Page 142 - ITPS-7-2

INNOSC Theranostics and
Pharmacological Sciences Dapsone enhance skin flap survival

(MD = 35.21, P < 0.001). However, no significant difference A B C
was observed between the control and dapsone 5 mg/kg
groups (P = 0.620). These results indicate that dapsone at
12.5 mg/kg exhibited statistically higher effectiveness than
dapsone at 5 mg/kg (MD = 26.48, P < 0.01) (Figure 2).
3.2. Microscopic ulceration and neutrophil
infiltration
Figure 3 illustrates the microscopic evaluation of flap injury
and ulceration using H&E staining in our histopathologic
assessment. Results revealed variations in ulcer thickness
among the study groups (F[3,8] = 113.9, P < 0.001).
Post hoc analysis revealed significant effects of dapsone
administration at both doses on ulcer thickness (MD = 88.67,
P < 0.001; MD = 178.3, P < 0.001, respectively) (Figure 3B).
Moreover, significant differences were observed among the
four groups regarding neutrophil infiltration (F[3,8]= 29.20,
P < 0.00) (Figure 3A). Tukey’s analysis confirmed that the
I/R injury in the random-pattern flap model promoted
neutrophil infiltration at the injury site (MD = −146.00,
P < 0.001). Notably, systemic administration of dapsone in
both the 5 and 12.5 mg/kg groups resulted in significantly
reduced neutrophil infiltration (MD = 98.33, P = 0.002;
MD = 128.330, P < 0.001, respectively). This effect did
not exhibit significant dose dependence (P = 0.357)
(Figure 3A).

3.3. Assessment of IL-8 level
As depicted in Figure 4, IL-8 levels were measured and
compared among groups. A one-way ANOVA confirmed
a statistically significant difference between study groups
(F[3,20] = 20.54, P < 0.001). The induction of I/R injury
in our skin flap model led to an increase in IL-8 levels,
as expected (MD = 80.5, P < 0.001). Administration of
dapsone significantly reduced IL-8 levels, regardless of the
dose administered (MD = 30.17, P = 0.039; MD = 38.67, Figure 2. Flap survival investigations following an ischemia/reperfusion
P = 0.006; for doses of 5 and 12.5 mg/kg, respectively). (I/R) injury. Upper panel: Dorsal skin flaps on day 7 following surgery: (A)
However, the effect of dapsone on the IL-8 levels did not Control group; (B) dapsone 5 mg/kg group; and (C) dapsone 12.5 mg/kg
appear to be dose-dependent (P = 0.84) (Figure 4). group. The necrotic area was defined by a dark color, edema, and eschar
formation, and the total flap area was delineated by the surgical borders.
3.4. Skin flap expression of VEGF and TNF-α Lower panel: The survival rate of the skin flap is quantified as the
percentage of necrosis over the area of the surgical flap. Administration of
Figure 5 presents the expression of VEGF and TNF-α in dapsone 12.5 mg/kg had a significant effect on the flap necrosis (P < 0.001).
the skin flap using IHC staining. We observed significant Notes: ns: Non-significant; ***P < 0.001.
differences in VEGF expression among the four groups
(F[3,8] = 83.04, P < 0.001) (Figure 5A), with the highest mean (Figure 5A). ANOVA analysis also confirmed statistically
VEGF expression observed in the sham group. Moreover, significant differences in TNF-α expression between the
the results revealed that the induction of I/R injury in our study groups (F[3,8] = 16.06, P = 0.001) (Figure 5B). As
skin flap model led to a decrease in the expression of VEGF expected, induction of I/R injury increased the expression
(MD = 35.45, P < 0.001). In addition, the IHC assessment of TNF-α in the skin flap (MD = 26.48, P < 0.01). Notably,
revealed higher VEGF expression in rats receiving dapsone both doses of dapsone significantly reduced the expression
at either 5 or 12.5 mg/kg compared with the control group level of TNF-α (MD = 19.35, P = 0.008; MD = 24.38,
(MD = 13.72, P = 0.002; MD = 22.08, P < 0.001; respectively) P = 0.002; respectively) (Figure 5B). Interestingly, the effect

Volume 7 Issue 2 (2024) 5 doi: 10.36922/itps.2241