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DOI: 10.1055/s-0044-1786867
Balancing Risks versus Benefits: Vitamin C Therapy versus Copper Oxide Nanoparticles Toxicity in Albino Rats' Submandibular Salivary Gland
Abstract
Objectives This study aimed to examine the suppressive effect of the natural antioxidant vitamin C (VC) against submandibular gland toxicity induced by copper oxide nanoparticles (CuO-NPs).
Materials and Methods Three groups of 30 mature male albino rats (4 weeks old) weighing between 150 and 200 g were selected. The rats were randomly assigned for 6 weeks to receive: intraperitoneal injection (IP) of vehicle (control group); IP of 2.5 mg/kg body weight (bw) of CuO-NPs (CuO-NPs group); and IP of 2.5 mg/kg bw of CuO-NPs, combined with a daily oral dose of 100 mg/kg bw of VC in drinking water via gavage (CuO-NPs/VC group). The rats were euthanized, and their submandibular glands were dissected for histological evaluation, including hematoxylin and eosin staining and immunohistochemistry for Ki-67 and caspase-3.
Statistical Analysis The area expression for Ki-67 and caspase-3 was statistically analyzed using GraphPad Prism. Following analysis of variance analysis, Tukey's post hoc was used for multiple comparisons. The significance level was set at p < 0.05.
Results CuO-NPs caused significant cytotoxic effects on submandibular salivary gland cells in albino rats. This led to an increase in Ki-67 and caspase-3 levels compared with the control group. VC administration improved tissue histology and reduced Ki-67 and caspase-3 levels in the VC/CuO-NPs group compared with rats treated with CuO-NPs alone.
Conclusion The study revealed significant cytotoxic effects of CuO-NPs on the submandibular salivary gland of albino rats. VC effectively mitigated these toxic effects, suggesting its potential as a readily available antioxidant.
Keywords
antioxidant - caspase 3 - copper oxide nanoparticles - CuO-NPs - Ki-67 - salivary gland - vitamin CPublication History
Article published online:
24 May 2024
© 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)
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References
- 1 Ingle AP, Duran N, Rai M. Bioactivity, mechanism of action, and cytotoxicity of copper-based nanoparticles: a review. Appl Microbiol Biotechnol 2014; 98 (03) 1001-1009
- 2 Ermini ML, Voliani V. Antimicrobial nano-agents: the copper age. ACS Nano 2021; 15 (04) 6008-6029
- 3 Tulinska J, Mikusova ML, Liskova A. et al. Copper oxide nanoparticles stimulate the immune response and decrease antioxidant defense in mice after six-week inhalation. Front Immunol 2022; 13: 874253
- 4 Waris A, Din M, Ali A. et al. A comprehensive review of green synthesis of copper oxide nanoparticles and their diverse biomedical applications. Inorg Chem Commun 2021; 123: 108369
- 5 Gaetke LM, Chow-Johnson HS, Chow CK. Copper: toxicological relevance and mechanisms. Arch Toxicol 2014; 88 (11) 1929-1938
- 6 Zhang H, Chang Z, Mehmood K. et al. Nano copper induces apoptosis in PK-15 cells via a mitochondria-mediated pathway. Biol Trace Elem Res 2018; 181 (01) 62-70
- 7 Shi M, Kwon HS, Peng Z, Elder A, Yang H. Effects of surface chemistry on the generation of reactive oxygen species by copper nanoparticles. ACS Nano 2012; 6 (03) 2157-2164
- 8 Sharma P, Goyal D, Chudasama B. Ecotoxicity of as-synthesised copper nanoparticles on soil bacteria. IET Nanobiotechnol 2021; 15 (02) 236-245
- 9 Cholewińska E, Ognik K, Fotschki B, Zduńczyk Z, Juśkiewicz J. Comparison of the effect of dietary copper nanoparticles and one copper (II) salt on the copper biodistribution and gastrointestinal and hepatic morphology and function in a rat model. PLoS One 2018; 13 (05) e0197083
- 10 Bakr MM, Al-Ankily MM, Shogaa SM, Shamel M. Attenuating effect of vitamin E against silver nano particles toxicity in submandibular salivary glands. Bioengineering (Basel) 2021; 8 (12) 219
- 11 Whayne TF, Saha SP, Mukherjee D. Antioxidants in the practice of medicine; what should the clinician know?. Cardiovasc Hematol Disord Drug Targets 2016; 16 (01) 13-20
- 12 Pehlivan FE, Vitamin C. An Antioxidant Agent. In: Hamza AH, ed. Vitamin C. London: InTech 2017; 23-35
- 13 Borgohain K, Singh JB, Rao MVR, Shripathi T, Mahamuni S. Quantum size effects in CuO nanoparticles. Phys Rev B Condens Matter Mater Phys 2000; 61 (16) 11093
- 14 El Mahdy MM, Eldin TAS, Aly HS, Mohammed FF, Shaalan MI. Evaluation of hepatotoxic and genotoxic potential of silver nanoparticles in albino rats. Exp Toxicol Pathol 2015; 67 (01) 21-29
- 15 Minigalieva IA, Katsnelson BA, Panov VG. et al. In vivo toxicity of copper oxide, lead oxide and zinc oxide nanoparticles acting in different combinations and its attenuation with a complex of innocuous bio-protectors. Toxicology 2017; 380: 72-93
- 16 Bashandy SAE. Beneficial effect of combined administration of vitamin C and vitamin E in amelioration of chronic lead hepatotoxicity. Egypt J Hosp Med 2006; 23 (01) 371-384
- 17 Naz S, Gul A, Zia M. Toxicity of copper oxide nanoparticles: a review study. IET Nanobiotechnol 2020; 14 (01) 1-13
- 18 Mahmoud A, Ghazy D, Farouk R, Adeeb M. Capsaicin induced histological and ultrastructural changes in the submandibular salivary gland of albino rats. Futur Dent J 2016; 2 (01) 22-27
- 19 Hassan SS, Attia MA, Attia AM, Nofal RA, Fathi A. Distribution of cytokeratin 17 in the parenchymal elements of rat's submandibular glands subjected to fractionated radiotherapy. Eur J Dent 2020; 14 (03) 440-447
- 20 Nurdiana S, Goh YM, Ahmad H. et al. Changes in pancreatic histology, insulin secretion and oxidative status in diabetic rats following treatment with Ficus deltoidea and vitexin. BMC Complement Altern Med 2017; 17 (01) 290
- 21 Ghonimi WAM, Alferah MAZ, Dahran N, El-Shetry ES. Hepatic and renal toxicity following the injection of copper oxide nanoparticles (CuO NPs) in mature male Westar rats: histochemical and caspase 3 immunohistochemical reactivities. Environ Sci Pollut Res Int 2022; 29 (54) 81923-81937
- 22 Anreddy RNR. Copper oxide nanoparticles induces oxidative stress and liver toxicity in rats following oral exposure. Toxicol Rep 2018; 5: 903-904
- 23 Chang YN, Zhang M, Xia L, Zhang J, Xing G. The toxic effects and mechanisms of CuO and ZnO nanoparticles. Materials (Basel) 2012; 5 (12) 2850-2871
- 24 Thit A, Selck H, Bjerregaard HF. Toxic mechanisms of copper oxide nanoparticles in epithelial kidney cells. Toxicol In Vitro 2015; 29 (05) 1053-1059
- 25 Carr AC, Maggini S. Vitamin C and immune function. Nutrients 2017; 9 (11) 1-25
- 26 Ferrada L, Magdalena R, Barahona MJ. et al. Two distinct faces of vitamin C: AA vs. DHA. Antioxidants 2021; 10 (02) 215
- 27 Patra RC, Swarup D, Dwivedi SK. Antioxidant effects of α tocopherol, ascorbic acid and L-methionine on lead induced oxidative stress to the liver, kidney and brain in rats. Toxicology 2001; 162 (02) 81-88
- 28 Malhotra JD, Miao H, Zhang K. et al. Antioxidants reduce endoplasmic reticulum stress and improve protein secretion. Proc Natl Acad Sci U S A 2008; 105 (47) 18525-18530
- 29 Sun X, Kaufman PD. Ki-67: more than a proliferation marker. Chromosoma 2018; 127 (02) 175-186
- 30 Taha RM, Hanafi R, Said M. Possible cytotoxic effects of silver nanoparticles on the parotid glands of albino rats. Oral Biol Oral Pathol Egyptian Dental J 2019; ;65(03(Oral Medicine, X-Ray, Oral Biology & Oral Pathology)): 2253-2263
- 31 Sharma S, Singh VK, Kumar A, Mallubhotla S. Effect of Nanoparticles on Oxidative Damage and Antioxidant Defense System in Plants. In: Molecular Plant Abiotic Stress. Hoboken, NJ, United States: John Wiley & Sons, Ltd; 2019: 315-333
- 32 Hengartner MO. The biochemistry of apoptosis. Nature 2000; 407 (6805): 770-776
- 33 Siddiqui MA, Alhadlaq HA, Ahmad J, Al-Khedhairy AA, Musarrat J, Ahamed M. Copper oxide nanoparticles induced mitochondria mediated apoptosis in human hepatocarcinoma cells. PLoS One 2013; 8 (08) e69534
- 34 Dey A, Manna S, Chattopadhyay S. et al. Azadirachta indica leaves mediated green synthesized copper oxide nanoparticles induce apoptosis through activation of TNF-α and caspases signaling pathway against cancer cells. J Saudi Chem Soc 2019; 23 (02) 222-238
- 35 Alqahtani MS, Hassan SS. Immunohistochemical evaluation of the pathological effects of diabetes mellitus on the major salivary glands of albino rats. Eur J Dent 2023; 17 (02) 485-491
- 36 Shafagh M, Rahmani F, Delirezh N. CuO nanoparticles induce cytotoxicity and apoptosis in human K562 cancer cell line via mitochondrial pathway, through reactive oxygen species and P53. Iran J Basic Med Sci 2015; 18 (10) 993-1000
- 37 Kaźmierczak-Barańska J, Boguszewska K, Karwowski BT. Nutrition can help DNA repair in the case of aging. Nutrients 2020; 12 (11) 1-20
- 38 Zhou J, Chen C, Chen X, Fei Y, Jiang L, Wang G. Vitamin C promotes apoptosis and cell cycle arrest in oral squamous cell carcinoma. Front Oncol 2020; 10: 976
- 39 Vital P, Castro P, Ittmann M. Oxidative stress promotes benign prostatic hyperplasia. Prostate 2016; 76 (01) 58-67