Effect of doxorubicin on hypertrophic scar model in the rabbit model

Introduction and Aim: Hypertrophic scars cause cosmetic problems, they also cause functioal problems such as itching, pain and contraction development in the joints. Preventing of hypertrophic scars and keloids before they occur is more important than treating them. Early diagnosis when the scar is immature and the covering epithelium is intact is the most important factor affecting the treatment outcome. Since we do not have sufficient information about the pathogenesis of hypertrophic scars and keloids, it may cause inadequate results in treatment in general. Many treatment methods have been described in the literature. Intralesional steroid injection, topical silicone gel application and pressure therapy are the most accepted and widely used conservative treatment options for hypertrophic scars and keloids today. Other treatment methods used include surgical excision, cryotherapy, radiotherapy, laser therapy, interferon application, colchicine, vitamins A and E, calcium channel blockers, antihistamines, pentoxifylline, bleomycin, cyclosporine, allantoin and creams containing onion extract. Doxorubicin; It is an anthracycline-derived antineoplastic agent used against small cell lung cancer, sarcomas, leukemias, breast, ovarian, thyroid and stomach cancers. In our study, we aimed to investigate the effects of Doxorubicin on hypertrophic scars based on its inhibition of collagen biosynthesis in fibroblasts involved in the pathogenesis of hypertrophic scars and its effects on TGF-β1 inhibition. Materials and methods: 16 New Zealand type male rabbits weighing 2300-3200 g; were divided into 4 groups as sham group, control group, Doxorubicin group and intralesional Triamcinolone acetonide group. No action was taken on the sham group. In other groups, a hypertrophic scar model was designed by creating 4 equally spaced circular excisional wounds of 6 mm diameter on the ventral hairless surface of each rabbit ear under sterile conditions. On the 16th day, epithelialization was completed and hypertrophic scar formations were observed. Rabbits in the sham group did not receive any treatment. In the control group, hypertrophic scars were followed without treatment. After epithelialization was completed and hypertrophic scar formation was observed on the 16th day, Doxorubicin 1mg/ml/dose was applied intralesionally to the Doxorubicin group on the 16th day, 23rd day, 30th day and 37th day. After epithelialization was completed and hypertrophic scar formation was observed on the 16th day, Triamcinolone acetonide 0.8mg/ml/dose was applied intralesionally to the Triamcinolone acetonide group on the 28th and 35th day. 44 days after the scars were created, hypertrophic scars and scar regression were evaluated clinically, and tissue samples were taken and examined by light microscopy. Scar elevation index, collagenization, vascularization, number of fibroblasts per mm2 in scars, and immunohistochemically alpha-smooth muscle actin (α-SMA) level were evaluated. Results: In macroscopic examination, in the control group, in which hypertrophic scars were followed without treatment, the scars were hard, nodular and hyperemic on palpation. The scars in the Triamcinolone acetonide and Doxorubicin groups were found to be softer, flatter and paler in color. Histopathologically, scar elevation index, collagenization and the number of fibroblasts counted per mm2 were found to be significantly lower in the Doxorubicin and Triamcinolone acetonide groups compared to the control group. α-SMA expression was found to be lower in the Doxorubicin group than in the Triamcinolone acetonide and control groups. Conclusion: In the rabbit ear hypertrophic scar model, Doxorubicin was found to improve scar appearance similar to Triamcinolone acetonide, and this improvement is also supported histopathologically. There was no significant difference in the scar elevation index, between the Triamcinolone acetonide and Doxorubicin groups, and a significant decrease was observed in both groups compared to the control group. The number of fibroblasts decreased significantly in the Doxorubicin group compared to the Triamcinolone and control groups. α-SMA level and collagen density were found to be lower in the Doxorubicin group than in the control and Triamcinolone acetonide groups. These findings suggest that Doxorubicin may be a new modality in the treatment of hypertrophic scars. Keywords: Doxorubicin, Hypertrophic scar, Scar elevation index, Triamcinolone acetonide