Diyabetik Yaraların İyileşmesinde Bazı Glikozaminoglikan Maddelerin (Kitosan ve Hyaluronan) Etkilerinin Karşılaştırılması

Bu çalışma, diyabetik yaralarda kitosan ve hyaluronanın etkilerinin karşılaştırılmasını amaçladı. Çalışma toplam kırk Yeni Zelanda tavşanı üzerinde yürütüldü. Tavşanlarda diyabet iki gün arayla iki defa 60 mg/kg dozda alloxan monohidrat uygulaması ile oluşturuldu. Anestezi altında tüm hayvanların bel bölgesinde iki adet 2 cm çapında dairesel tam kat deri yarası oluşturuldu. Çalışma grubundaki hayvanların yaralarından bir tanesine hyaluronan diğerine ise kitosan uygulandı. Post operatif 3., 6., 9., 11. ve 15. günlerde yara iyileşmesi makroskobik ve histopatolojik olarak incelendi ve yara kontraksiyon oranları ölçüldü. Sonuç olarak, ilk on günde kitosanın daha sonraki günlerde ise hyaluronanın diyabetli yara iyileşmesine olumlu katkı sağladıkları saptandı.

Comparison on the Effects of Some Glicosaminogylican Derives (Chitosan and Hyaluronan) in Diabetic Wound Healing

This study aimed to compare the effects of chitosan and hyaluronan on diabetic wounds. The study was conducted on forty New Zealand rabbits. Diabetes was created in rabbits by injection of 60mg/kg alloxan monohydrate intraperitonally twice two daysapart. Under anaesthesia, 2 cm of dimater two full thickness circular skin wounds were created on the lumbal region of all rabbits. Chitosan was aplied to one of the wounds and hyaluronan was aplied to the other wound on animals in experimental group. Wound healing were examined macroscopically and histopathologically and wound contraction rates were measured at postoperative 3th, 6th, 9th, 11th and 15th days. As a conclusion, it is determined that using chitosan in the first ten days and in the subsequent days using hyaluronan contribute positive effects on diabetic wound healing.

PDF

___

1. Menke NB., Ward KR., Witten TM., Bonchev DG., Diegelmann RF., 2007. Impaired wound healing. Clinics in Dermayology, 25,19-25.
2. Galkowska H., Wojewodzka U., Olszewski WL., 2006. Chemokines, cytokines, and growth factors in keratinocytes and dermal endothelial cells in the margin of chronic diabetic foot ulcers. Wound Repair and Regeneration, 14, 558-565.
3. Tan W., Krishnaraj R., Desai TA., 2001. Evaluatin of nanositructured composite collagen-chitosan matrices for tissue engineering. Tissue Engineering, 7, 203-210.
4. Ueno H., Mori T., Fujinaga T., 2001. Topical formulatin and wound healing applications of chitosan. Advanced of Drug Delivery Reviews, 52, 105-115.
5. Şenel S., Mc Clure SJ., 2004. Potential applications of chitosan in veterinary medicine. Advanced of Drug Delivery Reviews, 56, 1467-1480.
6. Ueno Y., Tanaka K., Mitsunobu M., Kadosawa F., 1999. Accelerating effects of chitosan for healing at early phase of experimental open wound in dogs. Biomaterials, 20, 1407-1414.
7. Ishihara M., Ono K., Sato M., Nakanishi K., Saito Y., Yura H., Matsui T., 2001. Acceleration of wound contraction and healing with a photocross linkable chitosan hydrogel. Wound Repair and Regeneration, 9, 513-521.
8. Ishihara M., Fujita M., Obara K., Hattori H., Nakamura S., Nambu M., Kiosawa Y., 2006. Controlled releases of FGF-2 and paclitaxel from chitosan hydrogels and their subsequent effects on wound repair, angiogenesis, and tumor growth. Current Drug Delivery, 3, 351-358.
9. Alemdaroğlu C., Degin Z., Çelebi N., Zor F., Öztürk S., Erdogan D., 2006. An investigation burn wound healing in rats with chitosan gel formulation containing epidermal growth factor. Burns, 32, 319-327.
10. Husseiny IN., Ahmed AK., 2012. Application of chitosan for wound repair in dogs. Life Science Journal, 9, 196-203.
11. Kim MS., Sung MJ., Se SB., Yoo SJ., Lim WK., Kim, HM., 2002. Water-soluble chitosan inhibits the production of proinflammatory cytokine in human astrocytoma cells activated by amyloid-? peptide and interleukin-1?. Neuroscience Letters, 321, 105-109.
12. Tole BP., 1997. Hyaluronan in morphogenesis. Jounal of Internal Medicine, 242, 35-40.
13. Clarris BJ., Fraser JRE., 1968. On the pericellular zone of some mammalian cells invitro. Experimental Cell Research, 49, 181-193.
14. Clarris BJ., Fraser JRE., Rodda SJ., 1974. Effect of cell-bound hyaluronic acide in infectivity of Newcastle virüs for human synovial cells in vitro. Annals of Rheumatic Diseases, 33, 240-242.
15. Kvam BJ., Fragonas E., Degrassi A., Kvam C., Matulova V., 1995. Oxygen derived free radical action on hyaluronan, on two HA ester derivatives, and on the metabolism of chondrocytes. Experimental Cell Research, 218, 79-86.
16. Presti D., Scott JE., 1994. Hyaluronan-mediated protective effect against cell damage caused by enzimatically produced hydroxyl (OH) radicals is depented on hyaluronan molecular mass. Cell Biochemical Functions, 12, 281-288.
17. Davidson JM., Nanney LB., Broadley KN., Whitset JS., Aquino AM., Beccaro M., 1991. Hyaluronate derivates and their application to wound healing: a preliminary observations. Clinical Materals, 8, 171-177.
18. Miller RS., Steward DL., Tami TA., Sillars MJ., Seiden AM., Shete M., Paskowski C., Welge J., 2003. The clinical effects of hyaluronic acid ester nasal dressing on intranasal wound healing after functional endoscopic sinus surgery. Otolaringology-Head and Neck Surgery, 128, 862- 869.
19. Akalan MA., Demirkan AÇ., 2013. Stereoloji ve Veteriner Hekimlikte Kullanım Alanları. Yüzüncü Yıl Üniversitesi Veteriner Fakültesi Dergisi, 24, 95- 100.
20. Jawad HAA., Diab JM., İbraheem KM., 2007. Effect of chitosan sheets on wound healing. The Journal of Veterinary Research, 6, 81-96.
21. Steel RG., Torrie JH., 1980. Principle and procedures of statistics ,2nd Ed., McDonald Book Co, Inc. New York.
22. SAS, 1994. SAS/STAT User's Guide. Statistics., Sas Institute, Cary.
23. Goren I., Muller E., Pfeilschifter J., Frank S., 2006. Severely impaired insulin signaling in chronic wounds of diabetic ob/ob mice: a potential role of tumor necrosis factor-alpha. American Journal of Pathology, 168, 765-777.
24. Galiano RD., 2004. Topical vascular endothelial growth factor accelerates diabetic wound healing through increased angiogenesis and by mobilizing and recruiting bone marrow-derived cells. American Journal of Pathology, 164, 1935-1947.
25. Maruyama K., 2007. Decreased macrophage number and activation lead to reduced lymphatic vessel formation and contribute to impaired diabetic would healing. American Journal of Pathology, 170, 1178-1191.
26. Falanga V., 2005. Wound healing and its impairment in the diabetic foot. Lancet, 366, 1736-1743.
27. Gibran NS., Jang YC., Isik FF., Greenhalgh DG., Muffley LA., Underwood RA., Usui ML., Larsen J., Smith DG., Bunnett N., Ansel JC., Olerud JE., 2002. Diminished neuropeptide levels contribute to the impaired cutaneous healing response associated with diabetes mellitus. The Journal of Surgery Research, 108, 122-128.
28. Brem H., Canic MT., 2007. Cellular and molecular basis of wound healing in diabetes. The Journal of Clinical Investigation, 117, 1219-1222.
29. Etuk EU., 2010. Animals models for studying diabetes mellitus. Agricultural Biological Journal of North American, 1, 130-134.
30. Viana GS., Medeiros AC., Lacerda AM., Leal LK., Vale TG., Matos FJ., 2004. Hypoglycemic and antilipemic effects of the aqueous extract from Cissus sicyoides. BMC Pharmacology, 8, 4-9.
31. Pradhan L., Cai X., Wu S., Andersen N., Martin M., Malek J., Gudhrie P., Veves A., LoGerfo WF., 2011. Gene expression of pro-inflammatory cytokines and neuropeptides in diabetic wound healing. Journal of Surgical Research, 167, 336-342.
32. Wang J., Wan R., Mo Y., Li M., Zhang Q., Chien S., 2010. Inracellular delivery of adenosine triphosphate enhanced healing process in full - thickness skin wounds in diabetic rabbits. The American Journal of Surgery, 199, 823-832.
33. Grinnel F., 1994. Fibroblasts, miyofibroblasts, and wound contraction. The Journal of Cell Biology, 124, 401-404.
34. Okamoto Y., Yano R., Miyatake K., Tomohiro I., Shigemasa Y., Minami S., 2003. Effects of chitin and chitosan on blood coagulation. Carbonhydrate Polymers, 53, 337-342.
35. Baum Cl., Arpey CJ., 2005. Normal cutaneous wound healing: Clinical correlation with cellular and molecular events. Dermatological Surgery, 31, 674-686.
36. Bauer EA., Couper TW., Huang JS., Altman J., Deuel TF., 1985. Stimulation of invitro human skin collagenase expression by platelet-derived growth factor. Proceedings of National Academic Science, 82, 4132-4136.
37. Brisett AE., Hom DB., 2003. The effects of tissue sealands, platelet gels, and growth factors on wound healing. Current Opinion Otolaryngology, Head and Neck Surgery, 11, 245-250.
38. Kim IY., Seo SJ., Moon HS., Yoo MK., Park IY., Kim BC., Cho CS., 2008. Chitosan and its derivatives for tissue engineering applications. Biotechnological Advances, 26, 1-21.
39. Mi FL., Shyu SS., Wu YB., Lee ST., Shyong JY., 2001. Fabrication and caracterization of a sponge-like assimetric chitosan membrane as a wound dressing. Biomaterials, 22, 165-173.
40. Jarmila V., Vavrikova E., 2013. Chitosan derivatives with antimicrobial, antitumour and anti oxidant activities-a review. Current Pharmaceutical Desing, 17, 3596-3607.
41. Ueno H., Nakamura F., Murakami M., Okumura M., Kadosawa T., Fujinaga T., 2001. Evaluation effects of chitosan for the extracelular marrix production by fibroblasts and the growth factors production by macrophages. Biomaterials, 22, 2125-2130.
42. Nishimura K., Ishihara C., Ukei S., Tokura S., Azuma I., 1986. Stimulation of cytokine production in mice using deacetylated chitin. Vaccine, 4, 151-156.
43. Noble P., Lake F., Henson P., Riches D., 1993. Hyaluronate activation of CD44 induces insülinlike grovth factor-1 expression by a tumor necrosis factor-? depended mechanism in murine macrophages. The Journal of Clinical Investigation, 91, 2368-2377.
44. Kobayashi H., Terao T., 1997. Hyaluronic acid - specific regulation of cytokines by human uterine fibroblsts. American Journal of Physiology, 276, 1151-1159.
45. Balasz EA., Denlinger JL., 1989. Clinical uses of hyaluronan. In "The Biology of Hyaluronan" Ed., D Evered., WJ Chichester, 3th ed., 265-280, Willey and Sons Company, Newyork.
46. Chen WYC., Abatangelo G., 1999. Functions of hyaluronan in wound repair. Wound Repair and Regeneration, 7, 79-89.
47. Foschi D., Castoldi L., Radaelli E., Albelli P., Calderini G., Rastrelli A., Mariscotti C., Marazzi M., Trabucchi E., 1990. Hyaluronic acid prevents oxigen fre-radical damage to granulation tissue: A study in rats. International Journal of Tissue Reaction, 12, 333-339.
48. Rooney P., Wang M., Kumar P., Kumar S., 1993. Angiogenic oligosaccarides of hyaluronan enhance the production of collagens by endothelial cells. The Journal of Cell Science, 105, 213-218.
49. Minami S., Okamoto Y., Tanioka S., Sashiwa H., Saimoto H., Matsuhashi A., Shigemasa Y., 1993. Effects of chitosan on wound healing. In "Carbonhydrates and Carbonhydrate Polymers" Ed., M Yalpani., 2nd ed., 141-152 ATL Press.
50. Okamoto Y., Minami S., Matsuhashi A., Sashiwa H., Saimoto H., Shigemasa Y., Tanigwa T., Tanaka Y., 1992. Application of chitin and chitosan in small animals. In "Advances in Chitin and Chitosan". Ed., JJ Brine, PA Standfort., JP Zikakis, 70-78 Elsevier Science, Newyork.
51. Longaker MT., Chiu ES., Adzick NS., Stern M., Harrison MR., Stern R., 1991. A prolonged presence of hyaluronic acid characterizes fetal wound fluid. Annals of Surgery, 213, 292-296.
52. Laurent C., 2009. Hyaluronic acid reduces connective tissue formation in midlle ears filled with absorbable gelatin sponge: An experimental study. American Journal of Otolaryngology, 7, 181-186.
53. West DC., Shaw DM., Lorenz P., Adzick NS., Longaker MT., 1997. Fibrotic healing of adult and late gestation fetal wounds correlates with increased hyaluronidase activity and removal of hyaluronan. International Journal Biochemical Cell Biology, 29, 201-210.
54. Tammi R., Ripellino JA., Margolis RU., Maibach HI., Tammi M., 1989. Hyaluronate accumulation in human epidermis treated with retinoic acid in skin organ cultures. The Journal of Investigations in Dermatology, 92, 326-332.
55. Riches DWH., 1996. Macrophage involvement in wound repair, modelling and fibrosis. In "The Molecular and Cellular Biology of Wound Repair" Ed., RAF Clark, 2.nd ed., 95-142. W.B Saunders Company, Newyork.
56. Robson MC., Steed DL., Franz MG., 2001. Wound healing: Biologic features and approaches to maximize healing trajectories. Currents Problems in Surgery, 38, 65-140.
57. Singer AJ., Clarck RA., 1999. Cutaneous wound healing. The New England Journal of Medicine, 341, 738-746.
58. Zykova SN., 2000. Altered cytokine and nitricoxide secretion in vitro by macrophages from diabetic type-2-like db/db nice. Diabetes, 49, 1451-1458.
59. Li J., Juan J., Kirsner R., 2007. Pathophysiology of acute wound healing. Clinics in Dermatology, 25, 9-18.
60. Witte SH., Olaifa AK., Lewis AJ., Eggleston RB., Halper J., Kietzmann M., 2009. Application of exogenous esterified hyaluronan to equine distal limb wounds. Journal of Equine Veterinary Science, 29, 197-205.
61. West., DC., Hampson N., Arnold F., Kumar S., 1985. Angiogenesis induced by degredation products of hyaluronic acid. Science, 228, 1324- 1326.
62. Sudarsa I., Semadi N., Riasa NP., 2012. Hyaluronic acid caused of wider epithelialization compare to normal saline in severe diabetic ulcer. Bali Medical Journal, 1, 32-35.