Metabolic profiling of kidney and urine in rats with lithium-induced nephrogenic diabetes insipidus by (1)H-NMR-based metabonomics.
Lithium (Li) treatment for bipolar affective disorders is associated with a variety of renal side effects. The metabolic response of the kidney to chronic Li treatment has rarely been studied. We applied a novel method of (1)H-nuclear magnetic resonance (NMR)-based metabonomics to integrate metabolic profiling and to identify the changes in the levels of metabolites in the kidney and urine from rats with Li-induced NDI. Metabolic profiles of urine and kidney homogenate [3 different zones (cortex, outer medulla, and inner medulla) or whole kidney] were investigated using high-resolution NMR spectroscopy coupled with pattern recognition methods. The accurate concentrations of metabolites in kidney homogenates and urine were rapidly measured using the target-profiling procedure, and the difference in the levels of metabolites was compared using multivariate analysis, such as principal component analysis and orthogonal partial least squares-discriminant analysis. Major endogenous metabolites for kidney homogenates contained products of glycolysis (glucose, lactate) and amino acids, as well as organic osmolytes (e.g., betaine, myo-inositol, taurine, and glycerophosphocholine). Many metabolites revealed changes in their levels, including decreased levels of organic osmolytes and amino acids in the inner medulla. A number of urinary metabolites were changed in Li-induced NDI, and in particular, elevated urinary levels of acetate, lactate, allantoin, trimethylamine, and creatine could suggest Li-induced renal cell stress or injury. Taken together, metabonomics of kidney tissue and urine based on (1)H-NMR spectroscopy could provide insight into the effects of Li-induced renal effects and cell injury.
Hwang
Geum-Sook
GS
Joint Bioanalytical Research Team, Korea Basic Science Institute, Seoul, Korea.
Yang
Ji-Young
JY
Ryu
Do Hyun
DH
Kwon
Tae-Hwan
TH
D000818:Animals; D018500:Diabetes Insipidus, Nephrogenic / Q000139:chemically induced* / Q000378:metabolism*; D004231:Diuresis; D007668:Kidney / Q000378:metabolism*; D018020:Lithium Compounds; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D055432:Metabolomics; D015999:Multivariate Analysis; D009994:Osmolar Concentration; D025341:Principal Component Analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D014556:Urine / Q000737:chemistry*
D018020:Lithium Compounds