4-[(3,5-二叔丁基-2-羟基亚苄基)氨基]苯甲酸乙酯对大鼠乙醇诱导的胃黏膜溃疡的胃保护作用。
Gastroprotective activity of ethyl-4-[(3,5-di-tert-butyl-2-hydroxybenzylidene) amino]benzoate against ethanol-induced gastric mucosal ulcer in rats.
作者信息
Halabi Mohammed Farouq, Shakir Raied Mustafa, Bardi Daleya Abdulaziz, Al-Wajeeh Nahla Saeed, Ablat Abdulwali, Hassandarvish Pouya, Hajrezaie Maryam, Norazit Anwar, Abdulla Mahmood Ameen
机构信息
Department of Biomedical Science, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; Al-Moalim Mohamed Awad Center for Scientific Miracles of Prophetic Medicine, College of Medicine, Taibah University, Al-Madinah Al-Munawarah, Saudi Arabia.
Department of Chemistry, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia; Department. of Chemistry, Ibn Al-Haitham, University of Baghdad. Baghdad, Iraq.
出版信息
PLoS One. 2014 May 6;9(5):e95908. doi: 10.1371/journal.pone.0095908. eCollection 2014.
BACKGROUND
The study was carried out to determine the cytotoxic, antioxidant and gastro-protective effect of ethyl-4-[(3,5-di-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 µg/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.
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裂解试验评估ETHAB对WRL68细胞系的细胞毒性，同时在体外评估其抗氧化活性。在抗溃疡研究中，将大鼠分为六组。第1组和第2组接受10%吐温20（赋形剂）。第3组接受20 mg/kg奥美拉唑。第4、5和6组分别接受5、10和20 mg/kg剂量的ETHAB。一小时后，第1组接受赋形剂。第2 - 6组接受无水乙醇以诱导胃黏膜损伤。在WRL68细胞系中，观察到IC50大于100 µg/mL。ETHAB在DPPH、FRAP、一氧化氮和金属螯合试验中显示出抗氧化活性。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预处理的大鼠胃黏膜得到保护，这可通过超氧化物歧化酶（SOD）、pH值、黏液分泌显著增加、胃损伤减少、丙二醛（MDA）水平降低以及胃黏膜明显变平来确定。组织学上，用ETHAB预处理导致相对更好的胃保护作用，这是由于黏膜下水肿减轻和白细胞浸润减少。PAS染色显示阿尔辛蓝摄取强度增加。在免疫组织化学方面，ETHAB显示Bax蛋白表达下调和Hsp70蛋白表达上调。
结论/意义：ETHAB的胃保护作用可能归因于抗氧化活性、胃壁黏液增加、胃内容物pH值、SOD活性增加、MDA水平降低、溃疡面积减小、胃黏膜变平、水肿减轻和黏膜下层白细胞浸润减少、PAS染色增加、Hsp70蛋白上调以及Bax表达受抑制。
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