Skip to main content
Top
Published in: Inflammation 3/2016

01-06-2016 | ORIGINAL ARTICLE

Melatonin can Ameliorate Radiation-Induced Oxidative Stress and Inflammation-Related Deterioration of Bone Quality in Rat Femur

Authors: Zelal Ünlü Çakir, Can Demirel, Sevil Cagiran Kilciksiz, Serkan Gürgül, S. Burhanedtin Zincircioğlu, Nurten Erdal

Published in: Inflammation | Issue 3/2016

Login to get access

ABSTRACT

The aim of the present study was to evaluate the radioprotective effects of melatonin on the biomechanical properties of bone in comparison to amifostine (WR-2721). Forty Sprague Dawley rats were divided equally into 5 groups namely; control (C), irradiation (R; single dose of 50 Gy), irradiation + WR-2721 (R + WR-2721; irradiation + 200 mg/kg WR-2721) radiation + melatonin 25 mg/kg (R + M25; irradiation + 25 mg/kg melatonin), and radiation + melatonin 50 mg/kg (R + M50; irradiation + 50 mg/kg melatonin). In order to measure extrinsic (organ-level mechanical properties of bone; the ultimate strength, deformation, stiffness, energy absorption capacity) and intrinsic (tissue-level mechanical properties of bone; ultimate stress, ultimate strain, elastic modulus, toughness) features of the bone, a three-point bending (TPB) test was performed for biomechanical evaluation. In addition, a bone mineral density (BMD) test was carried out. The BMD and extrinsic properties of the diaphyseal femur were found to be significantly higher in the R + M25 group than in group R (p < 0.05). A significant increase was observed in R + M50 (p < 0.05) in comparison to group R in the cross-sectional area of the femoral shaft and elastic modulus parameter. The protective effect of melatonin was similar to that of WR-2721. Thus, biomechanical quality of irradiated bone can be ameliorated by free radical scavenger melatonin.
Literature
1.
go back to reference Phulpin, B., G. Dolivet, P.Y. Marie, et al. 2010. Re-assessment of chronic radio-induced tissue damage in a rat hindlimb model. Experimental and Therapeutic Medicine 4: 553–560. Phulpin, B., G. Dolivet, P.Y. Marie, et al. 2010. Re-assessment of chronic radio-induced tissue damage in a rat hindlimb model. Experimental and Therapeutic Medicine 4: 553–560.
2.
go back to reference Jia, D., D. Gaddy, L.J. Suva, and P.M. Corry. 2011. Rapid loss of bone mass and strength in mice after abdominal irradiation. Radiation Research 176: 624–635.CrossRefPubMedPubMedCentral Jia, D., D. Gaddy, L.J. Suva, and P.M. Corry. 2011. Rapid loss of bone mass and strength in mice after abdominal irradiation. Radiation Research 176: 624–635.CrossRefPubMedPubMedCentral
3.
go back to reference Meerveld-Eggink, A., T.L. Bollen, H.K. Wijrdeman, and M. Los. 2013. Bone metastases or an insufficiency fracture? Oncology patients reporting pain or showing bone abnormalities on a scan. Nederland Tijdschrift vood Geneeskunde 157, A6098. Meerveld-Eggink, A., T.L. Bollen, H.K. Wijrdeman, and M. Los. 2013. Bone metastases or an insufficiency fracture? Oncology patients reporting pain or showing bone abnormalities on a scan. Nederland Tijdschrift vood Geneeskunde 157, A6098.
4.
go back to reference Szymczyk, K.H., I.M. Shapiro, and C.S. Adams. 2004. Ionizing radiation sensitizes bone cells to apoptosis. Bone 34: 148–156.CrossRefPubMed Szymczyk, K.H., I.M. Shapiro, and C.S. Adams. 2004. Ionizing radiation sensitizes bone cells to apoptosis. Bone 34: 148–156.CrossRefPubMed
5.
go back to reference Sakurai, T., Y. Sawada, M. Yoshimoto, M. Kawai, and J. Miyakoshi. 2007. Radiation-induced reduction of osteoblast differentiation in C2C12 cells. Journal of Radiation Research 48: 515–521.CrossRefPubMed Sakurai, T., Y. Sawada, M. Yoshimoto, M. Kawai, and J. Miyakoshi. 2007. Radiation-induced reduction of osteoblast differentiation in C2C12 cells. Journal of Radiation Research 48: 515–521.CrossRefPubMed
6.
go back to reference Hopewell, J.W. 2003. Radiation-therapy effects on bone density. Medical and Pediatric Oncology 41: 208–211.CrossRefPubMed Hopewell, J.W. 2003. Radiation-therapy effects on bone density. Medical and Pediatric Oncology 41: 208–211.CrossRefPubMed
7.
go back to reference Nyaruba, M.M., I. Yamamoto, H. Kimura, and R. Morita. 1998. Bone fragility induced by X-ray irradiation in relation to cortical bone-mineral content. Acta Radiologica 39: 43–46.CrossRefPubMed Nyaruba, M.M., I. Yamamoto, H. Kimura, and R. Morita. 1998. Bone fragility induced by X-ray irradiation in relation to cortical bone-mineral content. Acta Radiologica 39: 43–46.CrossRefPubMed
8.
go back to reference Tins, B.J., M. Garton, V.N. Cassar-Pullicino, P.N. Tyrrell, R. Lalam, and J. Singh. 2015. Stress fracture of the pelvis and lower limbs including atypical femoral fractures—a review. Insights into Imaging 6: 97–110.CrossRefPubMedPubMedCentral Tins, B.J., M. Garton, V.N. Cassar-Pullicino, P.N. Tyrrell, R. Lalam, and J. Singh. 2015. Stress fracture of the pelvis and lower limbs including atypical femoral fractures—a review. Insights into Imaging 6: 97–110.CrossRefPubMedPubMedCentral
9.
go back to reference Georgiou, K.R., S.K. Hui, and C.J. Xian. 2012. Regulatory pathways associated with bone loss and bone marrow adiposity caused by aging, chemotherapy, glucocorticoid therapy and radiotherapy. American Journal of Stem Cells 30: 205–224. Georgiou, K.R., S.K. Hui, and C.J. Xian. 2012. Regulatory pathways associated with bone loss and bone marrow adiposity caused by aging, chemotherapy, glucocorticoid therapy and radiotherapy. American Journal of Stem Cells 30: 205–224.
10.
go back to reference Johnke, R.M., J.A. Sattler, and R.R. Allison. 2014. Radioprotective agents for radiation therapy: Future trends. Future Oncology 10: 2345–2357.CrossRefPubMed Johnke, R.M., J.A. Sattler, and R.R. Allison. 2014. Radioprotective agents for radiation therapy: Future trends. Future Oncology 10: 2345–2357.CrossRefPubMed
11.
go back to reference Weiss, J.F. 1997. Pharmacologic approaches to protection against radiation-induced lethality and other damage. Environmental Health Perspectives 105: 1473–1478.CrossRefPubMedPubMedCentral Weiss, J.F. 1997. Pharmacologic approaches to protection against radiation-induced lethality and other damage. Environmental Health Perspectives 105: 1473–1478.CrossRefPubMedPubMedCentral
12.
go back to reference Demirel, C., S. Kilciksiz, S. Gurgul, N. Erdal, and A. Yildiz. 2011. N-acetylcysteine ameliorates γ-radiation-induced deterioration of bone quality in the rat femur. The Journal of International Medical Research 39: 2393–2401.CrossRefPubMed Demirel, C., S. Kilciksiz, S. Gurgul, N. Erdal, and A. Yildiz. 2011. N-acetylcysteine ameliorates γ-radiation-induced deterioration of bone quality in the rat femur. The Journal of International Medical Research 39: 2393–2401.CrossRefPubMed
13.
go back to reference Valko, M., D. LeibfritZ, J. Moncol, M.T. Cronin, M. Mazur, and J. Telser. 2007. Free radicals and antioxidants in normal physiological functions and human disease. The International Journal of Biochemistry & Cell Biology 39: 44–84.CrossRef Valko, M., D. LeibfritZ, J. Moncol, M.T. Cronin, M. Mazur, and J. Telser. 2007. Free radicals and antioxidants in normal physiological functions and human disease. The International Journal of Biochemistry & Cell Biology 39: 44–84.CrossRef
14.
go back to reference Margulies, B.S., T.A. Damron, and M.J. Allen. 2008. The differential effects of the radioprotectant drugs amifostine and sodium selenite treatment in combination with radiation therapy on constituent bone cells, Ewing’s sarcoma of bone tumor cells, and rhabdomyosarcoma tumor cells in vitro. Journal of Orthopaedic Research 26: 1512–1519.CrossRefPubMed Margulies, B.S., T.A. Damron, and M.J. Allen. 2008. The differential effects of the radioprotectant drugs amifostine and sodium selenite treatment in combination with radiation therapy on constituent bone cells, Ewing’s sarcoma of bone tumor cells, and rhabdomyosarcoma tumor cells in vitro. Journal of Orthopaedic Research 26: 1512–1519.CrossRefPubMed
15.
go back to reference Amstrup, A.K., T. Sikjaer, L. Mosekilde, and L. Rejnmark. 2013. Melatonin and the skeleton. Osteoporosis International 24: 2919–2927.CrossRefPubMed Amstrup, A.K., T. Sikjaer, L. Mosekilde, and L. Rejnmark. 2013. Melatonin and the skeleton. Osteoporosis International 24: 2919–2927.CrossRefPubMed
16.
go back to reference Topkan, E., H. Tufan, A.A. Yavuz, et al. 2008. Comparison of the protective effects of melatonin and amifostine on radiation-induced epiphyseal injury. International Journal of Radiation Biology 84: 796–802.CrossRefPubMed Topkan, E., H. Tufan, A.A. Yavuz, et al. 2008. Comparison of the protective effects of melatonin and amifostine on radiation-induced epiphyseal injury. International Journal of Radiation Biology 84: 796–802.CrossRefPubMed
17.
go back to reference Man, G.C., J.H. Wong, W.W. Wang, et al. 2011. Abnormal melatonin receptor 1B expression in osteoblasts from girls with adolescent idiopathic scoliosis. Journal of Pineal Research 50: 395–402.CrossRefPubMed Man, G.C., J.H. Wong, W.W. Wang, et al. 2011. Abnormal melatonin receptor 1B expression in osteoblasts from girls with adolescent idiopathic scoliosis. Journal of Pineal Research 50: 395–402.CrossRefPubMed
18.
go back to reference Tami, A.E., M.B. Schaffler, and M.L. Knothe Tate. 2003. Probing the tissue to subcellular level structure underlying bone’s molecular sieving function. Biorheology 40: 577–590.PubMed Tami, A.E., M.B. Schaffler, and M.L. Knothe Tate. 2003. Probing the tissue to subcellular level structure underlying bone’s molecular sieving function. Biorheology 40: 577–590.PubMed
19.
go back to reference Reiter, R.J., D.X. Tan, and A. Galano. 2014. Melatonin: Exceeding expectations. Physiology (Bethesda) 29: 325–333. Reiter, R.J., D.X. Tan, and A. Galano. 2014. Melatonin: Exceeding expectations. Physiology (Bethesda) 29: 325–333.
20.
go back to reference Liu, J., F. Huang, and H.W. He. 2013. Melatonin effects on hard tissues: Bone and tooth. International Journal of Molecular Sciences 14: 10063–10074.CrossRefPubMedPubMedCentral Liu, J., F. Huang, and H.W. He. 2013. Melatonin effects on hard tissues: Bone and tooth. International Journal of Molecular Sciences 14: 10063–10074.CrossRefPubMedPubMedCentral
21.
go back to reference Tan, D.X., L.C. Manchester, M.P. Terron, L.J. Flores, and R.J. Reiter. 2007. One molecule, many derivatives: A never-ending interaction of melatonin with reactive oxygen and nitrogen species? Journal of Pineal Research 42: 28–42.CrossRefPubMed Tan, D.X., L.C. Manchester, M.P. Terron, L.J. Flores, and R.J. Reiter. 2007. One molecule, many derivatives: A never-ending interaction of melatonin with reactive oxygen and nitrogen species? Journal of Pineal Research 42: 28–42.CrossRefPubMed
22.
go back to reference Akkus, O., R.M. Belaney, and P. Das. 2005. Free radical scavenging alleviates the biomechanical impairment of gamma radiation sterilized bone tissue. Journal of Orthopaedic Research 23: 838–845.CrossRefPubMed Akkus, O., R.M. Belaney, and P. Das. 2005. Free radical scavenging alleviates the biomechanical impairment of gamma radiation sterilized bone tissue. Journal of Orthopaedic Research 23: 838–845.CrossRefPubMed
23.
go back to reference Leppanen, O., H. Sievanen, J. Jokihaara, I. Pajamaki, and T.L. Jarvinen. 2006. Three-point bending of rat femur in the mediolateral direction: Introduction and validation of a novel biomechanical testing protocol. Journal of Bone and Mineral Research 21: 1231–1237.CrossRefPubMed Leppanen, O., H. Sievanen, J. Jokihaara, I. Pajamaki, and T.L. Jarvinen. 2006. Three-point bending of rat femur in the mediolateral direction: Introduction and validation of a novel biomechanical testing protocol. Journal of Bone and Mineral Research 21: 1231–1237.CrossRefPubMed
24.
go back to reference Akkus, O., F. Adar, and M.B. Schafflerc. 2004. Age-related changes in physicochemical properties of mineral crystals are related to impaired mechanical function of cortical bone. Bone 34: 443–453.CrossRefPubMed Akkus, O., F. Adar, and M.B. Schafflerc. 2004. Age-related changes in physicochemical properties of mineral crystals are related to impaired mechanical function of cortical bone. Bone 34: 443–453.CrossRefPubMed
25.
go back to reference Corwin, S.C. 2001. Bone mechanics handbook, 2nd ed, 7-1–7-26. New York: CRC Press LLC. Corwin, S.C. 2001. Bone mechanics handbook, 2nd ed, 7-1–7-26. New York: CRC Press LLC.
26.
go back to reference Brzoska, M.M., K. Majewska, and J. Moniuszko-Jakoniuk. 2005. Mechanical properties of femoral diaphysis and femoral neck of female rats chronically exposed to various levels of cadmium. Calcified Tissue International 76: 287–298.CrossRefPubMed Brzoska, M.M., K. Majewska, and J. Moniuszko-Jakoniuk. 2005. Mechanical properties of femoral diaphysis and femoral neck of female rats chronically exposed to various levels of cadmium. Calcified Tissue International 76: 287–298.CrossRefPubMed
27.
go back to reference Shirazi, A., G. Ghobadi, and M. Ghazi-Khansari. 2007. A radiobiological review on melatonin: A novel radioprotector. Journal of Radiation Research 48: 263–272.CrossRefPubMed Shirazi, A., G. Ghobadi, and M. Ghazi-Khansari. 2007. A radiobiological review on melatonin: A novel radioprotector. Journal of Radiation Research 48: 263–272.CrossRefPubMed
28.
go back to reference Yavuz, M.N., A.A. Yavuz, C. Ulku, et al. 2003. Protective effect of melatonin against fractionated irradiation-induced epiphyseal injury in a weanling rat model. Journal of Pineal Research 35: 288–294.CrossRefPubMed Yavuz, M.N., A.A. Yavuz, C. Ulku, et al. 2003. Protective effect of melatonin against fractionated irradiation-induced epiphyseal injury in a weanling rat model. Journal of Pineal Research 35: 288–294.CrossRefPubMed
29.
go back to reference Karslioglu, I., M.V. Ertekin, S. Taysi, et al. 2005. Radioprotective effects of melatonin on radiation-induced cataract. Journal of Radiation Research 46: 277–282.CrossRefPubMed Karslioglu, I., M.V. Ertekin, S. Taysi, et al. 2005. Radioprotective effects of melatonin on radiation-induced cataract. Journal of Radiation Research 46: 277–282.CrossRefPubMed
30.
go back to reference Sener, G., A.O. Sehirli, M. Keyer-Uysal, S. Arbak, Y. Ersoy, and B.C. Yeğen. 2002. The protective effect of melatonin on renal ischemia-reperfusion injury in the rat. Journal of Pineal Research 32: 120–126.CrossRefPubMed Sener, G., A.O. Sehirli, M. Keyer-Uysal, S. Arbak, Y. Ersoy, and B.C. Yeğen. 2002. The protective effect of melatonin on renal ischemia-reperfusion injury in the rat. Journal of Pineal Research 32: 120–126.CrossRefPubMed
31.
go back to reference Reiter, R.J., D.X. Tan, M.P. Terron, L.J. Flores, and Z. Czarnocki. 2007. Melatonin and its metabolites: New findings regarding their production and their radical scavenging actions. Acta Biochimica Polonica 54: 1–9.PubMed Reiter, R.J., D.X. Tan, M.P. Terron, L.J. Flores, and Z. Czarnocki. 2007. Melatonin and its metabolites: New findings regarding their production and their radical scavenging actions. Acta Biochimica Polonica 54: 1–9.PubMed
32.
go back to reference Reiter, R.J., J.R. Calvo, M. Karbownik, W. Qi, and D.X. Tan. 2000. Melatonin and its relation to the immune system and inflammation. Annals of the New York Academy of Sciences 917: 376–386.CrossRefPubMed Reiter, R.J., J.R. Calvo, M. Karbownik, W. Qi, and D.X. Tan. 2000. Melatonin and its relation to the immune system and inflammation. Annals of the New York Academy of Sciences 917: 376–386.CrossRefPubMed
33.
go back to reference Sánchez, A., A.C. Calpena, and B. Clares. 2015. Evaluating the oxidative stress in inflammation: Role of melatonin. International Journal of Molecular Sciences 16: 16981–17004.CrossRefPubMedPubMedCentral Sánchez, A., A.C. Calpena, and B. Clares. 2015. Evaluating the oxidative stress in inflammation: Role of melatonin. International Journal of Molecular Sciences 16: 16981–17004.CrossRefPubMedPubMedCentral
34.
go back to reference Green, D.E., and C.T. Rubin. 2014. Consequences of irradiation on bone and marrow phenotypes, and its relation to disruption of hematopoietic precursors. Bone 63: 87–94.CrossRefPubMed Green, D.E., and C.T. Rubin. 2014. Consequences of irradiation on bone and marrow phenotypes, and its relation to disruption of hematopoietic precursors. Bone 63: 87–94.CrossRefPubMed
35.
go back to reference Taylor, A.C., M. Horvat-Gordon, A. Moore, and P.A. Bartell. 2013. The effects of melatonin on the physical properties of bones and egg shells in the laying hen. PLoS One 8, e55663.CrossRefPubMedPubMedCentral Taylor, A.C., M. Horvat-Gordon, A. Moore, and P.A. Bartell. 2013. The effects of melatonin on the physical properties of bones and egg shells in the laying hen. PLoS One 8, e55663.CrossRefPubMedPubMedCentral
36.
go back to reference Burr, D.B. 2002. The contribution of the organic matrix to bone’s material properties. Bone 31: 8–11.CrossRefPubMed Burr, D.B. 2002. The contribution of the organic matrix to bone’s material properties. Bone 31: 8–11.CrossRefPubMed
37.
go back to reference Turner, C.H. 2002. Biomechanics of bone: Determinants of skeletal fragility and bone quality. Osteoporosis International 13: 97–104.CrossRefPubMed Turner, C.H. 2002. Biomechanics of bone: Determinants of skeletal fragility and bone quality. Osteoporosis International 13: 97–104.CrossRefPubMed
38.
go back to reference Turner, C.H., and D.B. Burr. 2001. Experimental techniques for bone mechanics. In Bone mechanics handbook, ed. S.C. Cowin. Boca Raton: CRC Press. Turner, C.H., and D.B. Burr. 2001. Experimental techniques for bone mechanics. In Bone mechanics handbook, ed. S.C. Cowin. Boca Raton: CRC Press.
39.
go back to reference Suzuki, N., M. Somei, A. Seki, R.J. Reiter, and A. Hattori. 2008. Novel bromomelatonin derivatives as potentially effective drugs to treat bone diseases. Journal of Pineal Research 45: 229–234.CrossRefPubMed Suzuki, N., M. Somei, A. Seki, R.J. Reiter, and A. Hattori. 2008. Novel bromomelatonin derivatives as potentially effective drugs to treat bone diseases. Journal of Pineal Research 45: 229–234.CrossRefPubMed
40.
go back to reference Ostrowska, Z., B. Kos-Kudla, B. Marek, et al. 2002. The influence of pinealectomy and melatonin administration on the dynamic pattern of biochemical markers of bone metabolism in experimental osteoporosis in the rat. Neuro Endocrinology Letters 23: 104–109.PubMed Ostrowska, Z., B. Kos-Kudla, B. Marek, et al. 2002. The influence of pinealectomy and melatonin administration on the dynamic pattern of biochemical markers of bone metabolism in experimental osteoporosis in the rat. Neuro Endocrinology Letters 23: 104–109.PubMed
41.
go back to reference Gürgül, S., N. Erdal, S.N. Yilmaz, A. Yildiz, and H. Ankarali. 2008. Deterioration of bone quality by long-term magnetic field with extremely low frequency in rats. Bone 42: 74–80.CrossRefPubMed Gürgül, S., N. Erdal, S.N. Yilmaz, A. Yildiz, and H. Ankarali. 2008. Deterioration of bone quality by long-term magnetic field with extremely low frequency in rats. Bone 42: 74–80.CrossRefPubMed
Metadata
Title
Melatonin can Ameliorate Radiation-Induced Oxidative Stress and Inflammation-Related Deterioration of Bone Quality in Rat Femur
Authors
Zelal Ünlü Çakir
Can Demirel
Sevil Cagiran Kilciksiz
Serkan Gürgül
S. Burhanedtin Zincircioğlu
Nurten Erdal
Publication date
01-06-2016
Publisher
Springer US
Published in
Inflammation / Issue 3/2016
Print ISSN: 0360-3997
Electronic ISSN: 1573-2576
DOI
https://doi.org/10.1007/s10753-016-0347-x

Other articles of this Issue 3/2016

Inflammation 3/2016 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.