Effect of amifostine on apoptotic inflammatory makers in cisplatin induced brain damage in rats

Mahmoud M. Masoud; Nabila A. El-Laithy; Eman R. Youness; Nadia M. Ahmed; Elsayed M.E. Mahdy; Wafaa Gh Shousha

doi:10.1515/jcim-2024-0250

Article

Effect of amifostine on apoptotic inflammatory makers in cisplatin induced brain damage in rats

Mahmoud M. Masoud , Nabila A. El-Laithy , Eman R. Youness , Nadia M. Ahmed , Elsayed M.E. Mahdy and Wafaa Gh Shousha

Published/Copyright: February 3, 2025

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From the journal Journal of Complementary and Integrative Medicine Volume 22 Issue 2

Abstract

Objectives

To lessen the negative effects of the medication, we assessed the neuroprotective impact of amifostine nanoparticles against the neurotoxicity generated by cisplatin.

Methods

60 adult male albino Wistar rats were arranged into six groups. Group 1; received saline intraperitonealy (IP) and served as negative control. Group 2; received IP injection of silica nano-emulsion, Group 3 received cispatin for three consecutive days at the end of the study, Group 4 received amifostine intrapretonealy (IP) before cisplatin injection, Group 5 received silica nano-emulsion alone for one month, group 6 received silica nano-emulsion in combination with cisplatin for three consecutive days at the end of the study.

Monocyte chemoattractant protein-1 (MCP-1) and glial fibrillary acidic protein (GFAP) were estimated by ELISA, butrylcholinesterase (BChE) by spectrophotometric method while caspase-3 as a marker of apoptosis by PCR.

Results

The mean levels of brain GFAP, MCP-1, and caspase-3 in the cisplatin group were considerably higher than those in the control group. However, there was a drop in the average level of brain BChE activity. Additionally, the injection of (SiNPs@AMF + cisplatin) increased BChE activities while reducing GFAP, MCP-1, and caspase-3 levels, thereby reversing the negative effects of cisplatin on the brain tissue. On the other hand, the group treated with SiNPs@AMF + cisplatin showed improvement in overall brain structure and minimal pyknotic nuclei and apoptotic neurons were found.

Conclusions

These outcomes demonstrated amifostine’s ability to lessen the histological changes brought on by cisplatin. To sum up, SiNPs@AMF may be a suitable and secure supplemental treatment agent to lessen cisplatin’s toxicity in the brain and enhance the treatment’s effects throughout chemotherapy.

Keywords: amifostine nanoparticles; BChE; caspase-3; cisplatin; neurotoxicity; GFAP

Corresponding author: Eman R. Youness, Medical Biochemistry Department, Medical Research and Clinical Studies Institute – National Research Centre, Cairo, Egypt, E-mail: hoctober2000@yahoo.com

Acknowledgments

We thank all the participants.

Research ethics: According to the standards set forth by the Animal Care and Use Committee of the National Research Centre, Dokki, Cairo, Egypt, all animals received human care (Ethical number: 19067).
Informed consent: Not applicable.
Author contributions: ER conceived the study, MMM collected the data, ERY, NMA, MMM did the biochemical analysis and the plagiarism. W Sh and ER and EME wrote the manuscript. All authors reviewed, and proofread the final manuscript.
Use of Large Language Models, AI and Machine Learning Tools: None declared.
Conflict of interest: None.
Research funding: None.
Data availability: The data and materials used in this study are available upon request from the authors.

References

1. Petrović, M, Todorović, D. Biochemical and molecular mechanisms of action of cisplatin in cancer cells. Facta Univ – Ser Med Biol 2016;18:12–18.Search in Google Scholar

2. Abdel-Wahab, WM, Moussa, FI. Neuroprotective effect of N-acetylcysteine against cisplatin-induced toxicity in rat brain by modulation of oxidative stress and inflammation. Drug Des Dev Ther 2019;13:1155–62. https://doi.org/10.2147/dddt.s191240.Search in Google Scholar PubMed PubMed Central

3. Mercantepe, T, Unal, D, Tümkaya, L, Yazici, ZA. Protective effects of amifostine, curcumin and caffeic acid phenethyl ester against cisplatin-induced testis tissue damage in rats. Exp Ther Med 2018;15:3404–12. https://doi.org/10.3892/etm.2018.5819.Search in Google Scholar PubMed PubMed Central

4. Bobylev, I, Joshi, AR, Barham, M, Neiss, WF, Lehmann, HC. Depletion of mitofusin-2 causes mitochondrial damage in cisplatin-induced neuropathy. Mol Neurobiol 2018;55:1227–35. https://doi.org/10.1007/s12035-016-0364-7.Search in Google Scholar PubMed

5. Gomaa, DHG, Hozayen, W, Al-shafeey, HM, Hussein Elkelawy, AM, Hashem, KS. Ginkgo biloba alleviates cisplatin-mediated neurotoxicity in rats via modulating APP/Aβ/P2X7R/P2Y12R and XIAP/BDNF-dependent caspase-3 apoptotic pathway. Appl Sci 2020;10:4786–16. https://doi.org/10.3390/app10144786.Search in Google Scholar

6. Yang, X, Ding, Y, Ji, T, Zhao, X, Wang, H, Zhao, X, et al.. Improvement of the in vitro safety profile and cytoprotective efficacy of amifostineagainst chemotherapy by PEGylationstrategy. Biochem Pharmacol 2016;108:11–21. https://doi.org/10.1016/j.bcp.2016.02.014.Search in Google Scholar PubMed

7. Koukourakis, MI, Ktenidou-Kartali, S, Bourikas, G, Kartalis, G, Tsatalas, C. Amifostine protects lymphocytes during radiotherapy and stimulates expansion of the CD95/Fas and CD31 expressing T-cells, in breast cancer patients. Cancer Immunol Immunother 2003;52:127–31. https://doi.org/10.1007/s00262-002-0342-y.Search in Google Scholar PubMed PubMed Central

8. Kouvaris, JR, Kouloulias, VE, Vlahos, LJ. Amifostine: the first selective-target and broad-spectrum radioprotector. Oncol 2007;12:738–47. https://doi.org/10.1634/theoncologist.12-6-738.Search in Google Scholar PubMed

9. Kou, L, Bhutia, YD, Yao, Q, He, Z, Sun, J, Ganapathy, V. Transporter-guided delivery of nanoparticles to improve drug permeation across cellular barriers and drug exposure to selective cell types. Front Pharmacol 2018;26:27. https://doi.org/10.3389/fphar.2018.00027.Search in Google Scholar PubMed PubMed Central

10. Mitchell, MJ, Billingsley, MM, Haley, RM, Wechsler, ME, Peppas, NA, Langer, R. Engineering precision nanoparticles for drug delivery. Nat Rev Drug Discov 2021;20:101–24. https://doi.org/10.1038/s41573-020-0090-8.Search in Google Scholar PubMed PubMed Central

11. Karavelioglu, E, Boyaci, MG, Simsek, N, Sonmez, MA, Koc, R, Karademir, M, et al.. Selenium protects cerebral cells by cisplatin induced neurotoxicity. Acta Cir Bras 2015;30:394–400. https://doi.org/10.1590/s0102-865020150060000004.Search in Google Scholar PubMed

12. Melis, M, Valkema, R, Krenning, EP, de Jong, M. Reduction of renal uptake of radiolabeled octreotate by amifostinecoadministration. J Nucl Med 2012;53:749–53. https://doi.org/10.2967/jnumed.111.098665.Search in Google Scholar PubMed

13. Spernath, L, Magdassi, S. Formation of silica nanocapsules from nanoemulsions obtained by the phase inversion temperature method. Micro & Nano Lett 2010;5:28–36. https://doi.org/10.1049/mnl.2009.0085.Search in Google Scholar

14. Refaie, AA, Ramadan, A, Sabry, NM, Khalil, WK, Mossa, ATH. Over-gene expression in the apoptotic, oxidative damage and liver injure in female rats exposed to butralin. Environ Sci Pollut Control Ser 2020;27:31383–93. https://doi.org/10.1007/s11356-020-09416-6.Search in Google Scholar PubMed

15. Khalil, WKB, Booles, HF, Hafiz, NAEM, El-Bassyouni, GET. Ameliorative effects of Brachidontesvariabilis calcium carbonate against bone loss in ovariectomizedrats. Int J Pharmacol 2018;14:477–87. https://doi.org/10.3923/ijp.2018.477.487.Search in Google Scholar

16. Halliwell, B. Oxidative stress and neurodegeneration: where are we now? J Neurochem 2006;97:1634–58. https://doi.org/10.1111/j.1471-4159.2006.03907.x.Search in Google Scholar PubMed

17. Marullo, R, Werner, E, Degtyareva, N, Moore, B, Altavilla, G, Ramalingam, SS, et al.. Cisplatin induces a mitochondrial-ROS response that contributes to cytotoxicity depending on mitochondrial redox status and bioenergetic functions. PLoS One 2013;8:e81162. https://doi.org/10.1371/journal.pone.0081162.Search in Google Scholar PubMed PubMed Central

18. Miller, RP, Tadagavadi, RK, Ramesh, G, Reeves, WB. Mechanisms of cisplatin nephrotoxicity. Toxins 2010;2:2490–518. https://doi.org/10.3390/toxins2112490.Search in Google Scholar PubMed PubMed Central

19. Mostafa, RE, Saleh, DO, Mansour, DF. Cisplatin-induced nephrotoxicity in rats: modulatory role of simvastatin and rosuvastatin against apoptosis and inflammation. J Appl Pharmaceut Sci 2018;8:043–50.Search in Google Scholar

20. Yang, Z, Wang, KK. Glial fibrillary acidic protein: from intermediate filament assembly and gliosis to neurobiomarker. Trends Neurosci 2015;38:364–74. https://doi.org/10.1016/j.tins.2015.04.003.Search in Google Scholar PubMed PubMed Central

21. Elhady, M, Youness, ER, AbuShady, MM, Nassar, MS, Elaziz, AA, Masoud, MM, Elhamed, WAA, et al.. Circulating glial fibrillary acidic protein and ubiquitin carboxy-terminal hydrolase-L1 as markers of neuronal damage in children with epileptic seizures. Child’s Nerv Syst 2021;37:879–84. https://doi.org/10.1007/s00381-020-04920-z.Search in Google Scholar PubMed

22. Petzold, A. Glial fibrillary acidic protein is a body fluid biomarker for glial pathology in human disease. Brain Res 2015;10:17–31. https://doi.org/10.1016/j.brainres.2014.12.027.Search in Google Scholar PubMed

23. Azzolini, F, Gilio, L, Pavone, L, Iezzi, E, Dolcetti, E, Bruno, A, et al.. Neuroinflammation is associated with GFAP and sTREM2 levels in multiple sclerosis. Biomolecules 2022;12:222. https://doi.org/10.3390/biom12020222.Search in Google Scholar PubMed PubMed Central

24. Hol, EM, Pekny, M. Glial fibrillary acidic protein (GFAP) and the astrocyte intermediate filament system in diseases of the central nervous system. Curr Opin Cell Biol 2015;32:121–30. https://doi.org/10.1016/j.ceb.2015.02.004.Search in Google Scholar PubMed

25. De Pablo, Y, Nilsson, M, Pekna, M, Pekny, M. Intermediate filaments are important for astrocyte response to oxidative stress induced by oxygen–glucose deprivation and reperfusion. Histochem Cell Biol 2013;140:81–91. https://doi.org/10.1007/s00418-013-1110-0.Search in Google Scholar PubMed

26. Zlatic, S, Comstra, HS, Gokhale, A, Petris MjandFaundez, V. Molecular basis of neurodegeneration and neurodevelopmental defects in Menkes disease. Neurobiol Dis 2015;81:154–61. https://doi.org/10.1016/j.nbd.2014.12.024.Search in Google Scholar PubMed PubMed Central

27. Yang, Y, Liu, H, Liu, F, Dong, Z. Mitochondrial dysregulation and protection in cisplatin nephrotoxicity. Arch Toxicol 2014;88:1249–56. https://doi.org/10.1007/s00204-014-1239-1.Search in Google Scholar PubMed PubMed Central

28. Singh, S, Anshita, D, Ravichandiran, V. MCP-1: function, regulation, and involvement in disease. Int Immunopharm 2021;101:107598. https://doi.org/10.1016/j.intimp.2021.107598.Search in Google Scholar PubMed PubMed Central

29. Li, Y, Deng, SL, Lian, ZX, Yu, K. Roles of toll-like receptors in nitroxidative stress in mammals. Cells 2019;8:576. https://doi.org/10.3390/cells8060576.Search in Google Scholar PubMed PubMed Central

30. Humanes, B, Camaño, S, Lara, JM, Sabbisetti, V, González-Nicolás, MÁ, Bonventre, JV, et al.. Cisplatin-induced renal inflammation is ameliorated by cilastatinnephroprotection. Nephrol Dial Transplant 2017;32:1645–55. https://doi.org/10.1093/ndt/gfx005.Search in Google Scholar PubMed PubMed Central

31. Masson, P, Carletti, E, Nachon, F. Structure, activities and biomedical applications of human butyrylcholinesterase protein and peptide letters. Protein Pept Lett 2009;16:1215–24. https://doi.org/10.2174/092986609789071207.Search in Google Scholar PubMed

32. Miladinović, DĆ, Borozan, S, Ivanović, S. Involvement of cholinesterases in oxidative stress induced by chlorpyrifos in the brain of Japanese quail. Poultry Sci 2018;97:1564–71. https://doi.org/10.3382/ps/pey018.Search in Google Scholar PubMed

33. Puche, EPM. Esterases and anti-tumoral chemotherapy: an interaction of clinical and toxicological interest. Clinicachimicaacta 2001;304:133–6. https://doi.org/10.1016/s0009-8981(00)00347-8.Search in Google Scholar PubMed

34. Haghnazari, L, Vaisi-Raygani, A, Keshvarzi, F, Ferdowsi, F, Goodarzi, M, Rahimi, Z, et al.. Effect of acetylcholinesterase and butyrylcholinesterase on intrauterine insemination, contribution to inflammations, oxidative stress and antioxidant status; A preliminary report. J Reproduction Infertil 2016;17:157.Search in Google Scholar

Received: 2024-07-24

Accepted: 2024-10-22

Published Online: 2025-02-03

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Articles in the same Issue

https://doi.org/10.1515/jcim-2024-0250

Keywords for this article

amifostine nanoparticles; BChE; caspase-3; cisplatin; neurotoxicity; GFAP