Antioxidant Effect in Nasopharyngeal Cancer Histopathology Degree on 40 PPM Formaldehyde-Inducted Rattus novergicus
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Putu Arta Wibawa , Anak Agung Ayu Niti Wedayani , Lale Maulin Prihatina , Eka Ari Yuliani , Sekar PratiwiDOI:
10.29303/jbt.v25i2.8805Published:
2025-04-23Issue:
Vol. 25 No. 2 (2025): April-JuniArticles
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Abstract
Formaldehyde exposure, implicated on the development of nasopharyngeal cancer (NPC), remains a significant concern worldwide, with increasing incidence, morbidity, and mortality cases. This study eager to investigate the antioxidant effect on degree of histopathology from formaldehyde exposure, assessing nasopharyngeal dysplasia progression toward malignancy. Rattus norvegicus divided equally into four groups: control, placebo, formaldehyde-induced (40 PPM), and formaldehyde-induced with antioxidant, followed by dysplasia degree examination under light microscope. The result revealed severe dysplasia in the formaldehyde group, indicating non-keratinizing squamous cell carcinoma. Additionally, antioxidant-treated group presented reduced severity, with lower degree of dysplasia. This result is indicating positive improvement of antioxidant effect toward NPC malignancy, supporting previous studies and further confirming genotoxicity and irritability of formaldehyde. Nevertheless, limitations, existed with lack of sample studied and dose-response analysis, were demanding deeper study need to be done.
References
Adamović, D., Čepić, Z., Adamović, S., Stošić, M., Obrovski, B., Morača, S., & Vojinović Miloradov, M. (2021). Occupational Exposure to Formaldehyde and Cancer Risk Assessment in an Anatomy Laboratory. International Journal of Environmental Research and Public Health, 18(21). https://doi.org/10.3390/ijerph182111198
Alwelaie, Y., Howaidi, A., Tashkandi, M., Almotairi, A., Saied, H., Muzzaffar, M., & Alghamdi, D. (2023). Revisiting the cytomorphological features of poorly differentiated thyroid carcinoma: a comparative analysis with indeterminate thyroid fine-needle aspiration samples. Journal of the American Society of Cytopathology, 12(5), 331–340. https://doi.org/10.1016/j.jasc.2023.05.002
Benedict, B., Kristensen, S. M., & Duxin, J. P. (2024). What are the DNA lesions underlying formaldehyde toxicity? DNA Repair, 138, 103667. https://doi.org/10.1016/j.dnarep.2024.103667
Chan, J. K. (2017). Virus-associated neoplasms of the nasopharynx and sinonasal tract: diagnostic problems. Modern Pathology, 30, S68–S83. https://doi.org/10.1038/modpathol.2016.189
Chen, S., Youhong, T., Tan, Y., He, Y., Ban, Y., Cai, J., … Xiang, B. (2020). EGFR-PKM2 signaling promotes the metastatic potential of nasopharyngeal carcinoma through induction of FOSL1 and ANTXR2. Carcinogenesis, 41(6), 723–733. https://doi.org/10.1093/carcin/bgz180
Clausen, P. A., Frederiksen, M., Sejbæk, C. S., Sørli, J. B., Hougaard, K. S., Frydendall, K. B., … Wolkoff, P. (2020). Chemicals inhaled from spray cleaning and disinfection products and their respiratory effects. A comprehensive review. International Journal of Hygiene and Environmental Health, 229, 113592. https://doi.org/10.1016/j.ijheh.2020.113592
Dahbi, Z., Alami, R., Elmejjabar, R., & Couhen, F. (2023). A closer look at nasopharyngeal cancer: A typical case report. Radiology Case Reports, 18(7), 2507–2510. https://doi.org/10.1016/j.radcr.2023.04.017
Dator, R. P., Murray, K. J., Luedtke, M. W., Jacobs, F. C., Kassie, F., Nguyen, H. D., … Balbo, S. (2022). Identification of Formaldehyde-Induced DNA–RNA Cross-Links in the A/J Mouse Lung Tumorigenesis Model. Chemical Research in Toxicology, 35(11), 2025–2036. https://doi.org/10.1021/acs.chemrestox.2c00206
Didier, A. J., Stiene, J., Fang, L., Watkins, D., Dworkin, L. D., & Creeden, J. F. (2023). Antioxidant and Anti-Tumor Effects of Dietary Vitamins A, C, and E. Antioxidants, 12(3), 632. https://doi.org/10.3390/antiox12030632
Du, T., Xiao, J., Qiu, Z., & Wu, K. (2019). The effectiveness of intensity-modulated radiation therapy versus 2D-RT for the treatment of nasopharyngeal carcinoma: A systematic review and meta-analysis. PloS One, 14(7), e0219611. https://doi.org/10.1371/journal.pone.0219611
George, S., & Abrahamse, H. (2020). Redox Potential of Antioxidants in Cancer Progression and Prevention. Antioxidants, 9(11), 1156. https://doi.org/10.3390/antiox9111156
Ghelli, F., Bellisario, V., Buglisi, M., Cocchi, E., Bono, R., & Santovito, A. (2020). Cytogenetic effects among workers exposed to formaldehyde. The possible role of some polymorphisms. European Journal of Public Health, 30(Supplement_5). https://doi.org/10.1093/eurpub/ckaa166.346
Ghelli, F., Buglisi, M., Bellisario, V., Santovito, A., & Bono, R. (2020). Formaldehyde in hospitals can still represent a risk factor. Oxidative stress and GSTT1 polymorphism. European Journal of Public Health, 30(Supplement_5). https://doi.org/10.1093/eurpub/ckaa166.340
Heath, J. E., Goicochea, L. B., & Staats, P. N. (2015). Biliary stent–related alterations can be distinguished from adenocarcinoma on bile duct brushings using a limited number of cytologic features. Journal of the American Society of Cytopathology, 4(5), 282–289. https://doi.org/10.1016/j.jasc.2015.06.006
Huang, S., Song, S., Nielsen, C. P., Zhang, Y., Xiong, J., Weschler, L. B., … Li, J. (2022). Residential building materials: An important source of ambient formaldehyde in mainland China. Environment International, 158, 106909. https://doi.org/10.1016/j.envint.2021.106909
Jena, A. B., Samal, R. R., Bhol, N. K., & Duttaroy, A. K. (2023). Cellular Red-Ox system in health and disease: The latest update. Biomedicine & Pharmacotherapy, 162, 114606. https://doi.org/10.1016/j.biopha.2023.114606
Kang, D. S., Kim, H. S., Jung, J.-H., Lee, C. M., Ahn, Y.-S., & Seo, Y. R. (2021). Formaldehyde exposure and leukemia risk: a comprehensive review and network-based toxicogenomic approach. Genes and Environment : The Official Journal of the Japanese Environmental Mutagen Society, 43(1), 13. https://doi.org/10.1186/s41021-021-00183-5
Kawanishi, M., Matsuda, T., & Yagi, T. (2014). Genotoxicity of formaldehyde: molecular basis of DNA damage and mutation. Frontiers in Environmental Science, 2. https://doi.org/10.3389/fenvs.2014.00036
Khoshakhlagh, A. H., Ghobakhloo, S., Al Sulaie, S., Yazdanirad, S., & Gruszecka-Kosowska, A. (2025). A Monte Carlo simulation and meta-analysis of health risk due to formaldehyde exposure at different seasons of the year in various indoor environments. Science of The Total Environment, 965, 178641. https://doi.org/10.1016/j.scitotenv.2025.178641
Khoshakhlagh, A. H., Omer, F., & Yazdanirad, S. (2024). The variation in exposure to ambient formaldehyde at different times of the year in various countries: A systematic review and meta-analysis. Journal of Hazardous Materials Advances, 16, 100467. https://doi.org/10.1016/j.hazadv.2024.100467
Kumar, S., Saxena, J., Srivastava, V. K., Kaushik, S., Singh, H., Abo-EL-Sooud, K., … Saluja, R. (2022). The Interplay of Oxidative Stress and ROS Scavenging: Antioxidants as a Therapeutic Potential in Sepsis. Vaccines, 10(10), 1575. https://doi.org/10.3390/vaccines10101575
La Torre, G., Vitello, T., Cocchiara, R. A., & Della Rocca, C. (2023a). Relationship between formaldehyde exposure, respiratory irritant effects and cancers: a review of reviews. Public Health, 218, 186–196. https://doi.org/10.1016/j.puhe.2023.03.009
La Torre, G., Vitello, T., Cocchiara, R. A., & Della Rocca, C. (2023b). Relationship between formaldehyde exposure, respiratory irritant effects and cancers: a review of reviews. Public Health, 218, 186–196. https://doi.org/10.1016/j.puhe.2023.03.009
Leso, V., Macrini, M. C., Russo, F., & Iavicoli, I. (2020). Formaldehyde Exposure and Epigenetic Effects: A Systematic Review. Applied Sciences, 10(7), 2319. https://doi.org/10.3390/app10072319
Li, T., Wei, Y., Qu, M., Mou, L., Miao, J., Xi, M., … He, R. (2021). Formaldehyde and De/Methylation in Age-Related Cognitive Impairment. Genes, 12(6), 913. https://doi.org/10.3390/genes12060913
Liu, X., Deng, Y., Huang, Y., Ye, J., Xie, S., He, Q., … Zhang, J. (2022). Nasopharyngeal Carcinoma Progression: Accumulating Genomic Instability and Persistent Epstein–Barr Virus Infection. Current Oncology, 29(9), 6035–6052. https://doi.org/10.3390/curroncol29090475
Luo, M., Zhou, L., Huang, Z., Li, B., Nice, E. C., Xu, J., & Huang, C. (2022). Antioxidant Therapy in Cancer: Rationale and Progress. Antioxidants, 11(6), 1128. https://doi.org/10.3390/antiox11061128
Marin, M. A., Closca, R.-M., Marin, A., Rakitovan, M., Nicoara, A., Poenaru, M., … Baderca, F. (2024). Clinical, Epidemiological, Morphological, and Immunohistochemical Aspects of Nasopharyngeal Carcinoma—4-Year Retrospective Study in the Western Part of Romania. Diagnostics, 14(7), 722. https://doi.org/10.3390/diagnostics14070722
Mazurkiewicz, W., Sak, J., Nowiński, M., & Fus-Mazurkiewicz, L. A. (2024). Environmental exposure to formaldehyde and effects on human health. Environmental Medicine, 27(2), 41–45. https://doi.org/10.26444/ms/189610
Michal, M., Agaimy, A., Contreras, A. L., Svajdler, M., Kazakov, D. V., Steiner, P., … Fetsch, J. F. (2018). Dysplastic Lipoma. American Journal of Surgical Pathology, 42(11), 1530–1540. https://doi.org/10.1097/PAS.0000000000001129
Miligi, L., Massari, S., Paredes Alpaca, R. I., Piro, S., Airoldi, C., Ranucci, A., … Aprea, M. C. (2020). Risk of nasopharyngeal cancer in productive sectors and formaldehyde exposure in bakeries industry. European Journal of Public Health, 30(Supplement_5). https://doi.org/10.1093/eurpub/ckaa166.1376
Möhner, M., Liu, Y., & Marsh, G. M. (2019). New insights into the mortality risk from nasopharyngeal cancer in the national cancer institute formaldehyde worker cohort study. Journal of Occupational Medicine and Toxicology, 14(1), 4. https://doi.org/10.1186/s12995-019-0224-2
Monahan, D. A., Wang, J., Lee, O., Revesz, E., Taft, N., Ivancic, D., … Khan, S. A. (2016). Cytologic atypia in the contralateral unaffected breast is related to parity and estrogen-related genes. Surgical Oncology, 25(4), 449–456. https://doi.org/10.1016/j.suronc.2015.12.001
Nakamura, J., Shimomoto, T., Collins, L. B., Holley, D. W., Zhang, Z., Barbee, J. M., … Bultman, S. J. (2017). Evidence that endogenous formaldehyde produces immunogenic and atherogenic adduct epitopes. Scientific Reports, 7(1), 10787. https://doi.org/10.1038/s41598-017-11289-8
Nielsen, G. D., Larsen, S. T., & Wolkoff, P. (2017). Re-evaluation of the WHO (2010) formaldehyde indoor air quality guideline for cancer risk assessment. Archives of Toxicology, 91(1), 35–61. https://doi.org/10.1007/s00204-016-1733-8
Niti Wedayani, A. A. A., Qadar Punagi, A., Audrey, N., Cangara, H., Kawi Junior, D. G., & Yusuf, R. S. (2023). Differences in Nasopharyngeal and Lung Histopathology in Wistar Rats (Rattus norvegicus) Given Inhaled Formaldehyde Exposure with Doses of 20, 30, and 40 ppm. Asian Pacific Journal of Cancer Biology, 8(4), 335–338. https://doi.org/10.31557/apjcb.2023.8.4.335-338
Nitti, M., Marengo, B., Furfaro, A. L., Pronzato, M. A., Marinari, U. M., Domenicotti, C., & Traverso, N. (2022). Hormesis and Oxidative Distress: Pathophysiology of Reactive Oxygen Species and the Open Question of Antioxidant Modulation and Supplementation. Antioxidants, 11(8), 1613. https://doi.org/10.3390/antiox11081613
Protano, C., Buomprisco, G., Cammalleri, V., Pocino, R. N., Marotta, D., Simonazzi, S., … Vitali, M. (2021). The Carcinogenic Effects of Formaldehyde Occupational Exposure: A Systematic Review. Cancers, 14(1), 165. https://doi.org/10.3390/cancers14010165
Qu, M., Lu, J., & He, R. (2017). Formaldehyde from Environment. In Formaldehyde and Cognition (pp. 1–19). Dordrecht: Springer Netherlands. https://doi.org/10.1007/978-94-024-1177-5_1
Romdhoni, A., Rejeki, P., Guo, H., Milla, C., Melbiarta, R., Visuddho, V., & Nugraha, D. (2023). Risk Factors Associated with Nasopharyngeal Cancer Incidences in Indonesia: A Systematic Review and Meta-Analysis. Asian Pacific Journal of Cancer Prevention, 24(4), 1105–1111. https://doi.org/10.31557/APJCP.2023.24.4.1105
Salthammer, T. (2019). Formaldehyde sources, formaldehyde concentrations and air exchange rates in European housings. Building and Environment, 150, 219–232. https://doi.org/10.1016/j.buildenv.2018.12.042
Song, Y., Cheng, W., Li, H., & Liu, X. (2022). The global, regional, national burden of nasopharyngeal cancer and its attributable risk factors (1990–2019) and predictions to 2035. Cancer Medicine, 11(22), 4310–4320. https://doi.org/10.1002/cam4.4783
Speit, G. (2002). Evaluation of mutagenic effects of formaldehyde in vitro: detection of crosslinks and mutations in mouse lymphoma cells. Mutagenesis, 17(3), 183–187. https://doi.org/10.1093/mutage/17.3.183
Swenberg, J. A., Moeller, B. C., Lu, K., Rager, J. E., Fry, R. C., & Starr, T. B. (2013). Formaldehyde carcinogenicity research: 30 years and counting for mode of action, epidemiology, and cancer risk assessment. Toxicologic Pathology, 41(2), 181–189. https://doi.org/10.1177/0192623312466459
Tommasi, C., Scartabellati, G., Giannarelli, D., Giorgi, U. De, Brighi, N., Fornarini, G., … Buti, S. (2023). The role of mean corpuscular volume and red cell distribution width in patients with metastatic renal cell carcinoma treated with tyrosine kinase inhibitors: the MARECAP retrospective study. Therapeutic Advances in Urology, 15. https://doi.org/10.1177/17562872231187216
Wahidah, P. U. K., & Yuliyani, E. A. (2023). Event of Nasopharyngeal Carcinoma in Coastal Areas: Review Article. Green Medical Journal, 5(1), 18–24. https://doi.org/10.33096/gmj.v5i1.124
Wang, H., Wang, H., Xiong, J., Huang, S., & Koutrakis, P. (2022). A rapid and robust method to determine the key parameters of formaldehyde emissions from building and vehicle cabin materials: Principle, multi-source application and exposure assessment. Journal of Hazardous Materials, 430, 128422. https://doi.org/10.1016/j.jhazmat.2022.128422
Wedayani, A. A. A. N., Abdul Qadar Punagi, Pieter, N. A. L., Muhammad Husni Cangara, Kristin, E., Kadriyan, H., … I Made Tobias Abdiman. (2024). Nasopharyngeal histopathology of Wistar rats induced by formaldehyde with tiered concentration. Bali Medical Journal, 13(2), 934–940. https://doi.org/10.15562/bmj.v13i1.4899
Xiong, H., Wang, S., Sun, Z., Li, J., Zhang, H., Liu, W., … Fan, C. (2022). The ROS‐responsive scavenger with intrinsic antioxidant capability and enhanced immunomodulatory effects for cartilage protection and osteoarthritis remission. Applied Materials Today, 26, 101366. https://doi.org/10.1016/j.apmt.2022.101366
Yu, H., Yin, X., Mao, Y., Chen, M., Tang, Q., & Yan, S. (2022). The global burden of nasopharyngeal carcinoma from 2009 to 2019: an observational study based on the Global Burden of Disease Study 2019. European Archives of Oto-Rhino-Laryngology, 279(3), 1519–1533. https://doi.org/10.1007/s00405-021-06922-2
Zahra, K. F., Lefter, R., Ali, A., Abdellah, E.-C., Trus, C., Ciobica, A., & Timofte, D. (2021). The Involvement of the Oxidative Stress Status in Cancer Pathology: A Double View on the Role of the Antioxidants. Oxidative Medicine and Cellular Longevity, 2021(1). https://doi.org/10.1155/2021/9965916
Zhang, P., Li, T., Wu, X., Nice, E. C., Huang, C., & Zhang, Y. (2020). Oxidative stress and diabetes: antioxidative strategies. Frontiers of Medicine, 14(5), 583–600. https://doi.org/10.1007/s11684-019-0729-1
Zhang, Yanting, Rumgay, H., Li, M., Cao, S., & Chen, W. (2023). Nasopharyngeal Cancer Incidence and Mortality in 185 Countries in 2020 and the Projected Burden in 2040: Population-Based Global Epidemiological Profiling. JMIR Public Health and Surveillance, 9, e49968. https://doi.org/10.2196/49968
Zhang, Yuna, Gu, S., Deng, H., & Shen, Z. (2024). Global epidemiological profile in nasopharyngeal carcinoma: a prediction study. BMJ Open, 14(12), e091087. https://doi.org/10.1136/bmjopen-2024-091087
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