Grading of Japanese Diet Intakes by 24-Hour Urine Analysis of Taurine and Soy Isoflavones in Relation to Cardiovascular Risks.

To investigate the association of the Japanese diet with risks for lifestyle-related diseases, the biomarkers of seafood and soybean consumption, taurine (T) and soy isoflavones (I), and others were analyzed in 24-hour urine (24U) samples collected from participants of the Cardiovascular Diseases and Alimentary Comparison (CARDIAC) Study coordinated by the World Health Organization (WHO). The data of T and I normalized for creatinine content in 24U were divided into five quintiles, T1 to T5, and I1 to I5. The total data of the collected samples were divided into 25 groups, which were obtained by 5 (T1-T5) × 5 (I1-I5) according to 24U excretions of T and I corresponding to the intake of seafood and soybeans from the least to the highest, respectively. Since these two nutrients were often consumed together in the Japanese diet, this characteristic was expressed as J1 to J5 based on the amounts of 24U T and I excretions. The risks for lifestyle-related diseases, obesity (body mass index, BMI), and cholesterolemia became lower during the transition from J1 to J5, while HDL cholesterol levels became higher from J1 to J5. On the contrary, urinary salt excretion and the sodium (Na)/potassium (K) ratio became higher from J1 to J5. Systolic blood measure was significantly lower in J3 than in J5. Diastolic blood pressure was also significantly lower in J3 than in J1. In conclusion, the higher the J score, which corresponds to Japanese dietary habits, the lower the BMI and cholesterol levels, as well as mortality rate from coronary heart disease, but the higher the average life expectancy among the Japanese. However, these higher J scorings were associated with high-salt intake and high Na/K ratios; therefore, they contributed to high blood pressure and high mortality rate caused by stroke in Japan. These results indicate that low-salt intake should be recommended to the Japanese who are consuming seafood and soy regularly in order to maintain lower blood pressure and to extend healthy life expectancy with a lower risk of stroke. Moreover, high scorings of the Japanese diet correspond to the high intake of magnesium (Mg) which is rich in seafood including seaweeds and soy. Therefore, low-salt seafood and soy intake is expected to reduce the incidence of the metabolic syndrome, the risk of which is inversely related to T and Mg intake.

Time-based investigation of urinary metabolic markers for Type 2 diabetes: Metabolomics approach for diabetes management.

Diabetes is considered one of the most important health emergencies worldwide and Egypt has 8.2 million diabetic patients according to the International Diabetes Federation report in 2017. The objective of this study was to monitor the time-course variation in the metabolic profile of diabetic rats to detect urinary metabolic biomarkers using the metabolomics approach. Type 2 diabetes was induced in male Wistar albino rats using a single intraperitoneal injection of 40 mg/kg of streptozotocin following oral administration of 10% fructose in drinking water for 3 weeks. Then, urine was collected for 24 h from rats at three time points (0, 2, and 4 weeks after confirmation of diabetes), and were analyzed by nuclear magnetic resonance (H1 -NMR), followed by multivariate data analysis. The results from H1 -NMR pointed out that d-glucose, taurine, l-carnitine, l-fucose, 1,5-anhydrosorbitol, and d-galactose levels showed consistent significant variation (p < 0.05) between the positive (diabetic) and negative (normal) controls during the whole experimental period. Also, with the disease progression, myoinositol, and l-phenylalanine levels were significantly altered (p < 0.05) after 2 weeks and this alteration was maintained till the end of the 4-week experimental period in the positive control group. From the results of the present study, it could be concluded that we cannot depend only on glucose levels for prognostic purposes since there are other metabolic disturbances in diabetes which need to be tracked for better disease prognosis.

1H NMR metabolomic and transcriptomic analyses reveal urinary metabolites as biomarker candidates in response to protein undernutrition in adult rats.

Protein undernutrition contributes to the development of various diseases in broad generations. Urinary metabolites may serve as non-invasive biomarkers of protein undernutrition; however, this requires further investigation. We aimed to identify novel urinary metabolites as biomarker candidates responsive to protein undernutrition. Adult rats were fed control (CT; 14 % casein) or isoenergetic low-protein (LP; 5 % casein) diets for 4 weeks. 1H NMR metabolomics was applied to urine, plasma and liver samples to identify metabolites responsive to protein undernutrition. Liver samples were subjected to mRNA microarray and quantitative PCR analyses to elucidate the mechanisms causing fluctuations in identified metabolites. Urinary taurine levels were significantly lower in the LP group than in the CT group at week 1 and remained constant until week 4. Hepatic taurine level and gene expression level of cysteine dioxygenase type 1 were also significantly lower in the LP group than in the CT group. Urinary trimethylamine N-oxide (TMAO) levels were significantly higher in the LP group than in the CT group at week 2 and remained constant until week 4. Hepatic TMAO level and gene expression levels of flavin-containing mono-oxygenase 1 and 5 were also significantly higher in the LP group than in the CT group. In conclusion, urinary taurine and TMAO levels substantially responded to protein undernutrition. Furthermore, changes in hepatic levels of these metabolites and gene expressions associated with their metabolic pathways were also reflected in their fluctuating urinary levels. Thus, taurine and TMAO could act as non-invasive urinary biomarker candidates to detect protein undernutrition.

Significance of taurine transporter (TauT) in homeostasis and its layers of regulation (Review).

Taurine (2­aminoethanesulfonic acid) contributes to homeostasis, mainly through its antioxidant and osmoregulatory properties. Taurine's influx and efflux are mainly mediated through the ubiquitous expression of the sodium/chloride­dependent taurine transporter, located on the plasma membrane. The significance of the taurine transporter has been shown in various organ malfunctions in taurine­transporter­null mice. The taurine transporter differentially responds to various cellular stimuli including ionic environment, electrochemical charge, and pH changes. The renal system has been used as a model to evaluate the factors that significantly determine the regulation of taurine transporter regulation.

Urinary Metabolic Profiling via LC-MS/MS Reveals Impact of Bovine Lactoferrin on Bone Formation in Growing SD Rats.

Lactoferrin (LF) exerts a promoting bone health function. The effects of LF on bone formation at the metabolic level have been less explored. Urinary metabolic profiling of growing Sprague-Dawley (SD) rats LF-supplemented (1000 mg/kg bw) for four weeks were explored by Liquid chromatography-tandem mass spectrometry (LC-MS/MS). The serum markers of bone formation and bone resorption, the bone mass, and the osteogenesis markers of femur were measured by an enzyme-linked immunosorbent assay, micro-computerized tomography, and immunohistochemistry, respectively. Compared with the control, LF supplementation improved bone formation (p < 0.05), reduced bone resorption (p < 0.05), enhanced femoral bone mineral density and microarchitecture (p < 0.05), and upregulated osteocalcin, osterix, and Runx-2 expression (p < 0.05) of femur. LF upregulated 69 urinary metabolites. KEGG and pathway enrichment analyses of those urinary metabolites, and the Person's correlation analyses among those urinary metabolites and bone status revealed that LF impacted on bone formation via regulatory comprehensive pathways including taurine and hypotaurine metabolism, arginine and proline metabolism, cyanoamino acid metabolism, nitrogen metabolism, nicotinate and nicotinamide metabolism, and fatty acid biosynthesis. The present study indicated the metabolomics is a useful and practical tool to elucidate the mechanisms by which LF augments bone mass formation in growing animals.

Urinary chemical fingerprint left behind by repeated NSAID administration: Discovery of putative biomarkers using artificial intelligence.

Prediction and early detection of kidney damage induced by nonsteroidal anti-inflammatories (NSAIDs) would provide the best chances of maximizing the anti-inflammatory effects while minimizing the risk of kidney damage. Unfortunately, biomarkers for detecting NSAID-induced kidney damage in cats remain to be discovered. To identify potential urinary biomarkers for monitoring NSAID-based treatments, we applied an untargeted metabolomics approach to urine collected from cats treated repeatedly with meloxicam or saline for up to 17 days. Applying multivariate analysis, this study identified a panel of seven metabolites that discriminate meloxicam treated from saline treated cats. Combining artificial intelligence machine learning algorithms and an independent testing urinary metabolome data set from cats with meloxicam-induced kidney damage, a panel of metabolites was identified and validated. The panel of metabolites including tryptophan, tyrosine, taurine, threonic acid, pseudouridine, xylitol and lyxitol, successfully distinguish meloxicam-treated and saline-treated cats with up to 75-100% sensitivity and specificity. This panel of urinary metabolites may prove a useful and non-invasive diagnostic tool for monitoring potential NSAID induced kidney injury in feline patients and may act as the framework for identifying urine biomarkers of NSAID induced injury in other species.

Time-Course Changes in Urine Metabolic Profiles of Rats Following 90-Day Exposure to Propoxur.

As a major kind of carbamate insecticide, propoxur plays an important role in agriculture, veterinary medicine, and public health. The acute toxicity of propoxur is mainly neurotoxicity due to the inhibition of cholinesterase. However, little is known regarding the toxicity of propoxur upon long-term exposure at low dose. In this study, Wistar rats were orally administrated with low dose (4.25 mg/kg body weight/day) for consecutive 90 days. And the urine samples in rats treated with propoxur for 30, 60, and 90 days were collected and analyzed by employing 1H NMR-based metabolomics approach. We found that propoxur caused significant changes in the urine metabolites, including taurine, creatinine, citrate, succinate, dimethylamine, and trimethylamine-N-oxide. And the alteration of the metabolites was getting more difference compared with that of the control as the exposure time extending. The present study not only indicated that the changed metabolites could be used as biomarkers of propoxur-induced toxicity but also suggested that the time-course alteration of the urine metabolomic profiles could reflect the progressive development of the toxicity following propoxur exposure.

Urinary Taurine Excretion and Risk of Late Graft Failure in Renal Transplant Recipients.

Taurine is a sulfur containing nutrient that has been shown to protect against oxidative stress, which has been implicated in the pathophysiology leading to late graft failure after renal transplantation. We prospectively investigated whether high urinary taurine excretion, reflecting high taurine intake, is associated with low risk for development of late graft failure in renal transplant recipients (RTR). Urinary taurine excretion was measured in a longitudinal cohort of 678 stable RTR. Prospective associations were assessed using Cox regression analyses. Graft failure was defined as the start of dialysis or re-transplantation. In RTR (58% male, 53 ± 13 years old, estimated glomerular filtration rate (eGFR) 45 ± 19 mL/min/1.73 m2), urinary taurine excretion (533 (210-946) µmol/24 h) was significantly associated with serum free sulfhydryl groups (ß = 0.126; P = 0.001). During median follow-up for 5.3 (4.5-6.0) years, 83 (12%) patients developed graft failure. In Cox regression analyses, urinary taurine excretion was inversely associated with graft failure (hazard ratio: 0.74 (0.67-0.82); P < 0.001). This association remained significant independent of potential confounders. High urinary taurine excretion is associated with low risk of late graft failure in RTR. Therefore, increasing taurine intake may potentially support graft survival in RTR. Further studies are warranted to determine the underlying mechanisms and the potential of taurine supplementation.

Effects of Dietary Taurine Supplementation on Blood and Urine Taurine Concentrations in the Elderly Women with Dementia.

The purpose of this research is to investigate the effects of dietary taurine supplementation on blood and urine taurine concentrations of the elderly women with dementia. Subjects were 31 female elderly with dementia hospitalized in a geriatric hospital. They were divided randomly into control group and dietary taurine supplemented group. Basically, same meals were served to both groups. Scorched rice water without taurine were served to control group. Scorched rice water containing 3 g of taurine were reserved to taurine group with lunch similarly. Food ingredients containing high concentration of taurine were eliminated from the meal menu. Blood and urine samples were obtained from each subject at the beginning of study, after 2 week and 4 weeks in the morning fasting state. Taurine concentrations in serum and urine were measured as taurine-fluorescamine derivatives using high performance liquid chromatography (HPLC). Data were analyzed using SPSS 20.0. The average taurine concentrations in serum and urine of subjects were 89.2 ± 9.5 µM and 876.7 ± 97.1 µM at the beginning. After 4 weeks, the taurine concentrations in serum and urine of dietary taurine supplemented group were 218.0 ± 15.6 µM and 6502.6 ± 380.6 µM, which were significantly higher compared to control group. Dietary taurine supplemented group showed positive changes in the score on language and execute performance. So taurine supplementation can provide beneficial effects to the elderly and the elderly with dementia.

Urine-NMR metabolomics for screening of advanced colorectal adenoma and early stage colorectal cancer.

Although colorectal cancer (CRC) is considered one of the most preventable cancers, no non-invasive, accurate diagnostic tool to screen CRC exists. We explored the potential of urine nuclear magnetic resonance (NMR) metabolomics as a diagnostic tool for early detection of CRC, focusing on advanced adenoma and stage 0 CRC. Urine metabolomics profiles from patients with colorectal neoplasia (CRN; 36 advanced adenomas and 56 CRCs at various stages, n = 92) and healthy controls (normal, n = 156) were analyzed by NMR spectroscopy. Healthy and CRN groups were statistically discriminated using orthogonal projections to latent structure discriminant analysis (OPLS-DA). The class prediction model was validated by three-fold cross-validation. The advanced adenoma and stage 0 CRC were grouped together as pre-invasive CRN. The OPLS-DA score plot showed statistically significant discrimination between pre-invasive CRN as well as advanced CRC and healthy controls with a Q2 value of 0.746. In the prediction validation study, the sensitivity and specificity for diagnosing pre-invasive CRN were 96.2% and 95%, respectively. The grades predicted by the OPLS-DA model showed that the areas under the curve were 0.823 for taurine, 0.783 for alanine, and 0.842 for 3-aminoisobutyrate. In multiple receiver operating characteristics curve analyses, taurine, alanine, and 3-aminoisobutyrate were good discriminators for CRC patients. NMR-based urine metabolomics profiles significantly and accurately discriminate patients with pre-invasive CRN as well as advanced CRC from healthy individuals. Urine-NMR metabolomics has potential as a screening tool for accurate diagnosis of pre-invasive CRN.

Liquid Chromatography-Mass Spectrometry-Based Metabolomics of Nonhuman Primates after 4 Gy Total Body Radiation Exposure: Global Effects and Targeted Panels.

Rapid assessment of radiation signatures in noninvasive biofluids may aid in assigning proper medical treatments for acute radiation syndrome (ARS) and delegating limited resources after a nuclear disaster. Metabolomic platforms allow for rapid screening of biofluid signatures and show promise in differentiating radiation quality and time postexposure. Here, we use global metabolomics to differentiate temporal effects (1-60 d) found in nonhuman primate (NHP) urine and serum small molecule signatures after a 4 Gy total body irradiation. Random Forests analysis differentially classifies biofluid signatures according to days post 4 Gy exposure. Eight compounds involved in protein metabolism, fatty acid ß oxidation, DNA base deamination, and general energy metabolism were identified in each urine and serum sample and validated through tandem MS. The greatest perturbations were seen at 1 d in urine and 1-21 d in serum. Furthermore, we developed a targeted liquid chromatography tandem mass spectrometry (LC-MS/MS) with multiple reaction monitoring (MRM) method to quantify a six compound panel (hypoxanthine, carnitine, acetylcarnitine, proline, taurine, and citrulline) identified in a previous training cohort at 7 d after a 4 Gy exposure. The highest sensitivity and specificity for classifying exposure at 7 d after a 4 Gy exposure included carnitine and acetylcarnitine in urine and taurine, carnitine, and hypoxanthine in serum. Receiver operator characteristic (ROC) curve analysis using combined compounds show excellent sensitivity and specificity in urine (area under the curve [AUC] = 0.99) and serum (AUC = 0.95). These results highlight the utility of MS platforms to differentiate time postexposure and acquire reliable quantitative biomarker panels for classifying exposed individuals.

Association between metabolic profiles in urine and bone mineral density of pre- and postmenopausal Chinese women.

OBJECTIVE: In the present study, we aimed to characterize the pathological development of menopausal osteoporosis, as well as to explore potential biomarkers and metabolic pathways involved in osteoporosis. METHODS: Urine samples from 322 female participants categorized by menopause status and different bone conditions were collected and analyzed based on a gas chromatography-mass spectrometry (GC-MS) approach. Multivariate and univariate statistical analyses were carried out for urinary metabolomic profile characterization and comparison. RESULTS: Seventeen metabolites in the low bone mineral density (BMD) groups were clearly differentiated from those in normal BMD groups. Among these 17 differentiating metabolites, taurine, ß-alanine, and 5-hydroxycaproic acid were found to be potential biomarkers of osteoporosis. The taurine metabolic pathway and the ß-alanine metabolic pathway were found to be related to menopause and bone loss. CONCLUSIONS: Based on the GC-MS metabolomic platform, four typical pathological phases during the progression of postmenopausal osteoporosis were described. Several differentiating metabolites and metabolic pathways were found to be closely related to the pathology of postmenopausal osteoporosis. Our results provided a solid foundation for further studies on early diagnosis and pathomechanistic evaluation.

The intervention effect of licorice in d-galactose induced aging rats by regulating the taurine metabolic pathway.

Licorice, an edible and officinal plant material, has attracted considerable attention for its wide range of pharmacological activities. Our previous study showed that licorice can ameliorate cognitive damage and improve oxidative stress and apoptosis in aging rats induced by d-galactose (d-gal). In this study, in order to further explore the changes of the metabolic profile during the aging process and the antiaging mechanism of licorice, the 1H NMR-based metabolomics approach was used to analyze serum and urine samples and identify a potential biomarker in d-gal induced aging rats. The results revealed that the taurine metabolic pathway was significantly correlated with the ageing process in d-gal induced rats. Furthermore, the taurine contents were significantly decreased in both the serum and urine samples of aging rats compared with the controls. At the same time, the levels of cysteine dioxygenase type I (CDO1), cysteine sulfinic acid decarboxylase (CSAD) and glutamate decarboxylase type I (GAD1), which are the key enzymes affecting the synthesis reactions, were decreased in aging rats compared with the controls. After licorice administration, the levels of taurine, CDO1 and CSAD were all significantly increased. These findings firstly demonstrated that the regulation of the taurine metabolic pathway is involved in the anti-aging effect of licorice in d-gal induced aging rats.

Sulfur speciation by HPLC-ICPQQQMS in complex human biological samples: taurine and sulfate in human serum and urine.

The advent of the triple quadrupole technology to the inductively coupled plasma mass spectrometry (ICPMS) technique has allowed a strong improvement in the accuracy and detection limits of ICPMS for non-metal elements such as sulfur by removing major polyatomic interferences. Up to now, there has been no report utilizing this development for sulfur speciation in complex human biological matrices. In the present report, we show the success of HPLC-ICPQQQMS for the simultaneous determination of two major sulfur metabolites, taurine and sulfate, in human urine and serum, by direct injection without the need for sample clean-up. The optimized chromatographic method was validated, tested for robustness, and applied for investigating the intra-individual variability in taurine urinary excretion in eight healthy volunteers over a period of 8 weeks. The limit of detection and limit of quantification for taurine determination was found to be 0.2 and 0.7 pmol, respectively. The concentrations found in the analyzed group of urine samples (n = 64) had a range, mean, and SD of 0.6-99, 20.4, and 23.2 µg mL-1 for taurine, and 115-1373, 616, and 259 µg mL-1 for sulfate. Taurine was found to exhibit a much higher intra-individual variability than sulfate. The developed method can be applied in large-scale epidemiological studies and clinical studies in order to establish the potential cardioprotective effects of taurine. Graphical abstract ᅟ.

Improved Extraction Repeatability and Spectral Reproducibility for Liquid Extraction Surface Analysis-Mass Spectrometry Using Superhydrophobic-Superhydrophilic Patterning.

A major problem limiting reproducible use of liquid extraction surface analysis (LESA) array sampling of dried surface-deposited liquid samples is the unwanted spread of extraction solvent beyond the dried sample limits, resulting in unreliable data. Here, we explore the use of the Droplet Microarray (DMA), which consists of an array of superhydrophilic spots bordered by a superhydrophobic material giving the potential to confine both the sample spot and the LESA extraction solvent in a defined area. We investigated the DMA method in comparison with a standard glass substrate using LESA analysis of a mixture of biologically relevant compounds with a wide mass range and different physicochemical properties. The optimized DMA method was subsequently applied to urine samples from a human intervention study. Relative standard deviations for the signal intensities were all reduced at least 3-fold when performing LESA-MS on the DMA surface compared with a standard glass surface. Principal component analysis revealed more tight clusters indicating improved spectral reproducibility for a human urine sample extracted from the DMA compared to glass. Lastly, in urine samples from an intervention study, more significant ions (145) were identified when using LESA-MS spectra of control and test urine extracted from the DMA. We demonstrate that DMA provides a surface-assisted LESA-MS method delivering significant improvement of the surface extraction repeatability leading to the acquisition of more robust and higher quality data. The DMA shows potential to be used for LESA-MS for controlled and reproducible surface extraction and for acquisition of high quality, qualitative data in a high-throughput manner.

Comparison of Urinary Excretion of Taurine Between Elderly with Dementia and Normal Elderly.

The purpose of this study was to investigate the differences in dietary intake, serum level and urinary excretion of taurine between the elderly with dementia and the normal elderly. Subjects with dementia were 22 (8 men, 14 women) and normal were 26 (2 men, 24 women). The general characteristics, anthropometric data were considered together. The blood and urine samples were obtained from the elderly in the morning fasting state. Taurine concentrations in serum and urinary excretion were determined using high performance liquid chromatography (HPLC). Dietary intake data were collected using questionnaires, and analyzed by Computer Aided Nutritional analysis program (CAN-pro 4.0). Statistical analyses were carried out using SPSS 20.0. There were no significant differences in age and BMI (body mass index) between the elderly with dementia and the normal elderly, however, blood total cholesterol, LDL cholesterol and HDL cholesterol levels of the elderly with dementia were relatively higher than the normal elderly. The elderly men with dementia took more lipid, riboflavin higher than the normal elderly men (P < 0.05). The elderly women with dementia took more nutrients except vitamin D, vitamin B12 and taurine than the normal elderly (P < 0.001). There were slight differences in serum taurine level between the two groups. However, urinary excretion of taurine in the elderly with dementia was significantly higher than the normal elderly (41.2%, P < 0.05).

Effect of Radiation on the Expression of Taurine Transporter in the Intestine of Mouse.

There has been a growing interest on the effects of radiation since the Fukushima nuclear power plant accident of 2011. Taurine has been reported to have a radioprotective effect in irradiated mice. However, the detailed mechanism of this radioprotective effect is still awaiting clarification. The aim of this study was to investigation how radiation affects the expression of taurine and to shed light on the mechanism accounting for radioprotective and radiation mitigating effect. Six-week-old male mice were randomly divided into two groups: IR group (7 Gy irradiation) and IR + Tau group (7 Gy irradiation + taurine 3000 mg/kg/day). We examined the survival rate, the expression of taurine and taurine transporter in the small intestine and the urinary taurine concentration. In this study, no statistically significant difference was found in the survival rate between IR Group and IR + Tau Group. Three days and 7 days after irradiation, the urinary taurine concentration of IR + Tau group increased more than that of IR group. Three days and 10 days after irradiation, the expression of taurine and taurine transporter in the small intestine of IR group and IR + Tau group decreased more than that of normal small intestine. It is reported that radiation exposure increases the urinary taurine concentration. We found that the radiation exposure decreases the expression of the taurine transporter in the small intestine of mouse. This finding suggests that a decrease in the expression of the taurine transporter promotes the release of taurine from the tissue into the urine.

Taurine Intake with Magnesium Reduces Cardiometabolic Risks.

WHO-CARDIAC (Cardiovascular Diseases and Alimentary Comparison) Study revealed the quintile analyses of 24-h urinary (24 U) taurine (T) and magnesium (Mg) excretions were inversely related with cardiometabolic risks (CMR) such as obesity, hypertension and hypercholesterolemia in 50 population samples in the world. To exclude the influence of ethnicity in the study, 24 U T and Mg excretions were analyzed for the association with CMR in one ethnicity, Japanese population.24 U T/creatinine (C) ratios were divided into 5 quintiles and the ratios of Japanese to the total of each quintile were analyzed from CARDIAC Study samples. The highest 24 U T quintile consisted of 60% Japanese, indicating high seafood consumption in Japanese.Over 600 Japanese aged 30-79 were invited to a health examination for blood pressure measurement and for fasting blood and 24 U samplings. Tertile analysis of 24 U T/C ratios in relation to CMR indicated the third tertile had significantly higher HDL cholesterol, 24 U potassium (K) and 24 U salt than the first (lowest) tertile. Tertile analysis of 24 U Mg/C ratios indicated the third tertile had significantly lower body mass index and significantly higher folic acid, 24 U isoflavones, K and salt than the first tertile after age and gender adjustment. The third tertile of both T/C and Mg/C had significantly lower body mass index, LDL/HDL and Na/K ratios, and significantly higher HDL cholesterol and folic acid than the first tertile, indicating seafood eaters taking Mg rich diets had lower risks of obesity, atherosclerosis, hypertension and higher folic acid, beneficial for healthy longevity.

Potential urinary biomarkers of nephrotoxicity in cyclophosphamide-treated rats investigated by NMR-based metabolic profiling.

The anticancer-drug cyclophosphamide (CP) is known to have nephrotoxicity. The aim of this study was to identify urinary biomarkers indicating CP-induced nephrotoxicity. We investigated the urine metabolic profiles using nuclear magnetic resonance spectrometry of rats administered with single high-doses of CP (0, 30, and 100 mg/kg body weight) and daily low-doses over a 4-week period (0, 1, 3, and 10 mg/kg body weight). Among 18 identified urinary metabolites, 2-oxoglutarate, citrate, hippurate, formate, valine, and alanine for short-term and 2-oxoglutarate, citrate, hippurate, isoleucine, leucine, allantoin, valine, and lysine for long-term were selected as potential biomarkers. Pathway-enrichment analysis suggested that the urinary metabolism of CP is related to valine, leucine, and isoleucine biosynthesis; taurine and hypotaurine metabolism; glyoxylate and dicarboxylate metabolism; citrate cycle; and alanine, aspartate, and glutamate metabolism, with high pathway impact. The potential biomarkers obtained in this study could be used to monitor CP-induced nephrotoxicity relative to dose and treatment time.

Determination of trimethylamine, trimethylamine N-oxide, and taurine in human plasma and urine by UHPLC-MS/MS technique.

BACKGROUND: Trimethylamine-N-oxide (TMAO) is produced in the liver from trimethylamine (TMA) and is an important cellular osmolyte and potential atherogenic factor. Taurine is involved in cholesterol metabolism and also serves as a cellular osmolyte. Given their significant biological functions, the development of reliable measurement techniques is crucial to further study their role in health and disease METHODS: A new ultrahigh performance liquid chromatography-tandem mass spectrometry method was developed and validated for the simultaneous determination of TMA, TMAO, and taurine in plasma and urine. The method consisted of a deproteinization step using methanol/acetonitrile (15:85) that contained 0.2% formic acid and isotope-labeled internal standards. Samples were separated by centrifugation and injected into the UHPLC system. Quantification was conducted using a triple-quadrupole mass spectrometer detector with electrospray ionization interface in positive mode. RESULTS: The limits of detection ranged from 0.08 to 0.12µmol/L. The calibration curves were linear (r≥0.999) over the range examined (0.15-400µmol/L) for all compounds. The inter- and intra-day coefficients of variations were≤14.5% for TMA and ≤8% for TMAO and taurine. TMAO and taurine were found to be stable in EDTA plasma for at least 14 months at -70°C. Mean recoveries ranged from 95% to 109% and the relative matrix effects were≤4.0%. The method was applied to study physiological and pre-analytical factors in plasma and urine samples. CONCLUSIONS: The new UHPLC-MS/MS method has good accuracy, precision, and recovery. The assay combines simple sample processing with a short run time, making it well suited for high-throughput routine clinical or research purposes.