Effect of alpha2-macroglobulin on osteoradionecrosis of mandible in rats

doi:10.19438/j.cjoms.2018.02.006

Abstract

Abstract: PURPOSE: To investigate the effect of alpha2-macroglobulin (α2M) injected before irradiation on mandibular osteoradionecrosis (ORN) in rats. METHODS: Eighteen male Sprague-Dawley rats were divided randomly into 3 groups: group A (control group), group B (radiotherapy alone) and group C (α2M applied 30 minutes before radiotherapy). All the rats were fixed by 3D-printed fixator after anesthesia. Rats in group B and C underwent 7 Gy irradiation for 5 days to the left hemimandible; at the same time, rats in group A underwent shame irradiation. Rats in group C were injected 0.5 mL 2000 mg/L α2M in sterile saline solution along the left mandible, and rats in group A and group B were injected 0.5mL sterile normal saline. Seven days after irradiation, all left molar teeth were extracted. 21days later, the rats were sacrificed and the left mandible were examined by gross manifestation, microcomputed tomography, and histology. SPSS 13.0 software package was used for statistical analysis. RESULTS: Compared with group A, 5 rats in group B developed mandibular ORN. On gross observation, serious weight loss, alopecia of the irradiated skin, oral ulcer and occlusive disorder were seen in the rats of group B. Lack of new bone formation within the socket was seen on Micro-CT three-dimensional reconstruction. Haematoxylin-eosin and Masson's staining showed that inflammations, necrosis, and fibrosis in the medulla. The rate of mandibular ORN in group was 5/6. However, the rats in group C exhibited less weight loss, alopecia and no occlusive disorder, and slight inflammation in the bone marrow. The cortical bone was close to the normal bone on Micro-CT . The rate of osteocytic lacunae was decreased compared with group B (P<0.001). The rate of mandibular ORN in group C was zero. CONCLUSIONS: Application of α2M before radiotherapy could well prevent mandibular ORN and had a good application prospects.

Key words: Alpha2-macroglobulin, Rat, Osteoradionecrosis

CLC Number:

R782.2

LI Jie, KONG Xiang-bo, CHEN Xue-ying, LIU Yang, ZHONG Wan-zhen, FANG Si-lian. Effect of alpha2-macroglobulin on osteoradionecrosis of mandible in rats[J]. China Journal of Oral and Maxillofacial Surgery, 2018, 16(2): 126-131.

References

[1] Sciubba JJ, Goldenberg D.Oral complications of radiotherapy[J]. Lancet Oncol, 2006, 7(2): 175-183.
[2] Lyons A, Ghazali N.Osteoradionecrosis of the jaws: current understanding of its pathophysiology and treatment[J]. Br J Oral Maxillofac Surg, 2008, 46(8): 653-660.
[3] Shaw R, Tesfaye B, Bickerstaff M, et al.Refining the definition of mandibular osteoradionecrosis in clinical trials: The cancer research UK HOPON trial (hyperbaric oxygen for the prevention of osteoradionecrosis)[J]. Oral Oncol, 2017, 64(1): 73-77.
[4] Lyons AJ, Brennan PA.Pentoxifylline - a review of its use in osteoradionecrosis[J]. Br J Oral Maxillofac Surg, 2017, 55(3): 230-234.
[5] Fang SL, Kong XB, Chen W, et al.Proteomic analysis of serum in patients with osteoradionecrosis of the jaws[J]. Int Dent J, 2012, 62(S1):24.
[6] Fang SL, Chen W, Wang SY, et al.Identification of differential proteins that related to bone metabolism in the serum of ORNJ patients[J]. Int Dent J, 2012, 62(S1):25.
[7] Uskokovic A, Dinic S, Mihailovic M, et al.STAT3/NFkappaB interplay in the regulation of alpha2-macroglobulin gene expression during rat liver development and the acute phase response[J]. IUBMB Life, 2007, 59(3): 170-178.
[8] 刘仰, 孔祥波, 李洁, 等. α2巨球蛋白减轻X射线所致人骨髓间充质干细胞成骨分化障碍[J]. 中国病理生理杂志, 2017, 33(11): 2032-2037.
[9] Monson LA, Jing XL, Donneys A, et al.Dose-response effect of human equivalent radiation in the mandible[J]. J Craniofac Surg, 2013, 24(5): 1593-1598.
[10] Lyons A, Osher J, Warner E, et al.Osteoradionecrosis--a review of current concepts in defining the extent of the disease and a new classification proposal[J]. Br J Oral Maxillofac Surg, 2014, 52(5): 392-395.
[11] Rivero JA, Shamji O, Kolokythas A.Osteoradionecrosis: a review of pathophysiology, prevention and pharmacologic management using pentoxifylline, alpha-tocopherol, and clodronate[J]. Oral Surg Oral Med Oral Pathol Oral Radiol, 2017, 124(5): 464-471.
[12] Raguse JD, Hossamo J, Tinhofer I, et al. Patient and treatment-related risk factors for osteoradionecrosis of the jaw in patients with head and neck cancer [J]. Oral Surg Oral Med Oral Pathol Oral Radiol, 2016, 121(3): 215-221.e1.
[13] Blery P, Espitalier F, Hays A, et al.Development of mandibular osteoradionecrosis in rats: Importance of dental extraction[J]. J Craniomaxillofac Surg, 2015, 43(9): 1829-1836.
[14] Manzon L, Rossi E, Fratto G.Management of osteonecrosis of the jaws induced by radiotherapy in oncological patients: preliminary results[J]. Eur Rev Med Pharmacol Sci, 2015, 19(2): 194-200.
[15] Rehman AA1, Zaman M2, Zia MK, et al. Conformational behavior of alpha-2-macroglobulin:Aggregation and inhibition induced by TFE[J]. Int J Biol Macromol, 2017, 104(Pt A): 539-546.
[16] Siddiqui T, Zia MK, Ali SS, et al.Reactive oxygen species and anti-proteinases[J]. Arch Physiol Biochem, 2016,122(1): 1-7.
[17] Chen X, Kong X, Zhang Z, et al.Alpha-2-macroglobulin as a radioprotective agent: a review[J]. Chin J Cancer Res, 2014, 26(5): 611-621.
[18] Bogojevic D, Poznanovic G, Grdovic N, et al.Administration of rat acute-phase protein alpha(2)-macroglobulin before total-body irradiation initiates cytoprotective mechanisms in the liver[J]. Radiat Environ Biophys, 2011, 50(1): 167-179.
[19] Mirjana M, Goran P, Nevena G, et al.The rat acute-phase protein alpha2-macroglobulin plays a central role in amifostine-mediated radioprotection[J]. J Radiol Prot, 2010, 30(3): 567-583.
[20] Wang Y, Zhu G, Wang J, et al.Irradiation alters the differentiation potential of bone marrow mesenchymal stem cells[J]. Mol Med Rep, 2016, 13(1): 213-223.