Advances in Clinical and Experimental Medicine
2015, vol. 24, nr 4, July-August, p. 629–635
Publication type: original article
Preliminary Study on J-Resolved NMR Method Usability for Toxic Kidney’s Injury Assessment
1 RootInnovation sp. z o.o., Wrocław, Poland
2 Department of Toxicology, Wroclaw Medical University, Poland
3 Department and Clinic of Pulmonology and Lung Cancers, Wroclaw Medical University, Poland
Background. Nowadays, the Nuclear Magnetic Resonance (NMR) techniques are tested for metabolomic urine profile in order to detect early damage of kidney.
Objectives. The purpose of this investigation was the initial assessment of two-dimensional J-resolved NMR urine spectra analysis usability for early kidney injuries detection. The amino acids (AA) and acids profile change after the exposure to nephrotoxic agent (the cisplatin infusion) was examined.
Material and Methods. The material was the urine of patients with non-small-cell lung cancer, treated with cisplatin in Pulmonology and Lung Cancers Clinic in Wrocław. The urine of healthy volunteers was also examined. The identification of metabolites in urine was based on two-dimensional JRES signals in spectra, described in Human Metabolites Database (HMD). The molar concentration of metabolites was calculated from the volume under the signals. The analysis was focused on amino acids and organic acids (lactid acid and pyruvic acid) profiles.
Results. Any specific amino acids were identified after cisplatin infusion in comparison to the state before infusion. However, the differences in concentration were observed over 2-fold increase in valine, isoleucine and leucine, over 3-fold in alanine. Also, the concentration of pyruvic and lactic acids increased significantly (p ≤ 0.05, p ≤ 0.01).
Conclusion. There were no specific amino acids identified in response to the infusion of cisplatin; however, some changes in the concentrations of amino acids and other small molecules were found. The analysis of two-dimensional JRES spectra showed an increase of alanine, leucine, isoleucine and valine concentration after the application of cisplatin. It seems that it is worth developing the JRES method based on special computer program.
NMR, JRES, aminoacids, nephrotoxicity, cisplatine.
- Miyataka H, Ozaki T, Himeno S: Effect of pH on 1H-NMR spectroscopy of mouse urine. Biol Pharm Bull 2007, 30, 667–670.
- Wang H, Bai J, Chen G, Li W, Xiang R, Su G, Pei Y: A metabolic profiling analysis of the acute hepatotoxicity and nephrotoxicity of Zhusha Anshen Wan compared with cinnabar in rats using (1)H NMR spectroscopy. J Ethnopharmacol 2013, 146, 572–580.
- Wishart DS, Jewison T, Guo AC, Wilson M, Knox C, Liu Y, Djoumbou Y, Mandal R, Aziat F, Dong E, Bouatra S, Sinelnikov I, Arndt D, Xia J, Liu P, Yallou F, Bjorndahl T, Perez-Pineiro R, Eisner R, Allen F, Neveu V, Greiner R, Scalbert A: HMDB 3.0-The Human Metabolome Database in 2013. Nucleic Acids Res 2013, DOI: 10.1093/nar/gks1065. Epub 2012 Nov 17.
- Parsons HM, Ludwig C, Günther UL, Viant MR: Improved classification accuracy in 1- and 2-dimensional NMR metabolomics data using the variance stabilising generalised logarithm transformation. BMC Bioinformatics 2007, 8, 234–239.
- Ludwig C, Viant MR: Two-dimensional J-resolved NMR spectroscopy: review of a key methodology in the metabolomics toolbox. Phytochem Anal 2010, 21, 22–32.
- Fonville JM, Maher AD, Coen M, Holmes E, Lindon JC, Nicholson JK: Evaluation of Full-Resolution J-Resolved 1H NMR Projections of Biofluids for Metabonomics Information Retrieval and Biomarker Identification. Anal Chem 2010, 82, 1811–1821.
- Smolinska A, Posma JM, Blanchet L, Ampt KAM, Attali A, Tuinstra T, Luider T, Doskocz M, Michiels PJ, Girard FC, Buydens LMC, Wijmenga SS: Simultaneous analysis of plasma and CSF by NMR and hierarchical models fusion. Anal Bioanal Chem 2012, 403, 947–959.
- RDC Team (R Development Core Team) R: A Language and Environment for Statistical Computing. http:// www.R–project.org, 2014.
- Barton RH, Nicholson JK, Elliott P, Elaine Holmes E: High-throughput 1H NMR-based metabolic analysis of human serum and urine for large-scale epidemiological studies: validation study. Int J Epidemiol 2008, 37, 31–40.
- Alum MF, Shaw PA, Sweatman BC, Ubhi BK, Haselden JH, Connor SC: 4,4-Dimethyl-4-silapentane-1- -ammonium trifluoroacetate (DSA), a promising universal internal standard for NMR-based metabolic profiling studies of biofluids, including blood plasma and serum. Metabolomics 2008, 4, 122–127.
- Pabla N, Dong Z: Cisplatin nephrotoxicity: mechanisms and renoprotective strategies. Kidney Int 2008, 73, 994–1007.
- Florea AM, Büsselberg D: Cisplatin as an Anti-Tumor Drug: Cellular Mechanisms of Activity, Drug Resistance and Induced Side Effects. Cancers (Basel) 2011, 3, 1351–1371.
- Mishra J, Mori K, Ma Q, Kelly C, Barasch J, Devarajan P: Neutrophil gelatinase-associated lipocalin: a novel early urinary biomarker for cisplatin nephrotoxicity. Am J Nephrol 2004, 24, 307–315.
- Portilla D, Li S, Nagothu KK, Megyesi J, Kaissling B, Schnackenberg L, Safirstein RL, Beger RD: Metabolomic study of cisplatin-induced nephrotoxicity. Kidney International 2006, 69, 2194–2204.
- Boudonck KJ, Német L, Mitchell MW, Keresztes L, Nyska A, Shinar D, Rosenstock M: Discovery of Metabolomics Biomarkers for Early Detection of Nephrotoxicity. Toxicol Pathol 2009, 37, 280–292.
- Portilla D, Schnackenberg L, Beger RD: Metabolomics as an Extension of Proteomic Analysis: Study of acute kidney injury. Semin Nephrol 2007, 27, 609–620.
- Verrey F, Singer D, Ramadan T, Vuille-dit-Bille RN, Mariotta L, Camargo SM: Kidney amino acid transport. Pflugers Arch 2009, 458, 53–60.
- Bröer S: Apical transporters for neutral amino acids: physiology and pathophysiology. Physiology (Bethesda) 2008, 23, 95–103.
- Bröer S: Amino Acid Transport Across Mammalian Intestinal and Renal Epithelia. Physiol Rev 2008, 88, 249–286.
- Chirino YI, Pedraza-Chaverri J: Role of oxidative and nitrosativestress in cisplatin-induced nephrotoxicity. Exp Toxicol Pathol 2009, 61, 223–242.
- Ali BH, Al Moundhri MS: Agents ameliorating or augmenting the nephrotoxicity of cisplatin and other platinum compounds: a review of some recent research. Food Chem Toxicol 2006, 44, 1173–1183.
- Chirino YI, Trujillo J, Sánchez-González DJ, Martínez-Martínez CM, Cruz C, Bobadilla NA, Pedraza-Chaverri J: Selective iNOS inhibition reduces renal damage induced by cisplatin. Toxicol Lett 2008, 176, 48–57.
- Sanchez-Gonzalez PD, Lopez-Hernandez FJ, Lopez-Novoa JM, Morales AI: An integrative view of the pathophysiological events leading to cisplatin nephrotoxicity. Crit Rev Toxicol 2011, 41, 803–821.
- Fleck Ch, Kretzschel I, Sperschneider T, Appenroth D: Renal amino acid transport in immature and adult rats during chromate and cisplatinum-induced nephrotoxicity. Amino Acids 2001, 20, 201–215.