Urinary metabolomics study on mice renal injury caused by calcium oxalate crystal based on UPLC-Q-TOF/MS platform

WANG Xuelei; CHAO Yufan; GAO Songyan; DONG Xin; WEN Xiaofei

doi:10.3969/j.issn.1006-0111.2019.02.006

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Article Navigation > Journal of Pharmaceutical Practice and Service > 2019 > 37(2): 126-134

WANG Xuelei, CHAO Yufan, GAO Songyan, DONG Xin, WEN Xiaofei. Urinary metabolomics study on mice renal injury caused by calcium oxalate crystal based on UPLC-Q-TOF/MS platform[J]. Journal of Pharmaceutical Practice and Service, 2019, 37(2): 126-134. doi: 10.3969/j.issn.1006-0111.2019.02.006

Citation:

WANG Xuelei, CHAO Yufan, GAO Songyan, DONG Xin, WEN Xiaofei. Urinary metabolomics study on mice renal injury caused by calcium oxalate crystal based on UPLC-Q-TOF/MS platform[J]. Journal of Pharmaceutical Practice and Service, 2019, 37(2): 126-134. doi: 10.3969/j.issn.1006-0111.2019.02.006

Urinary metabolomics study on mice renal injury caused by calcium oxalate crystal based on UPLC-Q-TOF/MS platform

doi: 10.3969/j.issn.1006-0111.2019.02.006

1.
Department of Urology, Shanghai East Hospital, Shanghai 200120, China
2.
School of Pharmacy, Naval Medical Universiry, Shanghai 200433, China

Received Date: 2018-11-16
Rev Recd Date: 2018-12-17

Abstract

Objective To explore the intrinsic mechanism of kidney injury due to calcium oxalate crystal by the study on the changes of metabolites in the urine of mice. Method UPLC-Q-TOF/MS-based metabolomics method was used to determine the changes of endogenous metabolites in mice urine with glyoxylate-induced mouse calcium oxalate crystal model.The multivariate statistics analysis and metabolite pathway analysis were performed by SIMCA-P and Metabo Analyst software respectively. Result Compared with the control group,the kidney tissue of the model group showed obvious calcium salt deposition and the serum creatinine and urea nitrogen levels increased abnormally.21 differential metabolites,such as uric acid,taurine and phenylalanine,were detected from the urine. Conclusion The differential metabolites mainly involve amino acid metabolism,energy metabolism,taurine metabolism,purine metabolism and VB₆ metabolism,which is of great importantce to the mechanism study and the biomaker screening for the early stage stone disease.
- metabolomics,
- calcium oxalate crystal,
- UPLC-Q-TOF/MS,
- glyoxylate,
- differential metabolites

References

[1]	XU H,ZISMAN A L,COE F L,et al.Kidney stones:an update on current pharmacological management and future directions[J].Expert Opin Pharmacother,2013,14(4):435-447.
[2]	ROMERO V,AKPINAR H,ASSIMOS D G.Kidney stones:a global picture of prevalence,incidence,and associated risk factors[J].Rev Urol,2010,12(2-3):e86-e96.
[3]	ZENG G H,MAI Z L,XIA S J,et al.Prevalence of kidney stones in China:an ultrasonography based cross-sectional study[J].BJU Int,2017,120:109-116.
[4]	SUTHERLAND J W,PARKS J H,COE F L.Recurrence after a single renal stone in a community practice[J].Miner Electrolyte Metab,1985,11(4):267-269.
[5]	RULE AD,BERGSTRALH E J,MELTON L J,et al.Kidney stones and the risk for chronic kidney disease[J].Clin J Am Soc Nephrol,2009,4(4):804-811.
[6]	EL-ZOGHBY Z M,LIESKE J C,FOLEY RN,et al.Urolithiasis and the risk of ESRD[J].Clin J Am Soc Nephrol,2012,7(9):1409-1415.
[7]	JOHNSON C M,WILSON D M,O'FALLON WM,et al.Renal stone epidemiology:a 25-year study in Rochester,Minnesota[J].Kidney Int,1979,16(5):624-631.
[8]	VERVAET B A,VERHULST A,DAUWE SE,et al.An active renal crystal clearance mechanism in rat and man[J].Kidney Int,2009,75(1):41-51.
[9]	KHAN S R.Reactive oxygen species as the molecular modulators of calcium oxalate kidney stone formation:evidence from clinical and experimental investigations[J].J Urol,2013,189(3):803-811.
[10]	KHAN S R.Reactive oxygen species,inflammation and calcium oxalate nephrolithiasis[J].Transl Androl Urol,2014,3(3):256-276.
[11]	TASCA A.Metabolic syndrome and bariatric surgery in stone disease etiology[J].Curr Opin Urol,2011,21(2):129-133.
[12]	MOHAMMADJAFARI H,BARZIN M,SALEHIFAR E,et al.Etiologic and epidemiologic pattern of urolithiasis in north iran;review of 10-year findings[J].Iran J Pediatr,2014,24(1):69-74.
[13]	NICHOLSON J K,LINDON J C,HOLMES E.‘Metabonomics’:understanding the metabolic responses of living systems to pathophysiological stimuli via multivariate statistical analysis of biological NMR spectroscopic data[J].Xenobiotica,1999,29(11):1181-1189.
[14]	ROCHFORT S.Metabolomics reviewed:a new "omics" platform technology for systems biology and implications for natural products research[J].J Nat Prod,2005,68(12):1813-1820.
[15]	OKADA A,NOMURA S,HIGASHIBATA Y,et al.Successful formation of calcium oxalate crystal deposition in mouse kidney by intraabdominal glyoxylate injection[J].Urol Res,2007,35(2):89-99.
[16]	高松燕.基于两种动物模型的结晶肾损伤形成机制及中药干预的代谢组学研究[D].上海:第二军医大学,2015.
[17]	CHAN E C,PASIKANTI K K,NICHOLSON J K.Global urinary metabolic profiling procedures using gas chromatography-mass spectrometry[J].Nat Protoc,2011,6(10):1483-1499.
[18]	SMILDE A K,van der WERF M J,BIJLSMA S,et al.Fusion of mass spectrometry-based metabolomics data[J].Anal Chem,2005,77(20):6729-6736.
[19]	TRYGG J,HOLMES E,LUNDSTEDT T.Chemometrics in metabonomics[J].J Proteome Res,2007,6(2):469-479.
[20]	WANG X,WANG H,ZHANG A,et al.Metabolomics study on the toxicity of aconite root and its processed products using ultraperformance liquid-chromatography/electrospray-ionization synapt high-definition mass spectrometry coupled with pattern recognition approach and ingenuity pathways analysis[J].J Proteome Res,2012,11(2):1284-1301.
[21]	WISHART D S,JEWISON T,GUO A C,et al.HMDB 3.0 The Human Metabolome Database in 2013[J].Nucleic Acids Res,2013,41(Database issue):D801-D807.
[22]	IANG X,CHEN X,LIANG Q,et al.Metabonomic study of Chinese medicine Shuanglong formula as an effective treatment for myocardial infarction in rats[J].J Proteome Res,2011,10(2):790-799.
[23]	高越.基于组学和网络药理学的养心氏片抗心衰作用机理研究[D].上海:第二军医大学,2016.
[24]	BOIRIE Y,ALBRIGHT R,BIGELOW M,et al.Impairment of phenylalanine conversion to tyrosine in end-stage renal disease causing tyrosine deficiency[J].Kidney Int,2004,66(2):591-596.
[25]	YOUNG B A,VON KORFF M,HECKBERT S R,et al.Association of major depression and mortality in Stage 5 diabetic chronic kidney disease[J].Gen Hosp Psychiatry,2010,32(2):119-124.
[26]	KERAI M D,WATERFIELD C J,KENYON S H,et al.Reversal of ethanol-induced hepatic steatosis and lipid peroxidation by taurine:a study in rats[J].Alcohol Alcohol,1999,34(4):529-541.
[27]	GUAN X,DEI-ANANE G,LIANG R,et al.Donor preconditioning with taurine protects kidney grafts from injury after experimental transplantation[J].J Surg Res,2008,146(1):127-134.
[28]	BADENHORST C P,van der SLUIS R,ERASMUS E,et al.Glycine conjugation:importance in metabolism,the role of glycine N-acyltransferase,and factors that influence interindividual variation[J].Expert Opin Drug Metab Toxicol,2013,9(9):1139-1153.
[29]	WILCOX B J,RITENOUR-RODGERS K J,ASSER A S,et al.N-acylglycine amidation:implications for the biosynthesis of fatty acid primary amides[J].Biochemistry,1999,38(11):3235-3245.
[30]	COSTA C G,GUERAND W S,STRUYS E A,et al.Quantitative analysis of urinary acylglycines for the diagnosis of beta-oxidation defects using GC-NCI-MS[J].J Pharm Biomed Anal,2000,21(6):1215-1224.
[31]	OMBRONE D,SALVATORE F,RUOPPOLO M.Quantitative liquid chromatography coupled with tandem mass spectrometry analysis of urinary acylglycines:application to the diagnosis of inborn errors of metabolism[J].Anal Biochem,2011,417(1):122-128.
[32]	LA MARCA G,RIZZO C.Analysis of organic acids and acylglycines for the diagnosis of related inborn errors of metabolism by GC-and HPLC-MS[J].Methods Mol Biol,2011,708:73-98.
[33]	KHAN S R.Reactive oxygen species,inflammation and calcium oxalate nephrolithiasis[J].Transl Androl Urol,2014,3(3):256-276.
[34]	KHAN S R.Renal tubular damage/dysfunction:key to the formation of kidney stones[J].Urol Res,2006,34(2):86-91.
[35]	KHAN S R.Role of renal epithelial cells in the initiation of calcium oxalate stones[J].Nephron Exp Nephrol,2004,98(2):e55-e60.
[36]	SCHEINMAN J I,VOZIYAN P A,BELMONT J M,et al.Pyridoxamine lowers oxalate excretion and kidney crystals in experimental hyperoxaluria:a potential therapy for primary hyperoxaluria[J].Urol Res,2005,33(5):368-371.
[37]	MITWALLI A,AYIOMAMITIS A,GRASS L,et al.Control of hyperoxaluria with large doses of pyridoxine in patients with kidney stones[J].Int Urol Nephrol,1988,20(4):353-359.
[38]	MILLINER D S,EICKHOLT J T,BERGSTRALH E J,et al.Results of long-term treatment with orthophosphate and pyridoxine in patients with primary hyperoxaluria[J].N Engl J Med,1994,331(23):1553-1558.
[39]	ORTIZ-ALVARADO O,MIYAOKA R,KRIEDBERG C,et al.Pyridoxine and dietary counseling for the management of idiopathic hyperoxaluria in stone-forming patients[J].Urology,2011,77(5):1054-1058.
[40]	DIJCKER J C,PLANTINGA E A,van BAAL J,et al.Influence of nutrition on feline calcium oxalate urolithiasis with emphasis on endogenous oxalate synthesis[J].Nutr Res Rev,2011,24(1):96-110.
[41]	JOHNSON R J,SANCHEZ-LOZADA L G,MAZZALI M,et al.What are the key arguments against uric acid as a true risk factor for hypertension[J].Hypertension,2013,61(5):948-951.
[42]	ROMERO F,PEREZ M,CHAVEZ M,et al.Effect of uric acid on gentamicin-induced nephrotoxicity in rats-role of matrix metalloproteinases 2 and 9[J].Basic Clin Pharmacol Toxicol,2009,105(6):416-424.
[43]	SHIMADA M,JOHNSON RJ,MAY W S Jr,et al.A novel role for uric acid in acute kidney injury associated with tumour lysis syndrome[J].Nephrol Dial Transplant,2009,24(10):2960-2964.

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通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142

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Urinary metabolomics study on mice renal injury caused by calcium oxalate crystal based on UPLC-Q-TOF/MS platform

1. Department of Urology, Shanghai East Hospital, Shanghai 200120, China

2. School of Pharmacy, Naval Medical Universiry, Shanghai 200433, China

Received Date: 2018-11-16

Rev Recd Date: 2018-12-17

Key words:

Abstract: Objective To explore the intrinsic mechanism of kidney injury due to calcium oxalate crystal by the study on the changes of metabolites in the urine of mice. Method UPLC-Q-TOF/MS-based metabolomics method was used to determine the changes of endogenous metabolites in mice urine with glyoxylate-induced mouse calcium oxalate crystal model.The multivariate statistics analysis and metabolite pathway analysis were performed by SIMCA-P and Metabo Analyst software respectively. Result Compared with the control group,the kidney tissue of the model group showed obvious calcium salt deposition and the serum creatinine and urea nitrogen levels increased abnormally.21 differential metabolites,such as uric acid,taurine and phenylalanine,were detected from the urine. Conclusion The differential metabolites mainly involve amino acid metabolism,energy metabolism,taurine metabolism,purine metabolism and VB₆ metabolism,which is of great importantce to the mechanism study and the biomaker screening for the early stage stone disease.

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Reference (43)

[1]	XU H,ZISMAN A L,COE F L,et al.Kidney stones:an update on current pharmacological management and future directions[J].Expert Opin Pharmacother,2013,14(4):435-447.
[2]	ROMERO V,AKPINAR H,ASSIMOS D G.Kidney stones:a global picture of prevalence,incidence,and associated risk factors[J].Rev Urol,2010,12(2-3):e86-e96.
[3]	ZENG G H,MAI Z L,XIA S J,et al.Prevalence of kidney stones in China:an ultrasonography based cross-sectional study[J].BJU Int,2017,120:109-116.
[4]	SUTHERLAND J W,PARKS J H,COE F L.Recurrence after a single renal stone in a community practice[J].Miner Electrolyte Metab,1985,11(4):267-269.
[5]	RULE AD,BERGSTRALH E J,MELTON L J,et al.Kidney stones and the risk for chronic kidney disease[J].Clin J Am Soc Nephrol,2009,4(4):804-811.
[6]	EL-ZOGHBY Z M,LIESKE J C,FOLEY RN,et al.Urolithiasis and the risk of ESRD[J].Clin J Am Soc Nephrol,2012,7(9):1409-1415.
[7]	JOHNSON C M,WILSON D M,O'FALLON WM,et al.Renal stone epidemiology:a 25-year study in Rochester,Minnesota[J].Kidney Int,1979,16(5):624-631.
[8]	VERVAET B A,VERHULST A,DAUWE SE,et al.An active renal crystal clearance mechanism in rat and man[J].Kidney Int,2009,75(1):41-51.
[9]	KHAN S R.Reactive oxygen species as the molecular modulators of calcium oxalate kidney stone formation:evidence from clinical and experimental investigations[J].J Urol,2013,189(3):803-811.
[10]	KHAN S R.Reactive oxygen species,inflammation and calcium oxalate nephrolithiasis[J].Transl Androl Urol,2014,3(3):256-276.
[11]	TASCA A.Metabolic syndrome and bariatric surgery in stone disease etiology[J].Curr Opin Urol,2011,21(2):129-133.
[12]	MOHAMMADJAFARI H,BARZIN M,SALEHIFAR E,et al.Etiologic and epidemiologic pattern of urolithiasis in north iran;review of 10-year findings[J].Iran J Pediatr,2014,24(1):69-74.
[13]	NICHOLSON J K,LINDON J C,HOLMES E.‘Metabonomics’:understanding the metabolic responses of living systems to pathophysiological stimuli via multivariate statistical analysis of biological NMR spectroscopic data[J].Xenobiotica,1999,29(11):1181-1189.
[14]	ROCHFORT S.Metabolomics reviewed:a new "omics" platform technology for systems biology and implications for natural products research[J].J Nat Prod,2005,68(12):1813-1820.
[15]	OKADA A,NOMURA S,HIGASHIBATA Y,et al.Successful formation of calcium oxalate crystal deposition in mouse kidney by intraabdominal glyoxylate injection[J].Urol Res,2007,35(2):89-99.
[16]	高松燕.基于两种动物模型的结晶肾损伤形成机制及中药干预的代谢组学研究[D].上海:第二军医大学,2015.
[17]	CHAN E C,PASIKANTI K K,NICHOLSON J K.Global urinary metabolic profiling procedures using gas chromatography-mass spectrometry[J].Nat Protoc,2011,6(10):1483-1499.
[18]	SMILDE A K,van der WERF M J,BIJLSMA S,et al.Fusion of mass spectrometry-based metabolomics data[J].Anal Chem,2005,77(20):6729-6736.
[19]	TRYGG J,HOLMES E,LUNDSTEDT T.Chemometrics in metabonomics[J].J Proteome Res,2007,6(2):469-479.
[20]	WANG X,WANG H,ZHANG A,et al.Metabolomics study on the toxicity of aconite root and its processed products using ultraperformance liquid-chromatography/electrospray-ionization synapt high-definition mass spectrometry coupled with pattern recognition approach and ingenuity pathways analysis[J].J Proteome Res,2012,11(2):1284-1301.
[21]	WISHART D S,JEWISON T,GUO A C,et al.HMDB 3.0 The Human Metabolome Database in 2013[J].Nucleic Acids Res,2013,41(Database issue):D801-D807.
[22]	IANG X,CHEN X,LIANG Q,et al.Metabonomic study of Chinese medicine Shuanglong formula as an effective treatment for myocardial infarction in rats[J].J Proteome Res,2011,10(2):790-799.
[23]	高越.基于组学和网络药理学的养心氏片抗心衰作用机理研究[D].上海:第二军医大学,2016.
[24]	BOIRIE Y,ALBRIGHT R,BIGELOW M,et al.Impairment of phenylalanine conversion to tyrosine in end-stage renal disease causing tyrosine deficiency[J].Kidney Int,2004,66(2):591-596.
[25]	YOUNG B A,VON KORFF M,HECKBERT S R,et al.Association of major depression and mortality in Stage 5 diabetic chronic kidney disease[J].Gen Hosp Psychiatry,2010,32(2):119-124.
[26]	KERAI M D,WATERFIELD C J,KENYON S H,et al.Reversal of ethanol-induced hepatic steatosis and lipid peroxidation by taurine:a study in rats[J].Alcohol Alcohol,1999,34(4):529-541.
[27]	GUAN X,DEI-ANANE G,LIANG R,et al.Donor preconditioning with taurine protects kidney grafts from injury after experimental transplantation[J].J Surg Res,2008,146(1):127-134.
[28]	BADENHORST C P,van der SLUIS R,ERASMUS E,et al.Glycine conjugation:importance in metabolism,the role of glycine N-acyltransferase,and factors that influence interindividual variation[J].Expert Opin Drug Metab Toxicol,2013,9(9):1139-1153.
[29]	WILCOX B J,RITENOUR-RODGERS K J,ASSER A S,et al.N-acylglycine amidation:implications for the biosynthesis of fatty acid primary amides[J].Biochemistry,1999,38(11):3235-3245.
[30]	COSTA C G,GUERAND W S,STRUYS E A,et al.Quantitative analysis of urinary acylglycines for the diagnosis of beta-oxidation defects using GC-NCI-MS[J].J Pharm Biomed Anal,2000,21(6):1215-1224.
[31]	OMBRONE D,SALVATORE F,RUOPPOLO M.Quantitative liquid chromatography coupled with tandem mass spectrometry analysis of urinary acylglycines:application to the diagnosis of inborn errors of metabolism[J].Anal Biochem,2011,417(1):122-128.
[32]	LA MARCA G,RIZZO C.Analysis of organic acids and acylglycines for the diagnosis of related inborn errors of metabolism by GC-and HPLC-MS[J].Methods Mol Biol,2011,708:73-98.
[33]	KHAN S R.Reactive oxygen species,inflammation and calcium oxalate nephrolithiasis[J].Transl Androl Urol,2014,3(3):256-276.
[34]	KHAN S R.Renal tubular damage/dysfunction:key to the formation of kidney stones[J].Urol Res,2006,34(2):86-91.
[35]	KHAN S R.Role of renal epithelial cells in the initiation of calcium oxalate stones[J].Nephron Exp Nephrol,2004,98(2):e55-e60.
[36]	SCHEINMAN J I,VOZIYAN P A,BELMONT J M,et al.Pyridoxamine lowers oxalate excretion and kidney crystals in experimental hyperoxaluria:a potential therapy for primary hyperoxaluria[J].Urol Res,2005,33(5):368-371.
[37]	MITWALLI A,AYIOMAMITIS A,GRASS L,et al.Control of hyperoxaluria with large doses of pyridoxine in patients with kidney stones[J].Int Urol Nephrol,1988,20(4):353-359.
[38]	MILLINER D S,EICKHOLT J T,BERGSTRALH E J,et al.Results of long-term treatment with orthophosphate and pyridoxine in patients with primary hyperoxaluria[J].N Engl J Med,1994,331(23):1553-1558.
[39]	ORTIZ-ALVARADO O,MIYAOKA R,KRIEDBERG C,et al.Pyridoxine and dietary counseling for the management of idiopathic hyperoxaluria in stone-forming patients[J].Urology,2011,77(5):1054-1058.
[40]	DIJCKER J C,PLANTINGA E A,van BAAL J,et al.Influence of nutrition on feline calcium oxalate urolithiasis with emphasis on endogenous oxalate synthesis[J].Nutr Res Rev,2011,24(1):96-110.
[41]	JOHNSON R J,SANCHEZ-LOZADA L G,MAZZALI M,et al.What are the key arguments against uric acid as a true risk factor for hypertension[J].Hypertension,2013,61(5):948-951.
[42]	ROMERO F,PEREZ M,CHAVEZ M,et al.Effect of uric acid on gentamicin-induced nephrotoxicity in rats-role of matrix metalloproteinases 2 and 9[J].Basic Clin Pharmacol Toxicol,2009,105(6):416-424.
[43]	SHIMADA M,JOHNSON RJ,MAY W S Jr,et al.A novel role for uric acid in acute kidney injury associated with tumour lysis syndrome[J].Nephrol Dial Transplant,2009,24(10):2960-2964.

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Urinary metabolomics study on mice renal injury caused by calcium oxalate crystal based on UPLC-Q-TOF/MS platform

doi: 10.3969/j.issn.1006-0111.2019.02.006

Abstract

References

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通讯作者: 陈斌, bchen63@163.com

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