Correlation between laxative effects of uridine and suppression of ER stress in loperamide induced constipated SD rats.
10.5625/lar.2017.33.4.298
- Author:
Ji Eun KIM
1
;
Bo Ram SONG
;
Woo Bin YUN
;
Jun Young CHOI
;
Jin Ju PARK
;
Mi Rim LEE
;
Dae Youn HWANG
Author Information
1. Department of Biomaterials Science, College of Natural Resources & Life Science/Life and Industry Convergence Research Institute, Pusan National University, Miryang 50463, Korea. dyhwang@pusan.ac.kr
- Publication Type:Original Article
- Keywords:
Uridine;
ER stress response;
Constipation;
Laxative effects;
Loperamide;
apoptosis
- MeSH:
Animals;
Apoptosis;
Carrier Proteins;
Colon, Transverse;
Constipation;
DNA;
Endoplasmic Reticulum;
Eukaryotic Initiation Factor-2;
Loperamide*;
Phosphorylation;
Rats*;
Uridine*
- From:Laboratory Animal Research
2017;33(4):298-307
- CountryRepublic of Korea
- Language:English
-
Abstract:
A correlation between endoplasmic reticulum (ER) stress and laxative effects was first reported in a constipation model treated with an aqueous extract of Liriope platyphylla (AEtLP) roots. To investigate the correlation between the laxative effect of uridine (Urd) and ER stress response, alterations in the key parameters for ER stress were measured in loperamide (Lop) induced constipation Sprague Dawley (SD) rats treated with Urd. The efficacy of the laxative effect of Urd was notable on the symptoms of chronic constipation, including alteration of stool parameters and structure of the transverse colon, in Lop induced constipated SD rats. In the PERK/eIF2-ATF4 pathway of ER stress response, the levels of eukaryotic initiation factor 2 alpha (eIF2α) phosphorylation and DNA damage-inducible protein (GADD34) transcripts were significantly enhanced in the Lop+Vehicle treated group. However, the levels were restored in the Lop+Urd treated group, although few differences were detected in the decrease rate. Similar changes were observed for levels of inositol-requiring enzyme 1 beta (IRE1β) phosphorylation and X-box binding protein 1 (XBP-1) transcript in the IRE1α/XBP pathway. Furthermore, the number of ER stress-induced apoptotic cells and Bax and Bcl-2 expression were recovered in the Lop+Urd treated group compared to the Lop+Vehicle treated group. The results of the present study therefore provide first evidence that the laxative effects of Urd may be tightly correlated with the recovery of ER stress response in constipation models.
