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. 2015 Mar;20(3):233-8.

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

Alireza Zandifar  1 , Sima Seifabadi  2 , Ehsan Zandifar  1 , Sajedeh Sohrabi Beheshti  3 , Abolfazl Aslani  4 , Shaghayegh Haghjooy Javanmard  5
Affiliations

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

Alireza Zandifar et al. J Res Med Sci. 2015 Mar.

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.

Keywords: L-arginine; nitric oxide; streptozotocin; vascular endothelial growth factor; wound healing.

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Conflict of interest statement

Conflict of Interest: All authors have read and approved the content of the manuscript. All authors disclose all potential conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject of the manuscript.

Figures

Figure 1
Figure 1
Wound fluid total nitrite concentration was measured by Griess reaction on day 5 post wounding. Data are reported in μmol/ml ± SDM (*P < 0.05)
Figure 2
Figure 2
Wound fluid vascular endothelial growth factor (VEGF)/total protein (TP) was measured on day 5 post wounding. Date are reported in VEGF/TP × 107 (*P < 0.05)
Figure 3
Figure 3
The histological scores of wound healing were examined by a pathologist, without knowledge of the prior treatment. Data are reported in mean scores ± SDM (*P < 0.05)
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