title: Metabolomics analysis for hydroxy-L-proline-induced calcium oxalate nephrolithiasis in rats based on ultra-high performance liquid chromatography quadrupole time-of-flight mass spectrometry.
abstract: About 80% of kidney stones are composed of calcium oxalate (CaOx) with variable amounts of calcium phosphate, and hyperoxaluria is considered as an important factor of CaOx nephrolithiasis. However, the underlying metabolic mechanisms of CaOx nephrolithiasis remain undefined. In this study, we successfully developed a rat model with hydroxy-L-proline (HLP) -induced CaOx nephrolithiasis. Rats were continuously orally administrated with HLP for 28 days. Urine and blood samples were collected from the rats treated with or without HLP at four different time points. UPLC-Q-TOF/MS was applied to profile the abundances of metabolites. To obtain more comprehensive analysis of metabolic profiling spectrum, combination of RP-LC and HILIC were applied. We identify 42 significant differential metabolites in the urine, and 13 significant differential metabolites in the blood. Pathway analysis revealed that the pathways involved in amino acid metabolism, taurine metabolism, bile acid synthesis, energy metabolism, TCA cycle, purine metabolism, vitamin metabolism, nicotinic acid and nicotinamide metabolism have been modulated by HLP treatment. This study suggested that a number of metabolic pathways are dysfunctional in the HLP induced crystal kidney injury, and further studies on those pathways are warranted to better understand the metabolic mechanism of CaOx nephrolithiasis.
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors.forename: Songyan
authors.initials: S
authors.lastname: Gao
authors.affiliation: Brigade of undergraduate student, Second Military Medical University, Shanghai 200433, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Yang
authors.affiliation: Department of Nephrology, Changhai Hospital, Shanghai 200433, China.
authors.forename: Zhongjiang
authors.initials: Z
authors.lastname: Peng
authors.affiliation: Brigade of undergraduate student, Second Military Medical University, Shanghai 200433, China.
authors.forename: Hongtao
authors.initials: H
authors.lastname: Lu
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.affiliation: Department of Nephrology, Changhai Hospital, Shanghai 200433, China.
authors.forename: Jiarong
authors.initials: J
authors.lastname: Ding
authors.affiliation: Department of Urology, The Third Affiliated hospital, Second Military Medical University, Shanghai 200433, China.
authors.forename: Xingang
authors.initials: X
authors.lastname: Cui
authors.affiliation: Department of Nephrology, Changhai Hospital, Shanghai 200433, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Dong