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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, 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-NC 4.0) ( https://creativecommons.org/licenses/by-nc/4.0/ )
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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
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