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Annona Muricata Yaprak Ekstratının Spinal Korddaki Radyoprotektif Etkileri ve Histopatolojik Sonuçları

Year 2024, Volume: 8 Issue: 2, 168 - 176, 30.08.2024
https://doi.org/10.29058/mjwbs.1359185

Abstract

Amaç: Radyoterapi (RT), primer ve metastatik tümörler için önemli bir kanser tedavisidir. Çok sayıda çalışma, DNA'nın, l ipitlerin ve
proteinlerin, iyonize radyasyon (IR) tarafından indüklenen serbest radikaller tarafından saldırıya uğradığını ve dolayısıyla ciddi hücresel
hasara yol açtığını göstermiştir. Yaygın olarak "graviola" olarak bilinen Annona muricata (AM) bitkisi tropik iklime sahip ülkelerde (Güney
Amerika, Batı Afrika, Güneydoğu Asya) yetişmekte olup antioksidan, antikanser, analjezik ve antispazmodik ajan olarak kullanılmaktadır.
Yerel halk tarafından geleneksel ve alternatif tıp amaçlı yaprakları, kökü, kabuğu, tohumları ve meyvesi çok çeşitli formlarda kullanılmaktadır.
Çalışmamızda graviola yaprakları kullanılmış olup, Güney Amerika’nın yerel halkından temin edilmiştir. Bu çalışma, graviolanın iyonize
radyasyonun omurilik hasarına karşı olası koruyucu etkisini değerlendirmeyi amaçladı.
Gereç ve Yöntemler: Benzer fizyolojik özelliklere sahip 32 adet erişkin dişi (250±50gr) Wistar Albino rat randomize olarak seçildi. Ratlar Grup
1 (n=8) (control grubu), Grup 2 (n=8) (Graviola grubu), Grup 3 (n=8) (RT grubu), Grup 4 (n=8) (Graviola+ RT grubu) şeklinde gruplandı. Öz,
etanol bazlı filtrasyon yoluyla Graviola bitkisinin kurutulmuş yapraklarından elde edildi. Oluşan öz, ratlara aktif bir bileşen olarak uygulandı.
Prone pozisyonda sabitlenmiş ratların spinal korduna toplam 20Gy (1GY/dk) dozda tek bir fraksiyon halinde uygulandı. Tüm analizler SPSS
ile yapıldı. Sonuçlar %95 güven aralığında değerlendirilecek olup, p<0.05 değeri anlamlı kabul edilecektir.
Bulgular: Dört ayrı grupta inflamatuar hücre infiltrasyonu, ödem, nöron şişmesi, gliosit hiperplazisi, nekroz, spinal kord kavitasyonu, Nissl
cisimcik kaybı, çekirdek çevresinde kavitasyon, piknotik çekirdek gibi parametreler incelendi. İstatistiksel analiz dört grup arasında yukarıdaki
parametreler değerlendirilerek yapılmıştır. Doku ve hücrelerin histomorfolojik bulguları skorlandı. Her kriter 0 ile 3 arasında puanlandı.
(0=normal, 1=Hafif, 2=orta ve 3=ağır).
Sonuç: Ratların RT'den önce graviola ile tedavisinin, control grubuna kıyasla omurilikte nekrotik hasarları önlediğini göstermiştir. RT'den
önce graviola yaprak ekstresi ile yapılan ön tedavinin, graviolanın antiinflamatuar özelliğinin nöronal korumaya katkıda bulunduğunu
desteklemektedir.

Ethical Statement

Etik Kurul Tarih: 02.07.2020 Etik kurul No: 2020-18-02/07 Sıçanlarda İyonize Radyasyona Bağlı Spinal Kord Hasarının Önlenmesinde Annona Muricata (Graviola)'nın Etkisi Protective Effects of Annona Muricata (Gravıola) on Radıatıon Spınal Cord

References

  • 1. Barton MB, Jacob S, Shafiq J, Wong K, Thompson SR, Hanna TP, Delaney GP. Estimating the demand for radiotherapy from the evidence: a review of changes from 2003 to 2012. Radiother Oncol. 2014 Jul;112(1):140-4.
  • 2. Poortmans P, Valentini V, Lievens Y. Expanding global access to radiotherapy: the European Society for Radiotherapy and Oncology perspective. Lancet Oncol. 2015 Sep;16(10):1148-9.
  • 3. Kirkpatrick JP, van der Kogel AJ, Schultheiss TE. Radiation dose-volume effects in the spinal cord. Int J Radiat Oncol Biol Phys. 2010 Mar 1;76(3 Suppl):S42-9.
  • 4. Klimo P Jr, Thompson CJ, Kestle JR, Schmidt MH. A meta- analysis of surgery versus conventional radiotherapy for the treatment of metastatic spinal epidural disease. Neuro Oncol. 2005 Jan;7(1):64-76.
  • 5. Fischer, A.W., Holfelder Lokales Amyloid im Gehirn. Deutsche Zeitschrift f. Chirurgie 227, 475–483 (1930).
  • 6. Schultheiss TE. The radiation dose-response of the human spinal cord. Int J Radiat Oncol Biol Phys. 2008 Aug 1;71(5):1455- 9.
  • 7. Wong CS, Fehlings MG, Sahgal A. Pathobiology of radiation myelopathy and strategies to mitigate injury. Spinal Cord. 2015 Aug;53(8):574-80.
  • 8. Schultheiss TE, Stephens LC, Maor MH. Analysis of the histopathology of radiation myelopathy. Int J Radiat Oncol Biol Phys. 1988 Jan;14(1):27-32.
  • 9. Moghadamtousi SZ, Fadaeinasab M, Nikzad S, Mohan G, Ali HM, Kadir HA. Annona muricata (Annonaceae): A Review of Its Traditional Uses, Isolated Acetogenins and Biological Activities. Int J Mol Sci. 2015 Jul 10;16(7):15625-58.
  • 10. Chan WJ, McLachlan AJ, Hanrahan JR, Harnett JE. The safety and tolerability of Annona muricata leaf extract: a systematic review. J Pharm Pharmacol. 2020 Jan;72(1):1-16.
  • 11. Akhondzadeh S, Naghavi HR, Vazirian M, Shayeganpour A, Rashidi H, Khani M. Passionflower in the treatment of generalized anxiety: a pilot double-blind randomized controlled trial with oxazepam. J Clin Pharm Ther. 2001 Oct;26(5):363-7.
  • 12. Souza DO, Dos Santos Sales V, de Souza Rodrigues CK, de Oliveira LR, Santiago Lemos IC, de Araújo Delmondes G, Monteiro ÁB, do Nascimento EP, Sobreira Dantas Nóbrega de Figuêiredo FR, Martins da Costa JG, Pinto da Cruz GM, de Barros Viana GS, Barbosa R, Alencar de Menezes IR, Bezerra Felipe CF, Kerntopf MR. Phytochemical Analysis and Central Effects of Annona Muricata Linnaeus: Possible Involvement of the Gabaergic and Monoaminergic Systems. Iran J Pharm Res. 2018 Fall;17(4):1306-1317.
  • 13. Champy P, Höglinger GU, Féger J, Gleye C, Hocquemiller R, Laurens A, Guérineau V, Laprévote O, Medja F, Lombès A, Michel PP, Lannuzel A, Hirsch EC, Ruberg M. Annonacin, a lipophilic inhibitor of mitochondrial complex I, induces nigral and striatal neurodegeneration in rats: possible relevance for atypical parkinsonism in Guadeloupe. J Neurochem. 2004 Jan;88(1):63-9.
  • 14. Mansour H.H., Elkady A.A., Elrefaei A.H., Hafez H.F. Radioprotective, antioxidant and antitumor efficacy of Annona muricata L. leaf extract. Indian J Biochem Biophys. 2018;55:205–214.
  • 15. Schultheiss TE, Kun LE, Ang KK, Stephens LC. Radiation response of the central nervous system. Int J Radiat Oncol Biol Phys. 1995 Mar 30;31(5):1093-112. Erratum in: Int J Radiat Oncol Biol Phys. 1995 Jul 15;32(4):1269.
  • 16. Li YQ, Chen P, Jain V, Reilly RM, Wong CS. Early radiation-induced endothelial cell loss and blood-spinal cord barrier breakdown in the rat spinal cord. Radiat Res. 2004 Feb;161(2):143- 52.
  • 17. de Sousa OV, Vieira GD, de Jesus R G de Pinho J, Yamamoto CH, Alves MS. Antinociceptive and anti-inflammatory activities of the ethanol extract of Annona muricata L. leaves in animal models. Int J Mol Sci. 2010 May 6;11(5):2067-78.
  • 18. Ishola IO, Awodele O, Olusayero AM, Ochieng CO. Mechanisms of analgesic and anti-inflammatory properties of Annona muricata Linn. (Annonaceae) fruit extract in rodents. J Med Food. 2014 Dec;17(12):1375-82.
  • 19. Dijkstra K, Hofmeijer J, van Gils SA, van Putten MJ. A Biophysical Model for Cytotoxic Cell Swelling. J Neurosci. 2016 Nov 23;36(47):11881-11890.
  • 20. Kim WS, Kim YE, Cho EJ, Byun EB, Park WY, Song HY, Kim K, Park SH, Byun EH. Neuroprotective effect of Annona muricata- derived polysaccharides in neuronal HT22 cell damage induced by hydrogen peroxide. Biosci Biotechnol Biochem. 2020 May;84(5):1001-1012.
  • 21. Kalderon N, Fuks Z. Structural recovery in lesioned adult mammalian spinal cord by x-irradiation of the lesion site. Proc Natl Acad Sci U S A. 1996 Oct 1;93(20):11179-84. Erratum in: Proc Natl Acad Sci U S A 1996 Dec 10;93(25):14992.
  • 22. LeRoux LG, Bredow S, Grosshans D, Schellingerhout D. Molecular imaging detects impairment in the retrograde axonal transport mechanism after radiation-induced spinal cord injury. Mol Imaging Biol. 2014 Aug;16(4):504-10.
  • 23. Sotoudeh A, Jahanshahi A, Zareiy S, Darvishi M, Roodbari N, Bazzazan A. The influence of low-level laser irradiation on spinal cord injuries following ischemia-reperfusion in rats. Acta Cir Bras. 2015 Sep;30(9):611-6.
  • 24. Li YQ, Guo YP, Jay V, Stewart PA, Wong CS. Time course of radiation- induced apoptosis in the adult rat spinal cord. Radiother Oncol. 1996 Apr;39(1):35-42.
  • 25. Moghadamtousi SZ, Kadir HA, Paydar M, Rouhollahi E, Karim ian H. Annona muricata leaves induced apoptosis in A549 cells through mitochondrial-mediated pathway and involvement of NF-κB. BMC Complement Altern Med. 2014 Aug 15;14:299.
  • 26. Okada S, Okeda R. Pathology of radiation myelopathy. Neuropathology. 2001 Dec;21(4):247-65.
  • 27. Okada S, Okeda R, Matsushita S, Kawano A. Histopathological and morphometric study of the late effects of heavy-ion irradiation on the spinal cord of the rat. Radiat Res. 1998 Sep;150(3):304-15.
  • 28. Schultheiss TE, Stephens LC. Radiation Myelopathy. AJNR Am J Neuroradiol. 1992 Jul-Aug;13(4):1056–8.
  • 29. Ana V. Coria-Téllez,Efigenia Montalvo-Gónzalez,Elhadi M. Yahia, Eva N. Obledo-Vázquez Annona muricata: A comprehensive review on its traditionalmmedicinal uses, phytochemicals, pharmacological activities, mechanisms of action and toxicity. Arabian Journal of Chemistry. 2018;11(5): 662- 91.
  • 30. Keskın, E., Elmas, O., Keser Sahın, H. H., Tonge, C., et al. (2022). The neuroprotective and anti-inflammatory effects of Annona muricata (Graviola) on radiation-induced rat sciatic nerve injury. Marmara Medical Journal, 35(2), 211-218.

Radioprotective Effects of Annona Muricata Leaf Extract in the Spinal Cord

Year 2024, Volume: 8 Issue: 2, 168 - 176, 30.08.2024
https://doi.org/10.29058/mjwbs.1359185

Abstract

Objective: The spinal cord is often involved in radiotherapy to treat malignancies and is considered as one of the most critical dose-limiting organs. Histopathological changes of radiation-induced spinal cord injury include gliosis, demyelination, and necrosis in the white matter, as well as vascular changes in both white and gray matter. All aerial parts of Annona muricata (AM) are used in traditional medicine practices, and previous studies revealed that AM leaf extract has radioprotective effect against gamma- irradiation. This study aimed to evaluate the possible protective effect of AM leaf extract against ionizing radiation spinal cord injury.
Methods: A total of 37 adult female Wistar Albino rats were divided into 4 groups (1 control and 3 intervention groups): Group 1 (control) received 0.01 mL/kg of distilled water by oral gavage once a day for 7 days, group 2 (AM group) received 300 mg/kg of AM leaf extract by oral gavage once a day for 7 days, group 3 (IR group) received a single dose of spinal cord radiation (20 Gy) after a 7-day treatment with 0.01 mL/kg of physiologic serum (saline), and group 4 (AM + IR group) received 300 mg/kg of AM leaf extract by oral gavage once a day for 7 days, with spinal cord radiation (20 Gy) applied 1 hour after the last gavage. After the sacrificing, spinal cords were dissected out, embedded in paraffin, and stained with Hematoxylin-Eosin, and 11 parameters were microscopically examined and scored.
Results: AM administration prior to irradiation (IR) lowered the histopathological scores for all parameters that were verified in the IR group at most severe levels: inflammatory cells infiltration, edema, neuron swelling, gliocytes hyperplasia, spinal cord cavitation (loosened tissue structure), pyknotic nuclei, vacuolar denaturation, and loss of Nissls substance. Necrosis was present in IR group and was higher compared to Control and AM treated groups. We noticed that necrosis was present in the AM group too and was higher compared to the control.
Conclusion: The data of our study suggest that pretreatment with 300 mg/kg of AM leaf extract prior to IR reduce inflammatory cells infiltration, edema, and neuron swelling. This supports the fact that AM-proposed anti-inflammatory property may contribute to neuroprotection. Similarly, AM was documented to have efficient protection on neural cells from apoptosis or necrosis.

References

  • 1. Barton MB, Jacob S, Shafiq J, Wong K, Thompson SR, Hanna TP, Delaney GP. Estimating the demand for radiotherapy from the evidence: a review of changes from 2003 to 2012. Radiother Oncol. 2014 Jul;112(1):140-4.
  • 2. Poortmans P, Valentini V, Lievens Y. Expanding global access to radiotherapy: the European Society for Radiotherapy and Oncology perspective. Lancet Oncol. 2015 Sep;16(10):1148-9.
  • 3. Kirkpatrick JP, van der Kogel AJ, Schultheiss TE. Radiation dose-volume effects in the spinal cord. Int J Radiat Oncol Biol Phys. 2010 Mar 1;76(3 Suppl):S42-9.
  • 4. Klimo P Jr, Thompson CJ, Kestle JR, Schmidt MH. A meta- analysis of surgery versus conventional radiotherapy for the treatment of metastatic spinal epidural disease. Neuro Oncol. 2005 Jan;7(1):64-76.
  • 5. Fischer, A.W., Holfelder Lokales Amyloid im Gehirn. Deutsche Zeitschrift f. Chirurgie 227, 475–483 (1930).
  • 6. Schultheiss TE. The radiation dose-response of the human spinal cord. Int J Radiat Oncol Biol Phys. 2008 Aug 1;71(5):1455- 9.
  • 7. Wong CS, Fehlings MG, Sahgal A. Pathobiology of radiation myelopathy and strategies to mitigate injury. Spinal Cord. 2015 Aug;53(8):574-80.
  • 8. Schultheiss TE, Stephens LC, Maor MH. Analysis of the histopathology of radiation myelopathy. Int J Radiat Oncol Biol Phys. 1988 Jan;14(1):27-32.
  • 9. Moghadamtousi SZ, Fadaeinasab M, Nikzad S, Mohan G, Ali HM, Kadir HA. Annona muricata (Annonaceae): A Review of Its Traditional Uses, Isolated Acetogenins and Biological Activities. Int J Mol Sci. 2015 Jul 10;16(7):15625-58.
  • 10. Chan WJ, McLachlan AJ, Hanrahan JR, Harnett JE. The safety and tolerability of Annona muricata leaf extract: a systematic review. J Pharm Pharmacol. 2020 Jan;72(1):1-16.
  • 11. Akhondzadeh S, Naghavi HR, Vazirian M, Shayeganpour A, Rashidi H, Khani M. Passionflower in the treatment of generalized anxiety: a pilot double-blind randomized controlled trial with oxazepam. J Clin Pharm Ther. 2001 Oct;26(5):363-7.
  • 12. Souza DO, Dos Santos Sales V, de Souza Rodrigues CK, de Oliveira LR, Santiago Lemos IC, de Araújo Delmondes G, Monteiro ÁB, do Nascimento EP, Sobreira Dantas Nóbrega de Figuêiredo FR, Martins da Costa JG, Pinto da Cruz GM, de Barros Viana GS, Barbosa R, Alencar de Menezes IR, Bezerra Felipe CF, Kerntopf MR. Phytochemical Analysis and Central Effects of Annona Muricata Linnaeus: Possible Involvement of the Gabaergic and Monoaminergic Systems. Iran J Pharm Res. 2018 Fall;17(4):1306-1317.
  • 13. Champy P, Höglinger GU, Féger J, Gleye C, Hocquemiller R, Laurens A, Guérineau V, Laprévote O, Medja F, Lombès A, Michel PP, Lannuzel A, Hirsch EC, Ruberg M. Annonacin, a lipophilic inhibitor of mitochondrial complex I, induces nigral and striatal neurodegeneration in rats: possible relevance for atypical parkinsonism in Guadeloupe. J Neurochem. 2004 Jan;88(1):63-9.
  • 14. Mansour H.H., Elkady A.A., Elrefaei A.H., Hafez H.F. Radioprotective, antioxidant and antitumor efficacy of Annona muricata L. leaf extract. Indian J Biochem Biophys. 2018;55:205–214.
  • 15. Schultheiss TE, Kun LE, Ang KK, Stephens LC. Radiation response of the central nervous system. Int J Radiat Oncol Biol Phys. 1995 Mar 30;31(5):1093-112. Erratum in: Int J Radiat Oncol Biol Phys. 1995 Jul 15;32(4):1269.
  • 16. Li YQ, Chen P, Jain V, Reilly RM, Wong CS. Early radiation-induced endothelial cell loss and blood-spinal cord barrier breakdown in the rat spinal cord. Radiat Res. 2004 Feb;161(2):143- 52.
  • 17. de Sousa OV, Vieira GD, de Jesus R G de Pinho J, Yamamoto CH, Alves MS. Antinociceptive and anti-inflammatory activities of the ethanol extract of Annona muricata L. leaves in animal models. Int J Mol Sci. 2010 May 6;11(5):2067-78.
  • 18. Ishola IO, Awodele O, Olusayero AM, Ochieng CO. Mechanisms of analgesic and anti-inflammatory properties of Annona muricata Linn. (Annonaceae) fruit extract in rodents. J Med Food. 2014 Dec;17(12):1375-82.
  • 19. Dijkstra K, Hofmeijer J, van Gils SA, van Putten MJ. A Biophysical Model for Cytotoxic Cell Swelling. J Neurosci. 2016 Nov 23;36(47):11881-11890.
  • 20. Kim WS, Kim YE, Cho EJ, Byun EB, Park WY, Song HY, Kim K, Park SH, Byun EH. Neuroprotective effect of Annona muricata- derived polysaccharides in neuronal HT22 cell damage induced by hydrogen peroxide. Biosci Biotechnol Biochem. 2020 May;84(5):1001-1012.
  • 21. Kalderon N, Fuks Z. Structural recovery in lesioned adult mammalian spinal cord by x-irradiation of the lesion site. Proc Natl Acad Sci U S A. 1996 Oct 1;93(20):11179-84. Erratum in: Proc Natl Acad Sci U S A 1996 Dec 10;93(25):14992.
  • 22. LeRoux LG, Bredow S, Grosshans D, Schellingerhout D. Molecular imaging detects impairment in the retrograde axonal transport mechanism after radiation-induced spinal cord injury. Mol Imaging Biol. 2014 Aug;16(4):504-10.
  • 23. Sotoudeh A, Jahanshahi A, Zareiy S, Darvishi M, Roodbari N, Bazzazan A. The influence of low-level laser irradiation on spinal cord injuries following ischemia-reperfusion in rats. Acta Cir Bras. 2015 Sep;30(9):611-6.
  • 24. Li YQ, Guo YP, Jay V, Stewart PA, Wong CS. Time course of radiation- induced apoptosis in the adult rat spinal cord. Radiother Oncol. 1996 Apr;39(1):35-42.
  • 25. Moghadamtousi SZ, Kadir HA, Paydar M, Rouhollahi E, Karim ian H. Annona muricata leaves induced apoptosis in A549 cells through mitochondrial-mediated pathway and involvement of NF-κB. BMC Complement Altern Med. 2014 Aug 15;14:299.
  • 26. Okada S, Okeda R. Pathology of radiation myelopathy. Neuropathology. 2001 Dec;21(4):247-65.
  • 27. Okada S, Okeda R, Matsushita S, Kawano A. Histopathological and morphometric study of the late effects of heavy-ion irradiation on the spinal cord of the rat. Radiat Res. 1998 Sep;150(3):304-15.
  • 28. Schultheiss TE, Stephens LC. Radiation Myelopathy. AJNR Am J Neuroradiol. 1992 Jul-Aug;13(4):1056–8.
  • 29. Ana V. Coria-Téllez,Efigenia Montalvo-Gónzalez,Elhadi M. Yahia, Eva N. Obledo-Vázquez Annona muricata: A comprehensive review on its traditionalmmedicinal uses, phytochemicals, pharmacological activities, mechanisms of action and toxicity. Arabian Journal of Chemistry. 2018;11(5): 662- 91.
  • 30. Keskın, E., Elmas, O., Keser Sahın, H. H., Tonge, C., et al. (2022). The neuroprotective and anti-inflammatory effects of Annona muricata (Graviola) on radiation-induced rat sciatic nerve injury. Marmara Medical Journal, 35(2), 211-218.
There are 30 citations in total.

Details

Primary Language English
Subjects Clinical Oncology
Journal Section Research Article
Authors

Özlem Elmas 0000-0001-8039-9610

Havva Hande Keser Şahin 0000-0003-1827-1039

Emrah Keskin 0000-0001-5326-741X

Özlem Apsar Başaran 0009-0006-5767-1456

Publication Date August 30, 2024
Submission Date December 14, 2023
Acceptance Date August 9, 2024
Published in Issue Year 2024 Volume: 8 Issue: 2

Cite

Vancouver Elmas Ö, Keser Şahin HH, Keskin E, Apsar Başaran Ö. Radioprotective Effects of Annona Muricata Leaf Extract in the Spinal Cord. Med J West Black Sea. 2024;8(2):168-76.

Medical Journal of Western Black Sea is a scientific publication of Zonguldak Bulent Ecevit University Faculty of Medicine.

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