Metabolomics approach to serum biomarker for loperamide-induced constipation in SD rats.
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 (1)H nuclear magnetic resonance ((1)H 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.
Department of Biomaterials Science, College of Natural Resources & Life Science, Pusan National University, Miryang, Korea.
Ji-Eun
JE
Kim
Department of Biomaterials Science, College of Natural Resources & Life Science, Pusan National University, Miryang, Korea.
Young-Ju
YJ
Lee
Department of Biomaterials Science, College of Natural Resources & Life Science, Pusan National University, Miryang, Korea.
Moon-Hwa
MH
Kwak
Department of Biomaterials Science, College of Natural Resources & Life Science, Pusan National University, Miryang, Korea.
Go
G
Jun
Department of Biomaterials Science, College of Natural Resources & Life Science, Pusan National University, Miryang, Korea.
Eun-Kyoung
EK
Koh
Department of Biomaterials Science, College of Natural Resources & Life Science, Pusan National University, Miryang, Korea.
Sung-Hwa
SH
Song
Department of Biomaterials Science, College of Natural Resources & Life Science, Pusan National University, Miryang, Korea.
Ji-Eun
JE
Seong
College of Pharmacy, Dankook University, Cheonan, Korea.
Ji Won
JW
Kim
College of Pharmacy, Dankook University, Cheonan, Korea. ; Department of Medical Laser, Graduate School, Dankook University, Cheonan, Korea.
Kyu-Bong
KB
Kim
Department of Chemistry and Chemistry Institute for Functional Materials, Pusan National University, Busan, Korea.
Suhkmann
S
Kim
Department of Biomaterials Science, College of Natural Resources & Life Science, Pusan National University, Miryang, Korea.
Dae-Youn
DY
Hwang
constipation; loperamide; metabolomics; serum; transverse colon