Comparison of the effect of topical versus systemic L-arginine on wound healing in acute incisional diabetic rat model

Abstract

Background: Diabetes is associated with endothelial dysfunction and impaired wound healing. The amino acid L-arginine is the only substrate for nitric oxide (NO) synthesis. The purpose of this study was to compare the topical versus systemic L-arginine treatment on total nitrite (NOx) and vascular endothelial growth factor (VEGF) concentrations in wound fluid and rate of wound healing in an acute incisional diabetic wound model. Materials and Methods: A total of 56 Sprague-Dawley rats were used of which 32 were rendered diabetic. Animals underwent a dorsal skin incision. Dm-sys-arg group (N = 8, diabetic) and Norm-sys-arg group (N = 8, normoglycemic) were gavaged with L-arginine. Dm-sys-control group (N = 8, diabetic) and Norm-sys-control group (N = 8, normoglycemic) were gavaged with water. Dm-top-arg group (N = 8, diabetic) and norm-top-arg group (N = 8, normoglycemic) received topical L-arginine gel. Dm-top-control group (N = 8, diabetic) received gel vehicle. On the day 5 the amount of NOx in wound fluid was measured by Griess reaction. VEGF/total protein in wound fluids was also measured on day 5 using enzyme-linked immunosorbent assay. All wound tissue specimens were fixed and stained to be evaluated for rate of healing. Data were analyzed using SPSS software (version 18.0, Chicago, IL, USA) through One-way analysis of variance test and Tukey's post-hoc. Results: In dm-sys-arg group, the level of NOx on day 5 was significantly more than dm-top-arg group (P < 0.05). VEGF content in L-arginine treated groups were significantly more than controls (P < 0.05). Rate of diabetic wound healing in dm-sys-arg group was significantly more than dm-top-arg group. Conclusion: Systemic L-arginine is more efficient than topical L-arginine in wound healing. This process is mediated at least in part, by increasing VEGF and NO in the wound fluid.