Clinical, histopathological and immunohistochemical evaluation of the effects of topical NPH-insulin on full-thickness open wounds: an in vivo study in diabetic and non-diabetic mice

Abstract

In diabetic patients, wound healing is disrupted due to impaired local circulation and infection or healing becomes impossible due to the gangrene. Recently, wound treatment models based on the use of topical insulin have been the subject of some studies. In this study, we aimed to evaluate the efficacy of topical NPH insulin use on wound healing for the treatment of full-thickness open wounds in diabetic and non-diabetic mice. A total of 72, non-diabetic and diabetic adult male Swiss Albino mice were used in the study. A full-thickness skin excision with a diameter of 1 cm was practiced on the back of all mice. Animals in diabetic and nondiabetic groups were divided into two sub-groups as NPH insulin used and control group. After the wound surface areas were digitally measured, the animals were sacrificed for histopathological and immunohistochemical examinations. Wound measurements revealed a significant reduction in the non-diabetic insulin treatment group at 7 th and 14 th days and at 3 rd , 7 th and 14 th days of treatment in the diabetic insulin treatment group. Histopathological examinations showed that there was a significant increase in granulomatous inflammation in the wound site in the non-diabetic insulin treatment group at 3 rd days and in the diabetic insulin treatment group at 14 th days. Immunohistochemical analyses showed that there was an increase in α-SMA at 3 rd days and a decrease in TGF-β1 at 14 th days in the diabetic insulin treatment group, while there was a significant decrease in IGF-I at 7 th days in all diabetic groups. Topical NPH insulin application significantly accelerated healing in the treatment of diabetic and non-diabetic wounds with tissue loss in mice.

Bir Vervet Maymununun Gluteal Bölgesindeki Maddi Kayıplı Deri Yarasının Topikal İnsülin İle Sağaltımı

“…The wound healing disorder in diabetes can be attributed to various factors, such as weak blood supply, reduced proliferative potential and low infl ammatory changes [16] . Some burn, surgical incision or diabetic wound animal studies were demonstrated that inadequate or non-healing wounds can be treated with topical insulin application [17][18][19][20][21] .…”

“…It was also observed that insulin regulates the use of glucose in cells, reduces exudate, bacterial growth, hypoxia at the wound site, and increases vascularization, proliferation and contraction [5] . Insulin is known to provide wound healing through certain growth factors such as Alphasmooth muscle actin (α-SMA), Insulin-like growth factor (IGF-1), Transforming Growth Factor-β1 [5,21] . It has also been reported that insulin provides endothelial cell migration without the use of the VEGF/VEGFR pathway [5] .…”

The effect of cold atmospheric plasma (NO) alone and in combination with NPH insulin on the full-thickness excisional wound healing in a diabetic rat model

“…The NPH insulin ointment was prepared according to Ozaydin et al (2018). It was applied to the wound area once daily in a 2 mm thin layer in the DI group and in the DINO group and massaged gently until it was absorbed by the wound.…”

“…The use of NO-releasing chitosan hydrogels to increase the efficacy of placenta-produced mesenchymal stem cells in the treatment of ischaemic hind limb wounds in humans has shown promising results and has enhanced angiogenesis (Gronbach et al 2020;Ahmed et al 2022). It has been reported that NO contributes to the carbohydrate metabolism and its bioavailability decreases during the development of type 2 diabetes mellitus (T2DM), and that NO donors can improve the insulin signalling, glucose homeostasis and insulin resistance (IR) in T2DM (Ozaydin et al 2018;Wang and Xu 2020). Topical notr protamine hagedorn (NPH) insulin is widely used in both diabetic and nondiabetic wounds due to its relatively low cost and potential wound healing ability.…”

“…Topical notr protamine hagedorn (NPH) insulin is widely used in both diabetic and nondiabetic wounds due to its relatively low cost and potential wound healing ability. The use of insulin in topical bioadhesives, hydrogels, local injections, sprays, creams and controlled release of bioactive insulin has been found to reduce the wound healing time (Zhao et al 2017;Ozaydin et al 2018;Yu et al 2019;Wang and Xu 2020).…”