The preventive effect of aqueous extract of Cinnamomum zeylanicum against cytotoxicity produced by cyclophosphamide in male white mice

Document Type : Research Paper

Author

Department of Biology, College of Education, Al-Qadisiyah University, Al-Qadisiyah, Iraq

10.22103/jab.2025.24761.1654

Abstract

Objective
Cinnamomum zeylanicum (true cinnamon) is a medicinal plant traditionally used for its wide range of therapeutic properties, including antioxidant, anti-inflammatory, antimicrobial, and cytoprotective effects. Recent studies have highlighted its bioactive compounds, such as cinnamaldehyde and eugenol, which may play a role in modulating oxidative stress and cellular damage. Cyclophosphamide is a widely used alkylating chemotherapeutic agent, particularly effective in treating various cancers and autoimmune conditions. However, its clinical utility is often limited due to its genotoxic and cytotoxic side effects, including chromosomal aberrations and reproductive toxicity. Developing adjunct therapies to mitigate these side effects is of increasing interest. This study aims to evaluate the protective role of C. zeylanicum against cyclophosphamide-induced genotoxicity and cytotoxicity in male albino mice, potentially supporting its use as a natural chemoprotective agent.
Materials and methods
Thirty adult male albino mice were randomly divided into three groups (n = 10 per group). Group I served as the negative control and received distilled water. Group II was administered a single intraperitoneal dose of cyclophosphamide (20 mg/kg body weight). Group III received both C. zeylanicum extract (100 mg/kg body weight) and cyclophosphamide (20 mg/kg). The study assessed chromosomal aberrations in bone marrow cells, abnormalities in sperm head morphology, and the mitotic index to determine the extent of genotoxic and cytotoxic effects.
Results
Mice treated with C. zeylanicum in combination with cyclophosphamide showed a significant reduction in chromosomal aberrations and sperm head abnormalities compared to the group receiving cyclophosphamide alone. Additionally, a notable increase in the mitotic index was observed in the co-treatment group, indicating a protective and possibly regenerative effect on bone marrow cell proliferation.
Conclusions
The findings of this study demonstrate that C. zeylanicum possesses a protective effect against cyclophosphamide-induced genotoxic and cytotoxic damage in male albino mice. Its antioxidative and anti-inflammatory constituents may help preserve cellular integrity and enhance recovery following chemotherapeutic insult. These results suggest that C. zeylanicum could be considered as a complementary therapeutic agent to reduce the adverse side effects of cyclophosphamide. Further research, including molecular analyses and clinical trials, is recommended to better understand its mechanisms of action and to evaluate its safety and efficacy in human subjects.

Keywords

References

Abd Elhalim, S. A., Sharada, H. M., Abulyazid, I., Aboulthana, W. M., & Abd Elhalim, S. T. (2017). Ameliorative effect of carob pods extract (Ceratonia siliqua L.) against cyclophosphamide-induced alterations in bone marrow and spleen of rats. Journal of Applied Pharmaceutical Science, 7(10), 168–181. https://doi.org/10.7324/JAPS.2017.71025
Ahlmann, M., & Hempel, G. (2016). The effect of cyclophosphamide on the immune system: Implications for clinical cancer therapy. Cancer Chemotherapy and Pharmacology, 78(4), 661–671. https://doi.org/10.1007/s00280-016-3152-1
Allen, J. W., Shuler, C. F., Menders, R. W., & Olatt, S. A. (1977). Simplified technique for in vivo analysis of SCE using 5-bromodeoxyuridine tablets. Cytogenetics and Cell Genetics, 18(4), 231–237. https://doi.org/10.1159/000130765
Amirteymoori, E., Khezri, A., Dayani, O., Mohammadabadi, M., Khorasani, S., Mousaie, A., & Kazemi-Bonchenari, M. (2021). Effects of linseed processing method (ground versus extruded) and dietary crude protein content on performance, digestibility, ruminal fermentation pattern, and rumen protozoa population in growing lambs. Italian Journal of Animal Science, 20(1), 1506–1517. https://doi.org/10.1080/1828051X.2021.1984324
Aneja, K. R., Joshi, R., & Sharma, C. (2009). Antimicrobial activity of Dalchini (Cinnamomum zeylanicum bark) extracts on some dental caries pathogens. Journal of Pharmaceutical Research, 2(9), 1387–1390. https://jopcr.com/#home
Arif, A., Alameri, A. A., Tariq, U. B., Ansari, S. A., Sakr, H. I., Qasim, M. T., Aljoborae, F. F. M., Ramírez-Coronel, A. A., Jabbar, H. S., Gabr, G. A., Mirzaei, R., & Karampoor, S. (2023). The functions and molecular mechanisms of Tribbles homolog 3 (TRIB3) implicated in the pathophysiology of cancer. International Immunopharmacology, 114, 109581. https://doi.org/10.1016/j.intimp.2022.109581
Bashar, B. S., Kareem, H. A., Hasan, Y. M., & others. (2022). Application of novel Fe₃O₄/Zn-metal organic framework magnetic nanostructures as an antimicrobial agent and magnetic nanocatalyst in the synthesis of heterocyclic compounds. Frontiers in Chemistry, 10, 1014731. https://doi.org/10.3389/fchem.2022.1014731
Emadi, A., Jones, R. J., & Brodsky, R. A. (2009). Cyclophosphamide and cancer: Golden anniversary. Nature Reviews Clinical Oncology, 6(11), 638–647. https://doi.org/10.1038/nrclinonc.2009.146
Ghobadi, E., Moloudizargari, M., Asghari, M. H., & Abdollahi, M. (2017). The mechanisms of cyclophosphamide-induced testicular toxicity and the protective agents. Expert Opinion on Drug Metabolism & Toxicology, 13(5), 525–536. https://doi.org/10.1080/17425255.2017.1277205
Habibi, E., Shokrzadeh, M., Chabra, A., Naghshvar, F., Keshavarz-Maleki, R., & Ahmadi, A. (2015). Protective effects of Origanum vulgare ethanol extract against cyclophosphamide-induced liver toxicity in mice. Pharmaceutical Biology, 53(1), 10–15. https://doi.org/10.3109/13880209.2014.908399
Hajalizadeh, Z., Dayani, O., Khezri, A., Tahmasbi, R., & Mohammadabadi, M. R. (2019). The effect of adding fennel (Foeniculum vulgare) seed powder to the diet of fattening lambs on performance, carcass characteristics, and liver enzymes. Small Ruminant Research, 175, 72-77. https://doi.org/10.1016/j.smallrumres.2019.04.011
Hayatsu, H., Arimoto, S., & Negishi, T. (1988). Dietary inhibitors of mutagenesis and carcinogenesis. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 202(2), 429–446. https://doi.org/10.1016/0027-5107(88)90204-7
IBM Corp. (2011). IBM SPSS Statistics for Windows (Version 20.0). IBM Corp.
Iqubal, A., Iqubal, M. K., Sharma, S., Ansari, M. A., Najmi, A. K., Ali, S. M., Ali, J., & Haque, S. E. (2019). Molecular mechanism involved in cyclophosphamide-induced cardiotoxicity: Old drug with a new vision. Life Sciences, 218, 112–131. https://doi.org/10.1016/j.lfs.2018.12.018
Jafari Ahmadabadi, S. A. A., Askari-Hemmat, H., Mohammadabadi, M., Asadi Fozi, M., & Mansouri Babhootki, M. (2023). The effect of cannabis seed on DLK1 gene expression in heart tissue of Kermani lambs. Agricultural Biotechnology Journal, 15(1), 217-234. https://doi.org/10.22103/jab.2023.21265.1471
Kaina, B. (2004). Mechanisms and consequences of methylating agent-induced SCEs and chromosomal aberrations: A long road traveled and still a far way to go. Cytogenetic and Genome Research, 104(1–4), 77–86. https://doi.org/10.1159/000077469
Kocahan, S., Dogan, Z., Erdemli, E., & Taskin, E. (2017). Protective effect of quercetin against oxidative stress-induced toxicity associated with doxorubicin and cyclophosphamide in rat kidney and liver tissue. Iranian Journal of Kidney Diseases, 11(2), 124.
Lemes, S. R., Chaves, D. A., Silva, N. J. D., Carneiro, C. C., Chen-Chen, L., Almeida, L. M., Gonçalves, P. J., & Melo-Reis, P. R. (2017). Antigenotoxicity protection of Carapa guianensis oil against mitomycin C and cyclophosphamide in mouse bone marrow. Anais da Academia Brasileira de Ciências, 89(3 Suppl), 2043–2051. https://doi.org/10.1590/0001-3765201720150797
Margiana, R., Alsaikhan, F., Al-Awsi, G. R. L., Patra, I., Sivaraman, R., Fadhil, A. A., Al-Baghdady, H. F. A., Qasim, M. T., Hameed, N. M., Mustafa, Y. F., & Hosseini-Fard, S. (2022). Functions and therapeutic interventions of non-coding RNAs associated with TLR signaling pathway in atherosclerosis. Cellular Signalling, 100, 110471. https://doi.org/10.1016/j.cellsig.2022.110471
Mohammadabadi, M., Babenko, O., Borshch, O. O., Kalashnyk, O., Ievstafiieva, Y., & Buchkovska, V. (2024). Measurement of the relative expression pattern of the UCP2 gene in different tissues of the Raini Cashmere goat. Agricultural Biotechnology Journal, 16(3), 317-332. https://doi.org/10.22103/jab.2024.24337.1627
Mohammadabadi, M., Golkar, A., & Askari Hesni, M. (2023). The effect of fennel (Foeniculum vulgare) on insulin-like growth factor 1 gene expression in the rumen tissue of Kermani sheep. Agricultural Biotechnology Journal, 15(4), 239-256. https://doi.org/10.22103/jab.2023.22647.1530
Mohammadabadi, M., Shaban Jorjandy, D., Arabpoor Raghabadi, Z., Abareghi, F., Sasan, H. A. and Bordbar, F. (2022). The task of fennel on DLK1 gene expression in sheep heart tissue. Agricultural Biotechnology Journal, 14(2), 155-170. https://doi.org/10.22103/jab.2022.19402.1399 
Safaei, S. M. H., Dadpasand, M., Mohammadabadi, M., Atashi, H., Stavetska, R., Klopenko, N., & Kalashnyk, O. (2022). An Origanum majorana leaf diet influences Myogenin gene expression, performance, and carcass characteristics in lambs. Animals, 13(1), 14. https://doi.org/10.3390/ani13010014  
Shahsavari, M., Mohammadabadi, M., Khezri, A., Afanasenko, V., & Kondratiuk, V. (2022). Effect of fennel (Foeniculum vulgare) seed powder consumption on insulin-like growth factor 1 gene expression in the liver tissue of growing lambs. Gene Expression, 21(2), 21–26. https://doi.org/10.14218/GE.2022.00017
Shahsavari, M., Mohammadabadi, M., Khezri, A., Asadi Fozi, M., Babenko, O., Kalashnyk, O., Oleshko, V., & Tkachenko, S. (2023). Correlation between insulin-like growth factor 1 gene expression and fennel (Foeniculum vulgare) seed powder consumption in muscle of sheep. Animal Biotechnology, 34(4), 882-892. https://doi.org/10.1080/10495398.2021.2000997  
Sharma, S., Sharma, G., & Mehta, A. (2012). Antimutagenicity protection of Ficus benghalensis extract against cyclophosphamide genotoxicity in rat bone marrow. Asian Journal of Pharmaceutical and Clinical Research, 5(2), 27–29. https://journals.innovareacademics.in/index.php/ajpcr
Shokri, S., Khezri, A., Mohammadabadi, M., & Kheyrodin, H. (2023). The expression of MYH7 gene in femur, humeral muscle, and back muscle tissues of fattening lambs of the Kermani breed. Agricultural Biotechnology Journal, 15(2), 217-236. https://doi.org/10.22103/jab.2023.21524.1486
Shubber, E. K., Al-Allak, B. M. A., & Nada, S. M. (1987). Spontaneous frequencies of chromosomal aberrations and SCE in human lymphocytes. II. Effects of serum, incubation time, and blood storage. Nucleus, 30, 21–28.
Uma, B., Prabhakar, K., Rajendran, S., & Lakshmi, S. (2009). Studies on GC/MS spectroscopic analysis of some bioactive antimicrobial compounds from Cinnamomum zeylanicum. Journal of Medicinal Plants, 8(31), 125–131. https://jmp.ir/article-1-340-en.html
Vahabzadeh, M., Chamani, M., Dayani, O., Sadeghi, A. A., & Mohammadabadi M. (2020). Effect of Origanum majorana leaf (Sweet marjoram) feeding on lamb’s growth, carcass characteristics, and blood biochemical parameters. Small Ruminant Research, 192, 106233. https://doi.org/10.1016/j.smallrumres.2020.106233
Zaman, G. S., Waleed, I., Obeid, R. A., Khudair, S. A. A., Al-Kahdum, S. A. A., Al-Majdi, K., Abed, A. S., Alsalamy, A., Qasim, M. T., & Alawadi, A. H. R. (2023). Electrochemical determination of zearalenone in agricultural food samples using a flower-like nanocomposite-modified electrode. Materials Chemistry and Physics, 305, 127986. https://doi.org/10.1016/j.matchemphys.2023.127986
Agricultural Biotechnology Journal
Volume 17, Issue 2
May 2025
Pages 151-170

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