Gastroprotective Activity of Ethyl-4-[(3,5-di-tert-butyl-2-hydroxybenzylidene) Amino]benzoate against Ethanol-Induced Gastric Mucosal Ulcer in Rats (Retracted Article)
Gastroprotective Activity of Ethyl-4-[(3,5-di-tert-butyl-2-hydroxybenzylidene) Amino]benzoate against Ethanol-Induced Gastric Mucosal Ulcer in Rats (Retracted Article)
复制标题
DOI：
10.1371/journal.pone.0095908
复制
发表时间：
2014-05-06
期刊：
影响因子：
3.7
通讯作者：
Abdulla, Mahmood Ameen
中科院分区：
文献类型：
--
作者：
Halabi, Mohammed Farouq;Shakir, Raied Mustafa;Abdulla, Mahmood Ameen
背景：本研究旨在确定 4-[(3,5-二叔丁基-2-羟基亚苄基)氨基]苯甲酸乙酯 (ETHAB) 对大鼠的细胞毒性、抗氧化和胃保护作用。方法/主要发现：使用 MTT 裂解测定对 WRL68 细胞系评估 ETHAB 的细胞毒性作用，同时在体外评估其抗氧化活性。在抗溃疡研究中，大鼠被分为六组。第 1 组和第 2 组接受 10% Tween 20（载体）。第 3 组接受 20 mg/kg 奥美拉唑。第 4、5 和 6 组分别接受剂量为 5、10 和 20 mg/kg 的 ETHAB。一个小时后，第一组收到了车辆。第2-6组接受无水乙醇以诱导胃粘膜损伤。在WRL68细胞系中，观察到IC50超过100μg/mL。 ETHAB 结果显示在 DPPH、FRAP、一氧化氮和金属螯合测定中具有抗氧化活性。即使在最高剂量（1000 mg/kg）下也没有急性毒性。显微镜检查显示，用 ETHAB 预处理的大鼠显示出对胃粘膜的保护，通过超氧化物歧化酶 (SOD)、pH 水平、粘液分泌显着增加、胃损伤减少、丙二醛 (MDA) 水平和显着平坦的胃粘膜来确定。从组织学角度来看，由于白细胞浸润减少了粘膜下水肿，因此 ETHAB 预处理产生了相对更好的胃保护作用。 PAS 染色显示阿尔新蓝的摄取强度增加。免疫组化方面，ETHAB显示Bax蛋白表达下调，Hsp70蛋白过表达。结论/意义：ETHAB的胃保护作用可能与抗氧化活性、增加胃壁粘液、胃内容物pH值、SOD活性、MDA水平降低、溃疡面积、胃粘膜变平、减少粘膜下层水肿和白细胞浸润、增加PAS染色、上调Hsp70 蛋白并抑制 Bax 的表达。
Background: The study was carried out to determine the cytotoxic, antioxidant and gastro-protective effect of ethyl-4-[(3,5di- tert-butyl-2-hydroxybenzylid ene)amino] benzoate (ETHAB) in rats.Methodology/Principal Findings: The cytotoxic effect of ETHAB was assessed using a MTT cleavage assay on a WRL68 cell line, while its antioxidant activity was evaluated in vitro. In the anti-ulcer study, rats were divided into six groups. Group 1 and group 2 received 10% Tween 20 (vehicle). Group 3 received 20 mg/kg Omeprazole. Groups 4, 5 and 6 received ETHAB at doses of 5, 10, and 20 mg/kg, respectively. After an hour, group 1 received the vehicle. Groups 2-6 received absolute ethanol to induce gastric mucosal lesions. In the WRL68 cell line, an IC50 of more than 100 mu g/mL was observed. ETHAB results showed antioxidant activity in the DPPH, FRAP, nitric oxide and metal chelating assays. There was no acute toxicity even at the highest dosage (1000 mg/kg). Microscopy showed that rats pretreated with ETHAB revealed protection of gastric mucosa as ascertained by significant increases in superoxide dismutase (SOD), pH level, mucus secretion, reduced gastric lesions, malondialdehyde (MDA) level and remarkable flattened gastric mucosa. Histologically, pretreatment with ETHAB resulted in comparatively better gastric protection, due to reduction of submucosal edema with leucocyte infiltration. PAS staining showed increased intensity in uptake of Alcian blue. In terms of immunohistochemistry, ETHAB showed down-expression of Bax proteins and over-expression of Hsp70 proteins.Conclusion/Significance: The gastroprotective effect of ETHAB may be attributed to antioxidant activity, increased gastric wall mucus, pH level of gastric contents, SOD activity, decrease in MDA level, ulcer area, flattening of gastric mucosa, reduction of edema and leucocyte infiltration of the submucosal layer, increased PAS staining, up-regulation of Hsp70 protein and suppressed expression of Bax.