Effects of Pirfenidone and Collagen-Polyvinylpyrrolidone on Macroscopic and Microscopic Changes, TGF-β1 Expression, and Collagen Deposition in an Experimental Model of Tracheal Wound Healing

Abstract

Tracheal stenosis (TS) is a fibrosis originated by prolonged inflammation and increased transforming growth factor beta 1 (TGF-β1) expression and collagen deposition (CD) in the tracheal wound. Several wound-healing modulators (WHMs) have been used to modulate the tracheal healing process and prevent TS, but they have failed, justifying the need to evaluate alternative WHM. The pirfenidone (PFD) and collagen-polyvinylpyrrolidone (Collagen-PVP) decrease inflammation and fibrosis. This study assessed the effect of PFD administration and Collagen-PVP topical application on macroscopic and microscopic changes, TGF-β1 expression, and CD in an experimental model of tracheal wound healing. Forty Wistar rats underwent cervical tracheoplasty, were divided into 4 groups (n = 10), and were treated with different WHM: group I, saline solution (SS); group II, Collagen-PVP; group III, mitomycin C (MMC); and group IV, 40 mg/kg PFD. Four weeks after surgery, the macroscopic and microscopic changes, in situ TGF-β1 expression, and CD in posttracheoplasty scars were evaluated. The animals treated with Collagen-PVP and PFD developed less inflammation and fibrosis than animals in the other study groups (p < 0.05, Kruskal-Wallis) and, moreover, showed lower TGF-β1 expression and CD than animals in group I (p < 0.05, ANOVA and Tukey's test). In conclusion, PFD and Collagen-PVP decrease inflammation, fibrosis, TGFβ-1 expression, and CD in the posttracheoplasty rats' scar.

Prevention of tracheal stenosis with pirfenidone after tracheotomy: An experimental study

“…Tracheal stenosis is a pathological scar with a prolonged inflammatory phase of cicatrization leading to fibrosis in the area of the lesion by the increased production of TGFβ, collagen synthesis, and increased levels of accumulation . Although the surgical methods used in the treatment of TS are the treatment of choice, they are still not effective by 100%.…”

“…The epithelial damage was assessed by the loss in the epithelial tissues. In order to evaluate the inflammation, the total number of inflammatory cells in the injured submucosal region were counted under 400× magnification, and the mean number of inflammatory cells per mm was evaluated. In the course of this evaluation, the findings qualified as (−), (+), (++), and (+++) were scored as 0, 1, 2, and 3, respectively.…”

“…Although its exact mechanism of action has not been established yet, it is suggested that it acts by decreasing the production rate of TGFβ‐1 (the growth factor beta), TNFα (tumor necrosis factor alpha), and IL‐1β (Interleukin‐1 beta) in the in vitro and in vivo fibrotic disease models . Despite the use of pirfenidone in primarily pulmonary fibrosis, as well as the experimental studies using it in the disorders manifesting with fibrosis—including the cutaneous scars, vocal fold scars, abdominal adhesions, intestinal and esophageal strictures, and benign biliary strictures—the number of studies on tracheal stenosis is limited …”

“…1,2 Current methods used in the treatment of tracheal stenosis include balloon dilatation, endoscopic laser surgery, tracheal resection, and end-to-end anastomoses. 3 However, the increased risk of restenosis after these treatment methods paved the way to search for innovative pharmacologic agents inhibiting the fibrosis, which is the main leading cause in the pathogenesis of fibrosis.…”

“…[4][5][6] Despite the use of pirfenidone in primarily pulmonary fibrosis, as well as the experimental studies using it in the disorders manifesting with fibrosis-including the cutaneous scars, 4 vocal fold scars, 7 abdominal adhesions, 8 intestinal 9 and esophageal strictures, 10 and benign biliary strictures 11 -the number of studies on tracheal stenosis is limited. 3,12,13 This study aimed to evaluate the effect of pirfenidone on the development of tracheal stenosis in the rats intubated with a tracheal tube.…”