Department of Chemistry, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia.
PLoS One. 2013;8(3):e59296. doi: 10.1371/journal.pone.0059296. Epub 2013 Mar 13.
Synthetic steroids, such as 9α-bromobeclomethasonedipropionate, have shown gastroprotective activity. For example, the potent glucocorticoid steroid, beclomethasone dipropionate, has been used for treatment of bowel ulcerations. The purpose of the present study was to evaluate the effect of a synthetic steroid, (20S)-22-acetoxymethyl-6β-methoxy-3α,5-dihydro-3'H-cyclopropa[3α,5]-5α-pregnane (AMDCP), on ethanol-induced gastric mucosa injuries in rats.
METHODOLOGY/PRINCIPAL FINDING: Rats were divided into 8 groups. The negative control and ethanol control groups were administered Tween 20 (10%v/v) orally. The reference control group, 20 mg/kg omeprazole (10% Tween 20, 5 mL/kg), was administrated orally. The experimental groups received 1, 5, 10, 15 or 20 mg/kg of the AMDCP compound (10% Tween 20, 5 mL/kg). After 60 min, Tween 20 and absolute ethanol was given orally (5 mL/kg) to the negative control group and to the rest of the groups, and the rats were sacrificed an hour later. The acidity of gastric content, gastric wall mucus and areas of mucosal lesions were assessed. In addition, histology and immunohistochemistry of the gastric wall were assessed. Prostaglandin E2 (PGE2) and malondialdehyde (MDA) content were also measured. The ethanol control group exhibited severe mucosal lesion compared with the experimental groups with fewer mucosal lesions along with a reduction of edema and leukocyte infiltration. Immunohistochemical staining of Hsp70 and Bax proteins showed over-expression and under-expression, respectively, in the experimental groups. The experimental groups also exhibited high levels of PGE2 as well as a reduced amount of MDA. AMDCP decreased the acidity and lipid peroxidation and increased the levels of antioxidant enzymes.
CONCLUSION/SIGNIFICANCE: The current investigation evaluated the gastroprotective effects of AMDCP on ethanol-induced gastric mucosal lesions in rats. This study also suggests that AMDCP might be useful as a gastroprotective agent.
合成类固醇，如 9α-溴贝氯米松二丙酸酯，已显示出胃保护活性。例如，强效糖皮质激素类固醇倍氯米松二丙酸酯已被用于治疗肠溃疡。本研究的目的是评估一种合成类固醇，（20S）-22-乙酰氧甲基-6β-甲氧基-3α,5-二氢-3'H-环丙烷[3α,5]-5α-孕烷（AMDCP）对乙醇诱导的大鼠胃黏膜损伤的影响。
方法/主要发现：大鼠分为 8 组。阴性对照组和乙醇对照组给予吐温 20（10%v/v）口服。参考对照组，20mg/kg 奥美拉唑（10%吐温 20,5mL/kg），口服给药。实验组给予 1、5、10、15 或 20mg/kg 的 AMDCP 化合物（10%吐温 20,5mL/kg）。60 分钟后，吐温 20 和无水乙醇给予阴性对照组和其余各组口服（5mL/kg），1 小时后处死大鼠。评估胃内容物酸度、胃壁黏液和黏膜损伤面积。此外，还评估了胃壁的组织学和免疫组织化学。还测量了前列腺素 E2（PGE2）和丙二醛（MDA）的含量。与实验各组相比，乙醇对照组表现出严重的黏膜损伤，黏膜损伤较少，水肿和白细胞浸润减少。Hsp70 和 Bax 蛋白的免疫组织化学染色分别显示过表达和低表达。实验组还表现出高水平的 PGE2 和低水平的 MDA。AMDCP 降低了酸度和脂质过氧化作用，增加了抗氧化酶的水平。
结论/意义：本研究评估了 AMDCP 对乙醇诱导的大鼠胃黏膜损伤的胃保护作用。本研究还表明，AMDCP 可能作为胃保护剂有用。
