Metabolomics approach to serum biomarker for loperamide-induced constipation in SD rats.
- Author:
Ji Eun KIM
1
;
Young Ju LEE
;
Moon Hwa KWAK
;
Go JUN
;
Eun Kyoung KOH
;
Sung Hwa SONG
;
Ji Eun SEONG
;
Ji Won KIM
;
Kyu Bong KIM
;
Suhkmann KIM
;
Dae Youn HWANG
Author Information
- Publication Type:Original Article
- Keywords: loperamide; constipation; metabolomics; serum; transverse colon
- MeSH: Amino Acids; Animals; Aspartate Aminotransferases; Biomarkers; Colon, Transverse; Constipation*; Creatinine; Diarrhea; Gastroenteritis; Glucose; Glutamic Acid; Glutamine; Glycerol; Inflammatory Bowel Diseases; L-Lactate Dehydrogenase; Lactic Acid; Loperamide; Magnetic Resonance Spectroscopy; Metabolomics*; Rats*; Succinic Acid; Weights and Measures
- From:Laboratory Animal Research 2014;30(1):35-43
- CountryRepublic of Korea
- Language:English
- Abstract: Loperamide has long been known as an opioid-receptor agonist useful as a drug for treatment of diarrhea resulting from gastroenteritis or inflammatory bowel disease as well as to induce constipation. To determine and characterize putative biomarkers that can predict constipation induced by loperamide treatment, alteration of endogenous metabolites was measured in the serum of Sprague Dawley (SD) rats treated with loperamide for 3 days using 1H nuclear magnetic resonance (1H NMR) spectral data. The amounts and weights of stool and urine excretion were significantly lower in the loperamide-treated group than the No-treated group, while the thickness of the villus, crypt layer, and muscle layer was decreased in the transverse colon of the same group. The concentrations of aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and creatinine (Cr) were also slightly changed in the loperamide-treated group, although most of the serum components were maintained at a constant level. Furthermore, pattern recognition of endogenous metabolites showed completely separate clustering of the serum analysis parameters between the No-treated group and loperamide-treated group. Among 35 endogenous metabolites, four amino acids (alanine, glutamate, glutamine and glycine) and six endogenous metabolites (acetate, glucose, glycerol, lactate, succinate and taurine) were dramatically decreased in loperamide-treated SD rats. These results provide the first data pertaining to metabolic changes in SD rats with loperamide-induced constipation. Additionally, these findings correlate the changes in 10 metabolites with constipation.
