Antiplatelet drug ticagrelor delays gastric ulcer healing in rats

Abstract

Abstract. Adenosine diphosphate P2Y 12 receptor antagonist clopidogrel is not sufficiently safe for the gastric mucosa in patients with high risk of peptic ulcer, since it may impair healing of gastric erosions. However, the safety of the novel P2Y 12 receptor antagonist ticagrelor in the gastric mucosa has not been elucidated to date. The present study aimed to examine whether ticagrelor delays gastric ulcer healing and to elucidate the involved mechanisms. Gastric kissing ulcers were produced in rats by luminal application of acetic acid solution, and ticagrelor was administered at dose of 10 or 20 mg/kg/day orally for 7 days. On day 8 after ulcer induction, the ulcer size, mucosal epithelial cell proliferation of the ulcer margin, expression levels of epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF), and signal transduction pathways for cell proliferation and angiogenesis were measured and compared between the ticagrelor-treated and untreated model groups. The results revealed that the ulcer size was significantly greater in the ticagrelor-treated group compared with the model group, while the mucosal epithelial cell proliferation of the ulcer margin was significantly decreased in the ticagrelor-treated group. In addition, ticagrelor significantly decreased the ulcer-stimulated expression levels of EGF, VEGF, phosphorylated extracellular signal-regulated kinase (ERK), phosphorylated P38 mitogen-activated protein kinase and nuclear factor-κB P65 at the ulcer margin (P<0.05). These findings suggested that ticagrelor delayed gastric ulcer healing. Furthermore, the possible mechanisms underlying the effect of ticagrelor were associated with its functions of attenuating the expression levels of VEGF and EGF, as well as suppressing the phosphorylation activation of ERK1/2, P38 and nuclear factor-κB P65. Finally, the gastric epithelial cell proliferation and angiogenesis were also inhibited.

YQFM Alleviates Side Effects Caused by Dasatinib through the ROCK/MLC Pathway in Mice

“…Some components may be present that could inhibit the main components from working, or competitive inhibition might exist between different components in YQFM, so further improvement is needed. Other drugs currently in clinical use, such as nonsteroidal anti-inflammatory drugs (Aspirin), antithrombotic drugs (Dabigatran-etexilate), and some chemotherapy drugs (Methotrexate), have reported gastrointestinal bleeding [ 31 , 45 , 46 ]. The key molecules involved in the bleeding process include VEGF, COX1/2, NF - κ B, ROCK, and MLC.…”

Total triterpenes from the fruits of Chaenomeles speciosa (Sweet) Nakai protects against indomethacin-induced gastric mucosal injury: involvement of TFF1-mediated EGF/EGFR and apoptotic pathways

“…At the same time, it is also a complex process of interaction between multiple cells and molecules. Epidermal growth factor (EGF) and its receptor (EGFR), trefoil factor 1(TFF1, A member of trefoil factor family) and proliferation cell nuclear antigen (PCNA) produced locally are involved in this process as important defensive cytokines by autocrine and/or paracrine actions . Binding of EGF to EGFR leads to EGFR and Src phosphorylations, triggers the signalling cascades causing the activations of Ras/Raf/MEK/ERK, PLC/PKC, PI3K/Akt, boosts cell proliferation, migration and differentiation, and thus facilitates damaged gastric mucosal repair and healing .…”

Protective effects of Naoxintong capsule alone and in combination with ticagrelor and atorvastatin in rats with Qi deficiency and blood stasis syndrome

“…2009 ), ATO group (8 mg/kg/d, the human equivalent dose in clinic) (Li et al. 2011 ), TIC group (20 mg/kg/d, the human equivalent dose in clinic) (Li et al. 2017 ), N&A group (NXT 500 mg/kg/d plus ATO 8 mg/kg/d), N&T group (NXT 500 mg/kg/d plus TIC 20 mg/kg/d).…”

“…The swimming exercise was performed from 8:00 am to 12:00 pm daily for 16 days. These QDBS animals were then randomly divided into 8 groups (n ¼ 10) for 12 weeks treatment, including model group, NXT-L group (250 mg/kg/d), NXT-M group (500 mg/kg/d, the human equivalent dose in clinic), NXT-H group (1000 mg/kg/d) (Chen et al 2009), ATO group (8 mg/kg/d, the human equivalent dose in clinic) (Li et al 2011), TIC group (20 mg/kg/d, the human equivalent dose in clinic) (Li et al 2017), N&A group (NXT 500 mg/kg/d plus ATO 8 mg/kg/d), N&T group (NXT 500 mg/ kg/d plus TIC 20 mg/kg/d). We treated rats with the above drugs which were dissolved with 0.5% CMC-Na orally once a day for 12 weeks, while animals in the normal group and model group received the same volume of 0.5% CMC-Na.…”