Halofuginone improves caustic-induced oxidative injury of esophagus in rats

• Published in: Esophagus : official journal of the Japan Esophageal Society Vol. 15; no. 2; pp. 59 - 68
• Main Authors: Cerit, Kıvılcım Karadeniz, Karakoyun, Berna, Bahadır, Elif, Yüksel, Meral, Bülbül, Nurdan, Ercan, Feriha, Dağlı, E. Tolga, Yeğen, Berrak Ç.
• Format: Journal Article
• Language: English
• Published: Tokyo Springer Japan 01-04-2018; Springer Nature B.V
• Subjects: Animals; Anti-Inflammatory Agents - therapeutic use; Apoptosis - drug effects; Burns; Burns, Chemical - drug therapy; Burns, Chemical - metabolism; Burns, Chemical - pathology; Caspase 3 - metabolism; Drug therapy; Esophagus; Esophagus - metabolism; Esophagus - pathology; Gastroenterology; Glutathione - metabolism; Inflammation; Male; Malondialdehyde - metabolism; Medicine; Medicine & Public Health; NF-kappa B - metabolism; Nitric Oxide - metabolism; Original Article; Oxidative Stress; Peroxidase - metabolism; Piperidines - therapeutic use; Quinazolinones - therapeutic use; Rats; Rats, Wistar; Reactive Oxygen Species - metabolism; Rodents; Surgical Oncology; Thoracic Surgery; Halofuginone; Caustic burn; Reactive oxygen metabolites; Oxidative injury
• ISSN: 1612-9059; 1612-9067
• DOI: 10.1007/s10388-017-0594-4

Background
The aim of this study is to evaluate the anti-inflammatory and anti-fibrotic effects of halofuginone in caustic esophageal burn injury in rats.
Materials and methods
Corrosive esophageal injury (CEI) was produced in male Wistar albino rats by instilling NaOH solution (1 ml, 37.5%) into the distal esophagus. Rats were decapitated on the 3rd day (early group) or 28th day (late group), and treated daily with either saline or halofuginone (100 µg/kg/day; i.p.), continued on alternate days after the third day. Histopathological evaluation and measurement of nitric oxide (NO), peroxynitrite (ONOO-) and oxygen-derived radicals by chemiluminescence (CL) were made in the distal 2 cm of the esophagus. Non-irrigated proximal esophageal samples were assessed for the levels of nuclear factor (NF)-κB, caspase-3, glutathione (GSH), malondialdehyde (MDA) and myeloperoxidase (MPO) activity.
Results
GSH, MDA, NF-κB and caspase-3 levels, and MPO activity in the proximal esophagus were not different among groups. Increased number of TUNEL (+) cells in the irrigated esophagus of the early and late caustic injury groups was reduced by halofuginone treatment. High microscopic damage scores in both early and late CEI groups were decreased with halofuginone treatment. NO, ONOO- and CL levels, which were elevated in the saline-treated early CEI group, were reduced by halofuginone treatment, but reduced NO and ONOO- levels in the late period of saline-treated group were increased by halofuginone.
Conclusion
In addition to its anti-fibrotic effects, current findings demonstrate that halofuginone exerts antioxidant and anti-apoptotic actions and supports therapeutic potential for halofuginone in CEI-induced oxidative stress.