Urinary Taurine Excretion Research Articles

Abstract P300: Modulation of Osmolyte Levels by ACE Inhibitors and SGLT-2 Inhibitors in Normotensive Rats

Hypertension is associated with disturbances in the water-electrolyte balance, leading to changes in osmotic pressure. Osmolytes, such as taurine among other compounds, play a critical role in maintaining cellular integrity under osmotic stress. This study evaluated the effects of ACE inhibitors (ACE-I) and SGLT-2 inhibitors (SGLT2i) on osmolyte homeostasis. Twelve-week-old male Sprague-Dawley (SD, n = 38) rats were divided into five groups: control (water), low and high doses of canagliflozin, and low and high doses of captopril. Metabolic studies were conducted in metabolic cages. Using liquid chromatography coupled with mass spectrometry (LC-MS), we measured osmolyte concentrations in blood, urine, kidney, liver and heart tissues. The obtained results demonstrated significant increases in liver taurine concentrations (13.34 ± 1.39 vs. 10.49 ± 1.45, p=0.029) and urinary taurine excretion (25.08 ± 2.81 vs. 16.54 ± 3.77, p=0.001) in the high-dose canagliflozin group compared to controls. Both treatments enhanced the total urinary excretion of L-alanine, β-alanine, choline, glycine, taurine, and carnitine. Additionally, canagliflozin increased the excretion of betaine and glycerophosphorylcholine (GPC). A reduction in serum β-alanine was noted in the captopril-treated rats. These findings highlight the novel effects of SGLT-2 inhibitors and ACE-I on osmolyte levels in normotensive rats, suggesting potential mechanisms contributing to their cardioprotective effects. Further research is required to elucidate the clinical significance of osmolyte changes in enhancing the protective effects of these drug classes.

Taurine drives body protein renewal and accretion in beef steers

The aims of the present study were to investigate the effects of dietary supplementation with rumen-protected taurine (RPT) on the whole-body protein turnover, the plasma metabolomics, and the whole blood cell transcriptomics in steers. Eight steers, averaging 220 ± 3.26 kg of liveweight, were allocated in a replicate 4 × 4 Latin square design. The experimental treatments consisted of four levels of RPT supplementation: 0, 25, 50, and 75 g RPT per day, added to a basal diet. The results showed that supplementation with RPT linearly decreased the fecal nitrogen (N) excretion (P = 0.001) and the 15N fractional recovery rate (P = 0.047), while it linearly increased the urinary excretion of taurine (P = 0.045) as well as the average daily weight gain (P = 0.003), the protein synthesis (P < 0.001), the protein degradation (P < 0.001) and the whole-body protein turnover (P < 0.001). Supplementation with RPT linearly increased the plasma concentrations of growth hormone (P = 0.005) and quadratically affected the plasma concentration of insulin-like growth factor-1 (P = 0.013), and it linearly decreased the plasma concentration of albumin (P = 0.022). Supplementation with RPT altered the whole blood cell mRNA expression and upregulated the expressions of the marker genes, including RPS6KB1, PRSS42, COL1A2, ENSBTAG00000013055 and ENSBTAG00000038159 which are related to protein metabolism. The plasma metabolomics profiling indicated that supplementation with RPT upregulated the plasma concentrations of taurine, lysine and methionine. The experiment revealed the impact and the mechanisms of taurine on driving whole-body protein turnover and protein accretion in steers. Two novel marker genes which could be related to body protein degradation in steers were identified.

Sex differences in amino acid composition in a rodent model of ARPKD, the PCK rat

Polycystic Kidney Disease (PKD) is a severe, genetically inherited disease that leads to renal failure. Like several other chronic kidney diseases, male sex is a risk factor for accelerated PKD. Rat models of both Autosomal Recessive and Dominant forms of PKD (PCK and Han:SPRD rats, respectively) exhibit sex differences in disease progression. Previous studies have found that amino acids (AAs) and peptides are predominant constituents of cystic fluid. We hypothesized that AA homeostasis in male and female cystic fluid would demonstrate sexual dimorphism, and these differences may provide essential information about the progression of cystogenesis. We quantified the AAs in cystic fluid, plasma, and urine in PCK and control Sprague Dawley (SD) rats (only plasma and urine for SD rats). Of the 42 AAs that were measured, only asparagine, serine, aspartic acid, glutamic acid, beta-alanine, cystathionine, and leucine were NOT significantly different between SD and PCK plasma values. Interestingly, only 18 AAs were significantly different in urine of PCK rats compared to SD rats. In SD rats, between sexes, 26 AAs were significantly different in plasma and 5 were significantly different in urine. Among PCK rats, 13 AAs in plasma, 9 AAs in urine, and 4 AAs in cystic fluid were significantly different between sexes. The 4 AAs that differed between male and female cystic fluid were 1-methylhistidine, 3-methylhistidine, ethanolamine, and taurine. Moreover, taurine was the most abundant AA in cystic fluid. Taurine concentrations in both plasma (165 ± 9 vs. 128 ± 4 μM, N=6, p=0.003) and cystic fluid (7508 ± 469 vs. 4557 ± 788 μM, N=6, p=0.01) were significantly different between sexes in the PCK rats (male vs. female, respectively). Urine values for the PCK rats (9705 ± 1863 vs. 7570 ± 1631 μM, N=6) were not significantly different in males and females; however, the average urinary taurine excretion in PCK rats was nearly 4-fold greater than SD rats (8637 ± 1223 vs. 2219 ± 465 μM, N=12, p&lt;0.0001). There were no significant differences in taurine concentrations between SD male and female rat plasma (202 ± 17 vs. 194 ± 7.0 μM, N=6) or urine (2044 ± 614 vs. 2395 ± 752 μM, N=6). Western blot of the taurine transporter, TauT, detected bands at 50 and 75 kDa, and both bands were significantly reduced by ~50% in PCK kidneys compared to SD kidneys. Lastly, immunolabeling in PCK kidney sections demonstrated that TauT is present at the apical membrane of cyst epithelia. These results point to a potential role for AAs, and specifically for taurine in cystogenesis, which likely varies by sex in diseased, but not healthy kidneys. R00 HL153686, BX004024, R01 DK126720, R01 DK129227. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

The effects of a hydrolyzed protein diet on the plasma, fecal and urine metabolome in cats with chronic enteropathy

Hydrolyzed protein diets are extensively used to treat chronic enteropathy (CE) in cats. However, the biochemical effects of such a diet on feline CE have not been characterized. In this study an untargeted 1H nuclear magnetic resonance spectroscopy-based metabolomic approach was used to compare the urinary, plasma, and fecal metabolic phenotypes of cats with CE to control cats with no gastrointestinal signs recruited at the Royal Veterinary College (RVC). In addition, the biomolecular consequences of a hydrolyzed protein diet in cats with CE was also separately determined in cats recruited from the RVC (n = 16) and the University of Bristol (n = 24) and whether these responses differed between dietary responders and non-responders. Here, plasma metabolites related to energy and amino acid metabolism significantly varied between CE and control cats in the RVC cohort. The hydrolyzed protein diet modulated the urinary metabolome of cats with CE (p = 0.005) in both the RVC and Bristol cohort. In the RVC cohort, the urinary excretion of phenylacetylglutamine, p-cresyl-sulfate, creatinine and taurine at diagnosis was predictive of dietary response (p = 0.025) although this was not observed in the Bristol cohort. Conversely, in the Bristol cohort plasma betaine, glycerol, glutamine and alanine at diagnosis was predictive of outcome (p = 0.001), but these same results were not observed in the RVC cohort. The biochemical signature of feline CE in the RVC cohort was consistent with that identified in human and animal models of inflammatory bowel disease. The hydrolyzed protein diet had the same effect on the urinary metabolome of cats with CE at both sites. However, biomarkers that were predictive of dietary response at diagnosis differed between the 2 sites. This may be due to differences in disease severity, disease heterogeneity, factors unrelated to the disease or small sample size at both sites. As such, further studies utilizing larger number of cats are needed to corroborate these findings.

Effects of taurine on rumen fermentation, nutrient digestion, rumen bacterial community and metabolomics and nitrogen metabolism in beef steers.

The objectives of this study were to investigate the effects of taurine on rumen fermentation, rumen bacterial community and metabolomics, nitrogen metabolism and plasma biochemical parameters in beef steers. Six castrated Simmental steers (liveweight 402 ± 34 kg) and three levels of taurine (0, 20, 40 g d-1 ) were assigned in a replicated 3 × 3 Latin square design. Each experimental period included 15 days for adaptation and 5 days for sampling. Supplementing taurine did not affect the ruminal pH or concentrations of ammonia nitrogen and volatile fatty acids (P > 0.10), but linearly increased the ruminal concentrations of taurine (P < 0.001) and microbial crude protein (P=0.041). Supplementing taurine linearly increased the neutral detergent fiber digestibility (P=0.018), and tended to linearly increase dry matter digestibility (P=0.095), tended to increase the fecal nitrogen excretion (P=0.065) and increased the urinary taurine excretion (P < 0.001). Supplementing taurine quadratically increased the plasma concentration of triglycerides (P=0.017), tended to linearly decrease growth hormone (P=0.074), but did not affect other plasma parameters (P > 0.10). Supplementing taurine modified the rumen bacterial community and increased the ruminal concentration of taurine metabolite 2-hydroxyethoxysulfonic acid (P < 0.001). It was concluded that taurine improved ruminal microbial crude protein synthesis and increased fiber digestibility through modifying rumen bacterial community. It is necessary to clarify the ruminal hydrolysis of taurine in steers. © 2023 Society of Chemical Industry.

Hepatic cysteine sulphinic acid decarboxylase depletion and defective taurine metabolism in a rat partial nephrectomy model of chronic kidney disease

BackgroundTaurine depletion occurs in patients with end-stage chronic kidney disease (CKD). In contrast, in the absence of CKD, plasma taurine is reported to increase following dietary L-glutamine supplementation. This study tested the hypothesis that taurine biosynthesis decreases in a rat CKD model, but is rectified by L-glutamine supplementation.MethodsCKD was induced by partial nephrectomy in male Sprague-Dawley rats, followed 2 weeks later by 2 weeks of 12% w/w L-glutamine supplemented diet (designated NxT) or control diet (NxC). Sham-operated control rats (S) received control diet.ResultsTaurine concentration in plasma, liver and skeletal muscle was not depleted, but steady-state urinary taurine excretion (a measure of whole-body taurine biosynthesis) was strongly suppressed (28.3 ± 8.7 in NxC rats versus 78.5 ± 7.6 μmol/24 h in S, P < 0.05), accompanied by reduced taurine clearance (NxC 0.14 ± 0.05 versus 0.70 ± 0.11 ml/min/Kg body weight in S, P < 0.05). Hepatic expression of mRNAs encoding key enzymes of taurine biosynthesis (cysteine sulphinic acid decarboxylase (CSAD) and cysteine dioxygenase (CDO)) showed no statistically significant response to CKD (mean relative expression of CSAD and CDO in NxC versus S was 0.91 ± 0.18 and 0.87 ± 0.14 respectively). Expression of CDO protein was also unaffected. However, CSAD protein decreased strongly in NxC livers (45.0 ± 16.8% of that in S livers, P < 0.005). L-glutamine supplementation failed to rectify taurine biosynthesis or CSAD protein expression, but worsened CKD (proteinuria in NxT 12.5 ± 1.2 versus 6.7 ± 1.5 mg/24 h in NxC, P < 0.05).ConclusionIn CKD, hepatic CSAD is depleted and taurine biosynthesis impaired. This is important in view of taurine’s reported protective effect against cardio-vascular disease - the leading cause of death in human CKD.

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 (β = 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.

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 abstractᅟ

Role of taurine in the pathogenesis of obesity.

Taurine is a sulfur-containing amino acid that is present in mammalian tissues in millimolar concentrations. Taurine is involved in a diverse array of biological and physiological functions, including bile salt conjugation, osmoregulation, membrane stabilization, calcium modulation, anti-oxidation, and immunomodulation. The prevalence of obesity and being overweight continues to rise worldwide at an alarming rate. Obesity is associated with a higher risk of metabolic and cardiovascular diseases, cancer, and other clinical conditions. Ingestion of taurine has been shown to alleviate metabolic diseases such as hyperlipidemia, diabetes, hypertension, and obesity in animal models. A global epidemiological survey showed that 24-h urinary taurine excretion, as a marker of dietary taurine intake, was inversely associated with BMI, blood pressure, and plasma cholesterol in humans. In addition, taurine chloramine, an endogenous product derived from activated neutrophils, has been reported to suppress obesity-induced oxidative stress and inflammation in adipocytes. Synthetic activity and concentration of taurine in adipose tissues and plasma have been shown to decrease in humans and animals during the development of obesity, suggesting a relationship between taurine deficiency and obesity. In this review, I summarize the effects of taurine on the progression of obesity in animal models and humans. Furthermore, I discuss possible mechanisms underlying the antiobesity effects of taurine.

Taurine in 24-h Urine Samples Is Inversely Related to Cardiovascular Risks of Middle Aged Subjects in 50 Populations of the World.

We previously showed that 24-h urinary taurine (Tau) excretion was inversely associated with mortality due to coronary heart diseases (CHD) and stroke. The aim of this study was to examine the association between 24-h urinary Tau/creatinine (Cre) ratio and cardiovascular disease risk factors, including body mass index (BMI), blood pressure (BP), serum total cholesterol (TC) and prevalence of obesity, hypertension and hypercholesterolemia.

PPARβ/δ modulates ethanol-induced hepatic effects by decreasing pyridoxal kinase activity

Because of the significant morbidity and lethality caused by alcoholic liver disease (ALD), there remains a need to elucidate the regulatory mechanisms that can be targeted to prevent and treat ALD. Toward this goal, minimally invasive biomarker discovery represents an outstanding approach for these purposes. The mechanisms underlying ALD include hepatic lipid accumulation. As the peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) has been shown to inhibit steatosis, the present study examined the role of PPARβ/δ in ALD coupling metabolomic, biochemical and molecular biological analyses. Wild-type and Pparβ/δ-null mice were fed either a control or 4% ethanol diet and examined after 4–7 months of treatment. Ethanol fed Pparβ/δ-null mice exhibited steatosis after short-term treatment compared to controls, the latter effect appeared to be due to increased activity of sterol regulatory element binding protein 1c (SREBP1c). The wild-type and Pparβ/δ-null mice fed the control diet showed clear differences in their urinary metabolomic profiles. In particular, metabolites associated with arginine and proline metabolism, and glycerolipid metabolism, were markedly different between genotypes suggesting a constitutive role for PPARβ/δ in the metabolism of these amino acids. Interestingly, urinary excretion of taurine was present in ethanol-fed wild-type mice but markedly lower in similarly treated Pparβ/δ-null mice. Evidence suggests that PPARβ/δ modulates pyridoxal kinase activity by altering Km, consistent with the observed decreased in urinary taurine excretion. These data collectively suggest that PPARβ/δ prevents ethanol-induced hepatic effects by inhibiting hepatic lipogenesis, modulation of amino acid metabolism, and altering pyridoxal kinase activity.

Effects of periconceptional undernutrition on maternal taurine concentrations in sheep

Taurine has an important role in numerous physiological processes, including many aspects of fetal development such as development of the pancreas and brain, and requirements increase during pregnancy. Periconceptional undernutrition has long-term effects on pancreas and brain function of the offspring, but the effects on maternal taurine economy are unknown. We, therefore, studied the effects of different periods of periconceptional undernutrition on maternal plasma and urine taurine concentrations before and during pregnancy. Four groups of singleton-bearing ewes were studied (n 10-11): controls fed ad libitum, and groups undernourished from 60d before until mating (PreC), from 2d before mating until 30d after mating (PostC) or from 60d before until 30d after mating (Pre+PostC). In PreC ewes, plasma taurine concentrations remained at control levels for the first 30d, and then decreased through the remainder of undernutrition, but recovered by 30d after mating; urinary taurine excretion was low at mating, but recovered similarly. In PostC ewes, plasma taurine concentrations recovered after 2 weeks despite ongoing undernutrition; urinary taurine excretion had recovered by 30d after mating. Pre+PostC ewes followed the same pattern as PreC for the first 60d, but plasma taurine concentrations and urinary excretion recovered slowly, and did not reach the control levels until 97d. These data suggest that different periods of mild periconceptional undernutrition in sheep have different but substantial effects on maternal taurine homoeostasis. These effects may be one mechanism by which maternal periconceptional undernutrition alters development of the offspring with implications for adult health.

Characterization of Organic Anion-Transporting Polypeptide (Oatp) 1a1 and 1a4 Null Mice Reveals Altered Transport Function and Urinary Metabolomic Profiles

Organic anion-transporting polypeptides (Oatp) 1a1 and 1a4 were deleted by homologous recombination, and mice were characterized for Oatp expression in liver and kidney, transport in isolated hepatocytes, in vivo disposition of substrates, and urinary metabolomic profiles. Oatp1a1 and Oatp1a4 proteins were undetected in liver, and both lines were viable and fertile. Hepatic constitutive messenger RNAs (mRNAs) for Oatp1a4, 1b2, or 2b1 were unchanged in Oatp1a1⁻/⁻ mice, whereas renal Oatp1a4 mRNA decreased approximately 50% (both sexes). In Oatp1a4⁻/⁻ mice, no changes in constitutive mRNAs for other Oatps were observed. Uptake of estradiol-17β-D-glucuronide and estrone-3-sulfate in primary hepatocytes decreased 95 and 75%, respectively, in Oatp1a1⁻/⁻ mice and by 60 and 30%, respectively, in Oatp1a4⁻/⁻ mice. Taurocholate uptake decreased by 20 and 50% in Oatp1a1⁻/⁻ and Oatp1a4⁻/⁻ mice, respectively, whereas digoxin was unaffected. Plasma area under the curve (AUC) for estradiol-17β-D-glucuronide increased 35 and 55% in male and female Oatp1a1⁻/⁻ mice, respectively, with a concurrent 50% reduction in liver-to-plasma ratios. In contrast, plasma AUC or tissue concentrations of estradiol-17β-D-glucuronide were unchanged in Oatp1a4⁻/⁻ mice. Plasma AUCs for dibromosulfophthalein increased nearly threefold in male Oatp1a1⁻/⁻ and Oatp1a4⁻/⁻ mice, increased by 40% in female Oatp1a4⁻/⁻ mice, and were unchanged in female Oatp1a1⁻/⁻ mice. In both lines, no changes in serum ALT, bilirubin, and cholesterol were noted. NMR analyses showed no generalized increase in urinary excretion of organic anions. However, urinary excretion of taurine decreased by 30-40% and was accompanied by increased excretion of isethionic acid, a taurine metabolite generated by intestinal bacteria, suggesting some perturbations in intestinal bacteria distribution.

Taurine's health influence on Japanese high school girls

BackgroundThe prevalence of metabolic syndrome (MS) in children and adolescents has been increasing at an alarming rate. MS risks during childhood and adolescence adversely affect health conditions in later life. Thus, the characterization of their MS risks is a critical research field. The aims of this study are to survey the health status of Japanese adolescent females, a poorly characterized population, and to investigate the potential relationship between their MS risks and dietary factors like potassium (K) and taurine.MethodsAnthropometric characteristics of 243 healthy school girls aged 13 to 18 years were measured. Serum levels of triglycerides, total cholesterol and high-density lipoprotein (HDL), and plasma levels of glucose and insulin were analyzed in fasting blood samples. We assessed overweight, disturbed lipid prolife, higher blood pressure (hBP) and higher plasma glucose (hGlc) levels as indicators of MS risks. The relationships between MS risks and urinary K or taurine excretion were investigated by dividing into higher and lower groups at medians of their urinary excretions.ResultsHalf of junior high school (JHS) and one-quarter of senior high school (SHS) girls had at least one MS risk. The quite common risk was hGlc, the rates being 21% in JHS girls and 14% in SHS. The prevalence of being overweight and obesity were only small portions, the rate being 0% and 0% in JHS girls, and 10% and 1% in SHS, respectively. Substantial differences in the prevalence of hBP were observed between JHS (22%) and SHS (4%) girls. Furthermore, higher urinary K excretion group showed a significant decrease in triglyceride level (P = 0.03) and increase in HDL level (P = 0.003) compared with the lower. Also, the higher urinary taurine excretion group exhibited a significant reduction in triglyceride level (P = 0.04) compared with the lower.ConclusionsThese results indicate that control of plasma glucose level rather than body weight is a crucial task in Japanese pubertal girls, and that a dietary habit rich in K and taurine could improve their lipid profile. Nutritional education based on these findings would help to prevent the future development of MS in Japanese female adolescents.

Taurine in morning spot urine for the useful assessment of dietary seafood intake in Japanese children and adolescents

BackgroundSince our previous report on WHO CARDIAC Study data demonstrated that 24-hour urinary (24U) taurine (Tau) excretion was a useful biomarker of seafood (SF) intake and inversely related to the mortality rates of stroke and coronary heart diseases in the world, we determined that SF is important in the risk reduction of lifestyle related-diseases. The amounts of dietary SF intake are so far estimated from a nutritional survey or 24U Tau excretion.The sodium/potassium ratio of spot urine (SU) and the 24U ratio were reported to be significantly correlated with. Therefore, we presently examined the relationship of Tau excretion in the morning SU with 24U Tau for simplifying the population comparison and the follow-up of SF intake changes in the process of food education program (FEP).MethodsAfter informed consent was obtained, 54 children aged 6-11 years (Children) and 193 adolescents aged 13-18 years (Adolescents) participated in collecting precisely 24U and SU of the first urination on the same day and answered the questionnaire including age and height and weight measurements. The urine samples were measured for creatinine (Cre) and Tau, and the association of these between 24U and SU were analyzed.ResultsThe success rates of 24U sampling were very high in Children and Adolescents, 96.4% and 82.4%, respectively. From the result of the multiple regression analysis of SU Tau/Cre and weight we obtained formulas for predicting 24U Tau excretion in Children and Adolescents as follows: Children: 24U Tau = 16.3 (weight) + 314.3 (SU Tau/Cre) -175.2; and Adolescents: 24U Tau = 20.2 (weight) + 644.7 (SU Tau/Cre) - 569.4.ConclusionsThe present study established the regression equation to estimate 24U Tau excretion from SU Tau/Cre and weight. These formulas are expected to contribute to the estimation of fish and SF intake and the follow-up of the change of the dietary behavior by FEP in Children and Adolescents.

Taurine deficiency in thalassemia major-induced osteoporosis treated with neridronate

The aetiology of thalassemia major-induced osteoporosis is multifactorial. Up to now, bisphosphonates seem to be a promising therapy. Taurine is found in a high concentration in bone cells enhancing bone tissue formation and inhibiting bone loss. Recently we found a decrease taurine plasma level in children affected by osteogenesis imperfecta during neridronate (amino-bisphosphonate) therapy suggesting a possible interaction between pharmacological effect of this drug and taurine availability. On the basis of these results, we performed plasma and urine amino acid (AA) analysis in thalassemia major-induced osteoporosis before and after 12 months of neridronate treatment. Twelve patients, five males and seven females, aged from 20 to 29 years following a hypertransfusion treatment protocol were enrolled in the study. Patients were treated with neridronate infusion every one month (30 mg in 100 ml of saline). Plasma and urine specimens for AA analysis, bone mineral density, bone mineral content and vertebral project area were examined at baseline (T0) and after 12 months of treatment (T12). A significant decrease was observed for plasma level and urinary excretion of taurine (T0 vs. T12 = p < 0.01) whereas bone mineral content and vertebral projection area showed a statistical significant increase (T0 vs. T12 = p < 0.05). These results and other experimental researches warrant further studies examining the long-term effect of taurine supplementation in association with neridronate treatment.

Metabonomic study on the toxicity of Hei-Shun-Pian, the processed lateral root of Aconitum carmichaelii Debx. (Ranunculaceae)

The purpose of this paper was to study the effects of Hei-Shun-Pian, the processed lateral root of Aconitum carmichaelii Debx. (Ranunculaceae), on the metabolic profile of rats, to discuss the mechanism of toxicology and to find out the potential biomarkers of the toxic effects. Twenty male Wistar rats were divided into four groups ( n = 5) and each group were administered orally with the decoction of Hei-Shun-Pian (88.1 g/kg per day, 35.6 g/kg per day, 17.6 g/kg per day) or equal volume of drinking water respectively for 14 days. Urine of every 24-h and the plasma of the last day were collected for NMR experiments, and then analyzed by multivariate analysis methods. Decreases in urinary excretion of taurine and trimethylamine- N-oxide (TMAO) and increases in urinary levels of citrate, 2-oxoglutarate (2-OG), succinate and hippurate were observed in the high and medium dosed groups at the early stage of the dosing period. Taurine level increased at the later stage of the dosing period to the normal value, and then even to a value higher than that of the control group at the end of the experiment. No metabolic differences were observed between low dosed and control groups until the later stage of the dosing period when a slight increase in urinary taurine level was observed, suggesting a cumulative effect. These results suggest the toxic effect of Hei-Shun-Pian on rat heart in a dose dependent manner.

Taurine Intestinal Absorption and Renal Excretion Test in Diabetic Patients

There is evidence that diabetes is characterized by taurine deficiency (1–4), which has been linked to diabetic retinopathy, neuropathy, and nephropathy (5–7). Taurine is involved in neuronal modulation, osmoregulation (8), and protection against oxidative stress (9). Its plasma levels are maintained within a normal range through protein intake, and de novo synthesis is limited by the activity of hepatic cysteinesulphinic acid decarboxylase, which is low in humans. Taurine depletion can occur rapidly (10), possibly leading to retinal, cardiac, neural, immune, and hemostatic dysfunction (4,11–14). The reasons for taurine deficiency in diabetes remain unclear. A decrease in the overall body pool (1,2) and/or internal redistribution between the intra- and extracellular compartments are possibilities. The former can be secondary to decreased oral intake, poor intestinal absorption, renal wasting, or a combination of factors. In diabetic rats, intestinal absorption of taurine is reduced (K.B., Camille Nassar, unpublished data), while urinary taurine excretion is enhanced (15). Kidney loss in uncontrolled diabetes is aggravated by severe hyperglycemia and ketoacidosis (4). Data are lacking, however, on urinary excretion and pharmacokinetics of taurine absorption in human diabetes with mild-to-moderate hyperglycemia. This pilot study was therefore conducted in patients with moderately impaired glucose control and in matched nondiabetic subjects to evaluate the pharmacokinetics of taurine absorption following an oral load and to elucidate the mechanism of taurine deficiency in diabetes. A total of 16 subjects were enrolled in the study: 6 patients with type 2 diabetes, 2 with type 1 diabetes, and 8 healthy subjects; subjects were pair-matched for age, sex, and BMI. …

Reduction of plasma taurine level in children affected by Osteogenesis Imperfecta during bisphosphonate therapy

Osteogenesis Imperfecta (OI) is a heritable disease of connective tissue characterized by increased bone fragility. To date, bisphosphonates seem to be the most promising therapy, at least for children. In the last decade experimental and clinical studies indicate that several amino acids are implicated in bone mineralization. Particularly, taurine is localized in matrices of the bone and can regulate osteoblast metabolism with antiosteopenic effect. To investigate a possible interaction between pharmacological effects of bisphosphonates and amino acids involved in bone metabolism, we performed plasma and urine amino acids analysis in children affected by OI before and during treatment with bisphosphonates. Fourteen prepubertal children with moderate to severe types of OI, 8 males and 6 females, aged from 2 to 11 years (mean (SD) 6,9 ± 2,53) were enrolled in the study. Patients were treated with neridronate infusion (1 mg/Kg/body weight) every three months. Plasma and urine specimens for amino acid analysis were kept at baseline (T0) and three months after each infusion of four consecutive cycles (T1–T4). A significant decrease in respect to the pre-treatment levels (T0) was observed after the fourth infusion for taurine ( p < 0.01). In addition, urinary excretion of this amino acid showed a significant decrease after the fourth infusion. No significant correlations were found between plasma level or urinary excretion of hydroxyproline, taurine, arginine and lysine in respect to bone mineral density. The progressive reduction of plasma taurine found in our patients treated with bisphosphonates could be implicated in the action mechanism of this drug in OI and possibly in other disorders of bone metabolism. This knowledge could provide new opportunities to improve treatment with bisphosphonates and address novel strategies for the therapeutic approach to bone disorders.

Copper Deficiency Does Not Lead to Taurine Deficiency in Rats

Copper deficiency has been reported to cause a decrease in urinary taurine excretion in rats. We determined whether Cu deficiency would decrease taurine status and the hepatic activities of cysteine dioxygenase (CDO) and/or cysteine sulfinic acid decarboxylase (CSAD) in rats. Ten weanling male rats were assigned to either a Cu-adequate (+Cu) or Cu-deficient (−Cu) group. All rats consumed a Cu-deficient purified diet and water ad-libitum for 16 wk. The water for the +Cu group contained 20 mg Cu/L as CuSO4. At wk 16, the groups differed (P < 0.05) in the following variables (means ± SEM, −Cu vs. +Cu): body weight (BW), 375 ± 19 vs. 418 ± 2.9 g; food intake, 16.2 ± 0.7 vs. 18.5 ± 0.4 g/d; hematocrit, 0.294 ± 0.027 vs. 0.436 ± 0.027; hemoglobin, 95.2 ± 9 vs 134 ± 10 g/L; liver Cu, 8.7 ± 2.0 vs. 65.9 ± 2.5 nmol/g; plasma Cu, 0.38 ± 0.09 vs. 13.4 ± 0.61 μmol/L; plasma ceruloplasmin activity, 1.75 ± 1.0 vs. 67.9 ± 8.4 IU; relative heart weight, 0.56 ± 0.04 vs. 0.35 ± 0.02% BW; relative liver weight, 4.06 ± 0.23 vs. 3.37 ± 0.06% BW; and liver CSAD activity, 18.8 ± 1.37 vs. 13.5 ± 1.11 nmol · min−1 · mg protein−1. The groups did not differ at wk 16 in: plasma taurine, 249 ± 14 vs. 298 ± 63 μmol/L; whole blood taurine, 386 ± 32 vs. 390 ± 25 μmol/L; urinary taurine excretion, 82.5 ± 15 vs. 52.0 ± 8.3 μmol/d; liver taurine, 2.6 ± 0.7 vs. 2.8 ± 0.4 μmol/g; liver total glutathione, 6.9 ± 0.48 vs. 6.3 ± 0.40 μmol/g; liver cyst(e)ine, 96 ± 7.1 vs. 99 ± 5.3 nmol/g and liver CDO activity, 2.19 ± 0.33 vs. 2.74 ± 0.21 nmol · min−1 · mg protein−1. These findings support the conclusion that Cu deficiency does not affect body taurine status.