Oxidative Stress Biomarkers in Hepatic and Cardiac Toxicity Induced by Copper Oxide Nanoparticles in Mice
محورهای موضوعی :Fatemeh Setudeh 1 , Mehran Arabi 2
1 - Department of Animal Sciences, Faculty of Basic Sciences, Shahrekord University, Shahrekord-88156 48456, Iran
2 - Department of Animal Sciences, Faculty of Basic Sciences, Shahrekord University, Shahrekord-88156 48456, Iran
کلید واژه: Oxidative stress, Nanotoxicity, Hepatic and cardiac toxicity,
چکیده مقاله :
Copper oxide nanoparticles (CuO-NPs) are used in products such as semiconductors, heat transfer fluids, lubricants, gas sensors, field emission emitters, catalysts, solar cells and lithium batteries, and antimicrobial equipment. Since oxidative stress is a key mechanism for cellular damage by nanoparticles, the present study investigated the oxidative stress induced by CuO-NPs in the liver and heart of adult male mice. Animals were randomly divided into 5 groups (n=15/group) including negative control (intact), pseudo-control (sham, receiving normal saline as a vehicle without nanoparticles), and three experimental groups received 1 ml of doses 10, 20 and 40 mg kg-1 b.w. of CuO-NPs intraperitoneally (IP), every other day for 21 days. Blood samples were collected to measure changes in the levels of hepatic necrosis biomarkers (ALT&AST) in the sera. Liver and heart homogenates were made to determine changes in the reactive oxygen species (ROS) level, malondialdehyde (MDA/LPO) content, activities of catalase (CAT) and glutathione peroxidase (GPx), along with total antioxidant capacity (TAC) value. Cardiac and hepatic samples were also examined histologically. No significant differences were observed between negative control and sham groups in all experiments. Data figured out the changes in oxidative stress biomarkers as illustrated by an increase in the ROS levels, MDA content, and CAT activity; a reduction in the activity of GPx and TAC value; and an elevation in the blood levels of ALT and AST. Tissue damages were also observed in the cardiac and hepatic samples. In brief, the aforementioned treatments exerted cardiac and hepatic toxicity, and it might be due to the induction of oxidative stress and related damages.
Copper oxide nanoparticles (CuO-NPs) are used in products such as semiconductors, heat transfer fluids, lubricants, gas sensors, field emission emitters, catalysts, solar cells and lithium batteries, and antimicrobial equipment. Since oxidative stress is a key mechanism for cellular damage by nanoparticles, the present study investigated the oxidative stress induced by CuO-NPs in the liver and heart of adult male mice. Animals were randomly divided into 5 groups (n=15/group) including negative control (intact), pseudo-control (sham, receiving normal saline as a vehicle without nanoparticles), and three experimental groups received 1 ml of doses 10, 20 and 40 mg kg-1 b.w. of CuO-NPs intraperitoneally (IP), every other day for 21 days. Blood samples were collected to measure changes in the levels of hepatic necrosis biomarkers (ALT&AST) in the sera. Liver and heart homogenates were made to determine changes in the reactive oxygen species (ROS) level, malondialdehyde (MDA/LPO) content, activities of catalase (CAT) and glutathione peroxidase (GPx), along with total antioxidant capacity (TAC) value. Cardiac and hepatic samples were also examined histologically. No significant differences were observed between negative control and sham groups in all experiments. Data figured out the changes in oxidative stress biomarkers as illustrated by an increase in the ROS levels, MDA content, and CAT activity; a reduction in the activity of GPx and TAC value; and an elevation in the blood levels of ALT and AST. Tissue damages were also observed in the cardiac and hepatic samples. In brief, the aforementioned treatments exerted cardiac and hepatic toxicity, and it might be due to the induction of oxidative stress and related damages.
1. Kahru A., Mortimer M., 2021. Advances in Nanotoxicology: Towards Enhanced Environmental and Physiological Relevance and Molecular Mechanisms. Nanomaterials. 11, 919.
2. Shin S.W., Song I.H., Um S.H., 2015. Role of physicochemical properties in nanoparticle toxicity. Nanomater. 5, 1351-1365.
3. Yu Z. , Li Q., Wang J., Yu Y., Wang Y., Zhou Q., Li P., 2020. Reactive oxygen species-related nanoparticle toxicity in the biomedical field. Nanoscale Res. Lett. 15, 1-14.
4. Abudayyak M., Guzel E., Özhan, G., 2020. Cupric Oxide Nanoparticles Induce Cellular Toxicity in Liver and Intestine Cell Lines. Adv Pharm Bull. 10(2), 213-220.
5. Huang Z., Wang X., Sun F., Fan C., Sun Y., Jia F., Yin G., Zhou T., Liu B., 2021. Super response and selectivity to H2S at room temperature based on CuO nanomaterials prepared by seed-induced hydrothermal growth. Mater. Des. 201, 109507.
6. Bhavyasree P.G., Xavier T.S., 2021. A critical green biosynthesis of novel CuO/C porous nanocomposite via the aqueous leaf extract of Ficus religiosa and their antimicrobial, antioxidant, and adsorption properties. Chem Eng J Adv. 8, 100152.
7. Horie M., Tabei Y., 2021. Role of oxidative stress in nanoparticles toxicity. Free Radic Res. 55(4), 331-342.
8. Costa P.M., Gosens I., Williams A., Farcal L., Pantano D., Brown D.M., Stone V., Cassee F.R., Halappanavar S., Fadeel B., 2018. Transcriptional profiling reveals gene expression changes associated with inflammation and cell proliferation following short-term inhalation exposure to copper oxide nanoparticles. J Appl Toxicol. 38(3), 385-397.
9. Anreddy R.N.R, 2018. Copper oxide nanoparticles induces oxidative stress and liver toxicity in rats following oral exposure. Toxicol Rep. 5, 903-904.
10. He H., Zou Z., Wang B., Xu G., Chen C., Qin X., Yu
C., Zhang J., 2020. Copper Oxide Nanoparticles Induce Oxidative DNA Damage and Cell Death via Copper Ion-Mediated P38 MAPK Activation in Vascular Endothelial Cells. Int J Nanomed. 15, 3291-3302.
11. Seyedalipour B., Barimani N., Dehpour Jooybari A.A., Hosseini S.M., Oshrieh M., 2015. Histopathological Evaluation of Kidney and Heart Tissues after Exposure to Copper Oxide Nanoparticles in Mus musculus. J Babol Univ Med Sci. 17(7), 44-50.
12. Torabi Farsani A., Arabi M., Shadkhast M., 2021. Ecotoxicity of chlorpyrifos on earthworm Eisenia fetida (Savigny, 1826): Modifications in oxidative biomarkers. Comp. Biochem. Physiol. Part C: Toxicol Pharmacol. 249, 109145.
13. Liu H., Guo H., Jian Z., Cui H., Fang J., Zuo Z., Deng J., Li Y., Wang X., Zhao L., 2020. Copper induces oxidative stress and apoptosis in the mouse liver. Oxid Med Cell Longev. 1359164.
14. Buege J.A., Aust S.D., 1978. Microsomal lipid peroxidation. Methods Enzymol. 52, 302-310.
15. Aebi H., Wyss S.R., Scherz B., Skvaril F., 1974. Heterogeneity of erythrocyte catalase II. Eur J Biochem. 48(1), 137-145.
16. Lawrence R.A., Burk R.F., 1976. Glutathione peroxidase activity in selenium-deficient rat liver. Biochem Biophys Res Commun. 71(4), 952-958.
17. Benzie I.F.F., Strain J.J., 1996. The ferric reducing ability of plasma (FRAP) as a measure of “antioxidant power”: The FRAP assay. Anal Biochem. 239, 70-76.
18. Bradford M.M., 1976. A rapid sensitive method for the quantification of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 72(1-2), 248-254.
19. Silva L.F.O., Santosh M., Schindler M., Gasparotto J., Dotto J.L., Oliveira M.L.S., Hochella Jr. M.F., 2021. Nanoparticles in fossil and mineral fuel sectors and their impact on environment and human health: A review and perspective. Gondwana Res. 92, 184-201.
20. Liu H., Lai W., Liu X., Yang H., Fang Y., Tian L., Li K., Nie H., Zhang W., Shi Y., Bian L., Ding S., Yan J., Lin B., Xi Z., 2021. Exposure to copper oxide nanoparticles triggers oxidative stress and endoplasmic reticulum (ER)-stress induced toxicology and apoptosis in male rat iver and BRL-3A cell. J Hazard Mater. 401, 123349.
21. Haywood S., Simpson D.M., Ross G., Beynon R.J., 2005. The greater susceptibility of North Ronaldsay sheep compared with Cambridge sheep to copper-induced oxidative stress, mitochondrial damage and hepatic stellate cell activation. J Comp Pathol. 133(2-3), 114-127.
22. Tseng H.L., Li C.J., Huang L.H., Chen C.Y., Tsai C.H., Lin C.N., Hsu H.Y., 2012. Quercetin 3-O-methyl ether protects FL83B cells from copper induced oxidative stress through the PI3K/Akt and MAPK/Erk pathway. Toxicol Appl Pharmacol. 264(1), 104-113.
23. Chang Y.N., Zhang M., Xia L., Zhang J., Xing G., 2012. The Toxic effects and mechanisms of CuO and ZnO nanoparticles. Materials. 5, 2850-2871.
24. Fu P.P., Xia Q., Hwang H.M., Ray P.C., Yu H., 2014. Mechanisms of nanotoxicity: generation of reactive oxygen species. J Food Drug Anal. 22, 64-75.
25. Tang H., Xu M., Luo J., Zhao L., Ye G., Shi F., Lv C., Chen H., Wang Y., Li Y., 2019. Liver toxicity assessments in rats following sub‑chronic oral exposure to copper nanoparticles. Environ Sci Eur. 31, 30.
26. Guo H., Li K., Wang W., Wang C., Shen Y., 2017. Effects of copper on hemocyte apoptosis, ROS production, and gene expression in white shrimp litopenaeus vannamei. Biol Trace Elem Res. 179(2), 318-326
27. Shi M., Kwon H.S., Peng Z., Elder A., Yang H., 2012. Effects of surface chemistry on the generation of reactive oxygen species by copper nanoparticles. ACS Nano. 6, 2157-2164.
28. Toduka Y., Toyooka T., Ibuki Y., 2012. Flow cytometric evaluation of nanoparticles using side-scattered light and reactive oxygen species-mediated fluorescence-correlation with genotoxicity. Environ Sci Technol. 46, 7629-7636.
29. Yang H., Liu C., Yang D.F., Zhang H.S., Xi Z., 2009. Comparative study of cytotoxicity, oxidative stress and genotoxicity induced by four typical nanomaterials: The role of particle size, shape and composition. J Appl Toxicol. 29, 69-78.
30. Lalhminghlui K., Jagetia G.C., 2018. Evaluation of the free-radical scavenging and antioxidant activities of Chilauni, Schima wallichii Korth in vitro. Future Sci OA. 4(2), FSO272.
31. Akhtar M.J., Kumar S., Alhadlaq H.A., Alrokayan S.A., Abu-Salah K.M., Ahamed M., 2016. Dose-dependent genotoxicity of CuO nanoparticles stimulated by reactive oxygen species in human lung epithelial cells. Toxicol Ind Health. 32(5), 809-821.
32. Hu X.K., Cook S., Wang P., Hwang H.M., 2009. In vitro evaluation of cytotoxicity of engineeredmetal oxide nanoparticles. Sci Total Environ. 407(8), 3070-3072.
33. Assadian E., Zarei M.H., Ghanadzadeh Gilani A., Farshin M., Degampanah H., Pourahmad J., 2018. Toxicity of Copper Oxide (CuO) Nanoparticles on Human Blood Lymphocytes. Biol Trace Elem Res. 184, 350-357.
34. Lange M., Wagner P.V., Fedorova M., 2021. Lipid composition dictates the rate of lipid peroxidation in artificial lipid droplets. Free Radic Res. 55(4), 469-480.
35. Goma A.A., El Okle O.S., Tohamy H.G., 2021. Protective effect of methylene blue against copper oxide nanoparticle-induced neurobehavioral toxicity. Behav Brain Res. 398, 112942.
36. Hassanen E.I., Tohamy A.F., Issa M.Y., Ibrahim M.A., Farroh K.Y., Hassan A.M., 2019. Pomegranate Juice Diminishes The Mitochondria-Dependent Cell Death And NF-kB Signaling Pathway Induced By Copper Oxide Nanoparticles On Liver And Kidneys Of Rats. Int J Nanomed. 2019, 8905-8922.
37. Feng W., Su S., Song C., Yu F., Zhou J., Li J., Jia R., Xu P., Tang Y., 2022. Effects of Copper Exposure on Oxidative Stress, Apoptosis, Endoplasmic Reticulum Stress, Autophagy and Immune Response in Different Tissues of Chinese Mitten Crab (Eriocheir sinensis). Antioxidants. 11, 2029.
38. Abdelazeim S.A., Shehata N.I., Aly H.F., ldin Shams S.G.E., 2020. Amelioration of oxidative stress-mediated apoptosis in copper oxide nanoparticles‑induced liver injury in rats by potent antioxidants. Sci Rep. 10(1), 10812.
39. Abdel-Latif H.M.R., Dawood M.A.O., Mahmoud S.F., Shukry M., Noreldin A.E., Ghetas
H.A., Khallaf M.A., 2021. Copper Oxide Nanoparticles Alter Serum Biochemical Indices, Induce Histopathological Alterations, and Modulate Transcription of Cytokines, HSP70, and Oxidative Stress Genes in Oreochromis niloticus. Animals (Basel). 11(3), 652.
40. Elkhateeb S.A., Ibrahim T.R., El‐Shal A.S., Abdel Hamid O.I., 2020. Ameliorative role of curcumin on copper oxide nanoparticles‐mediated renal toxicity in rats: An investigation of molecular mechanisms. J Biochem Mol Toxicol. 34(12), e22593.
41. Fahmy B., Cormier S.A., 2009. Copper oxide nanoparticles induce and cytotoxicity in airway epithelial cells. Toxicol In Vitro. 23, 1365-1371.
42. Adeniyi A.F., Adeleye J., Adeniyi C.Y., 2010. Diabetes, Sexual Dysfunction and Therapeutic Exercise: A 20 Year Review. Curr Diabetes Rev. 6(4), 201-206.
43. Kori-Siakpere O., Ubogu E.O., 2008. Sub-lethal hematological effects of zinc on the freshwater fish, Heteroclarias sp. (Osteichthyes: Clariidae). Afr J Biotech. 7(12), 2068-2073.
44. Yahya R.A.M., Azab A.E., El.M.Shkal K., 2019. Effects of Copper Oxide and/or Zinc Oxide Nanoparticles on Oxidative Damage and Antioxidant Defense System in Male Albino Rats. EAS J Pharm Pharmacol. 1(6), 135-144.
45. Tang H., Xu M., Luo J., Zhao L., Ye G., Shi F., Lv C., Chen H., Wang Y., Li Y., 2019. Liver toxicity assessments in rats following sub-chronic oral exposure to copper nanoparticles. Environ Sci Eur. 31, 30.
46. Mohammadyari A., Razavipour S.T., Mohammadbeigi M., Negahdary M., Ajdary M., 2014. Exploring vivo toxicity assessment of copper oxide nanoparticle in Wistar rats. J Biol Today’s World. 3(6), 124-128.
47. Anreddy R.R.N., Lonkala S., 2019. In vitro evaluation of copper oxide nanoparticle-induced cytotoxicity and oxidative stress using human embryonic kidney cells. Toxicol Indust Health. 35(2), 159-164.
48. Sarkar A., Das J., Manna P., Sil P.C., 2011. Nano-copper induces oxidative stress and apoptosis in kidney via both extrinsic and intrinsic pathways. Toxicology. 290(2-3), 208-217.
49. Ahamed M., Lateef R., Akhtar M.J., Rajanahalli P., 2022. Dietary Antioxidant Curcumin Mitigates CuO Nanoparticle-Induced Cytotoxicity through the Oxidative Stress Pathway in Human Placental Cells. Molecules. 27, 7378.
50. amrot A.V., Ram Singh S.P., Deenadhayalan R., Rajesh V.V., Padmanaban S., Radhakrishnan K., 2022. Nanoparticles, a Double-Edged Sword with Oxidant as Well as Antioxidant Properties-A Review. Oxygen. 2, 591-604.
51. Horie M., Tabei Y., 2021. Role of oxidative stress in nanoparticles toxicity. Free Radic Res. 55(4: Special issue), 331-342.
52. Torabi Farsani A., Arabi M., Shadkhast M., 2021. Ecotoxicity of chlorpyrifos on earthworm Eisenia fetida (Savigny, 1826): Modifications in oxidative biomarkers. Comp Biochem Physiol Part C. 249, 109145.
53. Arafaa A.F., Ghanema H.Z., Solimana M.S., EL-Meligyb E., 2017. Modulation effects of quercetin against copper oxide nanoparticles-induced liver toxicity in rats. Egyp Pharm J. 16, 78-86.
54. Yousef M.I., Roychoudhury S., Jafaar K.S., Slama P., Kesari K.K., Abdel-nabi kamel M., 2022. Aluminum Oxide and Zinc Oxide Induced Nanotoxicity in Rat Brain, Heart, and Lung. Physiol Res. 71, 677-694.
55. Dalle-Donne I., Scaloni A., Giustarini D., Cavarra E., Tell G., Lungarella G., Colombo R., Rossi R., Milzani A., 2005. Proteins as biomarkers of oxidative/nitrosative stress in diseases: The contribution of redox proteomics. Mass Spectrom. Rev. 24(1), 55-99.
56. Jiang Y.W., Gao G., Jia H.R., Zhang X., Zhao J., Ma N., Liu J.B., Liu P., Wu F.G., 2019. Copper Oxide Nanoparticles Induce Enhanced Radiosensitizing Effect via Destructive Autophagy. ACS Biomater Sci Eng. 5(3), 15-69.
57. Weiss R.H., Kim K., 2012. Metabolomics in the study of kidney diseases. Nat Rev Nephrol. 8, 22-33.
58. Zhang J., Wang B., Wang H., He H., Wu Q., Qin X., Yang X., Chen L., Xu G., Yuan Z., Yi Q., Zou Z., Yu C., 2018. Disruption of the superoxide anions-mitophagy regulation axis mediates copper xide nanoparticles-induced vascular endothelial cell death. Free Radic Biol Med. 129, 268-278.