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Protective Effects of Melatonin and Octreotide Against Radiation-Induced Intestinal Injury

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Abstract

Purpose

To compare the protective effects of the potent antioxidants, melatonin and octreotide, against radiation-induced intestinal injury.

Methods

A total of 42 male 3-month-old Swiss albino mice (40 ± 10 g) were matched according to body weight and randomly assigned to one of six groups: control; radiation treatment (RT) only; melatonin only (15 mg/kg, i.p.); melatonin + RT; octreotide only (50 μg/kg i.p.); and octreotide + RT. Intestinal damage was induced by exposure to a single whole-body radiation dose of 8 Gy. All mice tolerated the experimental interventions, and no deaths were observed.

Results

Irradiation induced architectural disorganization, including inflammatory mononuclear cell infiltration, villitis, and desquamation with eosinophilic necrosis, and diminished mucosal thickness, crypt height, and villous height. In the melatonin + RT and octreotide + RT groups, the villous pattern was well preserved; desquamation at villous tips and edema was prominent, but necrosis was absent. The radiation-induced decrease in mucosal thickness was significantly reduced by pretreatment with melatonin (p < 0.001) or octreotide (p = 0.01), although the protective effect was significantly greater for melatonin (p = 0.04). Pretreatment with melatonin also preserved villous height (p = 0.009) and crypt height (p = 0.03); although a similar trend was observed for pre-irradiation octreotide, the differences were not significant.

Conclusions

Melatonin and octreotide potently protected against radiation-induced intestinal injury in mice, but melatonin was significantly more effective in preserving the histological structure of the intestines, a finding that warrants confirmation in clinical studies.

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References

  1. Onal C, Topkan E, Efe E, Yavuz M, Sonmez S, Yavuz A. Comparison of rectal volume definition techniques and their influence on rectal toxicity in patients with prostate cancer treated with 3D conformal radiotherapy: a dose–volume analysis. Radiat Oncol. 2009;4:14.

    Article  PubMed  Google Scholar 

  2. Atahan IL, Onal C, Ozyar E, Yiliz F, Selek U, Kose F. Long-term outcome and prognostic factors in patients with cervical carcinoma: a retrospective study. Int J Gynecol Cancer. 2007;17:833–842.

    Article  CAS  PubMed  Google Scholar 

  3. Sauer R, Becker H, Hohenberger W, et al. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med. 2004;351:1731–1740.

    Article  CAS  PubMed  Google Scholar 

  4. Bosset JF, Calais G, Daban A, et al. Preoperative chemoradiotherapy versus preoperative radiotherapy in rectal cancer patients: assessment of acute toxicity and treatment compliance. Report of the 22921 randomised trial conducted by the EORTC radiotherapy group. Eur J Cancer. 2004;40:219–224.

    Article  CAS  PubMed  Google Scholar 

  5. Dearnaley DP, Khoo VS, Norman AR, et al. Comparison of radiation side-effects of conformal and conventional radiotherapy in prostate cancer: a randomised trial. Lancet. 1999;353:267–272.

    Article  CAS  PubMed  Google Scholar 

  6. Widmark A, Fransson P, Tavelin B. Self-assessment questionnaire for evaluating urinary and intestinal late side effects after pelvic radiotherapy in patients with prostate cancer compared with an age-matched control population. Cancer. 1994;74:2520–2532.

    Article  CAS  PubMed  Google Scholar 

  7. Andreyev HJ. Gastrointestinal problems after pelvic radiotherapy: the past, the present and the future. Clin Oncol (R Coll Radiol). 2007;19:790–799.

    CAS  Google Scholar 

  8. Nutting CM, Convery DJ, Cosgrove VP, et al. Reduction of small and large bowel irradiation using an optimized intensity-modulated pelvic radiotherapy technique in patients with prostate cancer. Int J Radiat Oncol Biol Phys. 2000;48:649–656.

    Article  CAS  PubMed  Google Scholar 

  9. Luxton G, Hancock SL, Boyer AL. Dosimetry and radiobiologic model comparison of IMRT and 3D conformal radiotherapy in treatment of carcinoma of the prostate. Int J Radiat Oncol Biol Phys. 2004;59:267–284.

    Article  PubMed  Google Scholar 

  10. Hussein MR, Abu-Dief EE, Kamel E, Abou El-Ghait AT, Abdulwahed SR, Ahmad MH. Melatonin and roentgen irradiation-induced acute radiation enteritis in albino rats: an animal model. Cell Biol Int. 2008;32:1353–1361.

    Article  CAS  PubMed  Google Scholar 

  11. Agrawal A, Choudhary D, Upreti M, Rath PC, Kale RK. Radiation induced oxidative stress: I. studies in Ehrlich solid tumor in mice. Mol Cell Biochem. 2001;223:71–80.

    Article  CAS  PubMed  Google Scholar 

  12. Reiter RJ, Calvo JR, Karbownik M, Qi W, Tan DX. Melatonin and its relation to the immune system and inflammation. Ann NY Acad Sci. 2000;917:376–386.

    Article  CAS  PubMed  Google Scholar 

  13. Topkan E, Karaoglu A. Octreotide in the management of chemoradiotherapy-induced diarrhea refractory to loperamide in patients with rectal carcinoma. Oncology. 2006;71:354–360.

    Article  CAS  PubMed  Google Scholar 

  14. Yavuz MN, Yavuz AA, Aydin F, Can G, Kavgaci H. The efficacy of octreotide in the therapy of acute radiation-induced diarrhea: a randomized controlled study. Int J Radiat Oncol Biol Phys. 2002;54:195–202.

    CAS  PubMed  Google Scholar 

  15. Topkan E, Tufan H, Yavuz AA, et al. Comparison of the protective effects of melatonin and amifostine on radiation-induced epiphyseal injury. Int J Radiat Biol. 2008;84:796–802.

    Article  CAS  PubMed  Google Scholar 

  16. Erbil Y, Dibekoglu C, Turkoglu U, et al. Nitric oxide and radiation enteritis. Eur J Surg. 1998;164:863–868.

    Article  CAS  PubMed  Google Scholar 

  17. Jahovic N, Cevik H, Sehirli AO, Yegen BC, Sener G. Melatonin prevents methotrexate-induced hepatorenal oxidative injury in rats. J Pineal Res. 2003;34:282–287.

    Article  CAS  PubMed  Google Scholar 

  18. Gibbs FP, Vriend J. The half-life of melatonin elimination from rat plasma. Endocrinology. 1981;109:1796–1798.

    Article  CAS  PubMed  Google Scholar 

  19. Abbasoglu SD, Erbil Y, Eren T, et al. The effect of heme oxygenase-1 induction by octreotide on radiation enteritis. Peptides. 2006;27:1570–1576.

    Article  CAS  PubMed  Google Scholar 

  20. Olgac V, Erbil Y, Barbaros U, et al. The efficacy of octreotide in pancreatic and intestinal changes: radiation-induced enteritis in animals. Dig Dis Sci. 2006;51:227–232.

    Article  CAS  PubMed  Google Scholar 

  21. Vardar E, Vardar R, Yukselen V, et al. Image-based assessment of esophageal stricture in experimental corrosive esophagitis in animals: an objective, adjunct diagnostic tool. Turk J Gastroenterol. 2009;20:3–8.

    PubMed  Google Scholar 

  22. Tan DX, Manchester LC, Reiter RJ, et al. Melatonin suppresses autoxidation and hydrogen peroxide-induced lipid peroxidation in monkey brain homogenate. Neuro Endocrinol Lett. 2000;21:361–365.

    CAS  PubMed  Google Scholar 

  23. Vural H, Sabuncu T, Arslan SO, Aksoy N. Melatonin inhibits lipid peroxidation and stimulates the antioxidant status of diabetic rats. J Pineal Res. 2001;31:193–198.

    Article  CAS  PubMed  Google Scholar 

  24. Karslioglu I, Ertekin MV, Taysi S, et al. Radioprotective effects of melatonin on radiation-induced cataract. J Radiat Res (Tokyo). 2005;46:277–282.

    Article  CAS  Google Scholar 

  25. Sener G, Sehirli AO, Satiroglu H, Kacmaz A, Ayanoglu-Dulger G, Yegen BC. Octreotide improves burn-induced intestinal injury in the rat. Peptides. 2003;24:123–127.

    Article  CAS  PubMed  Google Scholar 

  26. Savarese DM, Savy G, Vahdat L, Wischmeyer PE, Corey B. Prevention of chemotherapy and radiation toxicity with glutamine. Cancer Treat Rev. 2003;29:501–513.

    Article  CAS  PubMed  Google Scholar 

  27. Giris M, Erbil Y, Oztezcan S, et al. The effect of heme oxygenase-1 induction by glutamine on radiation-induced intestinal damage: the effect of heme oxygenase-1 on radiation enteritis. Am J Surg. 2006;191:503–509.

    Article  CAS  PubMed  Google Scholar 

  28. Somosy Z, Horvath G, Telbisz A, Rez G, Palfia Z. Morphological aspects of ionizing radiation response of small intestine. Micron. 2002;33:167–178.

    Article  CAS  PubMed  Google Scholar 

  29. Saclarides TJ. Radiation injuries of the gastrointestinal tract. Surg Clin North Am. 1997;77:261–268.

    Article  CAS  PubMed  Google Scholar 

  30. Garg S, Boerma M, Wang J, et al. Influence of sublethal total-body irradiation on immune cell populations in the intestinal mucosa. Radiat Res. 2010;173:469–478.

    Article  CAS  PubMed  Google Scholar 

  31. Guney Y, Hicsonmez A, Uluoglu C, et al. Melatonin prevents inflammation and oxidative stress caused by abdominopelvic and total body irradiation of rat small intestine. Braz J Med Biol Res. 2007;40:1305–1314.

    Article  CAS  PubMed  Google Scholar 

  32. Bilici D, Suleyman H, Banoglu ZN, et al. Melatonin prevents ethanol-induced gastric mucosal damage possibly due to its antioxidant effect. Dig Dis Sci. 2002;47:856–861.

    Article  CAS  PubMed  Google Scholar 

  33. Empey LR, Papp JD, Jewell LD, Fedorak RN. Mucosal protective effects of vitamin E and misoprostol during acute radiation-induced enteritis in rats. Dig Dis Sci. 1992;37:205–214.

    Article  CAS  PubMed  Google Scholar 

  34. Ozturk H, Yagmur Y, Uzunlar AK. Effects of melatonin administration on intestinal adaptive response after massive bowel resection in rats. Dig Dis Sci. 2006;51:333–337.

    Article  CAS  PubMed  Google Scholar 

  35. Kim JK, Lee CJ. Effect of exogenous melatonin on the ovarian follicles in gamma-irradiated mouse. Mutat Res. 2000;449:33–39.

    CAS  PubMed  Google Scholar 

  36. Reiter RJ, Tan DX, Manchester LC, Qi W. Biochemical reactivity of melatonin with reactive oxygen and nitrogen species: a review of the evidence. Cell Biochem Biophys. 2001;34:237–256.

    Article  CAS  PubMed  Google Scholar 

  37. Tan DX, Manchester LC, Reiter RJ, Qi WB, Karbownik M, Calvo JR. Significance of melatonin in antioxidative defense system: reactions and products. Biol Signals Recept. 2000;9:137–159.

    Article  CAS  PubMed  Google Scholar 

  38. Vijayalaxmi, Reiter RJ, Tan DX, Herman TS, Thomas CR. Jr. Melatonin as a radioprotective agent: a review. Int J Radiat Oncol Biol Phys. 2004;59:639–653.

    Article  PubMed  Google Scholar 

  39. Hussein MR, Abu-Dief EE, Abou El-Ghait AT, Adly MA, Abdelraheem MH. Morphological evaluation of the radioprotective effects of melatonin against X-ray-induced early and acute testis damage in albino rats: an animal model. Int J Exp Pathol. 2006;87:237–250.

    Article  PubMed  Google Scholar 

  40. Reiter RJ, Tan DX, Gitto E, Sainz RM, Mayo JC, Leon J, Manchester LC, Vijayalaxmi, Kilic E, Kilic U. Pharmacological utility of melatonin in reducing oxidative cellular and molecular damage. Pol J Pharmacol. 2004;56:159–170.

    CAS  PubMed  Google Scholar 

  41. Halliwell B, Whiteman M. Measuring reactive species and oxidative damage in vivo and in cell culture. How should you do it and what do the results mean? Br J Pharmacol. 2004;142:231–255.

    Article  CAS  PubMed  Google Scholar 

  42. Harris AG. Somatostatin and somatostatin analogues: pharmacokinetics and pharmacodynamic effects. Gut. 1994;35:S1–S4.

    Article  CAS  PubMed  Google Scholar 

  43. Wang J, Zheng H, Sung CC, Hauer-Jensen M. The synthetic somatostatin analogue, octreotide, ameliorates acute and delayed intestinal radiation injury. Int J Radiat Oncol Biol Phys. 1999;45:1289–1296.

    Article  CAS  PubMed  Google Scholar 

  44. Kacmaz A, Polat A, User Y, Tilki M, Ozkan S, Sener G. Octreotide improves reperfusion-induced oxidative injury in acute abdominal hypertension in rats. J Gastrointest Surg. 2004;8:113–119.

    Article  PubMed  Google Scholar 

  45. Petrelli NJ, Rodriguez-Bigas M, Rustum Y, Herrera L, Creaven P. Bowel rest, intravenous hydration, and continuous high-dose infusion of octreotide acetate for the treatment of chemotherapy-induced diarrhea in patients with colorectal carcinoma. Cancer. 1993;72:1543–1546.

    Article  CAS  PubMed  Google Scholar 

  46. Altun A, Ugur-Altun B. Melatonin: therapeutic and clinical utilization. Int J Clin Pract. 2007;61:835–845.

    Article  CAS  PubMed  Google Scholar 

  47. Gordon N. The therapeutics of melatonin: a paediatric perspective. Brain Dev. 2000;22:213–217.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

The authors wish to thank Assoc. Prof. Dr. S. Remzi Erdem, MD, PhD, Sebnem Kosdak, MD and Hande Ozge Altunkaynak MSc, from the Department of Pharmacology, Baskent University Faculty of Medicine, for their constructive criticism on the experimental design of the study and valuable help in preparing the drug solutions. This study is accepted as poster presentation at ECCO 15/ESMO 34 - Berlin, September 20–24, 2009.

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Authors and Affiliations

  1. Department of Radiation Oncology, Adana Research and Treatment Centre, Baskent University Medical Faculty, 01120, Adana, Turkey

    Cem Onal, Erkan Topkan, Melek Yavuz & Aydin Yavuz

  2. Department of Pathology, Baskent University Medical Faculty, Ankara, Turkey

    Fazilet Kayaselcuk

  3. Experimental Animals Breeding and Research Center, Baskent University Medical Faculty, Baglica, Ankara, Turkey

    Didem Bacanli

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  1. Cem Onal
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Correspondence to Cem Onal.

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Onal, C., Kayaselcuk, F., Topkan, E. et al. Protective Effects of Melatonin and Octreotide Against Radiation-Induced Intestinal Injury. Dig Dis Sci 56, 359–367 (2011). https://doi.org/10.1007/s10620-010-1322-2

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