• SAHAR M. MAHMOUD Assistant Professor of Physiology at Department of Zoology, Faculty of Science, Cairo University, Cairo, Egypt
  • RAMI B. KASSAB Assistant Professor of Physiology at Department of Zoology and Entomology, Faculty of Science, Helwan University, Cairo, Egypt
  • AHMED E. ABDEL MONEIM Professor of Physiology at Department of Zoology and Entomology, Faculty of Science, Helwan University, Cairo, Egypt


Objective: The present study was designed to evaluate the effect of zinc oxide nanoparticles (ZnO NPs) on Aluminum chloride (AlCl3)-induced hepato-renal injury. 

Methods: Animals were divided into, I-control group; rats received saline, II-AlCl3 group; animals received 100 mg AlCl3/kg body weight, III-ZnO NPs group; rats received 10 mg ZnO NPs/kg body weight, and IV group ZnO NPs+AlCl3. All rats were administered their respective doses daily for 6 w. Hepatorenal function parameters in sera; aminotransferases, bilirubin, urea, and creatinine were estimated. Lipid peroxide level and nitrite\nitrate ratio, glutathione content, glutathione peroxidase, glutathione reductase, catalase, superoxide dismutase activities and interleukin-1β, tumor necrosis factor-α levels were determined in both tissues. The histopathological and the immunohistochemical investigations of nuclear factor-kB expression were carried out. 

Results: ZnO NPs treatment to AlCl3-intoxicated rats significantly reduced Al accumulation (at p<0.05) in the hepatorenal tissue and increased zinc accumulation (at p<0.05) in liver and kidney, respectively, with respect to AlCl3-group, thus inhibiting oxidative stress and inflammation parameters represented by lipid peroxidation and nitric oxide levels (at p<0.05) compared to AlCl3 group and elevated antioxidant parameters (at p<0.05), compared to AlCl3 treated group, while suppressed interleukin-1β, tumor necrosis factor-α levels (at p<0.05) and the nuclear factor-kB activation in liver and kidney, especially in the kidney if compared to AlCl3-treated group. Hepatorenal function indices indicated significant decreases compared to AlCl3 group (at p<0.05).

Conclusion: Results indicated the ameliorative effect of ZnO NPs on aluminum-induced hepato-renal damage.

Keywords: Zinc nanoparticles, Aluminum, Inflammation, Oxidative stress, Liver, Kidney


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1. Verstraeten S, Aimo L, Oteiza PI. Aluminium and lead: molecular mechanisms of brain toxicity. Arch Toxicol 2008;82:789-802.
2. Bhadauria M. Combined treatment of HEDTA and propolis prevents aluminum-induced toxicity in rats. Food and chemical toxicology. Br Ind Biol Res Assoc 2012;50:2487-95.
3. Willhite CC, Karyakina NA, Yokel RA, Yenugadhati N, Wisniewski TM, Arnold IM, et al. Systematic review of potential health risks posed by pharmaceutical, occupational and consumer exposures to metallic and nanoscale aluminum, aluminum oxides, aluminum hydroxide and its soluble salts. Crit Rev Toxicol 2014;(44 Suppl 4):1-80.
4. Turkey H, Yousef MI, Biyikoglu F. Propolis prevents aluminum-induced genetic and hepatic damages in rat liver. Food Chem Toxicol 2010;48:2741-6.
5. Abdel Moneim AE, Othman MS, Mahmoud SM, El-Deib KM. Pomegranate peel attenuates aluminum-induced hepatorenal toxicity. Toxicol Mech Methods 2013;23:624-33.
6. El-Kenawy AM, Osman HEH, Daghestani MH. Role of propolis (bee glue) in improving histopathological changes of the kidney of rat treated with aluminum chloride. Environ Toxicol 2014;29:1000-10.
7. Mahitha B, Raju BDP, Mallikarjuna K, Durga Mahalakshmi C, Sushmal N, Bacopa monniera NJ. Stabilized silver nanoparticles attenuates oxidative stress induced by aluminum in albino mice. J Nanosci Nanotech 2015;15:1101-9.
8. Narayanan KB, Park HH. Pleiotropic functions of antioxidant nanoparticles for longevity and medicine. Adv Coll Sci 2013;201-202:30-42.
9. Abhinaya SR, Padmini R. Biofabrication of zinc oxide nanoparticles using pterocarpus marsupium and its biomedical applications. Asian J Pharm Clin Res 2019;12:245-9.
10. Jacob V, Rajiiv P. In vitro analysis: the antimicrobial and antioxidant activity of zinc oxide nanoparticles from Curcuma longa. Asian J Pharm Clin Res 2019;12:200-4.
11. Manyasree D, Kiranmyi P, Kolli VR. Characterization and antibacterial activity of ZnO nanoparticles synthesized by the co-precipitation method. Int J Appl Pharm 2018;10:224-8.
12. Nagajyothi PC, Cha SJ, Yang IJ, Sreekanth TV, Kim KJ, Shin HM. Antioxidant and anti-inflammatory activities of zinc oxide nanoparticles synthesized using Polygala tenuifolia root extract. J Photochem Photobiol Biol 2015;146:10-7.
13. Najafzadeh H, Ghoreishi SM, Mohammadian B, Rahimi E, Afzalzadeh MR, Kazemi Varnamkhasti M, et al. Serum biochemical and histopathological changes in liver and kidney in lambs after zinc oxide nanoparticles administration. Vet World 2013;6:534-7.
14. Abdel Moneim AE. Indigofera oblongifolia prevents lead acetate-induced hepatotoxicity, oxidative stress, fibrosis and apoptosis in rats. PLoS One 2016;11:1-18.
15. NIH (National Institute Of Health). Memorandum of Understanding Among the Animal and Plant Health Inspection Service USDA and the Food and Drug Administration, US Department of Health and Human Services and the National Institutes of Health Concerning Laboratory Animal Welfare. Office of Extramural Research: NIH, Bethesda; 2006.
16. NIH (National Institutes of Health). Memorandum of Understanding Between the Office of Laboratory Animal Welfare, National Institutes of Health, US Department of Health and Human Services and the Office of Research Oversight and the Office of Research and Development, Veterans Health Administration, US Department of Veterans Affairs Concerning Laboratory Animal Welfare. Office of Extramural Research: NIH, Bethesda; 2007.
17. Kubaszewski L, Ziola Frankowska A, Frankowski M, Nowakowski A, Czabak-Garbacz R, Kaczmarczyk J, et al. Atomic absorption spectrometry analysis of trace elements in degenerated intervertebral disc tissue. Med Sci Mon 2014;20:2157-64.
18. Reitman S, Frankel SA. Colorimetric method for the determination of serum glutamic oxaloacetic and glutamic pyruvic transaminases. Am J Clin Path 1957;28:56-63.
19. Walter M, Gerade H. Bilirubin assay. Microchem J 1970;15:231-6.
20. Fawcett JK, Scott JE. A rapid and precise method for the determination of Urea. J Clin Path 1960;13:156-9.
21. Schirmeister J, Willmann H, Kiefer H. Determination of creatinine in serum. D Med Wochen 1964;89:1940
22. Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 1979;95:351-8.
23. Green LC, Wagner DA, Glogowski J, Skipper PL, Wishnok JS, Tannenbaum SR. Analysis of nitrate, nitrite, and [15N]nitrate in biological fluids. Anal Biochem 1982;126:131-8.
24. Ellman GL. Tissue sulfhydryl groups. Arch Biochem Biophys 1959;82:70-7.
25. Sun Y, Oberley LW, Li Y. A simple method for clinical assay of superoxide dismutase. Clin Chem 1988;34:497-500.
26. Luck H. Catalase. In: HU Bergmeyer. Ed. Methods of enzymatic analysis. Academic Press: New York; 1965. p. 855-88.
27. Paglia DE, Valentine WN. Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med 1967;70:158-69.
28. Factor VM, Kiss A, Woitach JT, Wirth PJ, Thorgeirsson SS. Disruption of redox homeostasis in the transforming growth factor-alpha/c-myc transgenic mouse model of accelerated hepatocarcinogenesis. J Biol Chem 1998;273:15846-53.
29. Bancroft J, Gamble M. Bancroft's theory and practice of histological techniques. Eds. Vol. 6th Edition. Elsevier, London: Churchill Livingstone; 2008.
30. Mescher MJA. Basic histology: text and atlas. 13th Ed. McGraw-Hill Education; 2013. p. 329-39.
31. Badkoobeh P, Parivar K, Kalantar SM, Hosseini SD, Salabat A. Effect of nano-zinc oxide on doxorubicin-induced oxidative stress and sperm disorders in adult male wistar rats. Iran J Reprod Med 2013;11:355-64.
32. Roy R, Kumar S, Verma AK, Sharma A, Chaudhari BP, Tripathi A, et al. Zinc oxide nanoparticles provide an adjuvant effect to ovalbumin via a Th2 response in Balb/c mice. Int Immun 2014;26:159-72.
33. Bisht G, Rayamajhi S. ZnO nanoparticles: a promising anticancer agent. Nanobiomed 2016;3:9.
34. Yuan Y, Cai T, Xia X, Zhang RP, Cai CY. Nanoparticle delivery of anticancer drugs overcomes multidrug resistance in breast cancer, Drug Delivery 2016;23:3350–7.
35. Li J, Chen H, Wang B, Cai C, Yang X, Chai Z, et al. ZnO nanoparticles act as supportive therapy in DSS-induced ulcerative colitis in mice by maintaining gut homeostasis and activating Nrf2 signaling. Sci Rep 2017;7:43126.
36. Agarwal H, Nakara A, Shanmugam VK. Anti-inflammatory mechanism of various metal and metal oxide nanoparticles synthesized using plant extracts. Rev Biomed Pharmacoth 2019;109:2561–72.
37. Chen JK, Shih MH, Peir JJ. The use of radioactive zinc oxide nanoparticles in the determination of their tissue concentrations following intravenous administration in mice. Analyst 2010;135:1742–6.
38. Li CH, Shen CC, Cheng YW, Huang SH, Wu CC, Kao CC, et al. Organ biodistribution, clearance, and genotoxicity of orally administered zinc oxide nanoparticles in mice. Nano Toxicol 2012;6:746–56.
39. Amara S, Ben Slama I, Mrad I, Rihane N, Khemissi W, El Mir L, et al. Effects of zinc oxide nanoparticles and/or zinc chloride on biochemical parameters and mineral levels in rat liver and kidney. Hum Exp Toxicol 2014;33:1150-7.
40. Liu J, Wong HL, Moselhy J, Bowen B, Wu XY, Johnston MR. Targeting colloidal particulates to thoracic lymph nodes. Lung Can 2006;51:377–86.
41. Xiong D, Fang T, Yu L, Sima X, Zhu W. Effects of nano-scale TiO2, ZnO and their bulk counterparts on zebrafish: acute toxicity, oxidative stress, and oxidative damage. Sci Environ 2011;409:1444-52.
42. Lee CM, Jeong HJ, Yun KN, Kim DW, Sohn MH, Lee JK. Optical imaging to trace near-infrared fluorescent zinc oxide nanoparticles following oral exposure. Int J Nanomed 2012;7:3203–9.
43. Gao S, Wang X, Wang S, Zhu S, Rong R, Xu X. Complex effect of zinc oxide nanoparticles on cadmium chloride-induced hepatotoxicity in mice: protective role of metallothionein. Metall 2017;1:706-14.
44. Suntres ZE, Lui EM. Biochemical mechanism of metallothionein-carbon tetrachloride interaction in vitro. Biochem Pharmacol 1990;39:833-40.
45. Yaghmaei P, Esfahani Nejad H, Ahmadi R, Hayati Roodbari N, Ebrahim Habibi A. Maternal zinc intake of wistar rats has a protective effect in the alloxan-induced diabetic offspring. J Physiol Biochem 2013;69:35–43.
46. Canli EG, Canli M. Effects of aluminum, copper, and titanium nanoparticles on some blood parameters in wistar rats. Turk J Zool 2017;41:259-66.
47. Wong Ekkabut J, Xu Z, Triampo W, Tang IM, Tieleman DP, Monticelli L. Effect of lipid peroxidation on the properties of lipid bilayers: a molecular dynamics study. Biophys J 2007;93:4225-36.
48. Shati AA, Alamri SA. Role of saffron (Crocus sativus L.) and honey syrup on aluminum-induced hepatotoxicity. Sau Med J 2010;31:1106-13.
49. Sharma V, Singh P, Pandey AK, Dhawan A. Induction of oxidative stress, DNA damage and apoptosis in mouse liver after sub-acute oral exposure to zinc oxide nanoparticles. Mut Res Genet Toxicol Env Mut 2012;745:84-91.
50. Fazilati M. Investigation toxicity properties of zinc oxide nanoparticles on liver enzymes in the male rat. Eur J Exp Biol 2013;3:97-103.
51. John E, Laskow TC, Buchser WJ, Pitt BR, Basse PH. Zinc in innate and adaptive tumor immunity. J Transl Med 2010;8:118?20.
52. Ng KW, Khoo SP, Heng BC. The role of the tumor suppressor p53 pathway in the cellular DNA damage response to zinc oxide nanoparticles. Biomat 2011;32:8218-25.
53. Parat MO, Richard M, Beani, JC, Favier A. Involvement of zinc in Intracellular oxidant/antioxidant balance. Biol Trace Elem Res 1997;60:187-204.
54. Fridovich I. Superoxide anion radical (O• 2), superoxide dismutases, and related matters. J Biol Chem 1997;272:18515-7.
55. Peixoto EB, Pessoa BS, Biswas SK, Lopes de Faria JB. Antioxidant SOD mimetic prevents NADPH oxidase-induced oxidative stress and renal damage in the early stage of experimental diabetes and hypertension. Am J Neph 2009;29:309–18.
56. Afifi M, Abdelazim AM. Ameliorative effect of zinc oxide and silver nanoparticles on the antioxidant system in the brain of diabetic rats. Asian Pac J Trop Biomed 2015;5:874–7.
57. Bray TM, Bettger WJ. The physiological role of zinc as an antioxidant. Free Rad Biol Med 1990;8:281-91.
58. Bao B, Ahmad A, Azmi A, Li Y, Prasad A, Sarkar FH. The biological significance of zinc in inflammation and aging. In: Inflammation, Advancing age and Nutrition: Research and Clinical Interventions. 1st ed. Edited by Rahman I, Bagchi D. New York, NY, Elsevier Inc, Chapter 2; 2013. p. 15–27.
59. Habig WH, Pabst MJ, Jakoby WB. Glutathione S-transferases the first enzymatic step in mercapturic acid formation. J Biol Chem 1974;249:7130–9.
60. Halliwell B, Gutteridge JMC. Free radicals in biology and. Oxford University Press: New York; 1999.
61. Pigeolet E, Corbisier P, Houbion A, Lambert D, Michiels C, Raes M, et al. Glutathione peroxidase, superoxide dismutase, and catalase inactivation by peroxides and oxygen-derived free radicals. Mech Age Development 1990;15:283–97.
62. Greenwel P, Dominguez Rosales JA, Mavi G, Rivas Estilla AM, Rojkind M. Hydrogen peroxide: a link between acetaldehyde-?1 (i) collagen gene up-regulation and oxidative stress in mouse hepatic stellate cells. Hepatol 2000;31:109-16.
63. Pinzani M, Macias Barragan J. Update on the pathophysiology of liver fibrosis. Exp Rev Gastroent Hep 2010;4:459-72.
64. Dagher Z, Garcon G, Billet S. Role of nuclear factor-kappa B activation in the adverse effects induced by air pollution particulate matter (PM2.5) in human epithelial lung cells (L132) in culture. J Appl Toxicol 2007;27:284–90.
65. Szuster Ciesielska A, Plewka K, Daniluk J, Kandefer Szerszen M. Zinc supplementation attenuates ethanol-and acetaldehyde-induced liver stellate cell activation by inhibiting reactive oxygen species (ROS) production and by influencing intracellular signaling. Biochem Pharmacol 2009;78:301-14.
66. Situnayake RD, Crump BJ, Thurnham DI, Davies JA, Gearty J, Davis M. Lipid peroxidation and hepatic antioxidants in alcoholic liver disease. Gut 1990;31:1311-7.
67. Sorensen Zender I, Bhayana S, Susnik N, Rolli V, Batkai S, Arpita B, et al. Zinc-?2-glycoprotein exerts antifibrotic effects in kidney and heart. J Am Soc Neph 2015;26:2659–68.
68. Moos PJ, Olszewski K, Honeggar M. Responses of human cells to ZnO nanoparticles: a gene transcription study. Metall 2011;3:1199–211.
69. Kim MH, Seo JH, Kim HM, Jeong HJ. Aluminum-doped zinc oxide nanoparticles attenuate the TSLP levels via suppressing caspase-1 in activated mast cells. J Biom Appl 2016;30:1407–16.
70. Pei X, Xiao Z, Liu L, Wang G. Effects of dietary zinc oxide nanoparticles supplementation on growth performance, zinc status, intestinal morphology, microflora population, and immune response in weaned pigs. J Sci Food Agric 2019;99:1366-74.
71. Ho E. Zinc deficiency, DNA damage and cancer risk. J Nutr Biochem 2004;15:572-8.
72. Atef HA, Mansour MK, Ibrahim EM. Efficacy of zinc oxide nanoparticles and curcumin in amelioration the toxic effects in aflatoxicated rabbits. Int J Curr Microl Appl 2016;5:795-818.
73. Dawei AI, Zhisheng W, Anguo Z. Protective effects of Nano-ZnO on the primary culture mice intestinal epithelial cells in in vitro against oxidative injury. J Anim Vet Adv 2009;8:1964-7.
74. Dhawan DK, Chadha VD. Zinc: a promising agent in dietary chemoprevention of cancer. India J Med Res 2010;132:676-82.
75. Elshama SS, Abdallah ME, Abdel Karim RI. Zinc oxide nanoparticles: therapeutic benefits and toxicological hazards. Open Nanomed J 2018;5:16-22.
76. Kim MH, Jeong HJ. Zinc oxide nanoparticles suppress LPS-Induced NF-? B activation by inducing A20, a negative regulator of NF-? B, in RAW 264.7 macrophages. J Nanosci Nanotech 2015;15:6509–15.
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How to Cite
MAHMOUD, S. M., R. B. KASSAB, and A. E. A. MONEIM. “ZINC OXIDE NANOPARTICLES AMELIORATE ALUMINUM CHLORIDE-INDUCED HEPATO-RENAL OXIDATIVE STRESS AND INFLAMMATION IN RATS”. International Journal of Pharmacy and Pharmaceutical Sciences, Vol. 12, no. 1, Nov. 2019, pp. 11-20, doi:10.22159/ijpps.2020v12i1.35956.
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