GC/MS-based urinary metabolomics reveals systematic differences in metabolism and ethanol response between Sprague–Dawley and Wistar rats

Abstract

Abstract:Metabolic differences of experimental animals contribute to pharmacological variations. Sprague-Dawley (SD) and Wistar rats are commonly used experimental rats with similar genetic background, and considered interchangeable in practical researches. In this study, we present the urinary metabolomics results, based on gas chromatography coupled to mass spectrometry (GC/MS), which reveal the systematic metabolic differences between SD and Wistar rats under different perturbations such as fasting, feeding, and consecutive acute ethanol interventions. The different metabotypes between the two strains of rats involve a number of metabolic pathways and symbiotic gut microflora. SD rats exhibited higher individualized metabolic variations in the fasting and feeding states, and a stronger ability to recover from an altered metabolic profile with less hepatic injury from the consecutive ethanol exposure, as compared to Wistar rats. In summary, the GC/MS-based urinary metabolomics studies demonstrated an intrinsic metabolic difference between SD and Wistar rats, which warrants consideration in experimental design using these animal strains.

Global Metabolic Profiling for The Study of Alcohol-Related Disorders

“…The profiling technique that has been most applied for global metabolite profiling in the case of ethanol is LC-MS, particularly the combination of UPLC with TOF-MS [25][26][27][28][29][30][31][32][33], followed by 1 H NMR spectroscopy [34][35][36][37][38][39][40], with a single study that employed GC-MS [41]. In Tables 1 & 2 the metabolite profiling methods by NMR or LC-MS, respectively, are summarized.…”

“…Most of the published work on metabolomics for the study of alcohol-related metabolic dysfunctions relate to the ana lysis of urine or liver samples of rodents (rats or mice of different strains, wild type or transgenic) [25][26][27][28]30,31,[34][35][36][37][38][39]41] with limited reports describing metabolic profiling of brain, serum or plasma [29,30,33,34,[36][37][38]; there are also two recent studies on pancreatic tissue and the GI tract [32,40]. In the majority of studies in rodents, the alcohol was administered via oral gavage or in the animals drinking water [25,29,31,32,34,36,40,41] [26,27,35,37,38].…”

“…In the majority of studies in rodents, the alcohol was administered via oral gavage or in the animals drinking water [25,29,31,32,34,36,40,41] [26,27,35,37,38]. In some cases, the intragastric feeding model was also adopted [28,30], allowing a controlled 24 h a day delivery of ethanol that provides a robust and repeatable model of ethanol exposure.…”

“…The use of GC-MS has been reported only once for the metabolite profiling of samples for the study of ethanol-induced metabolic effects, [41] in two strains of rat to see the effect of differences in genetic background (see also [27]). Thus, as a part of a wider study the effect of acute ethanol exposure on two different populations of rats (Sprague-Dawley and Wistar) was examined through their urinary metabolite…”

“…In the urine, changes in the concentrations of some tryptophan metabolites were observed, together with alterations in metabolites such as arginine, hydroxyproline and taurine, which is a marker or liver damage. In addition, 4-hydroxyphenylacetic acid (a gut microfloral-derived metabolite) together with Reproduced with permission from [41] © Springer (2011).…”