Assessment of the Therapeutic Effects of Topical Short-Acting Insulin on Experimental Wound Healing in Rabbits Receiving Panthenol

Abstract

Wound healing is a complex, dynamic biological process aimed at restoring tissue integrity and normal function following injury; it involves a sequential series of cellular and molecular interactions encompassing the stages of hemostasis, inflammation, proliferation, and tissue remodeling. The efficiency of this process depends on the balance between factors that promote and those that inhibit healing; consequently, research efforts focus on developing therapeutic interventions capable of accelerating wound healing, improving the quality of regenerated tissue, and minimizing complications. The present study was conducted to evaluate the role of topical insulin—prepared as a carbomer-based gel at two different concentrations—in accelerating the healing of induced wounds in laboratory rabbits, as well as to assess the effect of combining it with panthenol on the wound-healing process. The animal study involved 42 male rabbits, in which surgical wounds measuring 2 cm² were created (one wound on each side). The rabbits were divided into seven equal groups (6 rabbits per group):The first group received no treatment, while the second was treated with gel. The third group was treated with topical 5% panthenol, whereas the fourth and fifth groups were treated with topical insulin at low (0.1 IU/mL) and high (0.5 IU/mL) concentrations, respectively. Finally, the sixth and seventh groups were treated with a mixture of panthenol and insulin at low and high concentrations, respectively. Treatment continued across all groups for 14 days, with wound size and contraction rate assessed on days 3, 7, 10, and 14 of the experiment. Additionally, levels of hydroxyproline, interleukin-6 (IL-6), TNF-alpha, catalase, and MDA were measured in the wound tissue, and histological changes in skin biopsies taken from the wounds were evaluated using Masson’s trichrome stains. The results demonstrated significant differences among the experimental groups (P≤0.05). Groups 1 and 2 exhibited the least improvement in wound size, contraction rate, hydroxyproline, and catalase levels, alongside elevated levels of Interleukin-6, TNF-alpha, and MDA. In contrast, the use of panthenol alone resulted in only limited improvement in these parameters compared to Groups 1 and 2. Conversely, topical insulin treatment led to significant improvements across these metrics; the 0.5 IU dose outperformed the 0.1 IU dose, indicating a dose-dependent response in stimulating collagen synthesis, as well as improvements in antioxidant status, inflammatory markers, and wound contraction capacity. The results demonstrated that the combination of topical insulin and panthenol achieved the greatest reduction in wound size and the highest rate of wound contraction. Additionally, this combination led to increased levels of hydroxyproline and catalase, alongside a significant decrease in levels of Interleukin-6, TNF-alpha, and MDA compared to all other groups; notably, there was no significant difference between the two insulin dosages when combined with panthenol regarding hydroxyproline measurements. These findings were corroborated by the histological analysis, which clearly illustrated the role of topical insulin—at both concentrations—in accelerating wound healing, particularly when used with topical panthenol. This indicates a synergistic effect between the two substances in enhancing collagen deposition and improving the reorganization of regenerating tissue. This effect is attributed to insulin's ability to stimulate fibroblast proliferation and increase the synthesis of structural proteins, as well as to the role of panthenol in supporting cell regeneration and improving the wound-healing environment. These results indicate that topical insulin is highly effective in accelerating wound healing in laboratory rabbits and that its combination with panthenol further enhances this efficacy, making it a promising therapeutic approach for improving wound healing and accelerating the restoration of the natural structure and function of injured tissues.