COMPARING THE EFFECTS OF SILDENAFIL CITRATE AND DEXPANTHENOL ON WOUND HEALING: AN EXPERIMENTAL STUDY

Öz

Objective Wound healing is a serious problem that causes high morbidity. Different pharmacological agents have been studied to accelerate wound healing and to prevent necrosis and ischemia, and still continue to work. Topical dexpanthenol is widely used in both ağırlığınwound healing and various dermatological diseases. The aim of this study was to compare the effects of topical sildenafil citrate and topical dexpanthenol on wound healing in rats. Material and Method A total of 30 female Wistar Albino rats, weighing 200- 250 gr, were used in the study. Rats were divided into 3 groups. A linear 2 cm full-thickness incision was made in the rat’s skin of the back. Steril saline irrigation was applied to all animals in the control group. Dexpanthenol was administered locally to the wounds of the rats in the second group, and 10% sildenafil citrate in the third group. Wound dimensions were measured on the 3rd, 5th, 7th, 10th, 14th, and 21st days. The full-thickness skin, including the incision, were removed for histopathological examination on the 21st days. Results We believe that sildenafil citrate can be used as a topical cream for wound healing, as it leads to significant reduction in wound size. Conclusion Although there was no statistically significant difference, we observed that the wound healing was better in the group where sildenafil citrate was applied locally on the wound.

Anahtar Kelimeler

• Wound healing
• sildenafil sitrate
• dexpanthenol
• rats

SİLDENAFİL SİTRAT VE DEKSPANTENOLÜN YARA İYİLEŞMESİ ÜZERİNDEKİ ETKİLERİNİN KARŞILAŞTIRILMASI: DENEYSEL ÇALIŞMA

Öz

Amaç Yara iyileşmesi cerrahide yüksek morbiditeye neden olabilen ciddi bir problemdir. Yara iyileşmesini hızlandırmak, nekrozu veya iskemiyi önlemek için değişik farmakolojik ajanlar çalışılmış ve halen yaygın olarak çalışılmaya devam etmektedir. Yara iyileşmesinde klinik pratikte topikal dekspantenolün geniş kulanım alanları mevcuttur. Topikal dekspantenol hem yara bakımında hem de dermatolojik hastalıkların tedavisinde kullanılmaktadır. Bu çalışmamızda, ratlarda oluşturulan deneysel yara modelinde lokal sildenafil sitrat ve topikal dekspantenol uygulamalarının etkilerinin karşılaştırılması amaçlanmıştır. Gereç ve Yöntem Çalışmada 200–250 gram arasında değişen 30 Adet Wistar Albino dişi rat kullanıldı. Hayvanlar üç gruba ayrıldı. Deney hayvanlarının anestezisini takiben sırt orta kesimlerine 2 cm uzunluğunda tam kat kalınlıkta deri defekti oluşturuldu. Yara pansumanında tüm hayvanların yaraları steril % 0.9 NaCl solüsyonu ile yıkandıktan sonra kontrol grubu olduğu gibi bırakılırken, irigasyon sonrası 2. gruba %5’lik dekspantenol krem, 3. gruba % 10’luk sildenafil krem uygulandı. Ratlarda yara boyutları 3., 5., 7., 10., 14. ve 21. günlerde ölçülerek kaydedildi ve 21. gün tüm ratların sırt kısımlarından insizyon hattını içerecek şekilde tam kat deri çıkarılarak histolojik incelemeye alındı. Bulgular Tüm gruplara genel olarak bakıldığında günlere göre yara boyutlarındaki küçülme ve histopatolojik bulgular açısından istatiksel olarak anlamlı fark saptanmadı. Sonuç Sildenafil sitratın yara boyutunda önemli bir azalmaya yol açtığı için yara iyileşmesi için topikal bir krem olarak kullanılabileceğine inanıyoruz.

Anahtar Kelimeler

• Yara iyileşmesi
• sildenafil sitrat
• dekspantenol
• rat

Kaynakça

1. 1. Proksch, E., de Bony, R., Trapp, S., & Boudon, S. (2017). Topical use of dexpanthenol: a 70th anniversary article. The Journal of dermatological treatment 28(8), 766–773
2. 2. Jamshidzadeh A, Azarpira N. (2011). The effects of topical sildenafil on wound healing in rat. Iranian Journal of Pharmaceutical Sciences 7(1): 43-48
3. 3. Jarrahi, M., & Vafaei, A. A. (2004). Effect of topical phenytoin cream on linear incisional wound healing in albino rats. Daru, 12(4), 156-158.
4. 4. Velnar, T., Bailey, T., & Smrkolj, V. (2009). The wound healing process: an overview of the cellular and molecular mechanisms. The Journal of international medical research, 37(5), 1528–1542.
5. 5. Erdem, C., & Çelebi, C. R. (Eds.). (1996). Tüm yönleriyle yara iyileşmesi. Türk Dermatopatoloji Derneği.
6. 6. Derici, H., Kamer, E., Ünalp, H. R., Diniz, G., Bozdag, A. D., Tansug, T., ... & Erbil, Y. (2010). Effect of sildenafil on wound healing: an experimental study. Langenbeck's archives of surgery, 395(6), 713-718.
7. 7. Soneja, A., Drews, M., & Malinski, T. (2005). Role of nitric oxide, nitroxidative and oxidative stress in wound healing. Pharmacological reports, 57, 108.
8. 8. Martin, P. (1997). Wound healing--aiming for perfect skin regeneration. Science, 276(5309), 75-81.

9. 9. Ziche, M., & Morbidelli, L. (2000). Nitric oxide and angiogenesis. Journal of neuro-oncology, 50(1), 139-148.
10. 10. Ebner, F., Heller, A., Rippke, F., & Tausch, I. (2002). Topical use of dexpanthenol in skin disorders. American journal of clinical dermatology, 3(6), 427-433.
11. 11. Romiti, R., & Romiti, N. (2002). Dexpanthenol cream significantly improves mucocutaneous side effects associated with isotretinoin therapy. Pediatric dermatology, 19(4), 368-371.
12. 12. Schmuth, M., Wimmer, M. A., Hofer, S., Sztankay, A., Weinlich, G., Linder, D. M., ... & Fritsch, E. (2002). Topical corticosteroid therapy for acute radiation dermatitis: a prospective, randomized, double‐blind study. British Journal of Dermatology, 146(6), 983-991.
13. 13. Lee, R. H., Efron, D., Tantry, U., & Barbul, A. (2001). Nitric oxide in the healing wound: a time-course study. Journal of Surgical Research, 101(1), 104-108.
14. 14. Chung, A. W., Radomski, A., Alonso-Escolano, D., Jurasz, P., Stewart, M. W., Malinski, T., et al. (2004). Platelet–leukocyte aggregation induced by PAR agonists: regulation by nitric oxide and matrix metalloproteinases. British journal of pharmacology, 143(7), 845.
15. 15. Cooke, J. P., & Losordo, D. W. (2002). Nitric oxide and angiogenesis. Circulation, 105(18), 2133–2135.
16. 16. Schwentker, A., Vodovotz, Y., Weller, R., & Billiar, T. R. (2002). Nitric oxide and wound repair: role of cytokines?. Nitric oxide, 7(1), 1-10.
17. 17. Stallmeyer, B., Kämpfer, H., Kolb, N., Pfeilschifter, J., & Frank, S. (1999). The function of nitric oxide in wound repair: inhibition of inducible nitric oxide-synthase severely impairs wound reepithelialization. Journal of Investigative Dermatology, 113(6), 1090-1098.
18. 18. Nakamura, H., Herzenberg, L. A., Bai, J., Araya, S., Kondo, N., Nishinaka, Y., et al. (2001). Circulating thioredoxin suppresses lipopolysaccharide-induced neutrophil chemotaxis. Proceedings of the National Academy of Sciences, 98(26), 15143-15148.
19. 19. Furchgott, R. F. (1996). The discovery of endothelium-derived relaxing factor and its importance in the identification of nitric oxide. Jama, 276(14), 1186-1188.
20. 20. Weller, R., Schwentker, A., Billiar, T. R., & Vodovotz, Y. (2003). Autologous nitric oxide protects mouse and human keratinocytes from ultraviolet B radiation-induced apoptosis. American Journal of Physiology-Cell Physiology, 284(5), C1140-C1148.
21. 21. Krischel, V., Bruch-Gerharz, D., Suschek, C., Kröncke, K. D., Ruzicka, T., & Kolb-Bachofen, V. (1998). Biphasic effect of exogenous nitric oxide on proliferation and differentiation in skin derived keratinocytes but not fibroblasts. Journal of Investigative Dermatology, 111(2), 286-291.
22. 22. Stamler, J. S., Jia, L., Eu, J. P., McMahon, T. J., Demchenko, I. T., Bonaventura, J., et al. (1997). Blood flow regulation by S-nitrosohemoglobin in the physiological oxygen gradient. Science, 276(5321), 2034-2037.
23. 23. Weller, R., Ormerod, A. D., Hobson, R. P., & Benjamin, N. J. (1998). A randomized trial of acidified nitrite cream in the treatment of tinea pedis. Journal of the American Academy of Dermatology, 38(4), 559-563.
24. 24. Salcido, R. (2008). Viagra and wound healing: the NO connection. Advances in skin & wound care, 21(3), 106-109.
25. 25. Sarifakioglu, N., Gokrem, S., Ates, L., Akbuga, U. B., & Aslan, G. (2004). The influence of sildenafil on random skin flap survival in rats: an experimental study. British journal of plastic surgery, 57(8), 769-772.
26. 26. Farsaie, S., Khalili, H., Karimzadeh, I., & Dashti-Khavidaki, S. (2012). An old drug for a new application: potential benefits of sildenafil in wound healing. Journal of Pharmacy & Pharmaceutical Sciences, 15(4), 483-498.
27. 27. Ayyıldız, A., Nuhoglu, B., Huri, E., Uysal, A., Üstün, H., Germiyanoglu, C., et al. (2005). Experimental study: The efficacy and dosage of sildenafil citrate on flap viability. Turk J Urol, 31, 163-169.