AccScience Publishing / ITPS / Volume 7 / Issue 2 / DOI: 10.36922/itps.2241
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ORIGINAL RESEARCH ARTICLE

The effect of dapsone on skin flap survival depends on modulation of inflammatory response and VEGF expression

Abolfazl Badripour1,2,3 Anahita Najafi1,4 Zahra Ebrahim Soltani1,2 Alireza Hasanzadeh1,4 Mohamad Behzadi5 Alireza Rahbar1,4 Armaghan Ahangarishizary1,4 Seyed Mohsen Ahmadi-Tafti3,6 Mohammad Ashouri3,6 Ahmadreza Dehpour1,7*
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1 Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran
2 Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran
3 Colorectal Surgery Research Center, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
4 Department of Medicine, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
5 Department of Surgery, Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran
6 Department of Surgery, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
7 Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
INNOSC Theranostics and Pharmacological Sciences 2024, 7(2), 2241 https://doi.org/10.36922/itps.2241
Submitted: 13 November 2023 | Accepted: 25 January 2024 | Published: 16 April 2024
© 2024 by the Author (s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
Abstract

The random-pattern skin flap is a common method used for reconstructing skin defects. However, flap ischemia necrosis remains a significant challenge in plastic surgery. Strategies aimed at reducing persistent inflammation and promoting blood supply through angiogenesis have been identified as crucial for improving flap survival. Dapsone, a chemotherapeutic agent known for its anti-inflammatory properties through multiple pathways, is of interest in this regard. This study aims to investigate the effect of dapsone on random-pattern flap survival in rats, along with its impact on inflammation and angiogenesis. The ischemia/reperfusion (I/R) injury rat models were created using a caudal-based dorsal skin flap with delayed I/R. Twenty-four male Sprague Dawley rats were divided into control, sham, and two treatment groups receiving dapsone at doses of 12.5 mg/kg/day and 5 mg/kg/day, respectively. On the 7th post-operative day, flap survival was evaluated. Neutrophil infiltration and ulceration were measured through microscopic examination, and interleukin (IL)-8 levels through enzyme-linked immunosorbent assay. Expression levels of vascular endothelial growth factor (VEGF) and tumor necrosis factor-alpha (TNF-α) were determined using an immunohistochemistry (IHC) array. The findings revealed an increased flap survival on day 7 post-operation following systemic administration of dapsone for 5 consecutive days. Dapsone at both dosages significantly reduced the ulcer thickness, neutrophil infiltration, and IL-8 levels. The IHC results revealed that VEGF expression was significantly higher in the treatment groups compared to the control group. Moreover, TNF-α expression was significantly lower in the treatment groups compared to the control group. In conclusion, we confirmed that treatment with dapsone promotes skin flap survival, and this effect aligned with a reduction in persistent inflammation and the enhancement of VEGF. Nonetheless, more studies are required to elucidate the precise anti-inflammatory mechanism of dapsone in I/R injuries.

Keywords
Dapsone
Inflammation
Ischemia/reperfusion injury
Skin flap
VEGF
Funding
None.
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Conflict of interest
The authors declare no conflict of interest.
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INNOSC Theranostics and Pharmacological Sciences, Electronic ISSN: 2705-0823 Published by AccScience Publishing