Page 139 - ITPS-7-2

INNOSC Theranostics and
Pharmacological Sciences Dapsone enhance skin flap survival

1. Introduction flap’s viable area. 17,18 The previous studies have shown
that the formation of new vessels in the flap is essential
The random-pattern skin flap is commonly used to for increasing the survival area of random-pattern skin
reconstruct skin defects in plastic surgery. Contrary to an flaps through an improvement in tissue blood supply.
axial flap, which is vascularized by a specifically identified Moreover, vascular endothelial growth factor (VEGF)
artery, a random-pattern skin flap is designed without promotes angiogenesis and significantly reduces distal
consideration for specific vessels and instead relies on flap necrosis. 19,20 Studies have shown that increased VEGF
subdermal plexuses and unnamed musculocutaneous expression correlates with enhanced angiogenesis and
arteries for blood supply. Following elevation from its increased flap survival area. VEGF secretion is stimulated
21
bed, the flap attempts to restore its hemodynamic balance. by hypoxia and inflammatory responses to an injury.
Disruption in tissue blood perfusion can lead to metabolic Following injury, activated platelets and neutrophils release
1
changes that may result in distal necrosis. Despite VEGF. 22,23 However, it is crucial to note that an excessive
admirable advances in flap surgeries, flap necrosis remains and persistent inflammatory response as a result of an I/R
a frequently encountered issue, posing complications for injury can potentially disturb angiogenesis and the healing
patients. Various techniques, including surgical delay process. It has been confirmed that inhibition of persistent
2-4
and the application of vascular endothelium growth inflammatory elements is accompanied by enhancement of
factor (VEGF), have been clinically used to increase the angiogenesis and prevention of tissue necrosis. 24
flap survival rate. However, these methods are associated
with high costs, time consumption, and inconvenience for Dapsone (4,4’-diamino-diphenyl sulfone) is an
patients. In experimental contexts, the administration of antibiotic agent belonging to the group of synthetic sulfones.
5-8
diverse stem cell types or the implementation of advanced It possesses both antimicrobial and anti-inflammatory
drug delivery methods, such as microneedles containing properties. Its bacteriostatic function arises from its ability
25
hyaluronic acid, has demonstrated promising outcomes to inhibit dihydrofolate synthesis in bacteria. The US
in enhancing vasculogenesis within skin flaps. Therefore, Food and Drug Administration-approved indications for
9
a proper pharmacologic agent represents an alternative dapsone include leprosy, dermatitis herpetiformis, and
26
therapy to increase the flap survival rate. The previous acne vulgaris. In addition, dapsone exhibits multiple
studies have indicated that flap necrosis primarily arises anti-inflammatory, anti-oxidative, and anti-apoptotic
from inadequate blood supply and subsequent ischemia/ properties. Dapsone functions by inhibiting beta-2
reperfusion (I/R) injury, oxidative stress, inflammatory integrin-mediated adherence of neutrophils, thereby
27,28
reactions, and possible surgical site infections. 10-12 preventing their chemotactic migration. In addition, it
Consequently, numerous potential pharmacologic agents can interfere with the function of enzymes and proteins in
targeting these contributing factors are being investigated the integrin family and demonstrates an inhibitory effect
on IL-8 and TNF-α production, both crucial in neutrophil-
clinically and experimentally to improve flap survival.
mediated inflammation and regulation of lymphocyte and
Inflammation plays a crucial role in the process of monocyte. 29,30
wound healing. However, during necrosis, an intense
Given its multiple functions in inflammation and
inflammatory response, characterized by excess neutrophil angiogenesis, dapsone emerges as a potential candidate
infiltration, exerts an inverse effect on healing. Thus, for preventing flap necrosis. In the present study, we
controlling inflammation is instrumental in enhancing flap aimed to investigate the random-pattern flap survival in
survival. It is worth mentioning that while endogenously rats treated with dapsone, along with exploring possible
regulated neutrophil infiltration within the initial days underlying inflammatory mechanisms. Furthermore, we
following injury is necessary for the healing process, aimed to assess the VEGF expression levels as an indicator
prolonged and persistent neutrophilia would lead to an of angiogenesis and flap survival, and TNF-α as a key
31
impaired healing process. 13,14 Interleukin (IL)-8, known as representative of the inflammatory response, respectively.
a potent chemotactic agent, mediates the infiltration and An overview of the study is illustrated in Figure 1.
activation of neutrophils. Moreover, it is well-established
that secretion of IL-8 mediates the production of cytokines, 2. Materials and methods
including tumor necrosis factor-alpha (TNF-α). 15,16 Recent
studies have suggested that, in addition to IL-8, TNF-α 2.1. Animals
also mediates neutrophil recruitment to the injured tissue Twenty-four male Sprague Dawley rats (weighing
and induces inflammatory responses. It has been suggested 270–300 g) were obtained from the animal house of
that reduction in TNF-α levels and neutrophil migration the Department of Pharmacology, Tehran University
alleviates the inflammatory response and increases the of Medical Sciences. To attain a constant experimental

Volume 7 Issue 2 (2024) 2 doi: 10.36922/itps.2241