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  • Title: Teprenone ameliorates diclofenac-induced small intestinal injury via inhibiting protease activated receptors 1 and 2 activity.
    Author: Chao G, Wang Z, Yang C, Qian Y, Zhang S.
    Journal: Biomarkers; 2021 Feb; 26(1):38-44. PubMed ID: 33176506.
    Abstract:
    OBJECTIVE: This study aimed to investigate specific protein expression of injured intestinal mucosa induced by diclofenac, and explore the protective effects of teprenone on it. METHODS: Intestinal damage of Sprague Dawley male rats was gradually induced by the intragastric administration of diclofenac. After the last drug administration, the intestinal mucosa was taken off with an interval of 24 h, subsequently, its general histological injury and ultrastructure were observed and analysed by a transmission electron microscope. The expression levels of PAR1 and PAR2 protein were detected by immunohistochemistry and real-time polymerase chain reaction (PCR). RESULTS: The Reuter and Chiu scores of small intestinal damage were 5.63 ± 1.30 and 4.25 ± 0.70 respectively in the model group, which could be protected by teprenone (100 mg/kg⋅day) with the degree of 55.7% and 44%. Optical microscopy and transmission electron microscope showed that intestinal mucosa and ultrastructure were severely damaged. Distributed in the cytoplasm or aligned with the nucleus, the expression of PAR1 and PAR2 was significantly upregulated after the administration of diclofenac, while it was relieved after the treatment of teprenone. CONCLUSION: Our study presents a new view that teprenone might protect NSAIDs-induced (diclofenac) intestinal injury via suppressing the expression of PAR1 and PAR2.
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