Glucan Improves Impaired Wound Healing in Diabetic Rats

Login to Download
PDF version
Author(s): 
Mehmet A. Gulcelik, MD; Halil Dincer, MD; Duygu Sahin, Msc; Omer Faruk Demir, MD; Erdinc Yenidogan, MD; Haluk Alagol, MD

Abstract: Purpose. Diabetes mellitus (DM) is a contributing factor to impaired wound healing in humans. A large body of evidence indicates that the diabetic state is associated with delayed or reduced wound repair capacity. The present study was designed to evaluate the efficacy of glucan on improving abdominal wall wound healing in rats with DM. Methods. Ninety-six female, Sprague-Dawley rats that weighed between 250 g and 300 g were used. A laparotomy was performed on all of the rats on the 14th day. Twenty-four healthy rats (group 1) served as the control. Streptozotocin was used to induce DM in groups 2 and 3 (n = 48). Rats in group 3 received glucan (n = 24). Rats in group 4 were not rendered with DM but received glucan (n = 24). The sutures were removed and abdominal bursting pressure was measured and recorded on the seventh postoperative day for all of the groups. Tissue samples were taken from the incision line for histopathological evaluation and hydroxyproline measurement. Results. In group 2, the bursting pressure was significantly lower than in groups 1, 3, and 4; the hydroxyproline content and histopathological evaluations also supported these findings. Conclusion. These results demonstrate that glucan improves impaired wound healing in rats with DM.



Address correspondence to:
Mehmet A. Gulcelik, MD
41. cadde 12/34
06520 Cukurambar, Ankara
Turkey
Phone: +90 532 745 22 14
Email: mgulcelik@yahoo.com



     Diabetes mellitus (DM) is a contributing factor to impaired wound healing in humans.1,2 A large body of evidence indicates that the diabetic state is associated with delayed or reduced wound repair capacity. Experimental studies of streptozotocin-induced or genetically diabetic rodents have demonstrated that cutaneous wound strength is decreased,3,4 and that the gastrointestinal tract appears to be similarly affected.5

     Beta-D-glucan is a commonly used macrophage activator and has been shown to improve normal anastomotic wound healing.1 It is a glucose polymer that is derived from yeast, which is employed as an immune stimulant in clinical studies.1 Systemic administration of beta-D-glucan promotes wound healing by increasing macrophage infiltration into the wound environment, thereby stimulating collagen synthesis and re-epithelization. Topical and systemic administration of beta glucan enhances wound healing by increasing macrophage infiltration into the wound area, and by stimulating tissue granulation, collagen deposition, re-epithelization, and tensile strength.6 Beta-D-glucan causes no serious side effects; it is inexpensive and can be safely used in patients.7 Cerci et al6 have reported that both topical and systemic beta glucan administration significantly improved wound-healing activity; systemic administration was more effective than topical application.

     Macrophages play an important role in the wound healing process by producing humoral factors and increasing fibroplasia, fibrogenesis, and angiogenesis in the wounded tissue. A decrease in the functionality of macrophages has been shown to impair wound healing and can be observed in DM.8–10 Similarly, enhanced macrophage function and an injection of macrophages into the wound have been demonstrated to accelerate wound healing.10

Methods

     This study used 96 female Sprague-Dawley rats that each weighed between 250 g–300 g. The animals were brought to the facility 24 hours before the operation. Each animal was placed in its own cage to adapt to the laboratory conditions.

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.