Teprenone ameliorates diclofenac-induced small intestinal injury via inhibiting protease activated receptors 1 and 2 activity

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.

Keywords:

• Teprenone
• diclofenac
• small intestinal injury
• PAR1
• PAR2

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This research was supported by Zhejiang Provincial Natural Science Foundation of China [Grant No. LY18H030001], the Medicine and Health Science and Technology Plan Projects in Zhejiang province [Grant No. 2017KY413], Traditional Chinese Medicine Science and Technology Plan of Zhejiang Province [Grant No. 2017ZA089, 2016ZB071, 2015ZZ012, 2014ZA030], National Natural Science Foundation of China [Grant No. 81573760], Medical Health Platform Plan Projects of Zhejiang Province [Grant No. 2015RCA020] and Zhejiang Provincial Natural Science Foundation of China [Grant No. LY16H030010].