Ocakci Ayse, Coskun Omer, Tumkaya Levent, Kanter Mehmet, Gurel Ahmet, Hosnuter Mubin, Uzun Lokman
Department of Health High School, Zonguldak Karaelmas University, Zonguldak, Turkey.
Int J Pediatr Otorhinolaryngol. 2006 Jan;70(1):45-52. doi: 10.1016/j.ijporl.2005.05.018. Epub 2005 Jun 23.
This study was evaluated to investigate the efficacy of Ebselen, which is an organoselenium compound and glutathione peroxidase mimic, on the prevention of stricture development after esophageal caustic injuries in the rat.
Thirty healthy male Wistar albino rats were utilized in this study. The rats were randomly allotted into one of three experimental groups: group A (sham) animals were uninjured. Caustic esophageal burn was created by applying 1 ml of 37.5% NaOH to the distal esophagus. Group B rats were injured but untreated. Group C rats were injured and received Ebselen (10 mg/kg/day) via the oral route. Blood and tissue samples for the biochemical and histopathological analysis were taken all rats at the end (28th day) of the experiment. Oxidative stress is believed to play a role in the pathogenesis of corrosive esophageal burns. To assess changes in the cellular antioxidant defense system, we measured the activities of antioxidant enzymes (such as glutathione peroxidase (GSHPx), superoxide dismutase (SOD), and catalase (CAT)) in esophagus homogenates. We also measured esophageal tissue malondialdehyde (MDA) levels, a marker of lipid peroxidation, to determine whether there is an imbalance between oxidant and antioxidant status. Efficacy of the treatment was assessed by measuring the stenosis index and histopathologic damage score and biochemically by determining tissue hydroxyproline content, lipid peroxidation and antioxidant enzyme levels.
The stenosis index in group B was significantly increased compared with group A and C (P<0.05). The hydroxyproline level was significantly increased in group B compared with group A and C (P<0.05). In group B, the histopathologic damage score was significantly higher than in group C (P<0.05). Treatment with Ebselen decreased tissue hydroxyproline levels, histological damage, and the stenosis index. Caustic esophageal burn increased the lipid peroxidation and also decreased the antioxidant enzyme levels in group B. Ebselen treatments for 28 days decreased the elevated lipid peroxidation and also increased the reduced antioxidant enzyme levels. Live weights of the rats was significantly decreased in group B compared with group A and C (P<0.05).
It is concluded that Ebselen has a preventive effect in the development of fibrosis and decrease the lipid peroxidation, and increase the antioxidant defense system activity in an experimental model of corrosive esophagitis in rats.
本研究旨在评估依布硒啉（一种有机硒化合物和谷胱甘肽过氧化物酶模拟物）对预防大鼠食管腐蚀性损伤后狭窄形成的疗效。
本研究使用了30只健康雄性Wistar白化大鼠。将大鼠随机分为三个实验组之一：A组（假手术组）动物未受伤。通过向远端食管施加1 ml 37.5%的氢氧化钠造成腐蚀性食管烧伤。B组大鼠受伤但未治疗。C组大鼠受伤并通过口服途径接受依布硒啉（10 mg/kg/天）。在实验结束时（第28天）采集所有大鼠的血液和组织样本进行生化和组织病理学分析。氧化应激被认为在腐蚀性食管烧伤的发病机制中起作用。为了评估细胞抗氧化防御系统的变化，我们测量了食管匀浆中抗氧化酶（如谷胱甘肽过氧化物酶（GSHPx）、超氧化物歧化酶（SOD）和过氧化氢酶（CAT））的活性。我们还测量了食管组织丙二醛（MDA）水平（脂质过氧化的标志物），以确定氧化剂和抗氧化剂状态之间是否存在失衡。通过测量狭窄指数和组织病理学损伤评分以及通过测定组织羟脯氨酸含量、脂质过氧化和抗氧化酶水平进行生化评估治疗效果。
与A组和C组相比，B组的狭窄指数显著增加（P<0.05）。与A组和C组相比，B组的羟脯氨酸水平显著增加（P<0.05）。在B组中，组织病理学损伤评分显著高于C组（P<0.05）。依布硒啉治疗降低了组织羟脯氨酸水平、组织学损伤和狭窄指数。腐蚀性食管烧伤增加了B组的脂质过氧化，也降低了抗氧化酶水平。依布硒啉治疗28天降低了升高的脂质过氧化，也增加了降低的抗氧化酶水平。与A组和C组相比，B组大鼠的体重显著降低（P<0.05）。
得出结论，依布硒啉在大鼠腐蚀性食管炎实验模型中对纤维化的发展具有预防作用，可降低脂质过氧化，并增加抗氧化防御系统活性。
