New approaches in education and health sciences management

New approaches in education and health sciences management

Effect of Arginine on Skin Wound Healing in Male Wistar Rats

Document Type : Original Article

Authors
1 Department of Anatomy & Cognitive Neurosciences, Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
2 Department of Biology and Anatomical Sciences, Faculty of Medicine, Shahiid Beheshti University of Medical Sciences, Tehran, Iran.
3 Department of Anatomy & Cognitive Neurosciences, Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
Abstract
Introduction: Arginine is an essential amino acid synthesized from citrulline in healthy individuals and modulates immune function, hormone secretion, and endothelial performance. Arginine and its active metabolites can influence all stages of wound healing, including collagen production, cell proliferation, and immune enhancement.
Materials and Methods: In this study, 24 adult male Wistar rats, with an average weight of 200-250 grams, were anesthetized through intramuscular injection of a ketamine-xylazine mixture. A skin incision, 15 mm in diameter. The rats were divided into four groups: control, 2% topical arginine, 5% topical arginine, and injection arginine, with each group consisting of six rats. After 15 days, the rats were sacrificed and the tissue samples were fixed in 10% formalin. After the tissue processing, stereological studies were performed using a light microscope
Results: In this study, number of fibroblast cells in injection arginine group decreased compared to control, 2% and 5% topical arginine groups. Also, dermis volume in injection arginine group decreased significantly compared to 2% and 5% topical arginine groups and control group, but dermis volume in 2% topical arginine group increased compared to control group.
Conclusion: This study shows a significant difference in the wound healing effect of topical arginine compared to injection arginine.
Keywords

Ethics Approval ID: IR.IAU.TMU.REC.1402.112 

1.             Leigh B, Desneves K, Rafferty J, Pearce L, King S, Woodward MC, Brown D, Martin R, Crowe TC. The effect of different doses of an arginine-containing supplement on the healing of pressure ulcers. J Wound Care. 2012;21(3):150-6. doi: 10.12968/jowc.2012.21.3.150
2.             Mahdirejei HA, Peeri M, Azarbayjani MA, Fattahi Masrour F. Fluoxetine combined with swimming exercise synergistically reduces lipopolysaccharide-induced depressive-like behavior by normalizing the HPA axis and brain inflammation in mice. Pharmacol Biochem Behav. 2023;232:173640. doi: 10.1016/j.pbb.2023.173640
3.             Jerônimo MS, Barros AD, MoritaI VE, Alves EO, Souza NL, Almeida RM, et al. Oral or topical administration of L-arginine changes the expression of TGF and iNOS and results in early wounds healing. Acta Cir Bras. 2016;31(9):586-596. doi: 10.1590/S0102-865020160090000003
4.             Mostafavinia A, Bidram M, Gomi Avili A, Mahmanzar M, Karimifard SA, Sajadi E, et al. An improvement in acute wound healing in rats by the synergistic effect of photobiomodulation and arginine. Lab Anim Res. 2019;35:28. doi: 10.1186/s42826-019-0025-x
5.             Debats IB, Booi DI, Wehrens KM, Cleutjens J, Deutz NE, van de Hogen E, et al. Oral arginine supplementation and the effect on skin graft donor sites: a randomized clinical pilot study. J Burn Care Res. 2009;30(3):417-26. doi: 10.1097/BCR.0b013e3181a28c15
6.             Wilkinson HN, Hardman MJ. Wound healing: cellular mechanisms and pathological outcomes. Open Biol. 2020;10(9):200223. doi: 10.1098/rsob.200223
7.             Barros CDS, Coutinho A, Tengan CH. Arginine Supplementation in MELAS Syndrome: What Do We Know about the Mechanisms? Int J Mol Sci. 2024;25(7):3629. doi: 10.3390/ijms25073629
8.             Mao G, Tian S, Shi Y, Yang J, Li H, Tang H, Yang W. Preparation and evaluation of a novel alginate-arginine-zinc ion hydrogel film for skin wound healing. Carbohydr Polym. 2023;311:120757. doi: 10.1016/j.carbpol.2023.120757
9. Fujiwara T, Kanazawa S, Ichibori R, Tanigawa T, Magome T, Shingaki K, et al. L-arginine stimulates fibroblast proliferation through the GPRC6A-ERK1/2 and PI3K/Akt pathway. PLoS One. 2014;9(3):e92168. doi: 10.1371/journal.pone.0092168
10. Amouzad Mahdirejei H, Peeri M, Azarbayjani MA, Masrour FF. Diazepam and exercise training combination synergistically reduces lipopolysaccharide-induced anxiety-like behavior and oxidative stress in the prefrontal cortex of mice. Neurotoxicology. 2023;97:101-108. doi: 10.1016/j.neuro.2023.06.004
11. Loehe F, Bruns CJ, Nitsch SM, Angele MK. The role of L-arginine following trauma and blood loss. Curr Opin Clin Nutr Metab Care. 2007;10(1):80-7. doi: 10.1097/MCO.0b013e328011bb1b
12. Kwon KC, Won JG, Seo JH, Kwon OS, Kim EH, Kim MS, et al. Effects of arginine glutamate (RE:pair) on wound healing and skin elasticity improvement after CO2 laser irradiation. J Cosmet Dermatol. 2022;21(10):5037-5048. doi: 10.1111/jocd.14957
13. Ibrahim RM, Kamoun EA, Badawi NM, El-Moslamy SH, Kh M, Salim SA. Cutting-edge biomaterials for advanced biomedical uses: self-gelation of l-arginine-loaded chitosan/PVA/vanillin hydrogel for accelerating topical wound healing and skin regeneration. RSC Adv. 2024;14(42):31126-31142. doi: 10.1039/d4ra04430d
14. Durmus AS, Tuzcu M, Ozdemir O, Orhan C, Sahin N, Ozercan IH, et al. Arginine Silicate Inositol Complex Accelerates Cutaneous Wound Healing. Biol Trace Elem Res. 2017;177(1):122-131. doi: 10.1007/s12011-016-0857-2
15. Mndlovu H, du Toit LC, Kumar P, Choonara YE. Tannic acid-loaded chitosan-RGD-alginate scaffolds for wound healing and skin regeneration. Biomed Mater. 2023;18(4). doi: 10.1088/1748-605X/acce88   
Volume 3, Issue 1
april 2026
Spring 2026
Pages 24-34

  • Receive Date 08 August 2025
  • Revise Date 13 September 2025
  • Accept Date 14 January 2026
  • First Publish Date 14 January 2026
  • Publish Date 19 April 2026