Bülent BAKAR, Önder BOZDOĞAN, Tarık ÇAVUŞOĞLU, Elif SARI, Bahram SARKARATI

The effect of low-dose methotrexate on autologous fat graft survival

Background/aim: The survival of autologous fat graft tissue is dependent on various factors such as vascularization and inflammation. The aim of the present study was to evaluate the possible beneficial effects of low-dose methotrexate (LD-MTX) on fat graft volume and survival. Materials and methods: A total of 13 male Wistar albino rats were divided into two groups, a control group and an LD-MTX group. An autologous fat graft obtained from the inguinal region of each rat was transferred to its back. LD-MTX was administered intraperitoneally in the LD-MTX group once a week for 4 weeks after the surgical procedure. The control group underwent surgery but was not administered MTX. Fat grafts were harvested for analyses. Results: The results showed that 2 months postoperatively the fat graft weights of the control and LD-MTX groups were not significantly different. In addition, the vascularity of the grafts was higher in the LD-MTX group than it was in the control group. The mean lipid peroxidation levels were essentially the same in the two groups, but myeloperoxidation was significantly lower in the LD-MTX group than it was in the other group. Conclusion: The results showed that LD-MTX administration may not preserve the quality and volume of transplanted fat tissue in rats.

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1. Coleman SR. Structural fat grafts: the ideal filler? Clin Plast Surg 2001; 28: 111-119.
2. Coleman SR. Structural fat grafting: more than a permanent filler. Plast Reconstr Surg 2006; 118 (Suppl. 3): 108S-120S.
3. Bishop A, Hong P, Bezuhly M. Autologous fat grafting for the treatment of velopharyngeal insufficiency: state of the art. J Plast Reconstr Aesthet Surg 2014; 67: 1-8.
4. Liao HT, Marra K, Rubin PJ. Application of platelet-rich plasma and platelet-rich fibrin in fat grafting: basic science and literature review. Tissue Eng Part B Rev 2014; 20: 267-276.
5. Nishimura T, Hashimoto H, Nakanishi I, Furukama M. Microvascular angiogenesis and apoptosis in the survival of free fat grafts. Laryngoscope 2000; 110: 1333-1338.
6. Topcu A, Aydin OE, Ünlü M, Barutcu A, Atabey A. Increasing the viability of fat grafts by vascular endothelial growth factor. Arch Facial Plast Surg. 2012; 14: 270-276.
7. Rodríguez-Flores J, Palomar-Gallego MA, Enguita-Valls AB, Rodríguez-Peralto JL, Torres J. Influence of platelet-rich plasma on the histologic characteristics of the autologous fat graft to the upper lip of rabbits. Aesthetic Plast Surg. 2011; 35: 480-486.
8. Yang M, Zhang F, Sailes FC, Zhang EW, Lin S, Das SK. Role of anti-TNF-α therapy in fat graft preservation. Ann Plast Surg. 2012; 68: 531-535.
9. Cronstein BN, Naime D, Ostad E. The antiinflammatory mechanism of methotrexate. Increased adenosine release at inflamed sites diminishes leukocyte accumulation in an in vivo model of inflammation. J Clin Invest 1993; 92: 2675-2682.
10. Imamura M, Hashino S, Kobayashi H, Kubayashi S, Hirano S, Minagawa T, Tanaka J, Fujii Y, Kobayashi M, Kasai M et al. Serum cytokine levels in bone marrow transplantation: synergistic interaction of interleukin-6, interferon-γ, and tumor necrosis factor-α in graft-versus-host disease. Bone Marrow Transplant 1994; 13: 745-751.
11. Montesinos MC, Takedachi M, Thompson LF, Wilder TF, Fernández P, Cronstein BN. The antiinflammatory mechanism of methotrexate depends on extracellular conversion of adenine nucleotides to adenosine by ecto-5-nucleotidase: findings in a study of ecto-5-nucleotidase gene-deficient mice. Arthritis Rheum 2007; 56: 1440-1445.
12. Mihara M, Uchiyama M. Determination of malonaldehyde precursor in tissues by thiobarbituric acid test. Anal Biochem 1977; 86: 271-278.
13. Suzuki K, Ota H, Sasagawa S, Sakatani T, Fujikura T. Assay method for myeloperoxidase in human polymorphonuclear leucocytes. Anal Biochem 1982; 127: 346-350.
14. Katchamart W, Trudeau J, Phumethum V, Bombardier C. Efficacy and toxicity of methotrexate (MTX) monotherapy versus MTX combination therapy with non-biological diseasemodifying antirheumatic drugs in rheumatoid arthritis: a systematic review and meta-analysis. Ann Rheum Dis 2009; 68: 1105-1112.
15. Chan ES, Cronstein BN. Molecular action of methotrexate in inflammatory diseases. Arthritis Res 2002; 4: 266-273.
16. Storb R, Deeg HJ, Whitehead J, Appelbaum F, Beatty P, Bensinger W, Buckner CD, Clift R, Doney K, Farewell V. Methotrexate and cyclosporine compared with cyclosporine alone for prophylaxis of acute graft versus host disease after marrow transplantation for leukemia. N Engl J Med 1986; 314: 729-735.
17. Nguyen A, Pasyk KA, Bouvier TN, Hassett CA, Argenta LC. Comparative study of survival of autologous adipose tissue taken and transplanted by different techniques. Plast Reconstr Surg 1990; 85: 378-386.
18. Billings E, May JW Jr. Historical review and present status of free fat graft autotransplantation in plastic and reconstructive surgery. Plast Reconstr Surg. 1989; 83: 368-381.
19. Nishimura T, Hashimoto H, Nakanishi I, Furukawa M. Microvascular angiogenesis and apoptosis in the survival of free fat grafts. Laryngoscope 2000; 110: 1333-1338.
20. Bartynski J, Marion M, Wang T. Histopathologic evaluation of adipose autografts in a rabbit ear model. Otolaryngol Head Neck Surg 1990; 102: 314-321.
21. Kanner J, German JB, Kinsella JE. Initiation of lipid peroxidation in biological systems. Crit Rev Food Sci Nutr. 1987; 25: 317-364.
22. Farber JL. Mechanisms of cell injury by activated oxygen species. Environ Health Perspect 1994; 102 (Suppl. 10): 17-24.
23. Bakar B, Köse EA, Kupana Ayva S, Sarkarati B, Kasımcan MO, Kılınç K. Effects of low-dose methotrexate in spinal cord injury in rats. Ulus Travma Acil Cerrahi Derg 2013; 19: 285-293.
24. Sanli AM, Serbes G, Sargon MF, Calişkan M, Kilinç K, Bulut H, Sekerci Z. Methothrexate attenuates early neutrophil infiltration and the associated lipid peroxidation in the injured spinal cord but does not induce neurotoxicity in the uninjured spinal cord in rats. Acta Neurochir (Wien) 2012;154: 1045- 1054.
25. Eto H, Suga H, Matsumoto D, Inoue D, Aoi N, Kato H, Araki J, Yoshimure K. Characterization of structure and cellular components of aspirated and excised adipose tissue. Plast Reconstr Surg. 2009;124: 1087-1097.