Histopathological and Immunohistochemical Study of the Effect of Sildenafil Citrate, Vitamin A, Vitamin C and Vitamin E on Wound Healing in Alloxan-Induced Diabetic Rats

Abstract

Objective: To examine the impact of sildenafil citrate, vitamin A (Vit A), vitamin C (Vt C) and vitamin E (Vit E) on wound healing in a rat model of diabetes (n = 100). Methods: Diabetes was induced in the rats by intraperitoneal (i.p.) administration of alloxan. After anaesthesia, a standard wound was created on the back of each rat using a 10-mm sterile punch. The rats were randomly divided into 10 groups (n = 10 in each), as follows: normal saline, glibenclamide, insulin, sildenafil, Vit A, Vit C, Vit E, Vit A + sildenafil, Vit C + sildenafil, Vit E + sildenafil daily for 15 days. The rats were sacrificed after being anaesthetized 3, 7 and 15 days later Wounded skin tissue samples were collected for histopathological and immunohistochemical analyses. Results: On the 7th day, epithelial regeneration was completed in groups 8 and 9. Angiogenesis was insufficient in group 2. In terms of connective tissue proliferation, partially matured connective tissue was observed in group 4. On the 15th day of the study, groups 8, 9 and 10 had mature connective tissue. However; group 1 still had exudate-containing neutrophils. Immunohistochemically, on the 3rd day, the level of inducible nitric oxide synthase (iNOS) reactivity was intense in macrophages and neutrophils surrounding the wound edges in groups 4, 8, 9 and 10. The level of iNOS reactivity was moderate in group 6 and less distinct in groups 1, 2, 3, 5 and 7. Conclusion: Sildenafil citrate, together with Vit A and Vit C, is beneficial in wound healing of diabetic rats.