Comparison of the Effects of Contractubex® Gel in an Experimental Model of Scar Formation in Rats: An Immunohistochemical and Ultrastructural Study

January 2012 | Volume 11 | Issue 1 | Original Article | 74 | Copyright © January 2012

Mustafa T. Sahin MD,a Sevinc Inan MD,b Serap Ozturkcan MD,a Elif Guzel MDc Cemal Bilac MD,a Gülsen Giray MD,b Sevda Muftuoglu MDd

aDepartment of Dermatology, Celal Bayar University Medical Faculty, Manisa, Turkey bDepartment of Histology and Embryology, Celal Bayar University Medical Faculty, Manisa, Turkey cDepartment of Histology and Embryology, Istanbul University Cerrahpasa Medical Faculty, Istanbul, Turkey dDepartment of Histology and Embryology, Hacettepe University Medical Faculty, Ankara, Turkey


In our study, we compared and discussed immunohistochemical and ultrastructural effects of extractum cepae-heparin sodium-allantoin mixture, heparin sodium and allantoin in the rat model. Since the effects of the onion extract-based compound have not been deeply characterized so far, we could not find a study comparing immunohistochemical and ultrastructural effects of Contractubex gel, heparin sodium, and allantoin in any animal model in the literature. The reduced dermal immunoreactivity for laminin, fibronectin, and TGF-β was associated with heparin-, allantoin-, and Contractubex gel treatment in our study. The gel-based extractum cepae-heparin sodium-allantoin mixture was found to have apparent keratinolytic and collagenase effects. The thinnest epidermis of the four groups and normal-appearing epidermal cells that had completed keratinization showed that Contractubex gel had apparent keratinolytic effects. The following findings show the effect of Contractubex gel on collagenase: [1] dermal papillary formation occurred earlier in the second group comparing to the other groups; [2] connective tissue formed, consisting of loosely-structured collagen fibers and vessels in the papillary dermis (Fibrosis did not develop, and scar formation completed close to normal cutaneous morphology.), and [3] scar formation reduced more effectively than no treatment, heparin monotherapy, or allantoin monotherapy groups.
We can emphasize that Contractubex gel results in better reduction of scar formation, since TGF-β, laminin, and fibronectin immunoreactivities were mild or moderate. We conclude that wound healing with extractum cepae-heparin sodium-allantoin mixture is better than no treatment, heparin monotherapy, and allantoin monotherapy groups according to immunohistochemical and ultrastructural measurements.


The authors have no relevant conflicts of interest to disclose.


  1. Alster TS, Tanzi EL. Hypertrophic scars and keloids. Etiology and management. Am J Clin Dermatol. 2003;4:235-243.
  2. Berman B, Flores F. The treatment of hypertrophic scars and keloids. Eur J Dermatol. 1998;8:591-595.
  3. Zurada JM, Kriegel D, Davis IC. Topical treatments for hypertrophic scars. J Am Acad Dermatol. 2006;55:1024-1031.
  4. Koc E, Arca E, Surucu B, et al. An open, randomized, controlled, comparative study of the combined effect of intralesional triamcinolone acetonide and onion extract gel and intralesional triamcinolone acetonide alone in the treatment of hypertrophic scars and keloids. Dermatol Surg. 2008;34:1507-1514.
  5. Willital GH, Heine H. Efficacy of Contractubex gel in the treatment of fresh scars after thoracic surgery in children and adolescents. Int J Clin Pharm Res. 1994;14:193-202.
  6. Stein G. Erfahrungen mit der Behandlung von Keloiden und hypertrophen Narben mit Contractubex comp. Therapiewoche. 1985;40:1199-1207.
  7. Chadzynska M, Jablonska S. Therapie von verbrennungsinduzierten hypertrophischen, keloidartigen Narben bei Kindern mit Contractubex. Deutsch Dermatol. 1989;37:1288-1299.
  8. Maragakis M, Willital GH, Michel G, et al. Possibilities of scar treatment after thoracic surgery. Drugs Exp Clin Res. 1995;21:199-206.
  9. Beuth J, Hunzelmann N, Van Leendert R, et al. Safety and efficacy of local administration of Contractubex to hypertrophic scars in comparison to corticosteroid treatment. Results of a multicenter, comparative epidemiological cohort study in Germany. In Vivo. 2006;20:277-284.
  10. Philipp K, Riedel F, Sauerbier M, et al. Targetting TGF-β in human keratinocytes and its potential role in wound healing. Int J Molecular Med. 2004;14:589-593.
  11. Wysocki AB. Fibronectin in acute and chronic wounds. J ET Nurs. 1992;19:166-170.
  12. Goldfinger LE, Hopkinson SB, deHart GW, et al. The alpha3 laminin subunit, alpha6beta4 and alpha3beta1 integrin coordinately regulate wound healing in cultured epithelial cells and in the skin. J Cell Sci. 1999;112:2615-2629.
  13. Helen A, Rajasree CR, Krishnakumar K, et al. Antioxidant role of oils isolated from garlic (Allium sativum Linn) and onion (Allium cepa Linn) on nicotine-induced lipid peroxidation. Vet Hum Toxicol. 1999;41:316-319.
  14. Appleton I. Wound healing: future directions. Invest Drugs. 2003;6:1067-1072.
  15. Bello YM, Phillips TJ. Recent advances in wound healing. JAMA. 2000;283:716-718.
  16. Villa A, Poochareon V, Berman B. Keloids and hypertrophic scars. In: Falabella AF, Kirsner RS, eds. Wound Healing. Boca Raton: Taylor & Francis Group; 2005:623-636.
  17. Corderio MF, Mead A, Ali RR, et al. Novel antisense oligonucleotides targeting TGF-beta inhibit in vivo scarring and improve surgical outcome. Gene Ther. 2003;10:59-71.
  18. Parish WE. Inflammation. In: Champion RH, Burton JL, Ebling FJG, eds. Textbook of Dermatology. Oxford: Blackwell Science Publ; 1992:219-252.
  19. Garner WL, Karmiol S, Rodriguez JL, et al. Phenotypic differences in cytokine responsiveness of hypertrophic scar versus normal dermal fibroblasts. J Inves Dermatol. 1993;101:875-879.
  20. Quaglino D Jr, Nanney LB, Ditesheim JA, et al. Transforming growth factor beta stimulates wound healing and modulates extracellular matrix gene expression in pig skin: incisional wound model. J Invest Dermatol. 1991;97:34-42.
  21. Nakao A, Fujii M, Matsumura R, et al. Transient gene transfer and expression of Smad7 prevents bleomycin-induced lung fibrosis in mice. J Clin Invest. 1999;104:5-11.
  22. Huang JS, Wang YH, Ling TY, et al. Synthetic TGF-beta antagonist accelerates wound healing and reduces scarring. FASEB J. 2002;16:1269-1270.