The neuroprotective and anti-inflammatory effects of Annona muricata (Graviola) on radiation-induced rat sciatic nerve injury

Abstract

Objective: This study aimed to evaluate Annona muricata’s (AM) radioprotective effects on sciatic nerve injury due to ionising radiation (IR).

Materials and Methods: Thirty-two adult female Wistar albino rats were separated into four equal groups; Control (C), Annona muricata leaf extracts (AME), radiation (RAD), radiation and AME (AME+RAD). In groups AME and AME+RAD, AME was administered at a dose of 300 mg/kg for the first day and 50 mg/every day for the following one week intraperitoneally. In RAD and AME+RAD, rats were exposed to a single dose of 20 Gray (Gy) IR to their right legs. All the subjects were sacrificed at the end of the first month. Oxidative stress biochemical parameters from blood samples were analysed. In addition, right sciatic nerves were extracted and histomorphology was evaluated.

Results: Statistically significant vasculature, degenerative and necrotic changes were observed in RAD, compared to C and AME (p<0.01). Swelling in myelin sheath was predominantly seen in RAD. Alterations in the level of catalase (p<0.01), superoxide dismutase (p<0.01) and glutathione peroxidase (p<0.05) in the AME+RAD group compared to the RAD group were found to be statistically significant.

Conclusion: Our study unveiled that AM could potentially enhance biochemical and histomorphological healing in the acute period on sciatic nerve injury due to IR.

Keywords

• Radiation
• Sciatic nerve
• Annona muricata
• Neuroprotection
• Oxidative stress

References

1. [1] Allen C, Her S, Jaffray DA. Radiotherapy for Cancer: Present and Future. Adv Drug Deliv Rev 2017; 109:1-2. doi: 10.1016/j. addr.2017.01.004
2. [2] Citrin DE. Recent developments in radiotherapy. N Engl J Med 2017; 377:1065-75. doi: 10.1056/NEJMra1608986
3. [3] Li Z, Wang D, Zhang Y, Wang S, Wang X, Li Y, et al. The efficacy and safety of Xuebijing injection in the treatment of radiation pneumonitis: A protocol for systematic review and meta-analysis. Medicine (Baltimore) 2021; 100:e24344. doi: 10.1097/MD.000.000.0000024344
4. [4] Pan CC, Kavanagh BD, Dawson LA, Li XA, Das SK, Miften M, et al. Radiation-associated liver injury. Int J Radiat Oncol Biol Phys 2010; 76:94-100. doi: 10.1016/j.ijrobp.2009.06.092
5. [5] Aktas S, Comelekoglu U, Yilmaz SN, et al. Electrophysiological, biochemical and ultrastructural effects of radiotherapy on normal rat sciatic nerve. Int J Radiat Biol 2013; 89:155-61. doi: 10.3109/09553.002.2013.734941
6. [6] Santos MLC, de Brito BB, da Silva FAF, Botelho A, de Melo FF. Nephrotoxicity in cancer treatment: An overview. World J Clin Oncol 2020; 11:190-204. doi: 10.5306/wjco.v11.i4.190
7. [7] Eblan MJ, Corradetti MN, Lukens JN, et al. Brachial plexopathy in apical non-small cell lung cancer treated with definitive radiation: dosimetric analysis and clinical implications. Int J Radiat Oncol Biol Phys 2013; 85:175-81. doi: 10.1016/j. ijrobp.2012.03.051
8. [8] McNeish BL, Zheutlin AR, Richardson JK, Smith SR. Primary cancer location predicts predominant level of brachial plexopathy. Muscle Nerve 2020; 62:386-9. doi: 10.1002/ mus.26994

9. [9] He B, Wang X, He Y, Li H, Yang Y, Shi Z, et al. Gamma rayinduced glial activation and neuronal loss occur before the delayed onset of brain necrosis. FASEB J 2020; 34:13361-75. doi: 10.1096/fj.202000365RR
10. [10] Shabeeb D, Musa AE, Keshavarz M, et al. Histopathological and functional evaluation of radiation-induced sciatic nerve damage: Melatonin as radioprotector. Medicina (Kaunas) 2019; 55:502. doi: 10.3390/medicina55080502
11. [11] Azzam EI, Jay-Gerin JP, Pain D. Ionizing radiation-induced metabolic oxidative stress and prolonged cell injury. Cancer Lett 2012; 327:48-60. doi: 10.1016/j.canlet.2011.12.012
12. [12] Helm JS, Rudel RA. Adverse outcome pathways for ionizing radiation and breast cancer involve direct and indirect DNA damage, oxidative stress, inflammation, genomic instability, and interaction with hormonal regulation of the breast. Arch Toxicol 2020; 94:1511-49. doi: 10.1007/s00204.020.02752-z
13. [13] Jacobo-Herrera NJ, Jacobo-Herrera FE, Zentella-Dehesa A, Andrade-Cetto A, Heinrich M, Perez-Plasencia C. Medicinal plants used in Mexican traditional medicine for the treatment of colorectal cancer. J Ethnopharmacol 2016; 179:391-402. doi: 10.1016/j.phymed.2020.153402
14. [14] Fischer N, Seo EJ, Efferth T. Prevention from radiation damage by natural products. Phytomedicine 2018; 47:192-200. doi: 10.1016/j.jep.2015.12.042
15. [15] Harvie M. Nutritional supplements and cancer: potential benefits and proven harms. Am Soc Clin Oncol Educ Book 2014: e478-86. doi: 10.1016/j.phymed.2017.11.005
16. [16] Liu YQ, Wang XL, He DH, Cheng YX. Protection against chemotherapy – and radiotherapy-induced side effects: A review based on the mechanisms and therapeutic opportunities of phytochemicals. Phytomedicine 2021; 80:153402. doi: 10.14694/edbook_am.2014.34.e478
17. [17] Moreau D, Huchot E, Gazaille V, Rossanaly-Vasram R, Andre M. Self medication with Annona muricata L. (corossol) as an anti-cancer agent in Reunion. Rev Mal Respir 2018; 35:948- 55. doi: 10.1016/j.rmr.2018.08.001
18. [18] Coria-Téllez AV, Montalvo-Gónzalez E, Yahia EM, Obledo- Vázquez EN. Annona muricata: A comprehensive review on its traditional medicinal uses, phytochemicals, pharmacological activities, mechanisms of action and toxicity. Arab J Chem 2018; 11:662-91. doi: 10.1016/j.arabjc.2016.01.004
19. [19] Balderrama-Carmona AP, Silva-Beltran NP, Galvez-Ruiz JC, Ruiz-Cruz S, Chaidez-Quiroz C, Moran-Palacio EF. Antiviral, antioxidant, and antihemolytic effect of Annona muricata L. leaves extracts. Plants (Basel) 2020; 9:1650. doi: 10.3390/ plants9121650
20. [20] Kim WS, Kim YE, Cho EJ, et al. Neuroprotective effect of Annona muricata-derived polysaccharides in neuronal HT22 cell damage induced by hydrogen peroxide. Biosci Biotechnol Biochem 2020; 84:1001-12. doi: 10.1080/09168.451.2020.1715201
21. [21] Cattin AL, Lloyd AC. The multicellular complexity of peripheral nerve regeneration. Curr Opin Neurobiol 2016; 39:38-46. doi: 10.1016/j.conb.2016.04.005
22. [22] Lin Z, Wu VW, Ju W, Yamada Y, Chen L. Radiation-induced changes in peripheral nerve by stereotactic radiosurgery: a study on the sciatic nerve of rabbit. J Neurooncol 2011; 102:179-85. doi: 10.1007/s11060.010.0309-3
23. [23] Stubblefield MD. Clinical evaluation and management of radiation fibrosis syndrome. Phys Med Rehabil Clin N Am 2017; 28:89-100. doi: 10.1016/j.pmr.2016.08.003
24. [24] Love S, Gomez S. Effects of experimental radiation-induced hypomyelinating neuropathy on motor end-plates and neuromuscular transmission. J Neurol Sci 1984; 65:93-109. doi: 10.1016/0022-510X(84)90070-4
25. [25] Ge X, Liao Z, Yuan J, et al. Radiotherapy-related quality of life in patients with head and neck cancers: a meta-analysis. Support Care Cancer 2020; 28:2701-12. doi: 10.1007/ s00520.019.05077-5
26. [26] Egemen E, Öcal Ö, Börcek AÖ, et al. İyonize radyasyon sonrası gelişen oksidatif beyin ve spinal kord hasarını iyileştirmede deksametazon ve melatoninin etkilerinin sıçan modelinde karşılaştırılması. J Nerv Sys Surg 2021; 7:83-95. doi:10.54306/ SSCD.2021.18189
27. [27] Presman DM, Hoijman E, Ceballos NR, Galigniana MD, Pecci A. Melatonin inhibits glucocorticoid receptor nuclear translocation in mouse thymocytes. Endocrinology 2006; 147: 5452-9. doi. org/10.1210/en.2006-0252
28. [28] Suzuki K. [Neurotoxicity of radiation]. Brain nerve 2015; 67:63-71. doi: 10.11477/mf.141.620.0087
29. [29] Okuhara Y, Shinomiya R, Peng F, et al. Direct effect of radiation on the peripheral nerve in a rat model. J Plast Surg Hand Surg 2014; 48:276-80. doi: 10.3109/2000656X.2014.882343
30. [30] El-Shahat AN. Ameliorative effect of graviola fruit juice on the damaged tissues of gamma-irradiated male rats. Pak J Zool 2021. doi: 10.17582/journal.pjz/202.011.13181133
31. [31] Moghadamtousi SZ, Rouhollahi E, Hajrezaie M, Karimian H, Abdulla MA, Kadir HA. Annona muricata leaves accelerate wound healing in rats via involvement of Hsp70 and antioxidant defence. Int J Surg 2015; 18:110-7. doi: 10.1016/j. ijsu.2015.03.026
32. [32] Keskin E, Elmas Ö, Keser Şahin HH, Güven B. Efficacy of Annona muricata (graviola) in experimental spinal cord injury: biochemical and histopathological analysis. Turkish Journal of Trauma and Emergency Surgery 2022; 28:233-41. doi: 10.14744/tjtes.2021.70728
33. [33] Heba H Mansour AAE, Amal H Elrefaei, Hafez F Hafez. Radioprotective, antioxidant and antitumor efficacy of Annona muricata L. leaf extract. Indian J Biochem Biophys 2018; 55:205-14.
34. [34] Kavita P, Jaimala S. Effect of Opuntia elatior on Alteration in Glutamic Oxaloacetic Transaminase activity induced by Gamma Radiation in Swiss Albino Mice. Int J Pharma Bio Sci 2020; 10:90-5. doi: 10.22376/ijpbs/lpr.2020.10.4.p90-95
35. [35] Najafi M, Motevaseli E, Shirazi A, Geraily G, Rezaeyan A, Norouzi F, et al. Mechanisms of inflammatory responses to radiation and normal tissues toxicity: clinical implications. Int J Radiat Biol 2018; 94:335-56. doi: 10.1080/09553.002.2018.1440092.
36. [36] Vasko MR, Guo C, Thompson EL, Kelley MR. The repair function of the multifunctional DNA repair/redox protein APE1 is neuroprotective after ionizing radiation. DNA Repair 2011; 10:942-52. doi: 10.1016/j.dnarep.2011.06.004
37. [37] Hadj Abdallah N, Baulies A, Bouhlel A, et al. Zinc mitigates renal ischemia-reperfusion injury in rats by modulating oxidative stress, endoplasmic reticulum stress, and autophagy. J Cell Physiol 2018; 233:8677-90. doi: 10.1002/jcp.26747
38. [38] Tawfik SS, Elkady AA, El Khouly WA. Crocin mitigates gammarays- induced hepatic toxicity in rats. Environ Sci Pollut Res Int 2019; 26:15414-9. doi: 10.1007/s11356.019.04724-y
39. [39] Park S, Imlay JA. High levels of intracellular cysteine promote oxidative DNA damage by driving the fenton reaction. J Bacteriol 2003; 185:1942-50. doi: 10.1128/JB.185.6.1942- 1950.2003
40. [40] Wu Z, Wang H, Fang S, Xu C. Roles of endoplasmic reticulum stress and autophagy on H2O2induced oxidative stress injury in HepG2 cells. Mol Med Rep 2018; 18:4163-74. doi: 10.3892/ mmr.2018.9443
41. [41] Fujiki Y, Bassik MC. A New Paradigm in Catalase Research. Trends Cell Biol 2021; 31:148-51. doi: 10.1016/j. tcb.2020.12.006
42. [42] Moghadamtousi SZ, Rouhollahi E, Karimian H, Fadaeinasab M, Abdulla MA, Kadir HA. Gastroprotective activity of Annona muricata leaves against ethanol-induced gastric injury in rats via Hsp70/Bax involvement. Drug Des Devel Ther 2014; 8:2099-110. doi: 10.2147/DDDT.S70096