for Future Radiotherapy: Radiosensitizing and Synergistic Effects on Tumor Cells. Theranostics. 2018;8(7):1824-1849. doi:10.7150/thno.22172
Jackson N, Cecchi D, Beckham W, Chithrani DB. Application of High-Z Nanoparticles to Enhance Current Radiotherapy Treatment. Molecules. 2024;29(11):2438. doi:10.3390/molecules29112438
Ge H, Wang D, Pan Y, et al. Sequence-Dependent DNA Functionalization of Upconversion Nanoparticles and Their Programmable Assemblies. Angew Chem Int Ed Engl. 2020;59(21):8133-8137. doi:10.1002/anie.202000831
Shi J, Yang X, Li Y, et al. MicroRNA-responsive release of Cas9/sgRNA from DNA nanoflower for cytosolic protein delivery and enhanced genome editing. Biomaterials. 2020;256:120221. doi:10.1016/j.biomaterials.2020.120221
Bakshi S, Zakharchenko A, Minko S, Kolpashchikov DM, Katz E. Towards Nanomaterials for Cancer Theranostics: A System of DNA-Modified Magnetic Nanoparticles for Detection and Suppression of RNA Marker in Cancer Cells. Magnetochemistry. 2019;5(2):24. doi:10.3390/magnetochemistry5020024
Ahmadzada T, Reid G, McKenzie DR. Fundamentals of siRNA and miRNA therapeutics and a review of targeted nanoparticle delivery systems in breast cancer. Biophys Rev. 2018;10(1):69-86. doi:10.1007/s12551-017-0392-1
Wang L, Hu C, Shao L. The antimicrobial activity of nanoparticles: present situation and prospects for the future. Int J Nanomedicine. 2017;12:1227-1249. doi:10.2147/IJN.S121956
Agarwal H, Nakara A, Shanmugam VK. Anti-inflammatory mechanism of various metal and metal oxide nanoparticles synthesized using plant extracts: A review. Biomed Pharmacother. 2019;109:2561-2572. doi:10.1016/j.biopha.2018.11.116
Tkachenko A, Pogozhykh D, Onishchenko A, et al. Gadolinium Orthovanadate GdVO4:Eu3+ Nanoparticles Ameliorate Carragttnan-indused intestinal Inflammation Journal of Farmacy and Nutrition Sciences, 2021;11:40-48. doi: https;//doi.org/ 10.29169/ 1927-5951.2021.11.06
Yefimova SL, Maksimchuk PO, Seminko VV, et al. Janus-faced redox activity of LnVO4:Eu3+ (Ln= Gd, Y, and La) nanoparticles. J Phys Chem C. 2019;123(24):15323-15329. doi.org/10.1021/acs.jpcc.9b03040
Maksimchuk PO, Hubenko KO, Grygorova GV, Klochkov VK, Sorokin AV, Yefimova SL. Impact of Eu3+ ions on prooxidant activity of ReVO4 : Eu3= nanoparticals. J Phys Chem C. 2021;125(2):1564-1569. doi.org/10. 1021/ acs.jpcc.Oc10028
Maksimchuk PO, Yefimova SL, Omielaieva VV, et al. X-ray Induced Hydroxyl Radical Generation by GdYVO4:Eu3+ Nanoparticles in Aqueous Solution: Main Mechanisms. Crystals. 2020;10(5):370. https://doi.org/10.3390/cryst10050370
Anselmo AC, Mitragotri S. Nanoparticles in the clinic: An update. Bioeng Transl Med. 2019;4(3):e10143. doi:10.1002/btm2.10143
Kasi PB, Mallela VR, Ambrozkiewicz F, Trailin A, Liška V, Hemminki K. Theranostics Nanomedicine Applications for Colorectal Cancer and Metastasis: Recent Advances. Int J Mol Sci. 2023;24(9):7922. doi:10.3390/ijms24097922
Davies J, Siebenhandl-Wolff P, Tranquart F, Jones P, Evans P. Gadolinium: pharmacokinetics and toxicity in humans and laboratory animals following contrast agent administration. Arch Toxicol. 2022;96(2):403-429. doi:10.1007/s00204-021-03189-8
Radulescu DM, Surdu VA, Ficai A, Ficai D, Grumezescu AM, Andronescu E. Green Synthesis of Metal and Metal Oxide Nanoparticles: A Review of the Principles and Biomedical Applications. Int J Mol Sci. 2023;24(20):15397. doi:10.3390/ijms242015397
Khan I, Saeed K, Nanoparticles properties? Applications and toxicitts. Arabian Journal of Chemistry 2019;12(7);908-931 doi:10. 1016/ i Arabic. 2017.05.0
Sun H, Jiang C, Wu L, Bai X, Zhai S. Cytotoxicity-Related Bioeffects Induced by Nanoparticles: The Role of Surface Chemistry. Front Bioeng Biotechnol. 2019;7:414. doi:10.3389/fbioe.2019.00414
Önal Acet B, Gül D, Stauber RH, Odabaşı M, Acet Ö. A Review for Uncovering the "Protein-Nanoparticle Alliance": Implications of the Protein Corona for Biomedical Applications. Nanomaterials (Basel). 2024;14(10):823. doi:10.3390/nano14100823
Maksimchuk P, Yefimova S, Hubenko K, et al. Dark reactive oxygen species generation in ReVO:Eu³⁺(Re=Gd, Y) nanoparticles in aqueous solutions. J Phys Chem C. 2020;124(6):3843-3850. doi:10.1021/acs.jpcc.9b10143
Yefimova SL, Maksimchuk PO, Hubenko KO, et al. Light-triggered redox activity of GdYVO4:Eu3+ nanoparticles. Spectrochim Acta A Mol Biomol Spectrosc. 2020;242:118741. doi:10.1016/j.saa.2020.118741
Onishchenko A, Myasoedov V, Yefimova S, et al. UV Light-Activated GdYVO4:Eu3+ Nanoparticles Induce Reactive Oxygen Species Generation in Leukocytes Without Affecting Erythrocytes In Vitro. Biol Trace Elem Res. 2022;200(6):2777-2792. doi:10.1007/s12011-021-02867-z
Weng TI, Chen HJ, Lu CW, et al. Exposure of Macrophages to Low-Dose Gadolinium-Based Contrast Medium: Impact on Oxidative Stress and Cytokines Production. Contrast Media Mol Imaging. 2018;2018:3535769. doi:10.1155/2018/3535769
Klochkov VK, Malyshenko AL, Sedyh OO, Malyukin YuV. Wet-chemical syntesis and characterization of luminescent colloidal nanoparticles ReVO4: Eu3+ (Re=La, Gd, Y) with rod- like and spindle-like shape. Fanctional materials. 2011;1:111-115.
Dzyubanovsky II, Vervega BM, Pidruchna SR, Melnyk NA. Syndrome of endogenous intoxication at experimental peritonitis against the background of diabetes. Bulletin of Scientific Research. 2019;1:135-139. doi:10.11603/2415-8798.2019.1.10004.
Stoscheck CM. Quantitation of protein. Methods Enzymol. 1990;182:50-68. doi:10.1016/0076-6879(90)82008-p
Botsoglou NA, Fletouris DJ, Papageorgiou G, et al. Rapid, sensitive, and specific thiobarbituric acid method for measuring lipid peroxidation in animal tissue, food, and feedstuff samples. Journal of Agricultural and Food Chemistry. 1994;42(9):1931-1937. doi:10.1021/JF00045A019
Cammansky I, Cruener V. Spectrofotometric methods for measuring diene conjugation. Clin Chem Acta. 1997;259:177-179
Tietze F. Enzymic method for quantitative determination of nanogram amounts of total and oxidized glutathione: applications to mammalian blood and other tissues. Anal Biochem. 1969;27(3):502-522. doi:10.1016/0003-2697(69)90064-5
Tupper J, Tozer GM, Dachs GU. Use of horseradish peroxidase for gene-directed enzyme prodrug therapy with paracetamol. Br J Cancer. 2004;90(9):1858-1862. doi:10.1038/sj.bjc.6601780
Zelditch ML, Swiderski DL, Sheets HD, Fink WL. Geometric Morphometrics for Biologists: A Primer. 3rd ed. Elsevier Academic Press; 2012:488 p. ISBN 978-0-12-386903-6
Yang B, Chen Y, Shi J. Reactive Oxygen Species (ROS)-Based Nanomedicine. Chem Rev. 2019;119:4881-4985. https://doi.org/10.1021/acs.chemrev.8b00626
Mosquera J, García I, Liz-Marzán LM. Cellular Uptake of Nanoparticles versus Small Molecules: A Matter of Size. Acc Chem Res. 2018;51(9):2305-2313. doi:10.1021/acs.accounts.8b00292
Nikitchenko YV, Klochkov VK, Kavok NS, et al. Age-Related Effects of Orthovanadate Nanoparticles Involve Activation of GSH-Dependent Antioxidant System in Liver Mitochondria. Biol Trace Elem Res. 2021;199(2):649-659. doi:10.1007/s12011-020-02196-7
Mundekkad D, Cho WC. Nanoparticles in Clinical Translation for Cancer Therapy. Int J Mol Sci. 2022;23(3):1685. doi:10.3390/ijms23031685
Xuan L, Ju Z, Skonieczna M, Zhou PK, Huang R. Nanoparticles-induced potential toxicity on human health: Applications, toxicity mechanisms, and evaluation models. MedComm (2020). 2023;4(4):e327. doi:10.1002/mco2.327
Min Y, Suminda GGD, Heo Y, Kim M, Ghosh M, Son YO. Metal-Based Nanoparticles and Their Relevant Consequences on Cytotoxicity Cascade and Induced Oxidative Stress. Antioxidants (Basel). 2023;12(3):703. doi:10.3390/antiox12030703
Huang C, Liu X, Wu Q, et al. Cardiovascular toxic effects of nanoparticles and corresponding molecular mechanisms. Environ Pollut. 2024;356:124360. doi:10.1016/j.envpol.2024.124360
Xi WS, Tang H, Liu YY, et al. Cytotoxicity of vanadium oxide nanoparticles and titanium dioxide-coated vanadium oxide nanoparticles to human lung cells. J Appl Toxicol. 2020;40(5):567-577. doi:10.1002/jat.3926
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