Prevention Effect of TGF-β Type I Receptor Kinase Inhibitor in Esophageal Stricture Formation after Corrosive Burn

Abstract

Corrosive burns lead to progressive esophageal stricture and dysphagia. There are many trials to prevent esophageal stricture formation after corrosive burn. EW-7197 has been proven in several animal models of fibrosis to have antifibrotic and antiproliferative effect. This study aimed to assess the effects of EW-7197 on prevention for esophageal stricture formation after corrosive esophageal burn. An animal study was carried out, where the animals were divided into three groups: a healthy group, a control group (corrosive burn without EW-7197), and a treatment group (corrosive burn with EW-7197). Corrosive esophageal burns were induced using 30% NaOH on the lower esophagus. For 3 weeks, the control group received vehicle and the treatment group received 20 mg/kg/day EW-7197. Treatment efficacy was assessed by measuring the stenosis ratio by esophagogram with contrast media on day 21. Histologic staining was performed to evaluate the fibrosis area ratio, and Western blotting was performed to evaluate fibrotic markers. Among 20 rats that underwent surgery, 14 survived. Three in the treatment group died because of esophageal perforation, and three in the control group died due to their debilitating status. The esophageal stenosis ratio was significantly lower in the treatment group than in the control group (12.1 ± 9.5% and 42.2 ± 8.3%, respectively; p = 0.001). The histologic fibrosis area ratio was also significantly lower in the treatment group (12.5 ± 3.0% and 21.6 ± 2.1%, respectively; p = 0.001). The treatment group showed lower expressions of profibrogenic proteins such as TGF-β1, pSmad3, and α-SMA. EW-7197 may be a good alternative for the prevention esophageal stricture formation after corrosive burn.

Severe Intentional Corrosive (Nitric Acid) Acute Poisoning: A Case Report and Literature Review

“…Since one of the major consequences of tissue exposure to corrosive substances implies excessive fibrogenic activity, and since the secondary development of strictures is also a problem, additional therapies should be considered in selected cases. Several experimental corrosive esophagitis animal models have been used to promote new antifibrotic and antiproliferative strategies, such as vitamin E (α-tocopherol), methylprednisolone or EW-7197, and a selective inhibitor of TGF (transforming growth factor) β type I receptor kinase [ 67 , 68 , 69 ]. The administration of these agents in the early phases of the poisoning may limit the collagen deposition and stricture formation, but to date, they still lack clinical general acceptance.…”