Department of Pharmacology, Faculty of Pharmacy, Ataturk University, 25240, Erzurum, Turkey.
Department of Biochemistry, Faculty of Pharmacy, Agri Ibrahim Cecen University, Agri, Turkey.
Naunyn Schmiedebergs Arch Pharmacol. 2020 Dec;393(12):2463-2472. doi: 10.1007/s00210-020-01956-5. Epub 2020 Aug 3.
Aprepitant is a selective SP/NK-1 receptor antagonist and used in postoperative and chemotherapeutics induced emesis and vomiting. The aim of our study is to show aprepitant may have beneficial effects on gastrointestinal complaints in cancer patients undergoing chemotherapeutics by indomethacin-induced gastric ulcer model. A total of 48 rats were fasted 24 h for ulcer experiment. Aprepitant doses of 5, 10, 20, and 40 mg/kg were evaluated for their antiulcer activity. Omeprazole (20 mg/kg) was used as a positive control group. Six hours after 25 mg/kg indomethacin administration, all stomachs were dissected out. After macroscopic analyses, tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), COX-1, and COX-2 mRNA levels and SOD activity, and GSH and MDA levels of stomachs were determined. Histopathological examinations were evaluated. Aprepitant administration exerted 48.14%, 49.62%, 65.92%, and 76.77% ulcer inhibition effects at 5, 10, 20, and 40 mg/kg, respectively. Aprepitant administration decreased oxidative stress and inflammatory parameters in stomach tissues dose dependently. Aprepitant administration increased stomach COX-2 mRNA levels at 20 and 40 mg/kg doses. Although aprepitant appears to be disadvantageous in terms of treating gastric ulcer due to COX enzyme inhibition according to the previous studies, aprepitant has been shown to have ulcer healing effect in our study. When aprepitant is given as an anti-nausea and vomiting drug to cancer patients undergoing chemotherapy, we can argue that it will not be necessary to add a new gastric protective agent as it also shows beneficial effects in gastrointestinal complaints.
阿瑞匹坦是一种选择性的 SP/NK-1 受体拮抗剂,用于术后和化疗引起的恶心和呕吐。我们的研究目的是通过吲哚美辛诱导的胃溃疡模型表明阿瑞匹坦可能对接受化疗的癌症患者的胃肠道不适有有益的影响。共有 48 只大鼠进行 24 小时禁食进行溃疡实验。评估了阿瑞匹坦 5、10、20 和 40mg/kg 剂量的抗溃疡活性。奥美拉唑(20mg/kg)用作阳性对照组。吲哚美辛(25mg/kg)给药 6 小时后,取出所有胃。进行宏观分析后,测定肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、COX-1 和 COX-2mRNA 水平以及胃的 SOD 活性、GSH 和 MDA 水平。评估组织病理学检查。阿瑞匹坦给药在 5、10、20 和 40mg/kg 时分别产生 48.14%、49.62%、65.92%和 76.77%的溃疡抑制作用。阿瑞匹坦给药剂量依赖性地降低胃组织中的氧化应激和炎症参数。阿瑞匹坦给药在 20 和 40mg/kg 剂量时增加胃 COX-2mRNA 水平。尽管根据先前的研究,阿瑞匹坦由于抑制 COX 酶而在治疗胃溃疡方面似乎不利,但在我们的研究中,阿瑞匹坦已显示出溃疡愈合作用。当阿瑞匹坦作为癌症患者化疗的止吐药物给予时,我们可以争辩说,由于它还对胃肠道不适有有益的影响,因此无需添加新的胃保护剂。