El-Sisi Alaa E, Sokar Samia S, Abu-Risha Sally E, Khira Doaa Y
Pharmacology & Toxicology Dept., Faculty of Pharmacy, Tanta University, Tanta, Egypt.
Heliyon. 2020 Aug 22;6(8):e04761. doi: 10.1016/j.heliyon.2020.e04761. eCollection 2020 Aug.
research in the treatment of gastric ulcer has involved the investigation of protective drugs. These drugs may be used as adjacent therapy with the traditional pharmacologic treatment of peptic ulcer. The present study is designed to investigate the gastro protective effects of diosmin (DIO), sildenafil (SILD) and their combinations with ranitidine (RANT) against indomethacin (INDO)-induced gastric ulcer in rats. Additionally, the potential mechanisms of their effect are addressed.
DIO (100 mg/kg) and SILD (10 mg/kg) were administered by oral route for seven days prior to ulcer induction. Moreover, other rats were treated with RANT (50 mg/kg) not only to compare efficiency of the medications but also, to help clarify potential mechanisms of their effect. Following, after 24 h of fasting, INDO (100 mg/kg) was administered for induction of gastric ulcer. Furthermore, rats in each group were sacrificed 4 h later. Biochemical analysis of DIO, SILD, RANT and their combinations pre-treated host tissues demonstrated reduction in tumor necrosis factor (TNF)-α and malondialdehyde (MDA) contents and concomitant increase in gastric pH, nitric oxide (NO) and reduced glutathione (GSH) contents.
It is observed, that SILD and DIO pre-treatment showed non-significant effect on gastric juice PH. However, their combinations with RANT is superior to using RANT alone. In addition, the results revealed, that combinations of (RANT and SILD) and (RANT and DIO) showed the highest increase in gastric tissue NO levels. But, these two combinations achieved the lowest MDA levels relative to the control (INDO) group. Despite, all groups displayed non-significant effect on reduced GSH content, (RANT and SILD) group increased GSH concentration by 39.75% relative to INDO group. In addition, DIO, RANT and (RANT and DIO) pre-treatment have anti-apoptotic activity on gastric mucosa. On the other hand, SILD did not affect caspase-3 immunostaining. These results are confirmed by histopathological findings.
The work outcomes provide a new gastro protective agents in clinical gastropathy. So, this study not only provides an efficient way for peptic ulcer protection, but also it may be considered for future studies in ulcer healing and gastric cancer.
胃溃疡治疗研究涉及保护性药物的调查。这些药物可与消化性溃疡的传统药物治疗联合使用。本研究旨在调查地奥司明（DIO）、西地那非（SILD）及其与雷尼替丁（RANT）的组合对吲哚美辛（INDO）诱导的大鼠胃溃疡的胃保护作用。此外，还探讨了其作用的潜在机制。
在诱导溃疡前7天，通过口服途径给予DIO（100mg/kg）和SILD（10mg/kg）。此外，用RANT（50mg/kg）治疗其他大鼠，不仅是为了比较药物的疗效，也是为了帮助阐明其作用的潜在机制。随后，禁食24小时后，给予INDO（100mg/kg）诱导胃溃疡。此外，4小时后处死每组大鼠。对DIO、SILD、RANT及其组合预处理的宿主组织进行生化分析，结果显示肿瘤坏死因子（TNF）-α和丙二醛（MDA）含量降低，同时胃pH值、一氧化氮（NO）和还原型谷胱甘肽（GSH）含量增加。
观察到，SILD和DIO预处理对胃液pH值无显著影响。然而，它们与RANT的组合优于单独使用RANT。此外，结果显示，（RANT和SILD）以及（RANT和DIO）的组合使胃组织NO水平升高幅度最大。但是，相对于对照组（INDO），这两种组合的MDA水平最低。尽管所有组对还原型GSH含量的影响均不显著，但（RANT和SILD）组相对于INDO组使GSH浓度增加了39.75%。此外，DIO、RANT和（RANT和DIO）预处理对胃黏膜具有抗凋亡活性。另一方面，SILD不影响半胱天冬酶-3免疫染色。组织病理学结果证实了这些结果。
该研究成果为临床胃病提供了新的胃保护剂。因此，本研究不仅为消化性溃疡的保护提供了一种有效方法，也可为未来溃疡愈合和胃癌的研究提供参考。
