Deferiprone has anti-inflammatory properties and reduces fibroblast migration in vitro

Abstract

Normal wound healing is a highly regulated and coordinated process. However, tissue injury often results in inflammation with excessive scar tissue formation after 40–70% of operations. Here, we evaluated the effect of the iron chelator deferiprone on inflammation and the migration of primary nasal fibroblasts and primary human nasal epithelial cells (HNECs) in vitro. The cytotoxicity of deferiprone was examined by the lactate dehydrogenase assay on primary nasal fibroblasts and air-liquid interface (ALI) cultures of HNECs. Wound closure was observed in scratch assays by using time-lapse confocal scanning laser microscopy. Interleukin-6 (IL-6) and type I and III collagen protein levels were determined by ELISA. Intracellular Reactive Oxygen Species (ROS) activity was measured by utilizing the fluorescent probe H2DCFDA. Deferiprone at 10 mM concentration was non-toxic to primary fibroblasts and HNECs for up to 48 hours application. Deferiprone had significant dose-dependent inhibitory effects on the migration, secreted collagen production and ROS release by primary nasal fibroblasts. Deferiprone blocked Poly (I:C)-induced IL-6 production by HNECs but did not alter their migration in scratch assays. Deferiprone has the potential to limit scar tissue formation and should be considered in future clinical applications.

Prevention of adhesions post-abdominal surgery: Assessing the safety and efficacy of Chitogel with Deferiprone in a rat model

“…Chitogel has haemostatic [ 11 ], anti-inflammatory and anti- proliferative properties [ 12 ]. Deferiprone’s potent anti-inflammatory and inhibitory effects on fibroblast migration potentiate Chitogel’s anti-adhesive properties [ 18 ]. Def also has inhibitory effects on Reactive Oxygen Species (ROS) generation and collagen secretion by primary fibroblasts [ 18 ].…”

“…Deferiprone’s potent anti-inflammatory and inhibitory effects on fibroblast migration potentiate Chitogel’s anti-adhesive properties [ 18 ]. Def also has inhibitory effects on Reactive Oxygen Species (ROS) generation and collagen secretion by primary fibroblasts [ 18 ]. This combined effect results in reduced fibrosis in the rat abdomen treated with Chitogel and Deferiprone when compared to Saline and Chitogel alone in both our abrasion and enterotomy with abrasion models.…”

“…The Def release profile from Chitogel has shown that the complete release of Def occurs within 72 h [ 19 ] and maximum serum levels are reached within 24 h [ 36 ]. These findings indicate that Def affects wound healing in the early stages of wound repair, a time when the production of ROS and associated inflammation is maximal [ 18 ]. Histological findings in the present study are concordant with these actions in the form of reduced fibroblastic proliferation and attenuated collagen deposition.…”

“…Def is an FDA-approved drug for the treatment of iron-overload conditions such as Thalassemia Major, which has also been shown to reduce reactive oxygen species (ROS), an important contributor to the inflammatory process in wound healing. In vitro Def has also been shown to reduce the migration and proliferation of fibroblasts in a time and dose-dependent manner [ 18 ]. Importantly, Def is released from Chitogel within 48 to 72 hours, a critical time-frame for the prevention of adhesion development [ 19 ].…”

Antibiotics Affect ROS Production and Fibroblast Migration in an In-vitro Model of Sinonasal Wound Healing

“…ROS signaling is concentration dependent; although sufficiently high ROS levels may induce apoptosis, moderate levels stimulate the inflammatory response and low levels activate metabolic signaling (Finkel, 2012). Manipulation of cellular ROS has been shown to slow the wound migration of fibroblasts in vitro (Mohammadpour et al, 2013;Ramezanpour et al, 2019a) and to inhibit postoperative adhesion formation in animal models of surgery (ten Raa et al, 2006).…”