GREEN-SYNTHESIZED ZINC OXIDE NANOPARTICLES FROM VERJUICE (Vitis vinifera) EXHIBIT HEPATOPROTECTIVE AND ANTIOXIDANT EFFECTS AGAINST CARBON TETRACHLORIDE -INDUCED TOXICITY IN MALE RATS

Authors

  • Pola Z. Aziz Department of Biology, College of Education, Salahaddin University-Erbil, Kurdistan Region, Iraq
  • Treefa F. Ismail Department of Biology, College of Education, Salahaddin University-Erbil, Kurdistan Region, Iraq

DOI:

https://doi.org/10.25271/sjuoz.2025.13.4.1633

Keywords:

carbon tetrachloride, Nanoparticles, Green synthesis, Copper Oxide, Ferulago Angulate [ Schltdl.] BOISS, Plant., hepatoprotection, liver function, oxidative stress biomarkers, superoxide dismutase, verjuice, zinc oxide nanoparticles

Abstract

Drug-induced liver injury, particularly that caused by carbon tetrachloride (CCl₄), poses significant clinical challenges due to oxidative stress and limited therapeutic options. This study investigated the hepatoprotective and antioxidant potential of green-synthesized zinc oxide nanoparticles (ZnO-NPs) using verjuice extract from unripe grapes in a CCl₄–induced rat model. The ZnO-NPs were characterized using UV-visible spectroscopy, X-ray diffraction, fourier transform infrared (FTIR) scanning electron microscopy, and energy-dispersive X-ray spectroscopy (EDX) analyses. Twenty male Wistar rats were assigned to four groups: control, CCl₄ toxicity (1 mL/kg twice weekly for 4 weeks), co-treatment (CCl₄ + ZnO-NPs 50 mg/kg daily for 4 weeks), and ZnO-NP post-treatment (CCl₄ for 4 weeks followed by ZnO-NPs 50 mg/kg daily for 4 weeks). ZnO-NPs significantly restored superoxide dismutase (SOD) activity and decreased malondialdehyde (MDA) levels to near control values, while normalizing alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) activities. Histopathological evaluation confirmed near-complete recovery of hepatic and renal architectures. These results demonstrate that verjuice-synthesized ZnO-NPs exert potent antioxidant and regenerative effects through the preservation of endogenous defenses and promotion of tissue repair, and the green synthesis approach offers an eco-friendly, biocompatible nanotherapeutic strategy with promising applications for drug-induced liver injury

Downloads

Download data is not yet available.

References

Adeyemi, J. O., Oriola, A. O., Onwudiwe, D. C., & Oyedeji, A. O. (2022). Plant extracts mediated metal-based nanoparticles: synthesis and biological applications. Biomolecules, 12(5), 627http://doi.org/10.3390/biom12050627

Alipour, M., Davoudi, P., & Davoudi, Z. (2012). Effects of unripe grape juice (verjuice) on plasma lipid profile, blood pressure, malondialdehyde and total antioxidant capacity in normal, hyperlipidemic and hyperlipidemic with hypertensive human volunteers. Journal of Medicinal Plants Research, 6(45), 5677-5683http://DOI.org/10.1186/s40360-018-0256-8

Angle, A. S. (2024). Green Synthesis Methods for Metallic Zinc Oxide Nanoparticles. Synthesizing and Characterizing Plant-Mediated Biocompatible Metal Nanoparticles, 63

Ansar, S., Abudawood, M., Alaraj, A. S., & Hamed, S. S. (2018). Hesperidin alleviates zinc oxide nanoparticle induced hepatotoxicity and oxidative stress. BMC Pharmacology and Toxicology, 19, 1-6http://DOI.org/10.1186/s40360-018-0256-8

Ashraf, H., Meer, B., Iqbal, J., Ali, J. S., Andleeb, A., Butt, H., . . . Drouet, S. (2023). Comparative evaluation of chemically and green synthesized zinc oxide nanoparticles: their in vitro antioxidant, antimicrobial, cytotoxic and anticancer potential towards HepG2 cell line. Journal of Nanostructure in Chemistry, 13(2), 243-261http://doi.org/10.1007/s40097-021-00460-3

Awadalla, A., Hussein, A. M., Yousra, M., Barakat, N., Hamam, E. T., El-Sherbiny, M., . . . Shokeir, A. A. (2021). Effect of zinc oxide nanoparticles and ferulic acid on renal ischemia/reperfusion injury: possible underlying mechanisms. Biomedicine & Pharmacotherapy, 140, 111686https://doi.org/10.1016/j.biopha.2021.111686

Bayram, Y., & Elgin Karabacak, C. (2022). Characterization of unripe grapes (Vitis vinifera L.) and its use to obtain antioxidant phenolic compounds by green extraction. Frontiers in Sustainable Food Systems, 6, 909894https://doi.org/10.3389/fsufs.2022.909894

Conde de la Rosa, L., Goicoechea, L., Torres, S., Garcia-Ruiz, C., & Fernandez-Checa, J. C. (2022). Role of oxidative stress in liver disorders. Livers, 2(4), 283-314https://doi.org/10.3390/livers2040023

Datta, S., Aggarwal, D., Sehrawat, N., Yadav, M., Sharma, V., Sharma, A., . . . Kumar, V. (2023). Hepatoprotective effects of natural drugs: Current trends, scope, relevance and future perspectives. Phytomedicine, 121, 155100https://doi.org/10.1016/j.phymed.2023.155100

Dhalaria, R., Verma, R., Kumar, D., Puri, S., Tapwal, A., Kumar, V., . . . Kuca, K. (2020). Bioactive compounds of edible fruits with their anti-aging properties: A comprehensive review to prolong human life. Antioxidants, 9(11), 1123https://doi.org/10.3390/antiox9111123

Dohadwala, M. M., & Vita, J. A. (2009). Grapes and cardiovascular disease. The Journal of nutrition, 139(9), 1788S-1793Shttps://doi.org/10.3945/jn.109.107474

El-Beltagi, H. S., Rageb, M., El-Saber, M. M., El-Masry, R. A., Ramadan, K. M., Kandeel, M., . . . Osman, A. (2024). Green synthesis, characterization, and hepatoprotective effect of zinc oxide nanoparticles from Moringa oleifera leaves in CCl4-treated albino rats. Heliyon, 10(9)https://doi.org/10.1016/j.heliyon.2024.e30627

El-Saadony, M. T., Fang, G., Yan, S., Alkafaas, S. S., El Nasharty, M. A., Khedr, S. A., . . . Elkafas, S. S. (2024). Green Synthesis of Zinc Oxide Nanoparticles: Preparation, Characterization, and Biomedical Applications-A Review. International Journal of Nanomedicine, 12889-12937https://doi.org/10.2147/IJN.S487188

Fiedot-Toboła, M., Dmochowska, A., Potaniec, B., Czajkowska, J., Jędrzejewski, R., Wilk-Kozubek, M., . . . Cybińska, J. (2021). Gallic acid based black tea extract as a stabilizing agent in ZnO particles green synthesis. Nanomaterials, 11(7), 1816https://doi.org/10.3390/nano11071816

Gulab, H., Fatima, N., Tariq, U., Gohar, O., Irshad, M., Khan, M. Z., . . . Jan, A. K. (2024). Advancements in zinc oxide nanomaterials: synthesis, properties, and diverse applications. Nano-Structures & Nano-Objects, 39, 101271https://doi.org/10.1016/j.nanoso.2024.101271

Gupta, J., Hassan, P., & Barick, K. (2023). Multifunctional ZnO nanostructures: a next generation nanomedicine for cancer therapy, targeted drug delivery, bioimaging, and tissue regeneration. Nanotechnology, 34(28), 282003DOI 10.1088/1361-6528/accc35

Hashim, M., Anjum, S., Mujahid, H., Alotaibi, K. S., Albattal, S. B., Ghamry, H. I., & Soliman, M. M. (2025). Thymoquinone loaded zinc oxide Nanoformulations synthesis, characterization and evaluation of their efficacy against carbon tetrachloride induced Hepatorenal toxicity in rats. Toxicology research, 14(2), tfaf037https://doi.org/10.1093/toxres/tfaf037

Herrera-Rodríguez, M. A., del Pilar Ramos-Godinez, M., Cano-Martínez, A., Segura, F. C., Ruiz-Ramírez, A., Pavón, N., . . . Delgado-Buenrostro, N. L. (2023). Food-grade titanium dioxide and zinc oxide nanoparticles induce toxicity and cardiac damage after oral exposure in rats. Particle and Fibre Toxicology, 20(1), 43https://doi.org/10.1186/s12989

Kausar, S., Jabeen, F., Latif, M. A., & Asad, M. (2023). Characterization, dose dependent assessment of hepatorenal oxidative stress, hematological parameters and histopathological divulging of the hepatic damages induced by Zinc oxide nanoparticles (ZnO-NPs) in adult male Sprague Dawley rats. Saudi Journal of Biological Sciences, 30(9), 103745https://doi.org/10.1016/j.sjbs.2023.103745

Kazmi, I., Al-Abbasi, F. A., Afzal, M., Altayb, H. N., Nadeem, M. S., & Gupta, G. (2021). Formulation and evaluation of kaempferol loaded nanoparticles against experimentally induced hepatocellular carcinoma: in vitro and in vivo studies. Pharmaceutics, 13(12), 2086https://doi.org/10.3390/pharmaceutics13122086

Kirubakaran, D., Wahid, J. B. A., Karmegam, N., Jeevika, R., Sellapillai, L., Rajkumar, M., & SenthilKumar, K. (2025). A comprehensive review on the green synthesis of nanoparticles: advancements in biomedical and environmental applications. Biomedical Materials & Devices, 1-26https://doi.org/10.1007/s44174-025-00295-4

Mohajan, H. K. (2025). A Study on Functions of Liver to Sustain a Healthy Liver. Innovation in Science and Technology, 4(1), 77-87http://doi:10.56397/IST.2025.01.08

Mohi-Ud-Din, R., Mir, R. H., Sawhney, G., Dar, M. A., & Bhat, Z. A. (2019). Possible pathways of hepatotoxicity caused by chemical agents. Current drug metabolism, 20(11), 867-879https://doi.org/10.2174/1389200220666191105121653

Mosquera-Murillo, K., Castañeda-Manquillo, A., Ángel-Camilo, K., Arciniegas-Grijalba, P., de Valdenebro, M. R., Mosquera-Sanchez, L., . . . Rodriguez-Paez, J. (2023). Evaluation of the toxicity of ZnO nanoparticles obtained by a chemical route on the nasal respiratory epithelium of the biomodel Mus musculus. Journal of Nanoparticle Research, 25(12), 258https://doi.org/10.1007/s11051-023-05902-3

Mostafa-Hedeab, G., Behairy, A., Abd-Elhakim, Y. M., Mohamed, A. A.-R., Noreldin, A. E., Dahran, N., . . . Eskandrani, A. A. (2023). Green synthesized zinc oxide nanoparticles using moringa olifera ethanolic extract lessens acrylamide-induced testicular damage, apoptosis, and steroidogenesis-related gene dysregulation in adult rats. Antioxidants, 12(2), 361https://doi.org/10.3390/antiox12020361

Naser, S. S., Ghosh, B., Simnani, F. Z., Singh, D., Choudhury, A., Nandi, A., . . . Suar, M. (2023). Emerging trends in the application of green synthesized biocompatible ZnO nanoparticles for translational paradigm in cancer therapy. Journal of Nanotheranostics, 4(3), 248-279https://doi.org/10.3390/jnt4030012

Nematbakhsh, M., Zolfaghari, B., Eshraghi, F., Safari, T., Pezeshki, Z., & Sorooshzadeh, S. M.-A. (2013). The effects of unripe grape extract on systemic blood pressure, nitric oxide production, and response to angiotensin II administration. Pharmacognosy research, 5(2), 60https://doi.org/10.4103/0974-8490.110511

Park, N., Kim, K. S., Lee, S., Choi, J. H., & Na, K. (2025). Enhanced stem cell-mediated therapeutic immune modulation with zinc oxide nanoparticles in liver regenerative therapy. Biomaterials, 320, 123232https://doi.org/10.1016/j.biomaterials.2025.123232

Pei, X., Tang, S., Jiang, H., Zhang, W., Xu, G., Zuo, Z., . . . Li, C. (2023). Paeoniflorin recued hepatotoxicity under zinc oxide nanoparticles exposure via regulation on gut-liver axis and reversal of pyroptosis. Science of The Total Environment, 904, 166885https://doi.org/10.1016/j.scitotenv.2023.166885

Salah Eddine, N., Tlais, S., Alkhatib, A., & Hamdan, R. (2020). Effect of four grape varieties on the physicochemical and sensory properties of unripe grape verjuice. International Journal of Food Science, 2020(1), 6457982https://doi.org/10.1155/2020/6457982

Sameri, M. J., Savari, F., Mard, S. A., Rezaie, A., & Kalantar, M. (2024). Zinc Oxide Nanoparticles Ameliorate Histological Alterations Through Apoptotic Gene Regulation in Rat Model of Liver Ischemia-Reperfusion Injury. Reports of Biochemistry & Molecular Biology, 12(4), 619https://doi.org/10.61186/rbmb.12.4.619

Saratale, G. D., Saratale, R. G., Kim, D.-S., Kim, D.-Y., & Shin, H.-S. (2020). Exploiting fruit waste grape pomace for silver nanoparticles synthesis, assessing their antioxidant, antidiabetic potential and antibacterial activity against human pathogens: a novel approach. Nanomaterials, 10(8), 1457https://doi.org/10.3390/nano10081457

Szymonik-Lesiuk, S., Czechowska, G., Stryjecka-Zimmer, M., Słomka, M., MĄldro, A., Celiński, K., & Wielosz, M. (2003). Catalase, superoxide dismutase, and glutathione peroxidase activities in various rat tissues after carbon tetrachloride intoxication. Journal of hepato-biliary-pancreatic surgery, 10, 309-315https://doi.org/10.1007/s00534-002-0824-5

Udayagiri, H., Sana, S. S., Dogiparthi, L. K., Vadde, R., Varma, R. S., Koduru, J. R., . . . Kim, S.-C. (2024). Phytochemical fabrication of ZnO nanoparticles and their antibacterial and anti-biofilm activity. Scientific Reports, 14(1), 19714https://doi.org/s41598-024-69044-9

Verma, R., Pathak, S., Srivastava, A. K., Prawer, S., & Tomljenovic-Hanic, S. (2021). ZnO nanomaterials: Green synthesis, toxicity evaluation and new insights in biomedical applications. Journal of Alloys and Compounds, 876, 160175https://doi.org/10.1016/j.jallcom.2021.160175

Wazir, H., Abid, M., Essani, B., Saeed, H., Khan, M. A., Nasrullah, F., . . . Muzammil, M. A. (2023). Diagnosis and treatment of liver disease: current trends and future directions. Cureus, 15(12)http//doi.org/ 10.7759/cureus.49920

Weber, L. W., Boll, M., & Stampfl, A. (2003). Hepatotoxicity and mechanism of action of haloalkanes: carbon tetrachloride as a toxicological model. Critical reviews in toxicology, 33(2), 105-136https://doi.org/10.1080/713611034

Zhao, D., Simon, J. E., & Wu, Q. (2020). A critical review on grape polyphenols for neuroprotection: Strategies to enhance bioefficacy. Critical Reviews in Food Science and Nutrition, 60(4), 597-625https://doi.org/10.1080/10408398.2018.1546668

Zhou, D.-D., Li, J., Xiong, R.-G., Saimaiti, A., Huang, S.-Y., Wu, S.-X., . . . Gan, R.-Y. (2022). Bioactive compounds, health benefits and food applications of grape. Foods, 11(18), 2755https://doi.org/10.3390/foods11182755

Downloads

Published

2025-10-04

How to Cite

aziz, P., & Ismail, T. (2025). GREEN-SYNTHESIZED ZINC OXIDE NANOPARTICLES FROM VERJUICE (Vitis vinifera) EXHIBIT HEPATOPROTECTIVE AND ANTIOXIDANT EFFECTS AGAINST CARBON TETRACHLORIDE -INDUCED TOXICITY IN MALE RATS. Science Journal of University of Zakho, 13(4), 519–530. https://doi.org/10.25271/sjuoz.2025.13.4.1633

Issue

Vol. 13 No. 4 (2025): October-December issue

Section

Science Journal of University of Zakho

License

Copyright (c) 2025 Pola Z. Aziz , Treefa F. Ismail

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Authors who publish with this journal agree to the following terms:

  • Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License [CC BY-NC-SA 4.0] that allows others to share the work with an acknowledgment of the work's authorship and initial publication in this journal.
  • Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work, with an acknowledgment of its initial publication in this journal.
  • Authors are permitted and encouraged to post their work online.