Department of Pediatric Surgery, School of Medicine, Marmara University, Fevzi Çakmak Mahallesi, Muhsin Yazicioğlu Caddesi, No: 10, Üst Kaynarca, Pendik, 34899, Istanbul, Turkey.
Department of Basic Health Sciences, Marmara University Health Sciences Faculty, Istanbul, Turkey.
Esophagus. 2018 Apr;15(2):59-68. doi: 10.1007/s10388-017-0594-4. Epub 2017 Oct 14.
The aim of this study is to evaluate the anti-inflammatory and anti-fibrotic effects of halofuginone in caustic esophageal burn injury in rats.
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.
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.
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.
本研究旨在评估卤泛群对大鼠腐蚀性食管烧伤的抗炎和抗纤维化作用。
雄性 Wistar 白化大鼠通过将 NaOH 溶液（1ml，37.5%）注入食管远端，造成腐蚀性食管损伤（CEI）。大鼠于第 3 天（早期组）或第 28 天（晚期组）断头，并每天用生理盐水或卤泛群（100μg/kg/天；腹腔注射）治疗，第三天后每隔一天继续治疗。在食管远端 2cm 处进行组织病理学评估，并通过化学发光（CL）测量一氧化氮（NO）、过氧亚硝酸盐（ONOO-）和氧衍生自由基。对未冲洗的近端食管样本进行核因子（NF）-κB、半胱天冬酶-3、谷胱甘肽（GSH）、丙二醛（MDA）和髓过氧化物酶（MPO）活性的评估。
早期和晚期腐蚀性损伤组的近端食管中 GSH、MDA、NF-κB 和半胱天冬酶-3 水平以及 MPO 活性无差异。早期和晚期腐蚀性损伤组灌洗食管中 TUNEL（+）细胞数量增加，经卤泛群治疗后减少。早期和晚期 CEI 组的显微镜下损伤评分均降低，经卤泛群治疗后降低。生理盐水处理的早期 CEI 组中升高的 NO、ONOO-和 CL 水平经卤泛群治疗后降低，但生理盐水处理晚期组中降低的 NO 和 ONOO-水平经卤泛群治疗后升高。
除了抗纤维化作用外，目前的研究结果表明，卤泛群还具有抗氧化和抗凋亡作用，支持卤泛群在 CEI 诱导的氧化应激中的治疗潜力。
