{"title":"The effect of dapsone on skin flap survival depends on modulation of inflammatory response and VEGF expression","authors":"Abolfazl Badripour, Anahita Najafi, Zahra Ebrahim Soltani, Alireza Hasanzadeh, M. Behzadi, Alireza Rahbar, Armaghan Ahangarishizary, Seyed Mohsen Ahmadi-Tafti, Mohammad Ashouri, Ahmadreza Dehpour","doi":"10.36922/itps.2241","DOIUrl":null,"url":null,"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.","PeriodicalId":13673,"journal":{"name":"INNOSC Theranostics and Pharmacological Sciences","volume":"28 19","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"INNOSC Theranostics and Pharmacological Sciences","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.36922/itps.2241","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 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.