Ameliorative Potentials of N-Acetylcysteine and Vitamin C on Zinc-oxide Nanoparticles Induced Hepato-renal Toxicity in Male Wistar Rats
DOI:
https://doi.org/10.4314/njbmb.v39i3.2Keywords:
Zinc-oxide Nanoparticles, N-acetylcysteine, Vitamin C, Oxidative Stress, Hepatoxicity, Renal toxicityAbstract
Zinc-oxide nanoparticles (ZnO-NPs) are prevalent in various companies and consumer products, raising concerns about their potential toxicity. Vitamin C and N-acetyl-cysteine (NAC) are known for their antioxidant properties, which may protect against cytotoxicity. However, limited information exists on their effects on ZnO-NPs-induced toxicity. This study investigates the ameliorative effects of N-acetylcysteine and vitamin C on hepato-renal toxicity of Zinc-oxide Nanoparticles in Male Wistar Rats. Twenty-five male Wistar rats (100-120g) were grouped namely; Control, ZnO-NPs, ZnO-NPs + NAC, ZnO-NPs + Vit. C, and ZnO-NPs + NAC + Vit. C. ZnO-NPs were administered orally at 200 mg/kg, with treatment groups receiving an additional 100 mg/kg of Vitamin C and NAC. After 28 days, blood samples were collected for analysis, including liver enzymes (AST, ALP, ALT), liver malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), urea, creatinine, and serum zinc levels. ZnO-NPs significantly increased liver creatinine, urea, AST, ALT, MDA, and serum zinc levels compared to the control group (P<0.05). NAC and Vitamin C, alone or combined, significantly reduced liver SOD levels (P<0.05). Co-treatment significantly decreased ALT, urea, and creatinine while significantly increasing liver SOD (P<0.05). NAC and Vitamin C co-treatment alleviated the toxic effects of ZnO-NPs-induced hepato–renal damage in male albino Wistar rats.
Downloads
References
Aebi, H., Mörikofer-Zwez, S., and von Wartburg, J. P. (1972). Alternative molecular forms of erythrocyte catalase. In Structure and Function of Oxidation–Reduction Enzymes Pergamon. pp. 345-351.
Ali, A. H., Hachem, M., and Ahmmed, M. K. (2024). Docosahexaenoic acid-loaded nanoparticles: A state-of-the-art of preparation methods, characterization, functionality, and therapeutic applications. Heliyon. https://doi.org/10.1016/j.heliyon.2024.e30946
Altun, H., Şahin, N., Kurutaş, E. B., Karaaslan, U., Sevgen, F. H., and Fındıklı, E. (2018). Assessment of malondialdehyde levels, superoxide dismutase, and catalase activity in children with autism spectrum disorders. Psychiatry and Clinical Psychopharmacology, 28(4), 408-415.
Ay, M., Charli, A., Jin, H., Anantharam, V., Kanthasamy, A., and Kanthasamy, A. G. (2021). Quercetin. Nutraceuticals, 29, 749–755.
Brzóska, M. M, Moniuszko-Jakoniuk, J., Piłat-Marcinkiewicz, B., and Sawicki, B., (2003). liver and kidney function and histology in rats exposed to cadmium and ethanol, Alcohol and Alcoholism, 38(1),2–10
Dennis, J. M., and Witting, P. K. (2017). Protective role for antioxidants in acute kidney disease. Nutrients, 9(7), 1-25, https://doi.org/10.3390/nu9070718
Didier, A. J., Stiene, J., Fang, L., Watkins, D., Dworkin, L. D., and Creeden, J. F. (2023). Antioxidant and anti-tumor effects of dietary vitamins A, C, and E. Antioxidants, 12(3), 1-26, https://doi.org/10.3390/antiox12030632
Ghonimi, N. A., Elsharkawi, K. A., Khyal, D. S., and Abdelghani, A. A. (2021). Serum malondialdehyde as a lipid peroxidation marker in multiple sclerosis patients and its relation to disease characteristics. Multiple Sclerosis and Related Disorders, 51, 102941. https://doi.org/10.1016/j.msard.2021.102941
Gounden, V., Bhatt, H., and Jialal, I. (2022). Renal function tests - StatPearls - NCBI Bookshelf. https://www.ncbi.nlm.nih.gov/books/NBK507821 Accessed on 24th February, 2024.
Gyurászová, M., Gurecká, R., Bábíčková, J., and Tóthová, U. (2020). Oxidative stress in the pathophysiology of kidney disease: Implications for noninvasive monitoring and identification of biomarkers. Oxidative Medicine and Cellular Longevity, 2020, 1–11.
Hashim, M., Mujahid, H., Hassan, S., Bukhari, S., Anjum, I., Hano, C., ... and Anjum, S. (2022). Implication of nanoparticles to combat chronic liver and kidney diseases: progress and perspectives. Biomolecules, 12(10), 1-22, https://doi.org/10.3390/biom12101337.
Hua-Qiao, T., Min, X., Qian, R., Ru-Wen, J., Qi-Ji, L., and Li, Y. L. (2016). The effect of ZnO nanoparticles on liver function in rats. International Journal of Nanomedicine, 11, 4275–4285.
Hussain, S., DanHuang, and Jiang J. (2016). "Toxicity of Zinc Oxide Nanoparticles in Human Cells: A Review." Environmental Toxicology and Pharmacology, 48, 161-171.
Iavicoli, I., Fontana, L., and Nordberg, G. (2016). The effects of nanoparticles on the renal system. Critical Reviews in Toxicology, 46(6), 490-560.
Kashani, K., Rosner, M. H., and Ostermann, M. (2020). Creatinine: From physiology to clinical application. European Journal of Internal Medicine, 72, 9–14.
Khan, Y., James M., and James K. (2020). "Zinc oxide nanoparticles: A review of their toxicity and applications. Journal of Nanomaterials, 10,1-14; https://doi.org/10.3390/nano10112113
Kumar, N., Saraber, P., Ding, Z., and Kusumbe, A. P. (2021). Diversity of vascular niches in bones and joints during homeostasis, ageing, and diseases. Frontiers in Immunology, 12, 798211. https://doi.org/10.3389/fimmu.2021.798211
Kunle-Alabi, O. T., Akindele, O. O., Odoh, M. I., Oghenetega, B. O., and Raji, Y. (2017). Comparative effects of coconut water and N-Acetyl cysteine on the hypothalamo-pituitary-gonadal axis of male rats. Songklanakarin Journal of Science and Technology, 39(6), 759-764.
Lala, V., Zubair, M., and Minter, D. A. (2022). Liver function tests - StatPearls - NCBI Bookshelf. 7957;308, https://doi.org/10.1211/PJ.2022.1.124202
Mansouri, E., Khorsandi, L., Orazizadeh, M., and Jozi, Z. (2015). Dose-dependent hepatotoxicity effects of zinc oxide nanoparticles. Nanomedicine Journal, 2(4), 273-282
Misra, H. P., and Fridovich, I. (1971). The generation of superoixide radical during the autoxidation of ferredoxins. The Journal of Biological Chemistry, 246(22), 6886–6890.
Moatamed, E. R., Hussein, A. A., El-Desoky, M. M., and Khayat, Z. E. (2019). Comparative study of zinc oxide nanoparticles and its bulk form on liver function of Wistar rat. Toxicology and Industrial Health, 35(10), 627-637.
Moldogazieva, N. T., Mokhosoev, I. M., Mel’nikova, T. I., Porozov, Y. B., and Terentiev, A. A. (2019). Oxidative stress and advanced lipoxidation and glycation end products (ALEs and AGEs) in aging and age‐related diseases. Oxidative Medicine and Cellular Longevity, 2019(1), 3085756. https://doi.org/10.1155/2019/3085756
Oghenetega, O. B., Oyovwi, M., Obidimma, E., Ijabodede, T., Oghenetega, E., Okwute, P., ... and Ugwuishi, E. (2024). Quercetin ameliorates zinc oxide nanoparticles-induced impaired testicular functions by regulating Inflammation, oxidative, and hormonal Status. Babcock University Medical Journal, 7(1), 147-159.
Pei, X., Jiang, H., Li, C., Li, D., and Tang, S. (2023). Oxidative stress-related canonical pyroptosis pathway, as a target of liver toxicity triggered by zinc oxide nanoparticles. Journal of Hazardous Materials, 442, 130039. https://doi.org/10.1016/j.jhazmat.2022.130039
Pizzino, G., Irrera, N., Cucinotta, M., Pallio, G., Mannino, F., Arcoraci, V., Squadrito, F., Altavilla, D., and Bitto, A. (2017). Oxidative stress: harms and benefits for human health. Oxidative Medicine and Cellular Longevity, 2017, 1–13.
Poli, V., Aparna, Y., Madduru, R., and Motireddy, S. R. (2022). Protective effect of Vitamin C and E on enzymatic and antioxidant system in liver and kidney toxicity of Cadmium in rats. Applied Food Research, 2(1), 100098. https://doi.org/10.1016/j.afres.2022.100098
Rajasekar, M., Mary, J., Sivakumar, M., and Selvam, M. (2024). Recent developments in sunscreens based on chromophore compounds and nanoparticles. Royal Society of Chemistry Advances, 14(4), 2529-2563.
Redza-Dutordoir, M., and Averill-Bates, D. A. (2016). Activation of apoptosis signalling pathways by reactive oxygen species. Biochimica et Biophysica Acta (BBA)-Molecular Cell Research, 1863(12), 2977-2992.
Roy, Z., Bansal, R., Siddiqui, L., and Chaudhary, N. (2023). Understanding the role of free radicals and antioxidant enzymes in human diseases. Current Pharmaceutical Biotechnology, 24(10), 1265-1276.
Sharma, V., Singh, P., Pandey, A. K., and Dhawan, A. (2012). Induction of oxidative stress, DNA damage and apoptosis in mouse liver after sub-acute oral exposure to zinc oxide nanoparticles. Mutation Research/Genetic Toxicology and Environmental Mutagenesis, 745(1-2), 84-91.
Samim, A. R., Singh, V. K., and Vaseem, H. (2022). Assessment of hazardous impact of nickel oxide nanoparticles on biochemical and histological parameters of gills and liver tissues of Heteropneustes fossilis. Journal of Trace Elements in Medicine and Biology, 74, 127059.
Tenório, M. C. D. S., Graciliano, N. G., Moura, F. A., Oliveira, A. C. M. D., and Goulart, M. O. F. (2021). N-Acetylcysteine (NAC): Impacts on human health. Antioxidants, 10(6), 1-34. https://doi.org/10.3390/antiox10060967
Wallin, B., Rosengren, B., Shertzer, H. G., and Camejo, G. (1993). Lipoprotein oxidation and measurement of thiobarbituric acid reacting substances formation in a single microtiter plate: its use for evaluation of antioxidants. Analytical Biochemistry, 208(1), 10–15.
Wang, C., Cheng, K., Zhou, L., He, J., Zheng, X., Zhang, L., ... and Wang, T. (2017). Evaluation of long-term toxicity of oral zinc oxide nanoparticles and zinc sulfate in mice. Biological Trace Element Research, 178, 276-282.
Additional Files
Published
Issue
Section
Categories
License
Copyright (c) 2025 Onome B. Oghenetega, Fathia O. Ibrahim, Gloria E. Oghenetega, Rufus O. Animashaun, Patrick G. Okwute (Author)
This work is licensed under a Creative Commons Attribution 4.0 International License.
