| ORIGINAL ARTICLES |
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Sesamol Alleviates the Cytotoxic Effect of Cyclophosphamide on Normal Human Lung WI-38 Cells via Suppressing RAGE/NF-κB/Autophagy Signaling |
| Soad Z. El-Emam |
| Department of Pharmacology and Toxicology, Faculty of Pharmacy, October 6 University, 6 October City, Giza 12566, Egypt |
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Abstract Cyclophosphamide (CYL) is a chemotherapeutic medication commonly used in managing various malignancies like breast cancer or leukemia. Though, CYL has been documented to induce lung toxicity. Mechanism of CYL toxicity is through oxidative stress and the release of damage-associated molecular patterns (DAMPs). Sesamol (SES) is a natural antioxidant isolated from Sesamum indicum and its effect against CYL-induced lung toxicity is not studied yet. This study aims to investigate whether SES could prevent any deleterious effects induced by CYL on lung using normal human lung cells, WI-38 cell line, without suppressing its efficacy. Cells were pretreated with SES and/or CYL for 24 h, then cell viability was estimated by MTS and trypan blue assays. The mode of cell death was determined by AO/EB staining. Additionally, caspase-3 level, oxidative stress, and inflammatory markers were evaluated by colorimetric and ELISA techniques. qRT-PCR was performed to evaluate RAGE, NF-κB, and Beclin-1 mRNA-expression. CYL-treated WI-38 cells developed a significantly increased cell death with enhanced oxidative and RAGE/NF-κb/Autophagy signaling, which were all attenuated after pretreatment with SES. Thus, we concluded that SES offered a protective role against CYL-induced lung injury via suppressing oxidative stress and RAGE/NF-κB/Autophagy signaling, which is a natural safe therapeutic option against CYL toxicities.
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Cyclophosphamide
Sesamol
Lung toxicity
Autophagy
Oxidative stress
RAGE
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Corresponding Authors:
Soad Z. El-Emam
E-mail: soadzakaria@o6u.edu.eg
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Issue Date: 04 June 2021
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1. M. Ahlmann, G. Hempel, Cancer Chemother. Pharmacol. 78, 661 (2016)
2. A. Iqubal, M.K. Iqubal, S. Sharma, M.A. Ansari, A.K. Najmi, S.M. Ali, J. Ali, S.E. Haque, Life Sci. 218, 112 (2019)
3. S. Sharma, P. Sharma, P. Kulurkar, D. Singh, D. Kumar, V. Patial, Phytomedicine 36, 108 (2017)
4. A. Abdelfattah-Hassan, S.I. Shalaby, S.I. Khater, E.S. El-Shetry, H. Abd El Fadil, S.A. Elsayed, Complement. Ther. Med. 46, 95 (2019)
5. D.H. El-kashef, Environ. Toxicol. Pharmacol. 58, 70 (2018)
6. J.M. Patel, Pharmacol. Ther. 47, 137 (1990)
7. J. Einhorn, Int. J. Radiat. Oncol. Biol. Phys. 11, 1375 (1985)
8. J.Y. Kim, J.S. Park, D. Strassheim, I. Douglas, F.D.D. Valle, K. Asehnoune, S. Mitra, S.H. Kwak, S. Yamada, I. Maruyama, A. Ishizaka, E. Abraham, Am. J. Physiol. Lung Cell Mol. Physiol. 288, 21 (2005)
9. J. Tanaka, K. Yamaguchi, H. Ishikura, M. Tsubota, F. Sekiguchi, Y. Seki, T. Tsujiuchi, A. Murai, T. Umemura, A. Kawabata, Neuropharmacology 79, 112 (2014)
10. S. Lee, C. Piao, G. Kim, J.Y. Kim, E. Choi, M. Lee, Eur. J. Pharm. Sci. 114, 275 (2018)
11. D. Tang, R. Kang, K.M. Livesey, H.J. Zeh, M.T. Lotze, Antioxid. Redox Signal. 15, 2185 (2011)
12. K.M. Livesey, D. Tang, H.J. Zeh, M.T. Lotze, Curr. Opin. Investig. Drugs 10, 1269 (2009)
13. Y.H. Kim, M.S. Kwak, J.M. Shin, R.A. Hayuningtyas, J.E. Choi, J.S. Shin, J. Cell Sci. (2018). https://doi.org/10.1242/jcs.211201
14. I. Tanida, T. Ueno, E. Kominami, Methods Mol. Biol. 445, 77 (2008)
15. A.F. Majdalawieh, Z.R. Mansour, Eur. J. Pharmacol. 855, 75 (2019)
16. P.G. Nayak, P. Paul, P. Bansal, N.G. Kutty, K.S.R. Pai, J. Pharm. Pharmacol. 65, 1083 (2013)
17. P. Prša, B. Karademir, G. Biçim, H. Mahmoud, I. Dahan, A.S. Yalçın, J. Mahajna, I. Milisav, Biochem. Pharmacol. 113, 113551 (2019)
18. A.R. Duarte, A.L. Chenet, F.J.S. de Almeida, C.M. Balbinotti Andrade, M.R. de Oliveira, Chem. Biol. Interact. 296, 171 (2018)
19. K.A. Teles, P. Medeiros-Souza, F.A.C. Lima, B.G. de Araújo, R.A.C. Lima, Rev. Bras. Reumatol. 57, 596 (2017)
20. E. Şengül, V. Gelen, S. Gedikli, S. Özkanlar, C. Gür, F. Çelebi, A. Çınar, Biomed. Pharmacother. 92, 303 (2017)
21. M. Chen, C. Zhang, J. Zhang, G. Kai, B. Lu, Z. Huang, L. Ji, Eur. J. Pharmacol. 856, 172421 (2019)
22. J.S. Roh, D.H. Sohn, Immune Netw. 18, e27 (2018)
23. A. Dhar, I. Dhar, A. Bhat, K.M. Desai, Life Sci. 146, 8 (2016)
24. S. Garg, R.K. Malhotra, S.I. Khan, S. Sarkar, P.N. Susrutha, V. Singh, S. Goyal, T.C. Nag, R. Ray, J. Bhatia, D.S. Arya, Phytomedicine 56, 147 (2019)
25. K. Kierdorf, G. Fritz, J. Leukoc. Biol. 94, 55 (2013)
26. J. Tobon-Velasco, E. Cuevas, M. Torres-Ramos, C.N.S. Neurol, Disord. Drug Targets 13, 1615 (2014)
27. P.Y. Chu, S.P. Chien, D.Z. Hsu, M.Y. Liu, Food Chem. Toxicol. 48, 1821 (2010)
28. P.S. Yashaswini, A.G.A. Rao, S.A. Singh, Int. J. Biol. Macromol. 94, 781 (2017)
29. X. Kang, M. Jing, G. Zhang, L. He, P. Hong, C. Deng, Mar. Drugs 17, 227 (2019)
30. G. Filomeni, D. De Zio, F. Cecconi, Cell Death Differ. 22, 377 (2015)
31. P. Lin et al., Deep Sea Res. Part II(162), 79-92 (2019)
32. J. Zhao, Q. Song, L. Wang, X. Dong, X. Yang, X. Bai, B. Song, M. Damaser, L. Li, PLoS ONE 10, 1 (2015)
33. L. Qu, C. Chen, Y. Chen, Y. Li, F. Tang, H. Huang, W. He, R. Zhang, L. Shen, Med. Sci. Monit. 25, 1828 (2019)
34. W. Strober, Current Protocols in Immunology (Wiley, New York, 2001).
35. B. Chazotte, Cold Spring Harb. Protoc. (2011). https://doi.org/10.1101/pdb.prot5557
36. K. Liu, P. Chengiu, R. Liu, X. Wu, Med. Sci. Monit. Basic Res. 21, 15 (2015) |
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