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Amifostine Protects Small Bowel Against Radiation-induced Apopitosis by Reducing Caspase-3

Year 2018, Volume: 8 Issue: 3, 611 - 619, 30.09.2018
https://doi.org/10.31832/smj.448417

Abstract

Objective: The aim of the study was to investigate the protective effect of amifostine against radiotherapy-induced small bowel injury.

Materials and Methods: Forty rats were divided equally into four groups as control, irradiation (IR), IR + Amifostine, IR+N-acetyl cysteine (NAC) groups. Caspase-3 expression, villus lengths, and microscopic tissue injury were evaluated histopathologically. Superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), myeloperoxidase (MPO) and malondialdehyde (MDA) were measured biochemically in jejunum tissue. Pre- and post-radiation weights of the rats were recorded.

Results: Caspase-3 was at the highest level in the IR group, at the lowest level in the control and weak in the Amifostine+IR group. The lowest microscopic score was determined in the IR group and the difference between the groups was statistically significant. CAT decreases after IR. However, Amifostine and NAC prevented radiation-induced catalase decline. In Amifostine+IR group, the villus length was significantly longer than that of the IR group. Amifostine was observed to protect against weight loss.







Conclusion: The results obtained from this study demonstrate that the administration of Amifostine can substantially reduce apopitosis and support the repair of the structure and function of intestinal tissues which have been damaged by exposure to radiation. These results also suggest that it may be a promising therapeutic agent.

References

  • 1 Kaliberov SA, and Buchsbaum D, 'Cancer Treatment with Gene Therapy and Radiation Therapy', in Advances in Cancer Research. Curiel DT, Fisher PB (eds.) (Elsevier, 2012), pp. 221-63.
  • 2 Shinomiya N, 'New Concepts in Radiation‐Induced Apoptosis:‘Premitotic Apoptosis’ and ‘Postmitotic Apoptosis’', J Cell Mol Med., 5 (2001), 240-53.
  • 3 Gracy RW, Talent JM, Kong Y, and Conrad CC, 'Reactive Oxygen Species: The Unavoidable Environmental Insult?', Mutat Res. 428 (1999), 17-22.
  • 4 Pulli B, Ali M, Forghani R, Schob S, Hsieh KL, Wojtkiewicz G, Linnoila JJ, Chen JW., et al., 'Measuring Myeloperoxidase Activity in Biological Samples', PloS one, 8 (2013), e67976.
  • 5 Pandey BN, and Mishra KP, 'Fluorescence and Esr Studies on Membrane Oxidative Damage by Gamma Radiation', Appl Magn Reson., 18 (2000), 483-92.
  • 6 Cox JD, Byhardt RW, Wilson JF, Haas JS, Komaki R, Olson LE, 'Complications of Radiation Therapy and Factors in Their Prevention', World J Surg, 10 (1986), 171-88.
  • 7 Weiss JF, Landauer MR., 'History and Development of Radiation-Protective Agents', Int J Radiat Biol., 85 (2009), 539-73.
  • 8 Irwin Fridovich, 'Superoxide Dismutases', Adv Enzymol Relat Areas Mol Biol, 58 (1986), 61-97.
  • 9 Ernest Beutler, Red Cell Metabolism: A Manual of Biochemical Methods (Grune & Stratton, 1975).
  • 10 Paglia DE, Valentine WN, 'Studies on the Quantitative and Qualitative Characterization of Erythrocyte Glutathione Peroxidase', J Lab Clin Med., 70 (1967), 158-69.
  • 11 Worthington Enzyme Manual, 'Worthington Biochemical Corp', Freehold, NJ, 43 (1972).
  • 12 Ohkawa H, Ohishi N, Yagi K. 'Assay for Lipid Peroxides in Animal Tissues by Thiobarbituric Acid Reaction', Anal Biochem., 95 (1979), 351-58.
  • 13 Lowry OH, 'Protein Measurement with Folin Phenol Regent', J. Biol. Chem., 193 (1951), 265-75.
  • 14 Grdina DJ, Murley JS, Kataoka Y, Baker KL, Kunnavakkam R, Coleman MC, et al., 'Amifostine Induces Antioxidant Enzymatic Activities in Normal Tissues and a Transplantable Tumor That Can Affect Radiation Response', Int J Radiat Oncol Biol Phys., 73 (2009), 886-96.
  • 15 Dorr W, and Hendry JH, 'Consequential Late Effects in Normal Tissues', Radiother Oncol, 61 (2001), 223-31.
  • 16 Burdelya LG, Krivokrysenko VI, Tallant TC, Strom E, Gleiberman AS, Gupta D, et al., 'An Agonist of Toll-Like Receptor 5 Has Radioprotective Activity in Mouse and Primate Models', Science, 320 (2008), 226-30.
  • 17 Komarova EA, Kondratov RV, Wang K, Christov K, Golovkina TV, Goldblum JR, et al., 'Dual Effect of P53 on Radiation Sensitivity in Vivo: P53 Promotes Hematopoietic Injury, but Protects from Gastro-Intestinal Syndrome in Mice', Oncogene, 23 (2004), 3265-71.
  • 18 Huang EY, Wang FS, Lin IH, Yang KD. 'Aminoguanidine Alleviates Radiation-Induced Small-Bowel Damage through Its Antioxidant Effect', Int J Radiat Oncol Biol Phys, 74 (2009), 237-44.
  • 19 Huang EY, Wang FS, Chen YM, Chen YF, Wang CC, Lin IH et al., 'Amifostine Alleviates Radiation-Induced Lethal Small Bowel Damage Via Promotion of 14-3-3sigma-Mediated Nuclear P53 Accumulation', Oncotarget, 5 (2014), 9756-69.
  • 20 Milas L, Hunter N, Reid BO, Thames HD Jr., 'Protective Effects of S-2-(3-Aminopropylamino) Ethylphosphorothioic Acid against Radiation Damage of Normal Tissues and a Fibrosarcoma in Mice', Cancer Res, 42 (1982), 1888-97.
  • 21 Oshima CT, Ribeiro DA, Gomes TS, Adios PC, Egami MI, Segreto HR., 'Amifostine Increases Fas and Caspase-3 Expression in Colonic Tissue of Irradiated Mice', Anticancer Res, 35 (2015), 2817-22.
  • 22 Rozalski M, Mirowski M, Balcerczak E, Krajewska U, Mlynarski U, Wierzbicki R. 'Induction of Caspase 3 Activity, Bcl-2 Bax and P65 Gene Expression Modulation in Human Acute Promyelocytic Leukemia Hl-60 Cells by Doxorubicin with Amifostine', Pharmacol Rep, 57 (2005), 360-6.
  • 23 Segreto HR, Oshima CT, Franco MF, Silva MR, Egami MI, Teixeira VP et al., 'Phosphorylation and Cytoplasmic Localization of Mapk P38 During Apoptosis Signaling in Bone Marrow Granulocytes of Mice Irradiated in Vivo and the Role of Amifostine in Reducing These Effects', Acta Histochem, 113 (2011), 300-7.
  • 24 Karbownik M, Reiter RJ, 'Antioxidative Effects of Melatonin in Protection against Cellular Damage Caused by Ionizing Radiation', Proc Soc Exp Biol Med, 225 (2000), 9-22.
  • 25 Kaya H, Delibas N, Serteser M, Ulukaya E, Ozkaya O. 'The Effect of Melatonin on Lipid Peroxidation During Radiotherapy in Female Rats', Strahlenther Onkol., 175 (1999), 285-88.
  • 26 YB Cihan, A Ozturk, SS Gokalp 'Protective Role of Royal Jelly against Radiation-Induced Oxidative Stress in Rats', UHOD, 27 (2013), 079-87.
  • 27 Neal R. Matthews RH. Lutz P. Ercal N.. 'Antioxidant Role of N-Acetyl Cysteine Isomers Following High Dose Irradiation'. Free Radic Biol Med. 34 (2003). 689-95.
  • 28 Cosar R. Yurut-Caloglu V. Eskiocak S. Ozen A. Altaner S. Ibis K. et al.. 'Radiation-Induced Chronic Oxidative Renal Damage Can Be Reduced by Amifostine'. Med Oncol. 29 (2012). 768-75.
  • 29 Demirel C. Cagiran Kilciksiz S. Gurgul S. Erdal N. Yigit S. Tamer L et al.. 'Inhibition of Radiation-Induced Oxidative Damage in the Lung Tissue: May Acetylsalicylic Acid Have a Positive Role?'. Inflammation. 39 (2016). 158-65.
  • 30 Kilciksiz S. Demirel C. Erdal N. Gürgül S. Tamer L. and Ayaz L. 'The Effect of N-Acetylcysteine on Biomarkers for Radiation-Induced Oxidative Damage in a Rat Model'. Acta Med Okayama. 62 (2008). 403-09.
  • 31 Das U. Sengupta A. Biswas S. Adhikary A. Dey Sharma R. Chakraborty A. et al.. 'Alteration of Murine Duodenal Morphology and Redox Signalling Events by Reactive Oxygen Species Generated after Whole Body Gamma-Irradiation and Its Prevention by Ferulic Acid'. Free Radic Res. 51 (2017). 886-910.
  • 32 Thomson ABR. Cheeseman CI . Keelan M. Fedorak R. and Clandinin MT. 'Crypt Cell Production Rate. Enterocyte Turnover Time and Appearance of Transport Along the Jejunal Villus of the Rat'. Biochim Biophys Acta.. 1191 (1994). 197-204.
  • 33 Zheng K. Wu W. Yang S. Huang L. Chen J. Gong C. et al.. 'Treatment of Radiation-Induced Acute Intestinal Injury with Bone Marrow-Derived Mesenchymal Stem Cells'. Exp Ther Med. 11 (2016). 2425-31.

Amifostin İnce Bağırsakları Kaspaz-3’ü Azaltarak Radyasyonun İndüklediği Apopitozise Karşı Korur

Year 2018, Volume: 8 Issue: 3, 611 - 619, 30.09.2018
https://doi.org/10.31832/smj.448417

Abstract

Amaç: Bu çalışmanın amacı, amifostinin
radyoterapiye bağlı ince bağırsak hasarına karşı koruyucu etkisini
araştırmaktır.

Materyal ve Metod: Kırk rat, kontrol, radyasyon (IR), IR + Amifostin, IR + N-asetil sistein
(NAC) grupları olmak üzere dört gruba eşit olarak ayrıldı. Kaspaz-3 ekspresyonu,
villus uzunlukları ve mikroskobik doku hasarı histopatolojik olarak
değerlendirildi. Jejunum dokusunda süperoksit dismutaz (SOD), katalaz (CAT),
glutatyon peroksidaz (GPx), miyeloperoksidaz (MPO) ve malondialdehid (MDA)
biyokimyasal olarak ölçüldü. Ratların radyasyon öncesi ve sonrası ağırlıkları
kaydedildi.

Bulgular: Kaspaz-3, IR grubunda en yüksek düzeyde, kontrol grubunda en düşük
düzeyde ve Amifostin + IR grubunda zayıftı. En düşük mikroskopik skor IR
grubunda belirlendi ve gruplar arasındaki fark istatistiksel olarak anlamlıydı.
CAT, IR'den sonra azalmıştı. Bununla birlikte, Amifostin ve NAC radyasyon
kaynaklı katalaz düşüşünü önledi. Amifostin + IR grubunda, villus uzunluğu, IR
grubundan anlamlı derecede daha uzundu. Amifostinin kilo kaybına karşı
korunduğu gözlendi.







Sonuç:
Bu çalışmadan elde edilen sonuçlar, Amifostin uygulamasının apopitozu büyük
ölçüde azaltabildiğini ve radyasyona maruziyetten zarar gören bağırsak
dokularının yapısını ve işlevini onardığını desteklemektedir. Bu sonuçlar Amifostinin
ümit verici bir terapötik ajan olabileceğini düşündürmektedir.

References

  • 1 Kaliberov SA, and Buchsbaum D, 'Cancer Treatment with Gene Therapy and Radiation Therapy', in Advances in Cancer Research. Curiel DT, Fisher PB (eds.) (Elsevier, 2012), pp. 221-63.
  • 2 Shinomiya N, 'New Concepts in Radiation‐Induced Apoptosis:‘Premitotic Apoptosis’ and ‘Postmitotic Apoptosis’', J Cell Mol Med., 5 (2001), 240-53.
  • 3 Gracy RW, Talent JM, Kong Y, and Conrad CC, 'Reactive Oxygen Species: The Unavoidable Environmental Insult?', Mutat Res. 428 (1999), 17-22.
  • 4 Pulli B, Ali M, Forghani R, Schob S, Hsieh KL, Wojtkiewicz G, Linnoila JJ, Chen JW., et al., 'Measuring Myeloperoxidase Activity in Biological Samples', PloS one, 8 (2013), e67976.
  • 5 Pandey BN, and Mishra KP, 'Fluorescence and Esr Studies on Membrane Oxidative Damage by Gamma Radiation', Appl Magn Reson., 18 (2000), 483-92.
  • 6 Cox JD, Byhardt RW, Wilson JF, Haas JS, Komaki R, Olson LE, 'Complications of Radiation Therapy and Factors in Their Prevention', World J Surg, 10 (1986), 171-88.
  • 7 Weiss JF, Landauer MR., 'History and Development of Radiation-Protective Agents', Int J Radiat Biol., 85 (2009), 539-73.
  • 8 Irwin Fridovich, 'Superoxide Dismutases', Adv Enzymol Relat Areas Mol Biol, 58 (1986), 61-97.
  • 9 Ernest Beutler, Red Cell Metabolism: A Manual of Biochemical Methods (Grune & Stratton, 1975).
  • 10 Paglia DE, Valentine WN, 'Studies on the Quantitative and Qualitative Characterization of Erythrocyte Glutathione Peroxidase', J Lab Clin Med., 70 (1967), 158-69.
  • 11 Worthington Enzyme Manual, 'Worthington Biochemical Corp', Freehold, NJ, 43 (1972).
  • 12 Ohkawa H, Ohishi N, Yagi K. 'Assay for Lipid Peroxides in Animal Tissues by Thiobarbituric Acid Reaction', Anal Biochem., 95 (1979), 351-58.
  • 13 Lowry OH, 'Protein Measurement with Folin Phenol Regent', J. Biol. Chem., 193 (1951), 265-75.
  • 14 Grdina DJ, Murley JS, Kataoka Y, Baker KL, Kunnavakkam R, Coleman MC, et al., 'Amifostine Induces Antioxidant Enzymatic Activities in Normal Tissues and a Transplantable Tumor That Can Affect Radiation Response', Int J Radiat Oncol Biol Phys., 73 (2009), 886-96.
  • 15 Dorr W, and Hendry JH, 'Consequential Late Effects in Normal Tissues', Radiother Oncol, 61 (2001), 223-31.
  • 16 Burdelya LG, Krivokrysenko VI, Tallant TC, Strom E, Gleiberman AS, Gupta D, et al., 'An Agonist of Toll-Like Receptor 5 Has Radioprotective Activity in Mouse and Primate Models', Science, 320 (2008), 226-30.
  • 17 Komarova EA, Kondratov RV, Wang K, Christov K, Golovkina TV, Goldblum JR, et al., 'Dual Effect of P53 on Radiation Sensitivity in Vivo: P53 Promotes Hematopoietic Injury, but Protects from Gastro-Intestinal Syndrome in Mice', Oncogene, 23 (2004), 3265-71.
  • 18 Huang EY, Wang FS, Lin IH, Yang KD. 'Aminoguanidine Alleviates Radiation-Induced Small-Bowel Damage through Its Antioxidant Effect', Int J Radiat Oncol Biol Phys, 74 (2009), 237-44.
  • 19 Huang EY, Wang FS, Chen YM, Chen YF, Wang CC, Lin IH et al., 'Amifostine Alleviates Radiation-Induced Lethal Small Bowel Damage Via Promotion of 14-3-3sigma-Mediated Nuclear P53 Accumulation', Oncotarget, 5 (2014), 9756-69.
  • 20 Milas L, Hunter N, Reid BO, Thames HD Jr., 'Protective Effects of S-2-(3-Aminopropylamino) Ethylphosphorothioic Acid against Radiation Damage of Normal Tissues and a Fibrosarcoma in Mice', Cancer Res, 42 (1982), 1888-97.
  • 21 Oshima CT, Ribeiro DA, Gomes TS, Adios PC, Egami MI, Segreto HR., 'Amifostine Increases Fas and Caspase-3 Expression in Colonic Tissue of Irradiated Mice', Anticancer Res, 35 (2015), 2817-22.
  • 22 Rozalski M, Mirowski M, Balcerczak E, Krajewska U, Mlynarski U, Wierzbicki R. 'Induction of Caspase 3 Activity, Bcl-2 Bax and P65 Gene Expression Modulation in Human Acute Promyelocytic Leukemia Hl-60 Cells by Doxorubicin with Amifostine', Pharmacol Rep, 57 (2005), 360-6.
  • 23 Segreto HR, Oshima CT, Franco MF, Silva MR, Egami MI, Teixeira VP et al., 'Phosphorylation and Cytoplasmic Localization of Mapk P38 During Apoptosis Signaling in Bone Marrow Granulocytes of Mice Irradiated in Vivo and the Role of Amifostine in Reducing These Effects', Acta Histochem, 113 (2011), 300-7.
  • 24 Karbownik M, Reiter RJ, 'Antioxidative Effects of Melatonin in Protection against Cellular Damage Caused by Ionizing Radiation', Proc Soc Exp Biol Med, 225 (2000), 9-22.
  • 25 Kaya H, Delibas N, Serteser M, Ulukaya E, Ozkaya O. 'The Effect of Melatonin on Lipid Peroxidation During Radiotherapy in Female Rats', Strahlenther Onkol., 175 (1999), 285-88.
  • 26 YB Cihan, A Ozturk, SS Gokalp 'Protective Role of Royal Jelly against Radiation-Induced Oxidative Stress in Rats', UHOD, 27 (2013), 079-87.
  • 27 Neal R. Matthews RH. Lutz P. Ercal N.. 'Antioxidant Role of N-Acetyl Cysteine Isomers Following High Dose Irradiation'. Free Radic Biol Med. 34 (2003). 689-95.
  • 28 Cosar R. Yurut-Caloglu V. Eskiocak S. Ozen A. Altaner S. Ibis K. et al.. 'Radiation-Induced Chronic Oxidative Renal Damage Can Be Reduced by Amifostine'. Med Oncol. 29 (2012). 768-75.
  • 29 Demirel C. Cagiran Kilciksiz S. Gurgul S. Erdal N. Yigit S. Tamer L et al.. 'Inhibition of Radiation-Induced Oxidative Damage in the Lung Tissue: May Acetylsalicylic Acid Have a Positive Role?'. Inflammation. 39 (2016). 158-65.
  • 30 Kilciksiz S. Demirel C. Erdal N. Gürgül S. Tamer L. and Ayaz L. 'The Effect of N-Acetylcysteine on Biomarkers for Radiation-Induced Oxidative Damage in a Rat Model'. Acta Med Okayama. 62 (2008). 403-09.
  • 31 Das U. Sengupta A. Biswas S. Adhikary A. Dey Sharma R. Chakraborty A. et al.. 'Alteration of Murine Duodenal Morphology and Redox Signalling Events by Reactive Oxygen Species Generated after Whole Body Gamma-Irradiation and Its Prevention by Ferulic Acid'. Free Radic Res. 51 (2017). 886-910.
  • 32 Thomson ABR. Cheeseman CI . Keelan M. Fedorak R. and Clandinin MT. 'Crypt Cell Production Rate. Enterocyte Turnover Time and Appearance of Transport Along the Jejunal Villus of the Rat'. Biochim Biophys Acta.. 1191 (1994). 197-204.
  • 33 Zheng K. Wu W. Yang S. Huang L. Chen J. Gong C. et al.. 'Treatment of Radiation-Induced Acute Intestinal Injury with Bone Marrow-Derived Mesenchymal Stem Cells'. Exp Ther Med. 11 (2016). 2425-31.
There are 33 citations in total.

Details

Primary Language English
Subjects Health Care Administration
Journal Section Articles
Authors

Neslihan Kurtul

A.yasir Bahar This is me

Fatma İnanç Tolun

Publication Date September 30, 2018
Submission Date July 27, 2018
Published in Issue Year 2018 Volume: 8 Issue: 3

Cite

AMA Kurtul N, Bahar A, İnanç Tolun F. Amifostine Protects Small Bowel Against Radiation-induced Apopitosis by Reducing Caspase-3. Sakarya Tıp Dergisi. September 2018;8(3):611-619. doi:10.31832/smj.448417

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