Glucan Improves Impaired Wound Healing in Diabetic Rats

1/1/2010
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Author(s):

Mehmet A. Gulcelik, MD; Halil Dincer, MD; Duygu Sahin, Msc; Omer Faruk Demir, MD; Erdinc Yenidogan, MD; Haluk Alagol, MD

Neoangiogenesis might maintain blood supply, thereby preventing wound ischemia. Thus, these factors alone or in combination can mediate the beneficial effects of beta-D-glucan on anastomotic wound healing.

In the present study, the mean values for bursting pressures and hydroxyproline levels of group 2, which is the group that was induced with DM but did not receive a glucan treatment, were lower than the other groups. These results correlate with previous studies.^3,29 The monocytes and thrombocytes play an important role in wound healing—they secrete cytokines that are chemotactic for fibroblasts, which synthesize collagen. A decrease in these blood members causes a decrease in wound fibroblast stimulation and lower collagen synthesis. Earlier reports further support our results and indicate that the hydroxyproline levels decreased in the DM group that did not receive glucan (group 2). Hydroxyproline, a nonessential amino acid, is the major component of extracellular tissue. It provides strength and support, and acts as an indicator of the amount of collagen in a tissue sample. The measurement of the hydroxyproline is acceptable as an index for collagen turnover. In the present study, DM significantly decreased the hydroxyproline content of the wound when compared to that of the control group; the beta glucan treatment increased hydroxyproline levels. The reason for this is an increase of collagen synthesis, which is a secondary reaction to the stimulation of cell infiltration by glucan.

Bursting pressure and tension strength are acceptable methods to test the mechanical durability of wound healing.^30–32 Bursting pressure was chosen because it is more closely related to physiological conditions. When bursting pressures were evaluated, the bursting pressure for the groups that received the glucan treatment was higher than that of the control group. The increased neovascularization, decreased necrosis, and increased inflammatory response in the histopathological examination of the groups that received the glucan treatment supports these findings. The results of the histopathology of the groups that received the glucan treatment correlate previous findings.²⁹ Beta-D-glucan stimulates macrophage synthesis and promotes wound healing by increasing macrophage infiltration into the wound environment, and stimulate collagen synthesis and re-epithelization. These factors alone or in combination may play a role in the effects glucan has on improving incisional wound healing.

Conclusion

Experimental studies provide only a general basis for clinical approaches, and the results of experimental studies cannot be directly applied to clinical protocols. However, the present study is a foundation for future clinical and experimental studies. Impaired abdominal wall wound healing in patients with DM can be improved by glucan, but further studies are needed to establish its clinical application.

References:

1. Goodson WH III, Hunt TK. Wound healing and the diabetic patient. Surg Gynecol Obstet. 1979;149(4):600–608.
2. Cruse PJ, Foord R. A five-year prospective study of 23,649 surgical wounds. Arch Surg. 1973;107(2):206–210.
3. Schäffer MR, Tantry U, Efron PA, Ahrendt GM, Thornton FJ, Barbul A. Diabetes- impaired healing and reduced wound nitric oxide synthesis: a possible pathophysiologic correlation. Surgery. 1997;121(5):513–519.
4. Greenwald DP, Shumway S, Zachary LS, et al. Endogenous versus toxin-induced diabetes in rats: a mechanical comparison of two skin wound-healing models. Plast Reconstr Surg. 1993;91(6):1087–1093.
5. Gottrup F, Andreassen TT. Healing of incisional wounds in stomach and duodenum: the influence of experimental diabetes. J Surg Res. 1981;31(1):61–68.
6. Cerci C, Yildirim M, Ceyhan M, Bozkurt S, Doguc D, Gokicimen A. The effects of topical and systemic beta glucan administration on wound healing impaired by corticosteroids. WOUNDS. 2008;20(12):341–346.
7. Cheung NK, Modak S. Oral (1→3),(1→4)-beta-glucan synergizes with antiganglioside GD2 Monoclonal antibody 3F8 in the therapy of neuroblastoma. Clin Cancer Res. 2002;8(5):1217–1223.
8. Zuloff-Shani A, Kachel E, Frenkel O, Orenstein A, Shinar E, Danon D. Macrophages suspensions prepared from a blood unit for treatment of refractory human ulcers. Transfus Apheresis Sci. 2004;30(2):163–167.
9. Compton R, Williams D, Browder W. The beneficial effect of enhanced macrophage function on the healing of bowel anastomoses. Am Surg. 1996;62(1):14–18.
10. Browder W, Williams D, Lucore P, Pretus H, Jones E, McNamee R. Effect of enhanced macrophage function on early wound healing. Surgery. 1988;104(2):224–230.
11. National Research Council. Institute of Laboratory Animal Resources Commission on Life Sciences. Washington, DC: National Academy Press; 1996.
12. Seyer-Hansen M, Andreassen TT, Oxlund H. Strength of colonic anastomoses and skin incisional wounds in old rats—influence by diabetes and growth hormone. Growth Horm IGF Res. 1999;9(4):254–261.
13. Atkinson JB, Kosi M, Srikanth MS, Takano K, Costin G. Growth hormone reverses impaired wound healing in protein-malnourished rats treated with corticosteroids. J Pediatr Surg. 1992;27(8):1026–1028.
14. Zaizen Y, Ford EG, Costin G, Atkinson JB. The effect of perioperative exogenous growth hormone on wound bursting strength in normal and malnourished rats. J Pediatr Surg. 1990;25(1):70–74.
15. Bergman I, Loxley R. Two improved and simplified methods for the spectrophotometric determination of hydroxyproline. Ann Chem. 1963;35:1961–1965.
16. Verhofstad MH, Lomme RM, de Man BM, Hendriks T. Intestinal anastomoses from diabetic rats contain supranormal levels of gelatinase activity. Dis Colon Rectum. 2002;45(4):554–561.
17. Greenwald DP, Shumway S, Zachary LS, et al. Endogenous versus toxin-induced diabetes in rats: a mechanical comparison of two skin wound-healing models. Plast Reconstr Surg. 1993;91(6):1087–1093.
18. Takeuchi T, Takehara K, Tajima T, Kato S, Hirata T. Impaired healing of gastric lesions in streptozotocin-induced diabetic rats: Effect of basic fibroblast growth factor. J Pharmacol Exp Ther. 1997;281(1):200–207.
19. Enser M, Avery NC. Mechanical and chemical properties of the skin and its collagen from lean and obese-hyperglycaemic mice. Diabetologia. 1984;27:44–49.
20. Leibovich S, Ross R. The role of macrophages in wound repair. A study with hydrocortisone and antimacrophage serum. Am J Pathol. 1975;78(1):71–100.
21. Diegelmann RF, Cohen IK, Kaplan AM. The role of macrophages in wound repair: a review. Plast Reconstr Surg. 1981;68(1):107–113.
22. Browder W, Williams D, Lucore P, Pretus H, Jones E, McNamee R. Effect of enhanced macrophage function on early wound healing. Surgery. 1988;104(2):224–230.
23. Williams DL, Sherwood ER, McNamee RB, Jones EL, Browder IW, Di Luzio NR. Chemoimmunotherapy of experimental hepatic metastases. Hepatology. 1987;7(6):1296–1304.
24. Portera CA, Love EJ, Memore L, et al. Effect of macrophage stimulation on collagen biosynthesis in the healing wound. Am Surg. 1997;63(2):125–131.
25. Burgaleta C, Golde DW. Effect of glucan on granulopoiesis and macrophage genesis in mice. Cancer Res. 1977;37(6):1739–1742.
26. Burgaleta C, Territo MC, Quan SG, Golde DW. Glucan-activated macrophages: functional characteristics and surface morphology. J Reticuloendothel Soc. 1978;23(3):195–204.
27. Battle J, Ha T, Li C, et al. Ligand binding to the (1 --> 3)-beta-D-glucan receptor stimulates NFkappaB activation, but not apoptosis in U937 cells. Biochem Biophys Res Commun. 1998;249(2):499–504.
28. Wei D, Zhang L, Williams DL, Browder IW. Glucan stimulates human dermal fibroblast collagen biosynthesis through a nuclear factor-1 dependent mechanism. Wound Repair Regen. 2002;10(3):161–168.
29. Dinc S, Durmus E, Gulcelik MA. Effects of beta-D-glucan on steroid-induced impairment of colonic anastomotic healing. Acta Chir Belg. 2006;106(1):63–67.
30. Atkinson JB, Kosi M, Srikanth MS, Takano K, Costin G. Growth hormone reverses impaired wound healing in protein-malnourished rats treated with corticosteroids. J Pediatr Surg. 1992;27(8):1026–1028.
31. Zaizen Y, Ford EG, Costin G, Atkinson JB. The effect of perioperative exogenous growth hormone on wound bursting strength in normal and malnourished rats. J Pediatr Surg. 1990;25(1):70–74.
32. Koruda MJ, Rolandelli RH. Experimental studies on the healing of colonic anastomoses, current research review. J Surg Res. 1990;48(5):504–515.