Changes in urinary taurine and hypotaurine excretion after two-thirds hepatectomy in the rat

Summary This study followed the time course of urinary taurine and hypotaurine excretion after two-thirds hepatectomy in rats. The excretion of both taurine and hypotaurine was elevated during 18th following the hepatectomy, with maximal excretion during the first 6h. Twelve and 24h after partial hepatectomy, the hepatic hypotaurine concentration was increased but liver taurine did not differ significantly from controls. No changes were observed in hypotaurine and taurine concentrations of heart, kidney, lung, muscle tissue and spleen. We postulate that partial hepatectomy induces a rapid increase of hepatic (hypo)taurine synthesis from precursor amino acids. The increased (hypo)taurine concentrations spill over into urine.     

Biochemical changes in a 100 km run: free amino acids, urea, and creatinine.

Free amino acids, urea, and creatinine were analyzed in venous blood and urine of 11 trained (28--81 years old) male subjects before, immediately after, and 1 day after a 100 km running competition. The urinary excretion per minute of all amino acids was lowered after the contest. The renal clearance of creatinine was reduced from 116 to 60 ml/min and the clearance of most amino acids was reduced to a similar extent. However, for the amino acids with a resting clearance under 1 ml/min (x), a high relative clearance ratio (y in % of x) was seen post-exercise: y = -92.3 (log10 x) +23.1, r = -0.83, showing that their high reabsorption capacity had been impaired. Serum concentrations of most free amino acids, including the branched-chain amino acids and alanine, were reduced to 35--85% of the pre-race values. The sulfur amino acids were elevated either at the end of (cystine, to 180%) or 24 h after (methionine, to 155%) the race. Urea production increased by 44% while creatinine production tended to decrease. The production of 3-methylhistidine remained unchanged. These findings are compatible with a stimulation of gluconegenesis at the expense of the amino acid pool without induction of muscle protein catabolism.     

Effect of selenium deficiency on tissue taurine concentration and urinary taurine excretion in the rat

The purpose of this study was to determine the effect of selenium deficiency on tissue taurine levels and urinary taurine excretion. Weanling male Sprague-Dawley rats were fed selenium-deficient or selenium-adequate diets for 20 weeks. As selenium deficiency developed, urinary taurine excretion increased in selenium-deficient rats compared to controls. At 12 weeks, the selenium-deficient rats excreted 1.7-fold more taurine than control rats. At the same time plasma glutathione peroxidase was 1.2% of control and plasma glutathione was 226% of control. At 20 weeks, renal taurine was decreased but renal glutathione was increased in selenium-deficient rats compared to controls. Feeding the experimental diet for 6 weeks without methionine supplementation caused a fall in urinary taurine excretion. However, there was no difference between selenium-deficient and control rats. These results indicate that selenium deficiency affects renal handling of taurine in the rat when dietary sulfur amino acids are not restricted.     

Biliary amino acid excretion in rats before and after bilateral nephrectomy.

In previous studies it could be shown that after bilateral nephrectomy (NX) the excretory function of the liver is disturbed. To further clarify whether or not this "renohepatic syndrome" is caused by toxic effects of uremia or by competition phenomena between various uraemic toxins an additional aspect was investigated: the biliary excretion of endogenous amino acids. Furthermore, previously it could be shown that renal and hepatic excretory functions overlap. Therefore, the renal excretion of effectively biliary eliminated amino acids (glutamic acid, alanine, tyrosine, isoleucine) is very low and vice versa. That means, that the renal excretion of amino acids with low hepatic elimination (tryptophan, citrulline, lysine, taurine) dominates. The hepatic excretion of amino acids is hardly altered after NX. Remarkably, the removal of both kidneys is followed by a distinct reduction in amino acid plasma concentrations, especially if these concentrations are relatively high in the controls. Interestingly, there is no correlation between plasma concentrations and biliary excretion of amino acids. But the calculation of the bile to plasma concentration ratios of amino acids makes it possible to differentiate three groups of amino acids: Amino acids excreted actively into bile (ratio > or = 1), amino acids with ratios below 1, indicating effective retention, and amino acids with ratios of about 1, whose hepatic handling is passive. After NX these ratios tended to approach 1; low ratios increased and high ratios decreased. That means, active processes involved in excretion or retention are obviously disturbed. These changes could indicate uraemic liver damage as proved regarding influence of NX on hepatic excretion of other endogenous substances and xenobiotics.     

Urinary excretion of immunoreactive prostaglandin F2α in healthy children and adults

The 24-hours urinary excretion of immunoreactive prostaglandin F_2α (U-iPGF_2α) in normal children on a free diet was not significantly different in 30 boys (aged 3–15 years; geometric mean 589 ng/24 h) compared to 27 girls (aged 4–14 years; mean 473 ng/24 h). In both sexes this excretion rose with age until adolescence where it reached a plateau.In normal adults the men had significantly higher (p < 0.001) excretions of U-iPGF_2α than the women; also body weight and urinary creatinine excretion were higher in men (p < 0.001).In the children, as well as in the total population, U-iPGF_2α correlated best with body weight (r = 0.44 and r = 0.48 respectively; p < 0.001) and the urinary creatinine excretion (r = 0.53 and 0.57 respectively; p < 0.001); both body weight and urinary creatinine excretion are reflections of total body development. After the correction for urinary creatinine excretion or for body weight, the sex difference in the adult U-iPGF_2α totally disappeared.     

Amino acid metabolism in leg muscle after an endotoxin injection in healthy volunteers

Decreased plasma amino acid concentrations and increased net release of amino acids from skeletal muscle, especially for glutamine, are common features in critically ill patients. A low dose of endotoxin administered to healthy volunteers was used as a human model for the initial phase of sepsis to study the early metabolic response to sepsis. Six healthy male volunteers were studied in the postabsorptive state. Blood samples from the forearm artery and femoral vein were taken during 4 h before and 4 h after an intravenous endotoxin injection (4 ng/kg body wt). In addition, muscle biopsies from the leg muscle were taken. Plasma concentration of the total sum of amino acids decreased by 19% (P = 0.001) and of glutamine by 25% (P = 0.004) the 3rd h after endotoxin administration. At the same time, muscle concentrations of the sum of amino acids and glutamine decreased by 11% (P = 0.05) and 9% (P = 0.09), respectively. In parallel, the efflux from the leg increased by 35% (P = 0.004) for the total sum of amino acids and by 43% (P = 0.05) for glutamine. In conclusion, intravenous endotoxin administration to healthy volunteers, used as a model for the initial phase of sepsis, resulted in a decrease in plasma amino acid concentrations. At the same time, amino acid concentrations in muscle tissue decreased, whereas the efflux of amino acids from leg skeletal muscle increased.     

Effect of regular training on the myocardial and plasma concentrations of taurine andα-amino acids in thoroughbred horses

Summary Exercise induces significant changes in the free intracellular amino acid pool in skeletal muscle but little is known of whether such changes also occur in cardiac muscle. In this study the effect of regular exercise on the size and the constituents of the free amino acid pool in the hearts and in the plasma of thoroughbred horses was investigated. The total free intracellular amino acid pool in the hearts of control horses was 30.9 ± 1.2mol/g wet weight (n = 6). Glutamine but not taurine was present at the highest concentration (13.5 ± 0.9 and 7.7 ± 0.69mol/g wet weight for glutamine and taurine respectively). As for the rest of the amino acids in the pool, only glutamate and alanine were present at levels greater than 1mol/g wet weight (4.6 ± 0.25 and 1.7 ± 0.14 for glutamate and alanine respectively). The tissue to plasma ratio was highest for taurine at 155, followed by glutamate at 111, aspartate and glutamine at 37, alanine at 5.8 and ratios of less than 3 for the rest of the amino acids. The total free intracellular amino acid pool in the hearts of exercised horses was slightly but not significantly lower than control (28.1 ±1.1mol/g wet weight, n = 6). Regular exercise increased the intracellular concentration of threonine, valine, isoleucine, leucine and phenylalanine but was only significant (p < 0.05) for threonine. This work has documented the profile of taurine and protein amino acids in the heart and in the plasma of thoroughbred horses and showed that in contrast to skeletal muscle, heart muscle does not show major changes in amino acids during regular exercise.     

Is there a correlation between taurine levels and xenobioticinduced perturbations in protein synthesis?: A study with tetracycline in rats

Summary Changes in urinary levels of taurine have been reported in rats following treatment with various xenobiotics including those which alter protein synthesis and/or are hepatotoxic. This paper reports on the time course of the urinary elevation of taurine following treatment of rats with tetracycline (50, 150 and 200mg.kg^-1). Maximum taurine excretion occurred 8–12h following dosing. Serum albumin and total protein were significantly lower after 24h (200mg.kg^-1). The increase in urinary taurine was dose-related and reflected in the raised serum levels of taurine 24h after dosing. Serum and urinary protein and [³H]-leucine incorporation into acid precipitable protein in liver and muscle were reduced by tetracycline (100, 150 and 200mg.kg^-1) 10h after dosing. The reduction in protein synthesis was correlated with increased urinary and serum levels of taurine at 10h. The use of taurine as a non-invasive marker of protein synthesis is discussed.     

Hypogonadism in liver cirrhosis: implication in altered amino acid metabolism in muscle

To investigate the relationship between hypogonadism and altered amino acid metabolism in patients with liver cirrhosis, we measured the basal levels of plasma testosterone, estradiol, and free amino acids, plus urinary 3-methylhistidine excretion, in 16 control and 19 cirrhotic patients. The concentration of plasma testosterone correlated significantly with that of plasma branched-chain amino acids, and inversely with urinary 3-methylhistidine excretion. This suggests that hypogonadism causes a disturbance in amino acid metabolism at least partly related to an augmented muscle protein turnover.     

Age-related changes of muscle and plasma amino acids in healthy children

The aim of the study was to explore if changes in muscle and plasma amino acid concentrations developed during growth and differed from levels seen in adults. The gradient and concentrations of free amino acids in muscle and plasma were investigated in relation to age in metabolic healthy children. Plasma and specimens from the abdominal muscle were obtained during elective surgery. The children were grouped into three groups (group 1: < 1 year, n = 8; group 2: 1–4 years, n = 13 and group 3: 5–15 years, n = 15). A reference group of healthy adults (21–38 years, n = 22) was included in their comparisons and reflected specific differences between children and adults. In muscle the concentrations of 8 out of 19 amino acids analysed increased with age, namely taurine, aspartate, threonine, alanine, valine, isoleucine, leucine, histidine, as well as the total sums of branched chain amino acids (BCAA), basic amino acids (BAA) and total sum of amino acids (P < 0.05). In plasma the concentrations of threonine, glutamine, valine, cysteine, methionine, leucine, lysine, tryptophane, arginine, BCAA, BAA and the essential amino acids correlated with age (P < 0.05). These results indicate that there is an age dependency of the amino acid pattern in skeletal muscle and plasma during growth.     

Effects of high salt diets and taurine on the development of hypertension in the stroke-prone spontaneously hypertensive rat

Summary. Taurine is present in high concentrations in mammalian tissues and has been implicated in cardiovascular control mechanisms. The aim of the present study was to evaluate the ability of taurine to attenuate salt-induced elevations in blood pressure and markers of damage to the kidney and cardiovascular system in stroke prone spontaneously hypertensive rats (SPSHR). Male SPSHR (6 weeks old) were placed on high salt diets that contained 1% (w/w) NaCl added to their normal chow for 84 days and then were switched to 3% added NaCl for the remaining 63 days of the study. SPSHR was given 1.5% taurine in the drinking water (n = 8), a taurine free diet (n = 8) or normal chow (n = 8). A final control group (n = 6) was not given high salt diets. High salt diets caused an acceleration in the development of hypertension in all groups. Taurine supplementation reduced ventricular hypertrophy and decreased urinary excretion of protein and creatinine. The taurine free diet did not alter serum or urinary excretion of taurine, but did result in elevated urinary nitrogen excretion, increased serum cholesterol levels, and impaired performance in a spatial learning task. Alterations in dietary taurine intake did not alter urinary or serum electrolytes (Na⁺, K⁺), but taurine supplementation did attenuate a rise in serum calcium seen with the high salt diets. Urinary excretion (μg/24 h) of epinephrine and dopamine was significantly reduced in SPSHR given 1% NaCl in the diet, but this effect was not seen in SPSHR on taurine free or supplemented diets. Taurine supplementation showed cardioprotective and renoprotective effects in SPSHR given high salt diets. Received April 12, 1999/Accepted September 13, 1999     

Co-variation of plasma sodium,taurine and other amino acid levels in critical illness

Summary.  This study investigates the relationship between changes in plasma sodium and changes in amino acid levels in a patient with post-traumatic sepsis and prolonged critical illness. Ninety-two consecutive measurements were performed at regular intervals over a period of many weeks; these consisted in the determination of full amino-acidograms, plasma sodium and complementary variables. A unique, highly significant inverse correlation between taurine and plasma sodium was found (r² = 0.48, p < 0.001). All other amino acids were unrelated, or much more weakly related, to sodium. Taurine was also strongly and directly related to phosphoethanolamine, glutamate and aspartate. Changes in sodium and in levels of these amino acids explained up to 86% of the variability of taurine. Besides, levels of these amino acids maintained a high degree of co-variation, remaining reciprocally related one to each other, directly, with r² ranging between 0.33 and 0.59 (p < 0.001 for all). There were similar findings for β-alanine, which however was measured inconsistently. These data provide gross clinical evidence of a specific link binding plasma sodium and taurine levels, and may be consistent with occurrence of opposite and interdependent shifts of sodium and taurine between intravascular and extravascular space, to maintain osmoregulation. Co-variation of taurine with the other amino acids may be related to the same phenomenon, and/or to similarities in transport systems and chemical structure, or true metabolic interactions. Received April 16, 2002 Accepted June 19, 2002 Published online November 14, 2002 RID="*" ID="*"  Presented at the 7^th International Congress on Amino Acids and Proteins, Vienna (Austria), August 6–10, 2001. Acknowledgements The authors acknowledge the kind assistance of Mr. Maurizio Cianfanelli, from the Catholic University School of Medicine, Rome, Italy. Authors' address: Dr. Carlo Chiarla, Via Augusto Tebaldi, 19, I-00168 Roma, Italy, E-mail: carlo.chiarla@rm.unicatt.it     

Changes in free amino acids in the brain during embryonic development in layer and broiler chickens

Developmental changes in the levels of the excitatory amino acids l-glutamate (Glu) and l-Aspartate (Asp) and inhibitory amino acids glycine (Gly) and γ-amino butyric acid (GABA), as well as taurine and its related amino acids l-methionine (Met), l-cysteine (Cys) and l-serine (Ser) in the brain and pectoralis muscle at various embryonic stages and hatch in broiler and layer type chickens were determined. Brain concentrations of Asp, GABA and taurine were higher than those in the muscle, but the difference in the two types was small. The concentrations of the precursors of taurine including Met, Cys and Ser were lower than that of taurine. In conclusion, the synthesis of some amino acids and their metabolites such as Asp, GABA and taurine in the chick embryo is very high in order to support brain development.     

Changes in plasma taurine levels after different endurance events

Summary The sulphonated amino acid taurine increased significantly in the plasma of trained athletes after three endurance exercises of different duration and intensity, a 90 min run on a treadmill at 75% of an individual's VO₂ peak, a Marathon, 42.2km and a 100km run, by 19%, 77% and 36%, respectively. Such results indicated that the speed at which the exercise is per formed, referred to as the intensity, rather than the duration of the exercise, correlated with the elevated taurine levels possibly indicating its release from muscle fibres. The plasma amino acid pool decreased significantly in relationship with the duration of the exercise, caused by their utilisation for glucogenesis. The possible sources of the increased plasma taurine are discussed.     

Plasma levels and renal handling of endogenous amino acids in snakes: a comparative study

Plasma levels of 22 endogenous amino acids were measured by ion-exchange chromatography in four species of snakes: Thamnophis sirtalis, T. radix, Aipysurus laevis, and Python molurus. Despite considerable interspecific variation in the amino acid composition, all species showed relatively high plasma concentrations of histidine, a feature apparently unique to reptiles. The renal handling of these amino acids was studied by renal clearance methods. As in other vertebrates, net tubular absorption of filtered amino acids predominated. However, net tubular secretion of taurine, cysteic acid and/or phosphoserine and beta-alanine was observed, with taurine being the predominant amino acid secreted. The percentage reabsorption of the total amino acids filtered by the snake kidneys ranged from 79 to 95%. Evidence for the postrenal absorption of amino acids in these reptiles is presented. In species that normally undergo hibernation (Thamnophis spp.), the ability of the kidney to reabsorb amino acids was depressed by cold acclimation. Cold acclimation significantly decreased plasma levels of all amino acids except taurine, whose concentration increased. The increase in plasma taurine level may have resulted from cellular osmoregulation. Under these conditions, renal excretion of taurine increased concomitantly with the increase in plasma taurine concentration.     

Melatonin and taurine reduce early glomerulopathy in diabetic rats

Oxidative stress occurs in diabetic patients and experimental models of diabetes. We examined whether two antioxidants, melatonin and taurine, can ameliorate diabetic nephropathy. Enhanced expression of glomerular TGF-beta1 and fibronectin mRNAs and proteinuria were employed as indices of diabetic nephropathy. Experimental diabetes was induced by intravenous injection of streptozotocin 50 mg/kg. Two days after streptozotocin, diabetic rats were assigned to one of the following groups: i) untreated; ii) melatonin supplement by 0.02% in drinking water; or iii) taurine supplement by 1% in drinking water. Four weeks after streptozotocin, diabetic rats (n = 6: plasma glucose 516+/-12 mg/dl) exhibited 6.1 fold increase in urinary protein excretion, 1.4 fold increase in glomerular TGF-beta1 mRNA, 1.7 fold increase in glomerular fibronectin mRNA, 2.2 fold increase in plasma lipid peroxides (LPO), and 44 fold increase in urinary LPO excretion above the values in control rats (n = 6: plasma glucose 188+/-14 mg/dl). Chronic administration of melatonin (n = 6) and taurine (n = 6) prevented increases in glomerular TGF-beta1 and fibronectin mRNAs and proteinuria without having effect on blood glucose. Both treatments reduced lipid peroxidation by nearly 50%. The present data demonstrate beneficial effects of melatonin and taurine on early changes in diabetic kidney and suggest that diabetic nephropathy associated with hyperglycemia is largely mediated by oxidative stress.     

The effect of taurine administration on vitamin C levels of several tissues in mice

Summary. Taurine (2-aminoethane sulphonic acid), a sulphur-containing beta amino acid, is the most prevalent free intracellular amino acid in many human and animal tissues. Vitamin C metabolism is also fluenced by sulphur-containing amino acids. The aim of this study is to investigate the effect of taurine administration on the vitamin C levels of plasma and several tissues (brain, liver, kidneys) in mice with incisional skin wounds. Animals were divided into two as control and taurine groups. Taurine was freshly dissolved in sterile saline and administered daily (60µl, ip) for five days in the taurine group. At the end of the fifth day, the animals were killed by decapitation. The brain, liver and kidneys were immediately removed. Vitamin C levels were measured in plasma and several tissues. The administration of taurine had no effect on the plasma vitamin C levels (P>0.05) but significantly increased in liver and kidneys (P<0.001). In conclusion, taurine may affect the vitamin C metabolism in tissues by different mechanisms.     

Urinary excretion of taurine in epilepsy

Evidence that taurine (2-aminoethanesulfonic acid) is related to the epilepsies is supported by work with both experimental animals and hurmans. It may function as a neurotransmitter or modulator of neurotransmission. Investigators using an automated amino acid analyzer reported lower mean urinary taurine excretion among epileptics. However, Rao et al. reported higher taurine excretion among epileptics using an older method. Analyses of the same epileptic and control urines by both methods coupled with paper and molecular size chromatography indicate that substances in addition to taurine are co-eluted with taurine using the older method, yielding spuriously high values. The resolution of this disparity is important because the urinary excretion of taurine may reflect primarily the influence of taurine transport alleles which may be polygenic components in the idiopathic epilepsies.     

Oxoproline kinetics and oxoproline urinary excretion during glycine- or sulfur amino acid-free diets in humans

L-5-oxoproline (L-5-OP) is an intermediate in glutathione synthesis, possibly limited by cysteine availability. Urinary 5-OP excretion has been proposed as a measure of glycine availability. We investigated whether 5 days of dietary sulfur amino acid (SAA-free) or glycine (Gly-free) restriction affects plasma kinetics of 5-OP and urinary excretion of L- and D-5-OP in 6 healthy men. On day 6, L-5-[1-(13)C]oxoproline and [3,3-(2)H(2)]cysteine were infused intravenously for 8 h (3 h fast/5 h fed). In a control study (adequate amino acid mixture), plasma oxoproline fluxes were 37.8 +/- 13.8 (SD) and 38.4 +/- 14.8 micromol x kg(-1) x h(-1); oxidation accounted for 85% of flux. Cysteine flux was 47.9 +/- 8.5 and 43.2 +/- 8.5 micromol x kg(-1) x h(-1) for fast and fed phases, respectively. Urinary excretion of L- and D-5-OP was 70 +/- 34 and 31.1 +/- 13.3 micromol/mmol creatinine, respectively, during days 3-5, and 46.4 +/- 13.9 and 22.4 +/- 8.3 micromol/mmol over the 8-h tracer study. The 5-OP flux for the Gly-free diet was higher (P = 0. 018) and tended to be higher for the SAA-free diet (P = 0.057) when compared with the control diet. Oxidation rates were higher on the Gly-free (P = 0.005) and SAA-free (P = 0.03) diets. Cysteine fluxes were lower on the the Gly-free (P = 0.01) and the SAA-free diets (P = 0.001) compared with the control diet. Rates of L-5-OP excretion were unchanged by withdrawal of SAA or Gly for 5 days but increased on day 6 (P = 0.005 and P = 0.019, respectively). Thus acute changes in the dietary availability of SAA and Gly alter oxoproline kinetics and urinary 5-OP excretion.     

Amino acid supplementation alters bone metabolism during simulated weightlessness.

High-protein and acidogenic diets induce hypercalciuria. Foods or supplements with excess sulfur-containing amino acids increase endogenous sulfuric acid production and therefore have the potential to increase calcium excretion and alter bone metabolism. In this study, effects of an amino acid/carbohydrate supplement on bone resorption were examined during bed rest. Thirteen subjects were divided at random into two groups: a control group (Con, n = 6) and an amino acid-supplemented group (AA, n = 7) who consumed an extra 49.5 g essential amino acids and 90 g carbohydrate per day for 28 days. Urine was collected for n-telopeptide (NTX), deoxypyridinoline (DPD), calcium, and pH determinations. Bone mineral content was determined and potential renal acid load was calculated. Bone-specific alkaline phosphatase was measured in serum samples collected on day 1 (immediately before bed rest) and on day 28. Potential renal acid load was higher in the AA group than in the Con group during bed rest (P < 0.05). For all subjects, during bed rest urinary NTX and DPD concentrations were greater than pre-bed rest levels (P < 0.05). Urinary NTX and DPD tended to be higher in the AA group (P = 0.073 and P = 0.056, respectively). During bed rest, urinary calcium was greater than baseline levels (P < 0.05) in the AA group but not the Con group. Total bone mineral content was lower after bed rest than before bed rest in the AA group but not the Con group (P < 0.05). During bed rest, urinary pH decreased (P < 0.05), and it was lower in the AA group than the Con group. These data suggest that bone resorption increased, without changes in bone formation, in the AA group.