Protective and therapeutic effectiveness of taurine in diabetes mellitus: a rationale for antioxidant supplementation.

PubMed

Sirdah, Mahmoud M

2015-01-01

Taurine, 2-amino ethanesulfonic acid, is a conditionally essential β amino acid which is not utilized in protein synthesis. Taurine is one of the most abundant free amino acids in mammals tissues and is one of the three well-known sulfur-containing amino acids; the others are methionine and cysteine which are considered as the precursors for taurine synthesis. Different scientific studies emphasize on the cytoprotective properties of taurine which included antioxidation, antiapoptosis, membrane stabilization, osmoregulation, and neurotransmission. Protective and therapeutic ameliorations of oxidative stress-induced pathologies were also attributed to taurine both in experimental and human models. Data demonstrating the beneficial effectiveness of taurine against type 1 and type 2 diabetes mellitus and their complications are growing and providing a better understanding of the underlying molecular mechanisms. Although the clinical studies are limited compared to the experimental ones, the present updated systematic review of the literature is set up to provide experimental and clinical evidences regarding the effectiveness of taurine in the context of diabetes mellitus and its complications. Gathering these scientific effects of taurine on diabetes mellitus could provide the physicians and specially the endocrinologists with a comprehensive overview on possible trends in the prevention and management of the disease and its complications through antioxidant supplementation. Copyright © 2014 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Biomolecular Chemistry of Isopropyl Fibrates

PubMed Central

Rath, Niharika; Kotheimer, Amenda; Miller, Chad; Zeller, Matthias; Rath, Nigam P.

2012-01-01

Isopropyl 2-[4-(4-chlorobenzoyl)-phenoxy]-2-methylpropanoic acid and isopropyl 2-(4-chlorophenoxy)-2-methylpropanoate, also known as fenofibrate and isopropyl clofibrate, are hypolipidemic agents of the fibrate family. In a previously reported triclinic structure of fenofibrate (polymorph I) the methyl groups of the isopropyl moiety (iPr) are located symmetrically about the carboxylate group. We report a new monoclinic form (polymorph II) of fenofibrate and a first structural description of isopropyl clofibrate, and in these the methyl groups are placed asymmetrically about the carboxylate group. In particular the dihedral (torsion) angle between the hydrogen atom on the secondary C and the C atom of the carboxyl group makes a 2.74° angle about the ester O-C bond in the symmetric fenofibrate structure of polymorph I, whereas the same dihedral angle is 45.94° in polymorph II and -30.9° in the crystal structure of isopropyl clofibrate. Gas phase DFT geometry minimizations of fenofibrate and isopropyl clofibrate result in lowest energy conformations for both molecules with a value of about ± 30° for this same angle between the O=C-O-C plane and the C-H bond of the iPr group. A survey of crystal structures containing an iPr ester group reveals that the asymmetric conformation is predominant. Although the hydrogen atom on the secondary C atom of the isopropyl group is located at a comparable distance from the carbonyl oxygen in the symmetric and asymmetric fenofibrate (2.52 and 2.28 Å) and the isopropyl clofibrate (2.36 Å) structures, this hydrogen atom participates in a puckered five membered ring arrangement in the latter two that is unlike the planar arrangement found in symmetric fenofibrate (polymorph I). Polar molecular surface area (PSA) values indicate fenofibrate and isopropyl clofibrate are less able to act as acceptors of hydrogen bonds than their corresponding acid derivatives. Surface area calculations show dynamic polar molecular surface area (PSAd) values of the iPr esters of the fibrates are lower than those of their acids, implying that the fibrates have better membrane permeability and a higher absorbability and hence are better prodrugs when these agents need to be orally administered. PMID:22246648

Modelling cortical cataractogenesis 22: is in vitro reduction of damage in model diabetic rat cataract by taurine due to its antioxidant activity?

PubMed

Kilic, F; Bhardwaj, R; Caulfeild, J; Trevithick, J R

1999-09-01

The protective effect of taurine in model in vitro diabetic cataract and the mechanism of this effect were investigated in isolated rat lenses. Isolated rat lenses were incubated in medium 199 in elevated glucose (55.6 m m) with taurine (5 m m). Taurine concentrations in the lenses were determined by amino acid analysis. Accumulative leakage of the intracellular enzyme lactate dehydrogenase (LDH) was used to estimate damage to the lens, as previously reported. In the clear lenses, prior to vacuole formation, after 1 or 2 days of incubation, the taurine and amino acids in lenses decreased progressively in concentration. In lenses incubated with 5 m m taurine, the level of taurine was increased towards that of control lenses. In taurine-treated lenses LDH leakage was significantly decreased, and lens clarity was maintained, similarly to that found previously for vitamin C and lipoic acid. To test whether taurine has similar antioxidant activity, we tested its ability to decrease luminol luminescence generated by (1) superoxide from hypoxanthine/xanthine oxidase and (2) peroxide from diluted glucose/glucose oxidase. For either superoxide or peroxide, the luminescence was decreased to zero, as a function of increasing taurine concentration, at 30 m m, approximately the physiological concentration of taurine in the lens. Spin trapping confirmed that taurine scavenged superoxide. This is consistent with a role for taurine as an important antioxidant protecting the lens against oxidative insults. Amino acids also had antioxidant activity in this assay, and as a group, when all activities were summed, their loss also contributed significantly to the antioxidant loss. Taken in conjunction with Wolff and Crabbe's observation of increased free radical generation by glucose auto-oxidation in diabetes, this suggests a push-pull mechanism for increased oxidative stress in diabetic cataract, involving both increased free radicals and decreased radical scavenging antioxidants. Copyright 1999 Academic Press.

Effect of rosuvastatin monotherapy and in combination with fenofibrate or omega-3 fatty acids on serum vitamin D levels.

PubMed

Makariou, Stefania E; Liberopoulos, Evangelos N; Agouridis, Aris P; Challa, Anna; Elisaf, Moses

2012-12-01

Low levels of 25(OH) vitamin D [25(OH)VitD] have been recognized as a new cardiovascular disease (CVD) risk factor. Statins seem to increase 25(OH)VitD concentration. To investigate whether combined treatment with the usual dose of rosuvastatin plus fenofibrate or omega-3 fatty acids would increase 25(OH)VitD levels compared with the high-dose rosuvastatin monotherapy in participants with mixed dislipidemia. We randomly allocated 60 patients with mixed dyslipidemia (low-density lipoprotein cholesterol: >160 mg/dL plus triglycerides: >200 mg/dL) to receive rosuvastatin 40 mg (n = 22), rosuvastatin 10 mg plus fenofibrate 200 mg (n = 21), or rosuvastatin 10 mg plus omega-3 fatty acids 2 g (n = 17) daily for 3 months. Our primary end point was changes in the levels of serum 25(OH)VitD. Rosuvastatin monotherapy was associated with a 53% increase in 25(OH)VitD (from 14.6 [1.0-38.0] to 17.8 [5.3-49.6] ng/mL; P = .000). Rosuvastatin plus micronized fenofibrate and rosuvastatin plus omega-3 fatty acids were associated with increases of 64% (from 14.1 [1.0-48.0] to 18.4 [6.7-52.4] ng/mL, P = .001) and 61% (from 10.4 [6.6-38.4] to 14.0 [9.6-37.6] ng/mL, P = .04), respectively. The changes in 25(OH)VitD after treatment were comparable in the 3 groups. High-dose rosuvastatin monotherapy and the usual dose of rosuvastatin plus fenofibrate or omega-3 fatty acids are associated with significant and similar increases in the 25(OH)VitD levels. This increase may be relevant in terms of CVD risk prevention.

Effect of gemfibrozil and fenofibrate on the pharmacokinetics of atorvastatin.

PubMed

Whitfield, Lloyd R; Porcari, Anthony R; Alvey, Christine; Abel, Robert; Bullen, William; Hartman, Daniel

2011-03-01

Coadministration of statins and fibrates is beneficial in some patients by allowing simultaneous reduction of triglycerides and low-density lipoprotein cholesterol alongside elevation of high-density lipoprotein cholesterol. However, the potential for drug interactions must be taken into consideration. Gemfibrozil increases systemic exposure to various different statins, whereas similar effects are not observed with fenofibrate, suggesting it may be a more appropriate choice for coadministration with statins. Gemfibrozil is reported to cause a moderate increase in the area under the curve (AUC) of atorvastatin, but the effect of fenofibrate on atorvastatin pharmacokinetics has not been described. This study compared the effects of multiple-dose administration of gemfibrozil and fenofibrate on the single-dose pharmacokinetics of atorvastatin. Gemfibrozil coadministration led to significant increases in the AUC of atorvastatin, 2-hydroxyatorvastatin, 2-hydroxyatorvastatin lactone, and 4-hydroxyatorvastatin lactone. In contrast, fenofibrate administration did not lead to clinically meaningful changes in the AUC for atorvastatin, atorvastatin lactone, 2-hydroxyatorvastatin, or 2-hydroxyatorvastatin lactone. The absence of a significant pharmacokinetic interaction between fenofibrate and atorvastatin is consistent with recent results showing no difference in safety profile between atorvastatin as monotherapy or in combination with fenofibric acid. Together, these data suggest that atorvastatin-fenofibrate combination therapy is unlikely to pose a risk to patients.

Comparative clinical study between the effect of fenofibrate alone and its combination with pentoxifylline on biochemical parameters and liver stiffness in patients with non-alcoholic fatty liver disease.

PubMed

El-Haggar, Sahar Mohamed; Mostafa, Tarek Mohamed

2015-07-01

Non-alcoholic fatty liver disease is a common health problem associated with increased liver and vascular specific complications. The purpose of this study was to assess and compare the effect of fenofibrate alone or in combination with pentoxifylline on the measured biochemical parameters, inflammatory pathway and liver stiffness in patients with non-alcoholic fatty liver disease. The study design was randomized controlled trial. From July 2013 to June 2014, we recruited 90 non-alcoholic fatty liver patients from the Internal Medicine Department at Tanta University Hospital, Egypt. They were classified randomly into two groups to receive fenofibrate 300 mg daily or fenofibrate 300 mg daily plus pentoxifylline 1200 mg/day in three divided doses for 24 weeks. Fasting blood sample was obtained before and 24 weeks after treatment for biochemical analysis of liver and lipid panels, tumor necrosis factor-alpha, hyaluronic acid, transforming growth factor beta 1, fasting plasma insulin and fasting glucose. Liver stiffness measurement was carried out using fibro-scan. Data were statistically analyzed by paired and unpaired Student's t test. The data obtained suggests that adding pentoxifylline to fenofibrate does not provide a beneficial effect on lipid panel, but has a beneficial effect on indirect biochemical markers of hepatic fibrosis, a direct marker linked to matrix deposition (hyaluronic acid), a cytokine/growth factor linked to liver fibrosis (transforming growth factor beta 1), the inflammatory pathway, insulin resistance and liver stiffness as compared to fenofibrate alone. The combination pentoxifylline plus fenofibrate may represent a new therapeutic strategy for non-alcoholic fatty liver disease as it resulted in more beneficial effects on direct and indirect markers of liver fibrosis, liver stiffness, insulin resistance and inflammatory pathway implicated in NAFLD.

Taurine and taurine-deficiency in the perinatal period.

PubMed

Aerts, Leona; Van Assche, Frans André

2002-01-01

Taurine, a non-protein sulfur amino-acid, is the most abundant free amino-acid in the body and plays an important role in several essential biological processes. Apart from its role in cholesterol degradation, it acts as neurotransmitter, and has a function as osmoregulator and antioxidant in most body tissues. During pregnancy, taurine accumulates in the maternal tissues, to be released in the perinatal period to the fetus via the placenta and to the newborn via the maternal milk. It is accumulated especially in the fetal and neonatal brain. Low maternal taurine levels result in low fetal taurine levels. Taurine-deficiency in the mother leads to growth retardation of the offspring, and to impaired perinatal development of the central nervous system and of the endocrine pancreas. The adult offspring of taurine-deficient mothers display signs of impaired neurological function, impaired glucose tolerance and vascular dysfunction; they may develop gestational diabetes and transmit the effects to the next generation. This transgeneration effect of taurine-deficiency in the perinatal period fits into the concept of fetal origin of adult disease.

Taurine reverses sodium fluoride-mediated increase in inflammation, caspase-3 activity, and oxidative damage along the brain-pituitary-gonadal axis in male rats.

PubMed

Adedara, Isaac A; Olabiyi, Bolanle F; Ojuade, TeminiJesu D; Idris, Umar F; Onibiyo, Esther M; Farombi, Ebenezer O

2017-09-01

Excessive exposure to fluoride is associated with male reproductive dysfunction in humans and animals. Taurine (2-aminoethane sulfonic acid) is a free intracellular β-amino acid with antioxidant, anti-inflammatory, and neuroprotective properties. However, the effect of taurine on fluoride-induced reproductive toxicity has not been reported. The present study investigated the influence of taurine on sodium fluoride (NaF)-induced functional changes along the brain-pituitary-gonadal axis in male rats. NaF was administered singly in drinking water at 15 mg·L -1 alone or orally co-administered by gavage with taurine at 100 and 200 mg·(kg body mass) -1 for 45 consecutive days. Results showed that taurine significantly prevented NaF-induced increase in oxidative stress indices as well as augmented antioxidant enzymes activities and glutathione level in the brain, testes, and epididymis of the treated rats. Moreover, taurine reversed NaF-induced elevation in inflammatory biomarkers and caspase-3 activity as well as histological damage in the brain, testes, and epididymis of the treated rats. The significant reversal of NaF-induced decreases in testosterone level and testicular activities of acid phosphatase, alkaline phosphatase, and lactate dehydrogenase by taurine was accompanied by enhancement of sperm functional characteristics in the treated rats. Taurine may be a possible chemopreventive candidate against reproductive dysfunction resulting from fluoride exposure.

Taurine suppresses osteoblastic differentiation of aortic valve interstitial cells induced by beta-glycerophosphate disodium, dexamethasone and ascorbic acid via the ERK pathway.

PubMed

Feng, Xiang; Li, Jian-ming; Liao, Xiao-bo; Hu, Ye-rong; Shang, Bao-peng; Zhang, Zhi-yuan; Yuan, Ling-qing; Xie, Hui; Sheng, Zhi-feng; Tang, Hao; Zhang, Wei; Gu, Lu; Zhou, Xin-min

2012-10-01

Aortic valve calcification (AVC) is an active process characterized by osteoblastic differentiation of the aortic valve interstitial cells (AVICs). Taurine is a free β-amino acid and plays important physiological roles including protective effect of cardiovascular events. To evaluate the possible role of taurine in AVC, we isolated human AVICs from patients with type A dissection without leaflet disease. We demonstrated that the cultured AVICs express SM α-actin, vimentin and taurine transporter (TAUT), but not CD31, SM-myosin or desmin. We also established the osteoblastic differentiation model of the AVICs induced by pro-calcific medium (PCM) containing β-glycerophosphate disodium, dexamethasone and ascorbic acid in vitro. The results showed that taurine attenuated the PCM-induced osteoblastic differentiation of AVICs by decreasing the alkaline phosphate (ALP) activity/expression and the expression of the core binding factor α1 (Cbfα1) in a dose-dependent manner (reaching the maximum protective effect at 10 mM), and taurine (10 mM) inhibited the mineralization level of AVICs in the form of calcium content significantly. Furthermore, taurine activated the extracellular signal-regulated protein kinase (ERK) pathway via TAUT, and the inhibitor of ERK (PD98059) abolished the effect of taurine on both ALP activity/expression and Cbfα1 expression. These results suggested that taurine could inhibit osteoblastic differentiation of AVIC via the ERK pathway.

Taurine-induced attenuation of MPP+ neurotoxicity in vitro: a possible role for the GABA(A) subclass of GABA receptors.

PubMed

O'Byrne, M B; Tipton, K F

2000-05-01

Taurine is a sulphur-containing beta-amino acid found in high (millimolar) concentrations in excitable tissues such as brain and heart. Its suggested roles include osmoregulator, thermoregulator, neuromodulator, and potential neurotransmitter. This amino acid has also been shown to be released in large concentrations during ischaemia and excitotoxin-induced neuronal damage. Here we report a protective effect of taurine against MPP(+)-induced neurotoxicity in coronal slices from rat brain. Significant protective effects were observed at taurine concentrations of 20 and 1 mM, suggesting a potential role for taurine in cases of neuronal insult. Studies with the synthetic taurine analogues taurine phosphonate, guanidinoethane sulphonate, and trimethyltaurine suggested the observed effect to be mediated via an extracellular mechanism. The use of GABA receptor ligands muscimol and bicuculline indicated the effect to be mediated through activation of GABA(A) receptors.

Effects of graded taurine levels on juvenile cobia

USDA-ARS?s Scientific Manuscript database

Taurine, which has multiple important physiological roles in teleost fish and mammals, is an amino acid not found in alternative protein sources not derived from animals. Although taurine is found in fish-meal-based feeds, its high water solubility leads to lower taurine levels in reduction-process-...

21 CFR 573.980 - Taurine.

Code of Federal Regulations, 2014 CFR

2014-04-01

..., AND RELATED PRODUCTS FOOD ADDITIVES PERMITTED IN FEED AND DRINKING WATER OF ANIMALS Food Additive Listing § 573.980 Taurine. The food additive taurine (2-amino-ethanesulfonic acid) may be safely used in... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Taurine. 573.980 Section 573.980 Food and Drugs...

21 CFR 573.980 - Taurine.

Code of Federal Regulations, 2013 CFR

2013-04-01

..., AND RELATED PRODUCTS FOOD ADDITIVES PERMITTED IN FEED AND DRINKING WATER OF ANIMALS Food Additive Listing § 573.980 Taurine. The food additive taurine (2-amino-ethanesulfonic acid) may be safely used in... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Taurine. 573.980 Section 573.980 Food and Drugs...

21 CFR 573.980 - Taurine.

Code of Federal Regulations, 2011 CFR

2011-04-01

..., AND RELATED PRODUCTS FOOD ADDITIVES PERMITTED IN FEED AND DRINKING WATER OF ANIMALS Food Additive Listing § 573.980 Taurine. The food additive taurine (2-amino-ethanesulfonic acid) may be safely used in... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Taurine. 573.980 Section 573.980 Food and Drugs...

21 CFR 573.980 - Taurine.

Code of Federal Regulations, 2010 CFR

2010-04-01

..., AND RELATED PRODUCTS FOOD ADDITIVES PERMITTED IN FEED AND DRINKING WATER OF ANIMALS Food Additive Listing § 573.980 Taurine. The food additive taurine (2-amino-ethanesulfonic acid) may be safely used in... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Taurine. 573.980 Section 573.980 Food and Drugs...

21 CFR 573.980 - Taurine.

Code of Federal Regulations, 2012 CFR

2012-04-01

..., AND RELATED PRODUCTS FOOD ADDITIVES PERMITTED IN FEED AND DRINKING WATER OF ANIMALS Food Additive Listing § 573.980 Taurine. The food additive taurine (2-amino-ethanesulfonic acid) may be safely used in... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Taurine. 573.980 Section 573.980 Food and Drugs...

In vivo substitution of choline for sodium evokes a selective osmoinsensitive increase of extracellular taurine in the rat hippocampus.

PubMed

Lehmann, A; Sandberg, M

1990-01-01

Recent investigations have demonstrated that taurine and phosphoethanolamine (PEA) are the amino acids most sensitive to microdialysis-perfusion with reduced concentrations of NaCl. The aim of the present work was to assess the importance of Na+ deficiency in evoking this response. Further, the previously described selectivity of replacement of Cl- with acetate with respect to amino acid release was reinvestigated. The hippocampus of urethane-anesthetized rats was dialyzed with Krebs-Ringer bicarbonate buffer, and amino acid concentrations of the perfusate were determined. Choline chloride was then stepwise substituted for NaCl, and, in some cases, mannitol (122 mM) was included in low sodium-containing media. In other experiments, NaCl was replaced with sodium acetate. The dialysate levels of taurine increased selectively in response to Na+ substitution. The elevation of taurine was linearly related to the increase in choline chloride, and maximal levels amounted to 335% of basal levels. The increase in extracellular taurine was not inhibited by perfusion with medium made hyperosmotic with mannitol. Replacement of Cl- with acetate stimulated the release of taurine to 652% of resting levels. In addition, PEA levels increased to 250% of control concentration. Other amino acids were unaffected by Cl- substitution. The results show that taurine transport is considerably more sensitive to Na+ depletion than glutamate transport, which also is known to be Na+ dependent. The taurine increase evoked by low Na+ is not caused by cellular swelling as it was unaffected by hyperosmolar medium. Finally, substitution of acetate for Cl- causes a specific elevation of extracellular taurine and PEA, possibly as a result of cytotoxic edema.

Comparison of taurine, GABA, Glu, and Asp as scavengers of malondialdehyde in vitro and in vivo

NASA Astrophysics Data System (ADS)

Deng, Yan; Wang, Wei; Yu, Pingfeng; Xi, Zhijiang; Xu, Lijian; Li, Xiaolong; He, Nongyue

2013-04-01

The purpose of this study is to determine if amino acid neurotransmitters such as gamma-aminobutyric acid (GABA), taurine, glutamate (Glu), and aspartate (Asp) can scavenge activated carbonyl toxicants. In vitro, direct reaction between malondialdehyde (MDA) and amino acids was researched using different analytical methods. The results indicated that scavenging activated carbonyl function of taurine and GABA is very strong and that of Glu and Asp is very weak in pathophysiological situations. The results provided perspective into the reaction mechanism of taurine and GABA as targets of activated carbonyl such as MDA in protecting nerve terminals. In vivo, we studied the effect of taurine and GABA as antioxidants by detecting MDA concentration and superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities. It was shown that MDA concentration was decreased significantly, and the activities of SOD and GSH-Px were increased significantly in the cerebral cortex and hippocampus of acute epileptic state rats, after the administration of taurine and GABA. The results indicated that the peripherally administered taurine and GABA can scavenge free radicals and protect the tissue against activated carbonyl in vivo and in vitro.

Role of the PPAR-α agonist fenofibrate in severe pediatric burn injury

PubMed Central

Elijah, Itoro E.; Børsheim, Elisabet; Maybauer, Dirk M.; Finnerty, Celeste C.; Herndon, David N.; Maybauer, Marc O.

2013-01-01

Fenofibrate is a peroxisome proliferator activated receptor alpha agonist that contains both pro and anti-inflammatory properties, and has been used in the treatment of dyslipidemia and diabetes for decades. Its receptors are expressed in the liver, skeletal muscle, cardiac, enteric, and renal cells, which allow it to provide systemic regulation of lipoprotein metabolism, fatty acid oxidation, and fatty acid transport. Hyperglycemia is a common complication found in the burn population because hepatic glucose production and catecholamine-mediated hepatic glycogenolysis are augmented. Insulin resistance occurs often in these patients and is associated with poor outcomes. In the pediatric burn population, fenofibrate has been found to ameliorate or decrease the number of hypoglycemic episodes when compared to management with insulin alone. Its mechanism of action is thought to involve an improvement in insulin signaling in skeletal muscle, as well as improvements in mitochondrial function, glucose oxidation, and insulin sensitivity. The long term use of fenofibrate in severely burned patients may improve hyperglycemia and insulin resistance, as well as improve wound healing, and reduce apoptosis, and oxidative stress. PMID:22226866

Statins and fenofibrate affect skeletal muscle chloride conductance in rats by differently impairing ClC-1 channel regulation and expression

PubMed Central

Pierno, S; Camerino, GM; Cippone, V; Rolland, J-F; Desaphy, J-F; De Luca, A; Liantonio, A; Bianco, G; Kunic, JD; George, AL; Camerino, D Conte

2009-01-01

Background and purpose: Statins and fibrates can produce mild to life-threatening skeletal muscle damage. Resting chloride channel conductance (gCl), carried by the ClC-1 channel, is reduced in muscles of rats chronically treated with fluvastatin, atorvastatin or fenofibrate, along with increased resting cytosolic calcium in statin-treated rats. A high gCl, controlled by the Ca2+-dependent protein kinase C (PKC), maintains sarcolemma electrical stability and its reduction alters muscle function. Here, we investigated how statins and fenofibrate impaired gCl. Experimental approach: In rats treated with fluvastatin, atorvastatin or fenofibrate, we examined the involvement of PKC in gCl reduction by the two intracellular microelectrodes technique and ClC-1 mRNA level by quantitative real time-polymerase chain reaction. Direct drug effects were tested by patch clamp analysis on human ClC-1 channels expressed in human embryonic kidney (HEK) 293 cells. Key results: Chelerythrine, a PKC inhibitor, applied in vitro on muscle dissected from atorvastatin-treated rats fully restored gCl, suggesting the involvement of this enzyme in statin action. Chelerythrine partially restored gCl in muscles from fluvastatin-treated rats but not in those from fenofibrate-treated rats, implying additional mechanisms for gCl impairment. Accordingly, a decrease of ClC-1 channel mRNA was found in both fluvastatin-and fenofibrate-treated rat muscles. Fenofibric acid, the in vivo metabolite of fenofibrate, but not fluvastatin, rapidly reduced chloride currents in HEK 293 cells. Conclusions and implications: Our data suggest multiple mechanisms underlie the effect of statins and fenofibrate on ClC-1 channel conductance. While statins promote Ca2+-mediated PKC activation, fenofibrate directly inhibits ClC-1 channels and both fluvastatin and fenofibrate impair expression of mRNA for ClC-1. PMID:19220292

Acute intraperitoneal administration of taurine decreases the glycemia and reduces food intake in type 1 diabetic rats.

PubMed

Gomez, Rosane; Caletti, Greice; Arbo, Bruno Dutra; Hoefel, Ana Lúcia; Schneider, Ricardo; Hansen, Alana Witt; Pulcinelli, Rianne Remus; Freese, Luana; Bandiera, Solange; Kucharski, Luiz Carlos; Barros, Helena Maria Tanhauser

2018-07-01

Taurine, an amino acid with antioxidant and osmoregulatory properties, has been studied for its possible antidiabetic properties in type 1 and type 2 diabetic animals. In type 2 diabetic mice, taurine decreases blood glucose through increased insulin secretion and insulin receptor sensitization. However, insulin is absent in type 1 diabetic individuals. The aim of this study was to evaluate the effects of taurine on parameters related to the energy balance that could explain the metabolic action of this amino acid in type 1 diabetic rats. Control and streptozotocin-induced diabetic rats received saline or taurine (100 mg/kg/day), intraperitoneally, for 30 days. Parameters such as palatable food intake, gastrointestinal transit rate, serum glucose, insulin, leptin, and glucagon levels were measured 60 min after the last taurine administration. Liver, kidneys, heart, and retroperitoneal fat were dissected and weighted. Glycogen levels were measured in the liver and soleus muscle. Our results showed that acute taurine administration decreased glycemia. It also decreased food intake in diabetic rats, without affecting other metabolic parameters. Altogether, our results suggest that in type 1 diabetic rats, taurine decreases blood glucose by a non-insulin-dependent mechanism. Due to the safety profile of taurine, and its effect on glycemia, this amino acid may help to design new drugs to add benefit to insulin therapy in type 1 diabetic individuals. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Ordered mesoporous silica to enhance the bioavailability of poorly water-soluble drugs: Proof of concept in man.

PubMed

Bukara, Katarina; Schueller, Laurent; Rosier, Jan; Martens, Mark A; Daems, Tinne; Verheyden, Loes; Eelen, Siemon; Van Speybroeck, Michiel; Libanati, Cristian; Martens, Johan A; Van Den Mooter, Guy; Frérart, Françoise; Jolling, Koen; De Gieter, Marjan; Bugarski, Branko; Kiekens, Filip

2016-11-01

Formulating poorly water soluble drugs using ordered mesoporous silica materials is an emerging approach to tackle solubility-related bioavailability problems. The current study was conducted to assess the bioavailability-enhancing potential of ordered mesoporous silica in man. In this open-label, randomized, two-way cross-over study, 12 overnight fasted healthy volunteers received a single dose of fenofibrate formulated with ordered mesoporous silica or a marketed product based on micronized fenofibrate. Plasma concentrations of fenofibric acid, the pharmacologically active metabolite of fenofibrate, were monitored up to 96h post-dose. The rate (C max /dose increased by 77%; t max reduced by 0.75h) and extent of absorption (AUC 0-24h /dose increased by 54%) of fenofibrate were significantly enhanced following administration of the ordered mesoporous silica based formulation. The results of this study serve as a proof of concept in man for this novel formulation approach. Copyright © 2016 Elsevier B.V. All rights reserved.

Effects of Taurine Supplementation on Growth in Low Birth Weight Infants: A Systematic Review and Meta-Analysis.

PubMed

Cao, Shun-Li; Jiang, Hong; Niu, Shi-Ping; Wang, Xiao-Hu; Du, Shan

2018-01-25

To summarize the available randomized controlled trials (RCTs) to evaluate the effect of taurine supplementation on growth in low birth weight infants (LBW). PubMed, EmBase, and Cochrane Library electronic databases were searched for published articles through March 2017. Analysis was done to examine the effect of taurine supplementation on growth, and sensitivity analysis was performed by removing each individual study from meta-analysis. Results of 9 trials totaling 216 LBW infants in the present meta-analysis were collected and analyzed. The conclusion of included studies demonstrated that taurine supplementation significantly reduced length gain (WMD:-0.18; P < 0.001), plasma glycine (WMD:-106.71; P = 0.033), alanine (WMD:-229.30; P = 0.002), leucine (WMD:-64.76; P < 0.001), tyrosine (WMD:-118.11; P < 0.001), histidine (WMD:-52.16; P < 0.001), proline (WMD: -84.29; P = 0.033), and asparagine-glutamine (WMD:-356.30; P < 0.001). However, taurine supplementation was associated with higher levels of acidic sterols (WMD:0.61; P = 0.024), total fatty acids (WMD:7.94; P = 0.050), total saturated fatty acids (WMD:9.70; P < 0.001), and unsaturated fatty acids (WMD:6.63; P < 0.001). Finally, taurine supplementation had little or no significant effect on weight gain, head circumference gain, plasma taurine, threonine, serine, citrulline, valine, methionine, isoleucine, phenylalanine, ornithine, lysine, arginine, glutamate, hydroxyproline, aspartate, dietary cholesterol, endogenous neutral sterols, cholesterol synthesis, and medium-chain triglycerides. The findings suggest that although there are several significant differences in plasma indeces, no significant effect on growth in LBW infants was observed with taurine supplementation.

Effect of supplemental taurine on juvenile channel catfish Ictalurus punctatus growth

USDA-ARS?s Scientific Manuscript database

Taurine is a beta-amino sulfur amino acid found in most animal tissues. It has many important biological functions in mammals including membrane stabilization, antioxidation, cellular osmoregulation, detoxification, neuromodulation, and brain and eye development. Taurine supplementation in juvenil...

Enhanced taurine release in cell-damaging conditions in the developing and ageing mouse hippocampus.

PubMed

Saransaari, P; Oja, S S

1997-08-01

Taurine has been shown to be essential for neuronal development and survival in the central nervous system. The release of preloaded [3H]taurine was studied in hippocampal slices from seven-day-, three-month- and 18-22-month-old mice in cell-damaging conditions. The slices were superfused in hypoxic, hypoglycemic and ischemic conditions and exposed to free radicals and oxidative stress. The release of taurine was greatly enhanced in the above conditions in all age groups, except in oxidative stress. The release was large in ischemia, particularly in the hippocampus of aged mice. Potassium stimulation was still able to release taurine in cell-damaging conditions in immature mice, whereas in adult and aged animals the release was so substantial that this additional stimulus failed to work. Taurine release was partially Ca2+-dependent in all cases. The massive release of the inhibitory amino acid taurine in ischemic conditions could act neuroprotectively, counteracting in several ways the effects of simultaneous release of excitatory amino acids. This protection could be of great importance in developing brain tissue, while also having an effect in aged brains.

Taurine transport into fetal cord blood cells: inhibition by cyclosporine A.

PubMed

Speake, Paul F; Zipitis, Christos S; Houston, Angela; D'Souza, Stephen

2004-10-01

Pregnant women undergoing long-term organ transplant treatment have an increased incidence of delivering infants with intrauterine growth restriction (IUGR). Cyclosporine A is used as an immunosuppressant in such women and indirect evidence suggests that IUGR might result from an effect of cyclosporine A on amino acid transport by the placenta. In this study we tested the hypothesis that the transport of an essential amino acid, taurine, by fetal tissue other than the placenta is modulated by cyclosporine A. Cord blood cells (CBCs) were used to test this hypothesis as an easily obtainable fetal tissue. Transport of taurine into CBCs was measured using standard tracer flux assays. Uptake of [(3)H] taurine by CBCs was linear over 15 minutes (76.2 +/- 16.6 fmol/10(6) cells/min, mean +/- SEM, n = 6) and inhibitable by 10 mM beta-alanine, a substrate of the system-beta taurine transport protein (6.7 +/- 1.0 fmol/10(6) cells/min, n = 6, P <.05, paired Student t test). Pre-incubation with cyclosporine A (5 microM) inhibited [(3)H] taurine uptake by 29.3%-5.3% (n = 8, P <.05, paired Student t test). These data show that amino acid transport via system-beta can be measured in CBCs and may be a useful model for amino acid transport studies in fetal cells. We also show that system-beta was inhibited by the immunosuppressant, cyclosporine A. This suggests that the increased incidence of IUGR reported in mothers treated with cyclosporine A may be due partially to effects on taurine uptake into fetal cells outside the placenta.

HUMAN LIVER FATTY ACID BINDING PROTEIN (L-FABP) T94A VARIANT ALTERS STRUCTURE, STABILITY, AND INTERACTION WITH FIBRATES

PubMed Central

Martin, Gregory G.; McIntosh, Avery L.; Huang, Huan; Gupta, Shipra; Atshaves, Barbara P.; Landrock, Kerstin K.; Landrock, Danilo; Kier, Ann B.; Schroeder, Friedhelm

2014-01-01

Although the human L-FABP T94A variant arises from the most commonly occurring SNP in the entire FABP family, there is a complete lack of understanding regarding the role of this polymorphism in human disease. It has been hypothesized that the T94A substitution results in complete loss of ligand binding ability and function analogous to L-FABP gene ablation. This possibility was addressed using recombinant human WT T94T and T94A variant L-FABP and cultured primary human hepatocytes. Non-conservative replacement of the medium sized, polar, uncharged T residue by a smaller, nonpolar, aliphatic A residue at position 94 of human L-FABP significantly increased L-FABP protein α-helical structure at the expense of β-sheet and concomitantly decreased thermal stability. T94A did not alter binding affinities for PPARα agonist ligands (phytanic acid, fenofibrate, fenofibric acid). While T94A did not alter the impact of phytanic acid and only slightly altered that of fenofibrate on human L-FABP secondary structure, the active metabolite fenofibric acid altered T94A secondary structure much more than that of WT T94T L-FABP. Finally, in cultured primary human hepatocytes the T94A variant exhibited significantly reduced fibrate-mediated induction of PPARα-regulated proteins such as L-FABP, FATP5, and PPARα itself. Thus, while T94A substitution did not alter the affinity of human L-FABP for PPARα agonist ligands, it significantly altered human L-FABP structure, stability, as well as conformational and functional response to fibrate. PMID:24299557

Role of taurine in the vasculature: an overview of experimental and human studies

PubMed Central

Abebe, Worku; Mozaffari, Mahmood S

2011-01-01

Taurine is a sulfur-containing amino acid-like endogenous compound found in substantial amounts in mammalian tissues. It exerts a diverse array of biological effects, including cardiovascular regulation, antioxidation, modulation of ion transport, membrane stabilization, osmoregulation, modulation of neurotransmission, bile acid conjugation, hypolipidemia, antiplatelet activity and modulation of fetal development. This brief review summarizes the role of taurine in the vasculature and modulation of blood pressure, based on experimental and human studies. Oral supplementation of taurine induces antihypertensive effects in various animal models of hypertension. These effects of taurine have been shown to be both centrally and peripherally mediated. Consistent with this, taurine produces endothelium-dependent and independent relaxant effects in isolated vascular tissue preparations. Oral administration of taurine also ameliorates impairment of vascular reactivity, intimal thickening, arteriosclerosis, endothelial apoptosis, oxidative stress and inflammation, associated primarily with diabetes and, to a lesser extent with obesity, hypertension and nicotine-induced vascular adverse events. In rat aortic vascular smooth muscle cells (VSMCs), taurine acts as an antiproliferative and antioxidant agent. In endothelial cells, taurine inhibits apoptosis, inflammation, oxidative stress and cell death while increasing NO generation. Oral taurine in hypertensive human patients alleviates the symptoms of hypertension and also reverses arterial stiffness and brachial artery reactivity in type 1 diabetic patients. However, despite these favorable findings, there is a need to further establish certain aspects of the reported results and also consider addressing unresolved related issues. In addition, the molecular mechanism (s) involved in the vascular effects of taurine is largely unknown and requires further investigations. Elucidation of the mechanisms through which taurine affects the vasculature could facilitate the development of therapeutic and/or diet-based strategies to reduce the burdens of vascular diseases. PMID:22254206

Effect of supplemental taurine on juvenile channel catfish Ictalurus punctatus growth performance

USDA-ARS?s Scientific Manuscript database

Taurine is a beta-amino sulfur amino acid found in most animal tissues that has many important biological functions including bile salt conjugation, cellular osmoregulation, neuromodulation, calcium signaling. The benefits of supplementing diets with taurine are just beginning to be realized in a n...

Fenofibrate--a lipid-lowering drug--reduces voluntary alcohol drinking in rats.

PubMed

Karahanian, Eduardo; Quintanilla, Maria Elena; Fernandez, Katia; Israel, Yedy

2014-11-01

The administration of disulfiram raises blood acetaldehyde levels when ethanol is ingested, leading to an aversion to alcohol. This study was aimed at assessing the effect of fenofibrate on voluntary ethanol ingestion in rats. Fenofibrate reduces blood triglyceride levels by increasing fatty acid oxidation by liver peroxisomes, along with an increase in the activity of catalase, which can oxidize ethanol to acetaldehyde. UChB drinker rats were allowed to consume alcohol 10% v/v freely for 60 days, until consumption stabilized at around 7 g ethanol/kg/24 h. About 1-1.2 g ethanol/kg of this intake is consumed in the first 2 h of darkness of the circadian cycle. Fenofibrate subsequently administered (50 mg/kg/day by mouth [p.o.]) for 14 days led to a 60-70% (p < 0.001) reduction of 24-h ethanol consumption. When ethanol intake was determined within the first 2 h of darkness, the reduction was 85-90% (p < 0.001). We determined whether animals chronically allowed access to ethanol and subsequently treated with fenofibrate, would a) increase liver catalase activity, and b) increase blood acetaldehyde levels after a 24-h ethanol deprivation and the subsequent administration of 1 g ethanol/kg. The oral administration of 1 g ethanol/kg produced a rapid increase in blood (arterial) acetaldehyde in fenofibrate-treated animals versus controls also administered 1 g/kg ethanol (70 μM vs. 7 μM; p < 0.001). Liver catalase activity following fenofibrate treatment was increased 3-fold (p < 0.01). Other hepatic enzymes responsible for the metabolism of ethanol (alcohol dehydrogenase and aldehyde dehydrogenase) remained unchanged. No liver damage was induced, as measured by serum glutamic-pyruvic transaminase (GPT) activity. The effect of fenofibrate in reducing alcohol intake was fully reversible. Overall, in rats allowed chronic ethanol intake, by mouth (p.o.), fenofibrate administration increased liver catalase activity and reduced voluntary ethanol intake. The administration of 1 g ethanol/kg (p.o.) to these animals increased blood acetaldehyde levels in fenofibrate-treated animals, suggesting the possible basis for the reduction in ethanol intake. Copyright © 2014 Elsevier Inc. All rights reserved.

Fenofibrate Decreases Insulin Clearance and Insulin Secretion to Maintain Insulin Sensitivity*

PubMed Central

Ramakrishnan, Sadeesh K.; Russo, Lucia; Ghanem, Simona S.; Patel, Payal R.; Oyarce, Ana Maria; Heinrich, Garrett; Najjar, Sonia M.

2016-01-01

High fat diet reduces the expression of CEACAM1 (carcinoembryonic antigen-related cell adhesion molecule 1), a transmembrane glycoprotein that promotes insulin clearance and down-regulates fatty acid synthase activity in the liver upon its phosphorylation by the insulin receptor. Because peroxisome proliferator-activated receptor α (PPARα) transcriptionally suppresses CEACAM1 expression, we herein examined whether high fat down-regulates CEACAM1 expression in a PPARα-dependent mechanism. By activating PPARα, the lipid-lowering drug fenofibrate reverses dyslipidemia and improves insulin sensitivity in type 2 diabetes in part by promoting fatty acid oxidation. Despite reducing glucose-stimulated insulin secretion, fenofibrate treatment does not result in insulin insufficiency. To examine whether this is mediated by a parallel decrease in CEACAM1-dependent hepatic insulin clearance pathways, we fed wild-type and Pparα−/− null mice a high fat diet supplemented with either fenofibrate or Wy14643, a selective PPARα agonist, and examined their effect on insulin metabolism and action. We demonstrated that the decrease in insulin secretion by fenofibrate and Wy14643 is accompanied by reduction in insulin clearance in wild-type but not Pparα−/− mice, thereby maintaining normoinsulinemia and insulin sensitivity despite continuous high fat intake. Intact insulin secretion in L-CC1 mice with protected hepatic insulin clearance and CEACAM1 levels provides in vivo evidence that insulin secretion responds to changes in insulin clearance to maintain physiologic insulin and glucose homeostasis. These results also emphasize the relevant role of hepatic insulin extraction in regulating insulin sensitivity. PMID:27662905

Omega-3 fatty acids as adjunctive treatment for bexarotene-induced hypertriglyceridaemia in patients with cutaneous T-cell lymphoma.

PubMed

Cabello, I; Servitje, O; Corbella, X; Bardés, I; Pintó, X

2017-04-01

Bexarotene is an oral retinoid approved for treating cutaneous T-cell lymphoma (CTCL) in patients resistant to first-line systemic treatment. Hypertriglyceridaemia is an unavoidable adverse effect of bexarotene therapy, and requires monitoring because of the risk of developing pancreatitis. Therefore, prophylactic hypolipidaemic therapy, usually with a fibrate alone, is required for preventing bexarotene-induced hypertriglyceridaemia. Despite these measures, a large number of patients develop very severe hypertriglyceridaemia. To assess the lipid metabolism changes before and after the use of a combination of omega-3 fatty acids (n-3 FA) plus fenofibrate compared with fenofibrate alone as a more effective lipid-lowering therapy in patients with CTCL treated with bexarotene. From January 2005 to January 2013, we analysed all 25 patients with CTCL treated with bexarotene. The first 18 consecutively enrolled patients received fenofibrate alone as a lipid-lowering therapy, and the next 7 consecutively enrolled patients received a combination of fenofibrate and n-3 FA. Data for all 25 consecutive patients with CTCL treated with bexarotene were evaluated. Of these, 24 patients (96%) developed hypertriglyceridaemia despite the hypolipidaemic therapy, with this being very severe (> 11.2 mmol/L) in 20% of the cases. Of the 18 patients receiving fenofibrate alone, 5 (28%) developed very severe hypertriglyceridaemia, compared with none of the 7 patients treated with the n-3 FA combination. Our results suggest that the n-3 FA combination may be more effective than fibrate alone for preventing bexarotene-induced hypertriglyceridaemia. © 2017 British Association of Dermatologists.

Restraint stress in lactating mice alters the levels of sulfur-containing amino acids in milk.

PubMed

Nishigawa, Takuma; Nagamachi, Satsuki; Ikeda, Hiromi; Chowdhury, Vishwajit S; Furuse, Mitsuhiro

2018-03-30

It is well known that maternal stress during the gestation and lactation periods induces abnormal behavior in the offspring and causes a lowering of the offspring's body weight. Various causes of maternal stress during the lactation period, relating to, for example, maternal nutritional status and reduced maternal care, have been considered. However, little is known about the effects on milk of maternal stress during the lactation period. The current study aimed to determine whether free amino acids, with special reference to sulfur-containing amino acids in milk, are altered by restraint stress in lactating mice. The dams in the stress group were restrained for 30 min at postnatal days 2, 4, 6, 8, 10 and 12. Restraint stress caused a reduction in the body weight of lactating mice. The concentration of taurine and cystathionine in milk was significantly higher in the stress group, though stress did not alter their concentration in maternal plasma. The ratio of taurine concentration in milk to its concentration in maternal plasma was significantly higher in the stress group, suggesting that stress promoted taurine transportation into milk. Furthermore, taurine concentration in milk was positively correlated with corticosterone levels in plasma. In conclusion, restraint stress in lactating mice caused the changes in the metabolism and in the transportation of sulfur-containing amino acids and resulted in higher taurine concentration in milk. Taurine concentration in milk could also be a good parameter for determining stress status in dams.

Taurine Biosynthesis in a Fish Liver Cell Line (ZFL) Adapted to a Serum-Free Medium

PubMed Central

Liu, Chieh-Lun; Watson, Aaron M.; Place, Allen R.; Jagus, Rosemary

2017-01-01

Although taurine has been shown to play multiple important physiological roles in teleosts, little is known about the molecular mechanisms underlying dietary requirements. Cell lines can provide useful tools for deciphering biosynthetic pathways and their regulation. However, culture media and sera contain variable taurine levels. To provide a useful cell line for the investigation of taurine homeostasis, an adult zebrafish liver cell line (ZFL) has been adapted to a taurine-free medium by gradual accommodation to a commercially available synthetic medium, UltraMEM™-ITES. Here we show that ZFL cells are able to synthesize taurine and be maintained in medium without taurine. This has allowed for the investigation of the effects of taurine supplementation on cell growth, cellular amino acid pools, as well as the expression of the taurine biosynthetic pathway and taurine transporter genes in a defined fish cell type. After taurine supplementation, cellular taurine levels increase but hypotaurine levels stay constant, suggesting little suppression of taurine biosynthesis. Cellular methionine levels do not change after taurine addition, consistent with maintenance of taurine biosynthesis. The addition of taurine to cells grown in taurine-free medium has little effect on transcript levels of the biosynthetic pathway genes for cysteine dioxygenase (CDO), cysteine sulfinate decarboxylase (CSAD), or cysteamine dioxygenase (ADO). In contrast, supplementation with taurine causes a 30% reduction in transcript levels of the taurine transporter, TauT. This experimental approach can be tailored for the development of cell lines from aquaculture species for the elucidation of their taurine biosynthetic capacity. PMID:28587087

Fenofibrate, but not ezetimibe, prevents fatty liver disease in mice lacking phosphatidylethanolamine N-methyltransferase.

PubMed

van der Veen, Jelske N; Lingrell, Susanne; Gao, Xia; Takawale, Abhijit; Kassiri, Zamaneh; Vance, Dennis E; Jacobs, René L

2017-04-01

Mice lacking phosphatidylethanolamine N -methyltransferase (PEMT) are protected from high-fat diet (HFD)-induced obesity and insulin resistance. However, these mice develop severe nonalcoholic fatty liver disease (NAFLD) when fed the HFD, which is mainly due to inadequate secretion of VLDL particles. Our aim was to prevent NAFLD development in mice lacking PEMT. We treated Pemt -/- mice with either ezetimibe or fenofibrate to see if either could ameliorate liver disease in these mice. Ezetimibe treatment did not reduce fat accumulation in Pemt -/- livers, nor did it reduce markers for hepatic inflammation or fibrosis. Fenofibrate, conversely, completely prevented the development of NAFLD in Pemt -/- mice: hepatic lipid levels, as well as markers of endoplasmic reticulum stress, inflammation, and fibrosis, in fenofibrate-treated Pemt -/- mice were similar to those in Pemt +/+ mice. Importantly, Pemt -/- mice were still protected against HFD-induced obesity and insulin resistance. Moreover, fenofibrate partially reversed hepatic steatosis and fibrosis in Pemt -/- mice when treatment was initiated after NAFLD had already been established. Increasing hepatic fatty acid oxidation can compensate for the lower VLDL-triacylglycerol secretion rate and prevent/reverse fatty liver disease in mice lacking PEMT. Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

Fenofibrate, but not ezetimibe, prevents fatty liver disease in mice lacking phosphatidylethanolamine N-methyltransferase[S

PubMed Central

van der Veen, Jelske N.; Lingrell, Susanne; Gao, Xia; Takawale, Abhijit; Kassiri, Zamaneh; Vance, Dennis E.; Jacobs, René L.

2017-01-01

Mice lacking phosphatidylethanolamine N-methyltransferase (PEMT) are protected from high-fat diet (HFD)-induced obesity and insulin resistance. However, these mice develop severe nonalcoholic fatty liver disease (NAFLD) when fed the HFD, which is mainly due to inadequate secretion of VLDL particles. Our aim was to prevent NAFLD development in mice lacking PEMT. We treated Pemt−/− mice with either ezetimibe or fenofibrate to see if either could ameliorate liver disease in these mice. Ezetimibe treatment did not reduce fat accumulation in Pemt−/− livers, nor did it reduce markers for hepatic inflammation or fibrosis. Fenofibrate, conversely, completely prevented the development of NAFLD in Pemt−/− mice: hepatic lipid levels, as well as markers of endoplasmic reticulum stress, inflammation, and fibrosis, in fenofibrate-treated Pemt−/− mice were similar to those in Pemt+/+ mice. Importantly, Pemt−/− mice were still protected against HFD-induced obesity and insulin resistance. Moreover, fenofibrate partially reversed hepatic steatosis and fibrosis in Pemt−/− mice when treatment was initiated after NAFLD had already been established. Increasing hepatic fatty acid oxidation can compensate for the lower VLDL-triacylglycerol secretion rate and prevent/reverse fatty liver disease in mice lacking PEMT. PMID:28159867

Taurocholic acid metabolism by gut microbes and colon cancer

PubMed Central

Ridlon, Jason M.; Wolf, Patricia G.; Gaskins, H. Rex

2016-01-01

ABSTRACT Colorectal cancer (CRC) is one of the most frequent causes of cancer death worldwide and is associated with adoption of a diet high in animal protein and saturated fat. Saturated fat induces increased bile secretion into the intestine. Increased bile secretion selects for populations of gut microbes capable of altering the bile acid pool, generating tumor-promoting secondary bile acids such as deoxycholic acid and lithocholic acid. Epidemiological evidence suggests CRC is associated with increased levels of DCA in serum, bile, and stool. Mechanisms by which secondary bile acids promote CRC are explored. Furthermore, in humans bile acid conjugation can vary by diet. Vegetarian diets favor glycine conjugation while diets high in animal protein favor taurine conjugation. Metabolism of taurine conjugated bile acids by gut microbes generates hydrogen sulfide, a genotoxic compound. Thus, taurocholic acid has the potential to stimulate intestinal bacteria capable of converting taurine and cholic acid to hydrogen sulfide and deoxycholic acid, a genotoxin and tumor-promoter, respectively. PMID:27003186

Taurine and neural cell damage.

PubMed

Saransaari, P; Oja, S S

2000-01-01

The inhibitory amino acid taurine is an osmoregulator and neuromodulator, also exerting neuroprotective actions in neural tissue. We review now the involvement of taurine in neuron-damaging conditions, including hypoxia, hypoglycemia, ischemia, oxidative stress, and the presence of free radicals, metabolic poisons and an excess of ammonia. The brain concentration of taurine is increased in several models of ischemic injury in vivo. Cell-damaging conditions which perturb the oxidative metabolism needed for active transport across cell membranes generally reduce taurine uptake in vitro, immature brain tissue being more tolerant to the lack of oxygen. In ischemia nonsaturable diffusion increases considerably. Both basal and K+-stimulated release of taurine in the hippocampus in vitro is markedly enhanced under cell-damaging conditions, ischemia, free radicals and metabolic poisons being the most potent. Hypoxia, hypoglycemia, ischemia, free radicals and oxidative stress also increase the initial basal release of taurine in cerebellar granule neurons, while the release is only moderately enhanced in hypoxia and ischemia in cerebral cortical astrocytes. The taurine release induced by ischemia is for the most part Ca2+-independent, a Ca2+-dependent mechanism being discernible only in hippocampal slices from developing mice. Moreover, a considerable portion of hippocampal taurine release in ischemia is mediated by the reversal of Na+-dependent transporters. The enhanced release in adults may comprise a swelling-induced component through Cl- channels, which is not discernible in developing mice. Excitotoxic concentrations of glutamate also potentiate taurine release in mouse hippocampal slices. The ability of ionotropic glutamate receptor agonists to evoke taurine release varies under different cell-damaging conditions, the N-methyl-D-aspartate-evoked release being clearly receptor-mediated in ischemia. Neurotoxic ammonia has been shown to provoke taurine release from different brain preparations, indicating that the ammonia-induced release may modify neuronal excitability in hyperammonic conditions. Taurine released simultane ously with an excess of excitatory amino acids in the hippocampus under ischemic and other neuron-damaging conditions may constitute an important protective mechanism against excitotoxicity, counteracting the harmful effects which lead to neuronal death. The release of taurine may prevent excitation from reaching neurotoxic levels.

Effect of taurine on ischemia-reperfusion injury.

PubMed

Schaffer, Stephen W; Jong, Chian Ju; Ito, Takashi; Azuma, Junichi

2014-01-01

Taurine is an abundant β-amino acid that regulates several events that dramatically influence the development of ischemia-reperfusion injury. One of these events is the extrusion of taurine and Na+ from the cell via the taurine/Na+ symport. The loss of Na+ during the ischemia-reperfusion insult limits the amount of available Na+ for Na+/Ca2+ exchange, an important process in the development of Ca2+ overload and the activation of the mitochondrial permeability transition, a key process in ischemia-reperfusion mediated cell death. Taurine also prevents excessive generation of reactive oxygen species by the respiratory chain, an event that also limits the activation of the MPT. Because taurine is an osmoregulator, changes in taurine concentration trigger "osmotic preconditioning," a process that activates an Akt-dependent cytoprotective signaling pathway that inhibits MPT pore formation. These effects of taurine have clinical implications, as experimental evidence reveals potential promise of taurine therapy in preventing cardiac damage during bypass surgery, heart transplantation and myocardial infarction. Moreover, severe loss of taurine from the heart during an ischemia-reperfusion insult may increase the risk of ventricular remodeling and development of heart failure.

Levels of inflammation and oxidative stress, and a role for taurine in dystropathology of the Golden Retriever Muscular Dystrophy dog model for Duchenne Muscular Dystrophy.

PubMed

Terrill, Jessica R; Duong, Marisa N; Turner, Rufus; Le Guiner, Caroline; Boyatzis, Amber; Kettle, Anthony J; Grounds, Miranda D; Arthur, Peter G

2016-10-01

Duchenne Muscular Dystrophy (DMD) is a fatal skeletal muscle wasting disease presenting with excessive myofibre necrosis and increased inflammation and oxidative stress. In the mdx mouse model of DMD, homeostasis of the amino acid taurine is altered, and taurine administration drastically decreases muscle necrosis, dystropathology, inflammation and protein thiol oxidation. Since the severe pathology of the Golden Retriever Muscular Dystrophy (GRMD) dog model more closely resembles the human DMD condition, we aimed to assess the generation of oxidants by inflammatory cells and taurine metabolism in this species. In muscles of 8 month GRMD dogs there was an increase in the content of neutrophils and macrophages, and an associated increase in elevated myeloperoxidase, a protein secreted by neutrophils that catalyses production of the highly reactive hypochlorous acid (HOCl). There was also increased chlorination of tyrosines, a marker of HOCl generation, increased thiol oxidation of many proteins and irreversible oxidative protein damage. Taurine, which functions as an antioxidant by trapping HOCl, was reduced in GRMD plasma; however taurine was increased in GRMD muscle tissue, potentially due to increased muscle taurine transport and synthesis. These data indicate a role for HOCl generated by neutrophils in the severe dystropathology of GRMD dogs, which may be exacerbated by decreased availability of taurine in the blood. These novel data support continued research into the precise roles of oxidative stress and taurine in DMD and emphasise the value of the GRMD dogs as a suitable pre-clinical model for testing taurine as a therapeutic intervention for DMD boys. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Taurine in pediatric nutrition: review and update.

PubMed

Gaull, G E

1989-03-01

Taurine was long considered an end product of the metabolism of the sulfur-containing amino acids, methionine and cyst(e)ine. Its only clearly recognized biochemical role had been as a substrate in the conjugation of bile acids. Taurine is found free in millimolar concentrations in animal tissues, particularly those that are excitable, rich in membranes, and generate oxidants. Various lines of evidence suggest one major nutritional role as protecting cell membranes by attenuating toxic substances and/or by acting as an osmoregulator. The totality of evidence suggests that taurine is nonessential in the rodent, it is an essential amino acid in the cat, and it is conditionally essential in man and monkey. Absence from the diet of a conditionally essential nutrient does not produce immediate deficiency disease but, in the long term, can cause problems. Taurine is now added to many infant formulas as a measure of prudence to provide improved nourishment with the same margin of safety for its newly identified physiologic functions as that found in human milk. Such supplementation can be justified by the finding of improved fat absorption in preterm infants and in children with cystic fibrosis, as well as by salutary effects on auditory brainstem-evoked responses in preterm infants. Experimental findings in animal models and in human cell models provide further justification for taurine supplementation of infant formulas.

Effect of taurine on the concentrations of glutamate, GABA, glutamine and alanine in the rat striatum and hippocampus.

PubMed

Molchanova, Svetlana M; Oja, Simos S; Saransaari, Pirjo

2007-01-01

Taurine, a non-protein amino acid, acts as an osmoregulator and inhibitory neuromodulator in the brain. Here we studied the effects of intraperitoneal injections of taurine on the concentrations of glutamate and GABA, and their precursors, glutamine and alanine, in the rat striatum and hippocampus. Injections of 0.25, 0.5 and 1 g/kg taurine led to a gradual increase in taurine tissue concentrations in both hippocampus and striatum. Glutamate and GABA also increased in the hippocampus, but not in the striatum. Glutamine increased and alanine decreased markedly in both brain structures. The results corroborate the neuromodulatory role of taurine in the brain. Taurine administration results in an imbalance in inhibitory and excitatory neurotransmission in the glutamatergic (hippocampus) and GABAergic (striatum) brain structures, affecting more markedly the neurotransmitter precursors.

Taurine deficiency, synthesis and transport in the mdx mouse model for Duchenne Muscular Dystrophy.

PubMed

Terrill, Jessica R; Grounds, Miranda D; Arthur, Peter G

2015-09-01

The amino acid taurine is essential for the function of skeletal muscle and administration is proposed as a treatment for Duchenne Muscular Dystrophy (DMD). Taurine homeostasis is dependent on multiple processes including absorption of taurine from food, endogenous synthesis from cysteine and reabsorption in the kidney. This study investigates the cause of reported taurine deficiency in the dystrophic mdx mouse model of DMD. Levels of metabolites (taurine, cysteine, cysteine sulfinate and hypotaurine) and proteins (taurine transporter [TauT], cysteine deoxygenase and cysteine sulfinate dehydrogenase) were quantified in juvenile control C57 and dystrophic mdx mice aged 18 days, 4 and 6 weeks. In C57 mice, taurine content was much higher in both liver and plasma at 18 days, and both cysteine and cysteine deoxygenase were increased. As taurine levels decreased in maturing C57 mice, there was increased transport (reabsorption) of taurine in the kidney and muscle. In mdx mice, taurine and cysteine levels were much lower in liver and plasma at 18 days, and in muscle cysteine was low at 18 days, whereas taurine was lower at 4: these changes were associated with perturbations in taurine transport in liver, kidney and muscle and altered metabolism in liver and kidney. These data suggest that the maintenance of adequate body taurine relies on sufficient dietary intake of taurine and cysteine availability and metabolism, as well as retention of taurine by the kidney. This research indicates dystrophin deficiency not only perturbs taurine metabolism in the muscle but also affects taurine metabolism in the liver and kidney, and supports targeting cysteine and taurine deficiency as a potential therapy for DMD. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

Identification of a novel bile acid in swans, tree ducks, and geese: 3alpha,7alpha,15alpha-trihydroxy-5beta-cholan-24-oic acid.

PubMed

Kakiyama, Genta; Iida, Takashi; Goto, Takaaki; Mano, Nariyasu; Goto, Junichi; Nambara, Toshio; Hagey, Lee R; Schteingart, Claudio D; Hofmann, Alan F

2006-07-01

By HPLC, a taurine-conjugated bile acid with a retention time different from that of taurocholate was found to be present in the bile of the black-necked swan, Cygnus melanocoryphus. The bile acid was isolated and its structure, established by (1)H and (13)C NMR and mass spectrometry, was that of the taurine N-acyl amidate of 3alpha,7alpha,15alpha-trihydroxy-5beta-cholan-24-oic acid. The compound was shown to have chromatographic and spectroscopic properties that were identical to those of the taurine conjugate of authentic 3alpha,7alpha,15alpha-trihydroxy-5beta-cholan-24-oic acid, previously synthesized by us from ursodeoxycholic acid. By HPLC, the taurine conjugate of 3alpha,7alpha,15alpha-trihydroxy-5beta-cholan-24-oic acid was found to be present in 6 of 6 species in the subfamily Dendrocygninae (tree ducks) and in 10 of 13 species in the subfamily Anserinae (swans and geese) but not in other subfamilies in the Anatidae family. It was also not present in species from the other two families of the order Anseriformes. 3alpha,7alpha,15alpha-Trihydroxy-5beta-cholan-24-oic acid is a new primary bile acid that is present in the biliary bile acids of swans, tree ducks, and geese and may be termed 15alpha-hydroxy-chenodeoxycholic acid.

A Novel Selective PPARα Modulator (SPPARMα), K-877 (Pemafibrate), Attenuates Postprandial Hypertriglyceridemia in Mice.

PubMed

Sairyo, Masami; Kobayashi, Takuya; Masuda, Daisaku; Kanno, Koutaro; Zhu, Yinghong; Okada, Takeshi; Koseki, Masahiro; Ohama, Tohru; Nishida, Makoto; Sakata, Yasushi; Yamashita, Shizuya

2018-02-01

Fasting and postprandial hypertriglyceridemia (PHTG) are caused by the accumulation of triglyceride (TG)-rich lipoproteins and their remnants, which have atherogenic effects. Fibrates can improve fasting and PHTG; however, reduction of remnants is clinically needed to improve health outcomes. In the current study, we investigated the effects of a novel selective peroxisome proliferator-activated receptor α modulator (SPPARMα), K-877 (Pemafibrate), on PHTG and remnant metabolism. Male C57BL/6J mice were fed a high-fat diet (HFD) only, or an HFD containing 0.0005% K-877 or 0.05% fenofibrate, from 8 to 12 weeks of age. After 4 weeks of feeding, we measured plasma levels of TG, free fatty acids (FFA), total cholesterol (TC), HDL-C, and apolipoprotein (apo) B-48/B-100 during fasting and after oral fat loading (OFL). Plasma lipoprotein profiles after OFL, which were assessed by high performance liquid chromatography (HPLC), and fasting lipoprotein lipase (LPL) activity were compared among the groups. Both K-877 and fenofibrate suppressed body weight gain and fasting and postprandial TG levels and enhanced LPL activity in mice fed an HFD. As determined by HPLC, K-877 and fenofibrate significantly decreased the abundance of TG-rich lipoproteins, including remnants, in postprandial plasma. Both K-877 and fenofibrate decreased intestinal mRNA expression of ApoB and Npc1l1; however, hepatic expression of Srebp1c and Mttp was increased by fenofibrate but not by K-877.Hepatic mRNA expression of apoC-3 was decreased by K-877 but not by fenofibrate. K-877 may attenuate PHTG by suppressing the postprandial increase of chylomicrons and the accumulation of chylomicron remnants more effectively than fenofibrate.

PPAR-alpha agonist treatment increases trefoil factor family-3 expression and attenuates apoptosis in the liver tissue of bile duct-ligated rats.

PubMed

Karakan, Tarkan; Kerem, Mustafa; Cindoruk, Mehmet; Engin, Doruk; Alper, Murat; Akın, Okan

2013-01-01

Peroxisome proliferators-activated receptor alpha activation modulates cholesterol metabolism and suppresses bile acid synthesis. The trefoil factor family comprises mucin-associated proteins that increase the viscosity of mucins and help protect epithelial linings from insults. We evaluated the effect of short-term administration of fenofibrate, a peroxisome proliferators activated receptor alpha agonist, on trefoil factor family-3 expression, degree of apoptosis, generation of free radicals, and levels of proinflammatory cytokines in the liver tissue of bile duct-ligated rats. Forty male Wistar rats were randomly divided into four groups: 1 = sham operated, 2 = bile duct ligation, 3 = bile duct-ligated + vehicle (gum Arabic), and 4 = bile duct-ligated + fenofibrate (100 mg/kg/day). All rats were sacrificed on the 7 th day after obtaining blood samples and liver tissue. Liver function tests, tumor necrosis factor-alpha and interleukin 1 beta in serum, and trefoil factor family-3 mRNA expression, degree of apoptosis (TUNEL) and tissue malondialdehyde (malondialdehyde, end-product of lipid peroxidation by reactive oxygen species) in liver tissue were evaluated. Fenofibrate administration significantly reduced serum total bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma-glutamyl transferase, and tumor necrosis factor-alpha and interleukin-1β levels. Apoptosis and malondialdehyde were significantly reduced in the fenofibrate group. Trefoil factor family-3 expression increased with fenofibrate treatment in bile duct-ligated rats. The peroxisome proliferators-activated receptor alpha agonist fenofibrate significantly increased trefoil factor family-3 expression and decreased apoptosis and lipid peroxidation in the liver and attenuated serum levels of proinflammatory cytokines in bile duct-ligated rats. Further studies are needed to determine the protective role of fenofibrate in human cholestatic disorders.

Biodegradation pathway of an anionic surfactant (Igepon TC-42) during recycling waste water through plant hydroponics for advanced life support during long-duration space missions

NASA Astrophysics Data System (ADS)

Levine, L. H.; Kagie, H. R.; Garland, J. L.

The degradation of an anionic surfactant (Igepon TC-42) was investigated as part of an integrated study of direct recycling of human hygiene water through hydroponic plant growth systems. Several chemical approaches were developed to characterize the degradation of Igepon and to measure the accumulation of intermediates such as fatty acids and methyl taurine. Igepon was rapidly degraded as indicated by the reduction of methylene blue active substances (MBAS) and component fatty acids. The Igepon degradation rate continued to increase over a period of several weeks following repeated daily exposure to 18 μg/l Igepon. The accumulation of free fatty acids and methyl taurine was also observed during decomposition of Igepon. The concentration of methyl taurine was below detection limit (0.2 nmol/ml) during the slow phase of Igepon degradation, and increased to 1-2 nmol/ml during the phase of rapid degradation. These findings support a degradation pathway involving initial hydrolysis of amide to release fatty acids and methyl taurine, and subsequent degradation of these intermediates.

Influence of endogenous opiates on the hypotensive action of taurine in DOCA-salt rats.

PubMed

Sato, Y; Fujita, T

1988-12-01

We studied the role of endogenous opiate activation in the hypotensive action of taurine, a sulphur amino acid, in deoxycorticosterone acetate (DOCA)-salt hypertensive rats. Previous work had shown that supplementation with 1% taurine reduced blood pressure when given after DOCA-salt hypertension had been established. In the present study, in conscious rats, intraperitoneal injection of naloxone, an opiate antagonist, increased blood pressure in taurine-supplemented DOCA-salt rats, but not in DOCA-salt rats or vehicle-treated control rats. These results suggest that activation of an endogenous opiate might contribute to the hypotensive action of taurine in DOCA-salt hypertensive rats.

Peroxisome proliferator-activated receptor-α activation attenuates 3-nitropropionic acid induced behavioral and biochemical alterations in rats: possible neuroprotective mechanisms.

PubMed

Bhateja, Deepak Kumar; Dhull, Dinesh K; Gill, Aneet; Sidhu, Akramdeep; Sharma, Saurabh; Reddy, B V Krishna; Padi, Satyanarayana S V

2012-01-05

Peroxisome proliferators activated receptor is regarded as potential therapeutic targets to control various neurodegenerative disorders. However, none of the study has elucidated its effect in the treatment of Huntington's disease. We explored whether peroxisome proliferators activated receptor-α agonist may attenuate various behavioral and biochemical alterations induced by systemic administration of 3-nitropropionic acid (3-NP), an accepted experimental animal model of Huntington's disease phenotype. Intraperitoneal administration of 3-NP (20mg/kg., i.p.) for 4days in rats produced hypolocomotion, muscle incoordination, and cognitive dysfunction. Daily treatment with fenofibrate (100 or 200mg/kg., p.o.), 30min prior to 3-NP administration for a total of 4days, significantly improved the 3-NP induced motor and cognitive impairment. Biochemical analysis revealed that systemic 3-NP administration significantly increased oxidative and nitrosative stress (increase lipid peroxidation, protein carbonyls and nitrite level), lactate dehydrogenase activity whereas, decreased the activities of catalase, superoxide dismutase, reduced glutathione, and succinate dehydrogenase. Fenofibrate treatment significantly attenuated oxidative damage, cytokines and improved mitochondrial complexes enzyme activity in brain. In the present study, MK886, a selective inhibitor of peroxisome proliferators activated receptor-α was employed to elucidate the beneficial effect through either receptor dependent or receptor independent neuroprotective mechanisms. Administration of MK886 (1mg/kg, i.p.) prior to fenofibrate (200mg/kg, p.o.) abolished the effect of fenofibrate. The results showed that receptor dependent neuroprotective effects of fenofibrate in 3-NP administered rats provide a new evidence for a role of PPAR-α activation in neuroprotection that is attributed by modulating oxidative stress and inflammation. Copyright © 2011. Published by Elsevier B.V.

[Plasma levels of mediator amino acids in patients with Parkinson disease].

PubMed

Vitreshchak, T V; Poleshchuk, V V; Piradov, M A

2004-01-01

Content of neurotransmitter amino acids before and after treatment with He-Ne-laser was measured in blood of two groups of the Parkinson's disease patients distinguished by low (first group) and high (second group) activity of monoamine oxidase B and Cu/Zn-superoxide dismutase. An increase in taurine level at the early stage of the disease (first group of patients) suggests that taurine may be a marker of compensatory abilities of the organism. The violation of the glutamate/taurine balance at the later stages of the disease and its normalization following the laserotherapy accompanied improvement of neurological symptoms.

A Cross-Reactivity of Fenofibric Acid With MDMA DRI Assay.

PubMed

Bugier, Sarah; Garcia-Hejl, Carine; Vest, Philippe; Plantamura, Julie; Chianea, Denis; Renard, Christophe

2016-09-01

Within the framework of routine fitness examinations, French Air Force military crew underwent urine testing for 3,4 methylenedioxymetamphetamine (MDMA [ecstasy]). The cross-reactivity of a dyslipidemic drug, fenofibrate, with an MDMA immunoassay was studied and confirmed on a large population sample. A 3-year retrospective study was performed on the MDMA DRI Ecstasy Assay on the Unicel DXC 600. In the event of positive test result, a confirmatory testing was carried out by gas chromatography/mass spectrometry (GC/MS) to establish the presence of MDMA. When analysis by GC/MS did not confirm the presence of MDMA, a false-positive result was suspected and the samples were analyzed by high-performance liquid chromatography-mass spectrometry to identify a potential interfering substance. A total of 15,169 urine samples, from 7,803 patients, were tested for 3 years. Of the tested samples, 22 (0.15%) were positive by DRI Ecstasy Assay. None of them were positive by GC/MS. A cross-reactivity of fenofibrate's metabolite with MDMA using this assay was systematically found. Fenofibrate's interference with MDMA immunoassay was confirmed. Fenofibrate being widely prescribed, physicians had to be alerted that this treatment could lead to false-positive results. Reprint & Copyright © 2016 Association of Military Surgeons of the U.S.

The physiological and pathophysiological roles of taurine in adipose tissue in relation to obesity.

PubMed

Murakami, Shigeru

2017-10-01

Obesity is caused by an imbalance between energy intake and energy expenditure. It is established that obesity is a state of low-grade chronic inflammation, which is characterized by enlarged hypertrophied adipocytes, increased infiltration by macrophages and marked changes in the secretion of adipokines and free fatty acids. The effects of taurine on the pathogenesis of obesity have been reported in animals and humans. Although the mechanisms underlying the anti-obesity action of taurine remain to be defined, taurine seems to ameliorate obesity through stimulation of energy expenditure, modulation of lipid metabolism, anorexic effect, anti-inflammatory and anti-oxidative effects. Recent studies revealed that taurine supplementation reduces the infiltration of macrophages and modulates the polarization of adipose tissue macrophages in high-fat diet-induced obese mice. In addition, taurine downregulates the production of pro-inflammatory cytokines by adipocytes, suggesting that taurine plays an anti-inflammatory role in adipose tissue. This article reviews the effects and mechanisms of taurine on the development of obesity, focusing on the role of taurine in white adipose tissue. Copyright © 2017 Elsevier Inc. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Galatola, G.; Jazrawi, R.P.; Bridges, C.

/sup 75/Se-homocholic acid-taurine (/sup 75/SeHCAT) is the first available gamma-labeled bile acid, and should therefore be handled more efficiently and specifically by the liver than previous hepatoscintigraphic agents. We have measured serum and hepatic kinetics for /sup 75/SeHCAT, and compared them with those for the conventional hepatobiliary scintigraphic agent 99mTc-hepatoiminodiacetic acid, and with serum kinetics for the corresponding natural bile acid, (/sup 14/C)cholic acid-taurine. We used a dynamic scintigraphic technique and serial blood sampling in 8 subjects. Initial hepatic uptake rate was identical to initial serum disappearance rate (14% dose/min) for /sup 75/SeHCAT, but significantly lower for 99mTc-hepatoiminodiacetic acid (6%more » vs. 14% dose/min, p less than 0.001). Hepatic transit time was shorter for /sup 75/SeHCAT (13 min vs. 22 min, p less than 0.02), net hepatic excretory rate was more rapid (1.4% vs. 0.8% dose/min, p less than 0.001), and urinary excretion was lower (1.0% vs. 9.0% dose, p less than 0.001). Initial and late-plasma disappearance rates were significantly lower for /sup 75/SeHCAT (14.3% and 1.5% dose/min) than for (/sup 14/C)cholic acid-taurine (21.3% and 2.8% dose/min, respectively), and plasma clearance was also lower (2/sup 75/ vs. 670 ml/min). In vitro, /sup 75/SeHCAT was bound to serum proteins more completely than (/sup 14/C)cholic acid-taurine (90.4% vs. 86.5%, p less than 0.005). We conclude that /sup 75/SeHCAT provides a hepatoscintigraphic agent that is handled more efficiently and specifically by the liver than the conventionally used agent 99mTc-hepatoiminodiacetic acid. It is not cleared from the serum as rapidly as (/sup 14/C)cholic acid-taurine, probably due to its stronger protein binding. The clinical value of /sup 75/SeHCAT in assessing liver disease should be investigated.« less

Role of taurine in the pathogenesis of obesity.

PubMed

Murakami, Shigeru

2015-07-01

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. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

LC-MS/MS methods for the determination of edaravone and/or taurine in rat plasma and its application to a pharmacokinetic study.

PubMed

Tang, Dao-quan; Bian, Ting-ting; Zheng, Xiao-xiao; Li, Ying; Wu, Xiao-wen; Li, Yin-jie; Du, Qian; Jiang, Shui-shi

2014-09-01

Three liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods were respectively developed and validated for the simultaneous or independent determination of taurine and edaravone in rat plasma using 3-methyl-1-p-tolyl-5-pyrazolone and sulfanilic acid as the internal standards (IS). Chromatographic separations were achieved on an Agilent Zorbax SB-Aq (100 × 2.1 mm, 3.5 µm) column. Gradient 0.03% formic acid-methanol, isocratic 0.1% formic acid-methanol (90:10) and 0.02% formic acid-methanol (40:60) were respectively selected as the mobile phase for the simultaneous determination of two analytes, taurine or edaravone alone. The MS acquisition was performed in multiple reaction monitoring mode with a positive and negative electrospray ionization source. The mass transitions monitored were m/z [M + H](+) 175.1 → 133.0 and [M + H](+) 189.2 → 147.0 for edaravone and its IS, m/z [M - H](-) 124.1 → 80.0 and [M - H](-) 172.0 → 80.0 for taurine and its IS, respectively. The validated methods were successfully applied to study the pharmacokinetic interaction of taurine and edaravone in rats after independent intravenous administration and co-administration with a single dose. Our collective results showed that there were no significant alterations on the main pharmacokinetic parameters (area under concentration-time curve, mean residence time, half-life and clearance) of taurine and edaravone, implying that the proposed combination therapy was pharmacologically feasible. Copyright © 2014 John Wiley & Sons, Ltd.

Reciprocal regulation between taurine and glutamate response via Ca2+- dependent pathways in retinal third-order neurons

PubMed Central

2010-01-01

Although taurine and glutamate are the most abundant amino acids conducting neural signals in the central nervous system, the communication between these two neurotransmitters is largely unknown. This study explores the interaction of taurine and glutamate in the retinal third-order neurons. Using specific antibodies, both taurine and taurine transporters were localized in photoreceptors and Off-bipolar cells, glutamatergic neurons in retinas. It is possible that Off-bipolar cells release juxtaposed glutamate and taurine to activate the third-order neurons in retina. The interaction of taurine and glutamate was studied in acutely dissociated third-order neurons in whole-cell patch-clamp recording and Ca2+ imaging. We find that taurine effectively reduces glutamate-induced Ca2+ influx via ionotropic glutamate receptors and voltage-dependent Ca2+ channels in the neurons, and the effect of taurine was selectively inhibited by strychnine and picrotoxin, but not GABA receptor antagonists, although GABA receptors are present in the neurons. A CaMKII inhibitor partially reversed the effect of taurine, suggesting that a Ca2+/calmodulin-dependent pathway is involved in taurine regulation. On the other hand, a rapid influx of Ca2+ through ionotropic glutamate receptors could inhibit the amplitude and kinetics of taurine-elicited currents in the third-order neurons, which could be controlled with intracellular application of BAPTA a fast Ca2+ chelator. This study indicates that taurine is a potential neuromodulator in glutamate transmission. The reciprocal inhibition between taurine and glutamate in the postsynaptic neurons contributes to computation of visual signals in the retinal neurons. PMID:20804625

Interaction of GABA-mimetics with the taurine transporter (TauT, Slc6a6) in hyperosmotic treated Caco-2, LLC-PK1 and rat renal SKPT cells.

PubMed

Rasmussen, Rune Nørgaard; Lagunas, Candela; Plum, Jakob; Holm, René; Nielsen, Carsten Uhd

2016-01-20

The aim of the present study was to investigate if basic GABA-mimetics interact with the taurine transporter (TauT, Slc6a6), and to find a suitable cell based model that is robust towards extracellular changes in osmolality during uptake studies. Taurine uptake was measured in human Caco-2 cells, porcine LLC-PK1 cells, and rat SKPT cells using radiolabelled taurine. Hyperosmotic conditions were obtained by incubation with raffinose (final osmolality of 500mOsm) for 24h prior to the uptake experiments. Expression of the taurine transporter, TauT, was investigated at the mRNA level by real-time PCR. Uptake of the GABA-mimetics gaboxadol and vigabatrin was investigated in SKPT cells, and quantified by liquid scintillation or HPLC-MS/MS analysis, respectively. The uptake rate of [(3)H]-taurine was Na(+) and Cl(-) and concentration dependent with taurine with an apparent Vmax of 6.3±1.6pmolcm(-2)min(-1) and a Km of 24.9±15.0μM. β-alanine, nipecotic acid, gaboxadol, GABA, vigabatrin, δ-ALA and guvacine inhibited the taurine uptake rate in a concentration dependent manner. The order of affinity for TauT was β-alanine>GABA>nipecotic acid>guvacine>δ-ALA>vigabatrin>gaboxadol with IC50-values of 0.04, 1.07, 2.02, 4.19, 4.94, 31.4 and 39.9mM, respectively. In conclusion, GABA mimetics inhibited taurine uptake in hyperosmotic rat renal SKPT cells. SKPT cells, which seem to be a useful model for investigating taurine transport in the short-term presence of high concentrations of osmolytes. Furthermore, analogues of β-alanine appear to have higher affinities for TauT than GABA-analogues. Copyright © 2015 Elsevier B.V. All rights reserved.

Biodegradation pathway of an anionic surfactant (Igepon TC-42) during recycling waste water through plant hydroponics for advanced life support during long-duration space missions.

PubMed

Levine, L H; Kagie, H R; Garland, J L

2003-01-01

The degradation of an anionic surfactant (Igepon TC-42) was investigated as part of an integrated study of direct recycling of human hygiene water through hydroponic plant growth systems. Several chemical approaches were developed to characterize the degradation of Igepon and to measure the accumulation of intermediates such as fatty acids and methyl taurine. Igepon was rapidly degraded as indicated by the reduction of methylene blue active substances (MBAS) and component fatty acids. The Igepon degradation rate continued to increase over a period of several weeks following repeated daily exposure to 18 micrograms/l Igepon. The accumulation of free fatty acids and methyl taurine was also observed during decomposition of Igepon. The concentration of methyl taurine was below detection limit (0.2 nmol/ml) during the slow phase of Igepon degradation, and increased to 1-2 nmol/ml during the phase of rapid degradation. These findings support a degradation pathway involving initial hydrolysis of amide to release fatty acids and methyl taurine, and subsequent degradation of these intermediates. Published by Elsevier Science Ltd on behalf of COSPAR.

Biodegradation pathway of an anionic surfactant (Igepon TC-42) during recycling waste water through plant hydroponics for advanced life support during long-duration space missions

NASA Technical Reports Server (NTRS)

Levine, L. H.; Kagie, H. R.; Garland, J. L.

2003-01-01

The degradation of an anionic surfactant (Igepon TC-42) was investigated as part of an integrated study of direct recycling of human hygiene water through hydroponic plant growth systems. Several chemical approaches were developed to characterize the degradation of Igepon and to measure the accumulation of intermediates such as fatty acids and methyl taurine. Igepon was rapidly degraded as indicated by the reduction of methylene blue active substances (MBAS) and component fatty acids. The Igepon degradation rate continued to increase over a period of several weeks following repeated daily exposure to 18 micrograms/l Igepon. The accumulation of free fatty acids and methyl taurine was also observed during decomposition of Igepon. The concentration of methyl taurine was below detection limit (0.2 nmol/ml) during the slow phase of Igepon degradation, and increased to 1-2 nmol/ml during the phase of rapid degradation. These findings support a degradation pathway involving initial hydrolysis of amide to release fatty acids and methyl taurine, and subsequent degradation of these intermediates. Published by Elsevier Science Ltd on behalf of COSPAR.

Effect of perfusion of bile salts solutions into the oesophagus of hiatal hernia patients and controls.

PubMed Central

Bachir, G S; Collis, J L

1976-01-01

Tests of the response to perfusion of the oesophagus were made in 54 patients divided into three groups. Group I consisted of patients with symptomatic hiatal hernia, group II hiatal hernia patients with peptic stricture, and group III normal individuals. Each individual oesophagus was perfused at a rate of 45-65 drops per minute over 25 minutes with six solutions: normal saline, N/10 HCl, taurine conjugates of bile salts in normal saline, taurine conjugates of bile salts in N/10 HCl, glycine conjugates of bile salts in normal saline, and taurine and glycine conjugates in a ratio of 1 to 2 in normal saline. It was found that acidified taurine solutions were more irritating than acid alone. With a 2mM/l solution of taurine in acid, symptoms are produced even in controls. With a 1 mM/l solution of the same conjugates, the majority of normal people feel slight heartburn or nothing, and therefore perfusion into the oesophagus of such a solution could be used as a test for oesophagitis. PMID:941112

Taurine activates delayed rectifier KV channels via a metabotropic pathway in retinal neurons

PubMed Central

Bulley, Simon; Liu, Yufei; Ripps, Harris; Shen, Wen

2013-01-01

Taurine is one of the most abundant amino acids in the retina, throughout the CNS, and in heart and muscle cells. In keeping with its broad tissue distribution, taurine serves as a modulator of numerous basic processes, such as enzyme activity, cell development, myocardial function and cytoprotection. Despite this multitude of functional roles, the precise mechanism underlying taurine's actions has not yet been identified. In this study we report findings that indicate a novel role for taurine in the regulation of voltage-gated delayed rectifier potassium (KV) channels in retinal neurons by means of a metabotropic receptor pathway. The metabotropic taurine response was insensitive to the Cl− channel blockers, picrotoxin and strychnine, but it was inhibited by a specific serotonin 5-HT2A receptor antagonist, MDL11939. Moreover, we found that taurine enhanced KV channels via intracellular protein kinase C-mediated pathways. When 5-HT2A receptors were expressed in human embryonic kidney cells, taurine and AL34662, a non-specific 5-HT2 receptor activator, produced a similar regulation of KIR channels. In sum, this study provides new evidence that taurine activates a serotonin system, apparently via 5-HT2A receptors and related intracellular pathways. PMID:23045337

Different effects of fenofibrate on metabolic and cardiovascular risk factors in mixed dyslipidemic women with normal thyroid function and subclinical hypothyroidism.

PubMed

Krysiak, Robert; Gilowski, Wojciech; Szkrobka, Witold; Okopien, Bogusław

2014-12-01

Subclinical hypothyroidism is suggested to increase cardiovascular risk. No previous study compared the effect of any fibrate on plasma levels of lipids and other cardiovascular risk factors in patients with different thyroid function status. The study included three age-, weight- and lipid-matched groups of women with mixed dyslipidemia in different thyroid function status: patients with untreated subclinical hypothyroidism (group 1, n = 18), women with treated hypothyroidism (group 2, n = 15), and subjects without thyroid disorders (group 3, n = 19). Plasma lipids, glucose homeostasis markers, as well as plasma levels of uric acid, high-sensitivity C-reactive protein (hsCRP), homocysteine, and fibrinogen were determined before and after 12 weeks of fenofibrate therapy. Despite similar plasma lipid levels, mixed dyslipidemic patients with untreated hypothyroidism had decreased insulin sensitivity, as well as higher circulating levels of uric acid, hsCRP, homocysteine, and fibrinogen in comparison with the other groups. The effect of fenofibrate on plasma lipids and, with the exception of homocysteine, on circulating levels of all investigated risk factors was stronger in patients from groups 2 and 3 than in patients from group 1. The obtained results indicate that the effect of fenofibrate on plasma lipids and circulating levels of cardiovascular risk factors is partially related to thyroid function. They also suggest that to improve the strength of fibrate action in dyslipidemic patients with subclinical hypothyroidism, they should be administered together with L-thyroxine. © 2014 John Wiley & Sons Ltd.

Ammonia-induced mitochondrial dysfunction and energy metabolism disturbances in isolated brain and liver mitochondria, and the effect of taurine administration: relevance to hepatic encephalopathy treatment

PubMed Central

Niknahad, Hossein; Jamshidzadeh, Akram; Zarei, Mahdi; Ommati, Mohammad Mehdi

2017-01-01

Introduction Ammonia-induced oxidative stress, mitochondrial dysfunction, and energy crisis are known as some the major mechanisms of brain injury in hepatic encephalopathy (HE). Hyperammonemia also affects the liver and hepatocytes. Therefore, targeting mitochondria seems to be a therapeutic point of intervention in the treatment of HE. Taurine is an abundant amino acid in the human body. Several biological functions including the mitochondrial protective properties are attributed to this amino acid. The aim of this study is to evaluate the effect of taurine administration on ammonia-induced mitochondrial dysfunction. Material and methods Isolated mice liver and brain mitochondria were exposed to different concentrations of ammonia (1, 5, 10, and 20 mM) and taurine (1, 5, and 10 mM), and several mitochondrial indices were assessed. Results It was found that ammonia inhibited mitochondrial dehydrogenases activity caused collapse of mitochondrial membrane potential (MMP), induced mitochondrial swelling (MPP), and increased reactive oxygen species (ROS) in isolated liver and brain mitochondria. Furthermore, a significant amount of lipid peroxidation (LPO), along with glutathione (GSH) and ATP depletion, was detected in ammonia exposed mitochondria. Taurine administration (5 and 10 mM) mitigated ammonia-induced mitochondrial dysfunction. Conclusions The current investigation demonstrates that taurine is instrumental in preserving brain and liver mitochondrial function in a hyperammonemic environment. The data suggest taurine as a potential protective agent with a therapeutic capability against hepatic encephalopathy and hyperammonemia. PMID:29062904

Taurine release from the developing and ageing hippocampus: stimulation by agonists of ionotropic glutamate receptors.

PubMed

Saransaari, P; Oja, S S

1997-12-30

The inhibitory amino acid taurine has been held to function as a modulator and osmoregulator in the brain, being of particular importance in the immature brain. The release of preloaded [3H]taurine was now studied in hippocampal slices from developing (7-day-old), adult (3-month-old) and ageing (6-24-month-old) mice focussing on the effects of agonists of ionotropic glutamate receptors. N-methyl-D-aspartate (NMDA), kainate and 2-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) potentiated taurine release concentration-dependently at each age, more so in the immature than in the adult and ageing hippocampus. The effect of kainate was blocked by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) in the developing and aged hippocampus and those of AMPA and NMDA by 6-nitro-7-sulphamoylbenzo[f]quinoxaline-2,3-dione (NBQX) and dizocilpine a(MK-801) at every age studied. This indicates the involvement of NMDA and AMPA receptors in taurine release throughout the life-span of mice, while the kainate-receptor-mediated release does not appear to function in adults. The increased hippocampal taurine release evoked by ionotropic glutamate receptors could act neuroprotectively, counteracting by several mechanisms the harmful effects of the simultaneous release of excitatory amino acids. The substantial release of taurine in the immature hippocampus might be particularly significant in view of the vulnerability of brain tissue to excitotoxicity at early age.

Taurine Bromamine: Reactivity of an Endogenous and Exogenous Anti-Inflammatory and Antimicrobial Amino Acid Derivative

PubMed Central

Bertozo, Luiza De Carvalho; Morgon, Nelson Henrique; De Souza, Aguinaldo Robinson; Ximenes, Valdecir Farias

2016-01-01

Taurine bromamine (Tau-NHBr) is produced by the reaction between hypobromous acid (HOBr) and the amino acid taurine. There are increasing number of applications of Tau-NHBr as an anti-inflammatory and microbicidal drug for topical usage. Here, we performed a comprehensive study of the chemical reactivity of Tau-NHBr with endogenous and non-endogenous compounds. Tau-NHBr reactivity was compared with HOBr, hypochlorous acid (HOCl) and taurine chloramine (Tau-NHCl). The second-order rate constants (k2) for the reactions between Tau-NHBr and tryptophan (7.7 × 102 M−1s−1), melatonin (7.3 × 103 M−1s−1), serotonin (2.9 × 103 M−1s−1), dansylglycine (9.5 × 101 M−1s−1), tetramethylbenzidine (6.4 × 102 M−1s−1) and H2O2 (3.9 × M−1s−1) were obtained. Tau-NHBr demonstrated the following selectivity regarding its reactivity with free amino acids: tryptophan > cysteine ~ methionine > tyrosine. The reactivity of Tau-NHBr was strongly affected by the pH of the medium (for instance with dansylglycine: pH 5.0, 1.1 × 104 M−1s−1, pH 7.0, 9.5 × 10 M−1s−1 and pH 9.0, 1.7 × 10 M−1s−1), a property that is related to the formation of the dibromamine form at acidic pH (Tau-NBr2). The formation of singlet oxygen was observed in the reaction between Tau-NHBr and H2O2. Tau-NHBr was also able to react with linoleic acid, but with low efficiency compared with HOBr and HOCl. Compared with HOBr, Tau-NHBr was not able to react with nucleosides. In conclusion, the following reactivity sequence was established: HOBr > HOCl > Tau-NHBr > Tau-NHCl. These findings can be very helpful for researchers interested in biological applications of taurine haloamines. PMID:27110829

Combination therapy of fenofibrate and ursodeoxycholic acid in patients with primary biliary cirrhosis who respond incompletely to UDCA monotherapy: a meta-analysis

PubMed Central

Zhang, Yan; Li, Sainan; He, Lei; Wang, Fan; Chen, Kan; Li, Jingjing; Liu, Tong; Zheng, Yuanyuan; Wang, Jianrong; Lu, Wenxia; Zhou, Yuqing; Yin, Qin; Xia, Yujing; Zhou, Yingqun; Lu, Jie; Guo, Chuanyong

2015-01-01

Background Although the effectiveness of treatment with ursodeoxycholic acid (UDCA) and fenofibrate for primary biliary cirrhosis (PBC) has been suggested by small trials, a systematic review to summarize the evidence has not yet been carried out. Methods A meta-analysis of all long-term randomized controlled trials comparing the combination of UDCA and fenofibrate with UDCA monotherapy was performed via electronic searches. Results Six trials, which included 84 patients, were assessed. Combination therapy with UDCA and fenofibrate was more effective than UDCA monotherapy in improving alkaline phosphatase (mean difference [MD]: −90.44 IU/L; 95% confidence interval [CI]: −119.95 to −60.92; P<0.00001), gamma-glutamyl transferase (MD: −61.58 IU/L; 95% CI: −122.80 to −0.35; P=0.05), immunoglobulin M (MD: −38.45 mg/dL; 95% CI: −64.38 to −12.51; P=0.004), and triglycerides (MD: −0.41 mg/dL; 95% CI: −0.82 to −0.01; P=0.05). However, their effects on pruritus (odds ratio [OR]: 0.39; 95% CI: 0.09–1.78; P=0.23), total bilirubin (MD: −0.05 mg/dL; 95% CI: −0.21 to 0.12; P=0.58), and alanine aminotransferase (MD: −3.31 IU/L; 95% CI: −14.60 to 7.97; P=0.56) did not differ significantly. This meta-analysis revealed no significant differences in the incidence of adverse events (OR: 0.21; 95% CI: 0.03–1.25; P=0.09) between patients treated with combination therapy and those treated with monotherapy. Conclusion In this meta-analysis, combination therapy with UDCA and fenofibrate was more effective in reducing alkaline phosphatase than UDCA monotherapy, but it did not improve clinical symptoms. There did not appear to be an increase in adverse events with combination therapy. PMID:26045661

Intracerebroventricular administration of taurine impairs learning and memory in rats.

PubMed

Ito, Koichi; Arko, Matevž; Kawaguchi, Tomohiro; Kikusui, Takefumi; Kuwahara, Masayoshi; Tsubone, Hirokazu

2012-03-01

Taurine is a semi-essential amino acid widely distributed in the body and we take in it from a wide range of nutritive-tonic drinks to improve health. To date, we have elucidated that oral supplementation of taurine does not affect learning and memory in the rat. However, there are few studies concerning the direct effects of taurine in the brain at the behavior level. In this study, we intracerebroventricularly administered taurine to rats and aimed to elucidate the acute effects on learning and memory using the Morris water maze method. Escape latency, swim distance, and distance to zone, which is the integral of the distance between the rats and the platform for every 0.16 seconds, were adopted as parameters of the ability of learning and memory. We also tried to evaluate the effect of intraperitoneal taurine administration. Escape latency, swim distance, and distance to zone were significantly longer in the intracerebroventricularly taurine-administered rats than in the saline-administered rats. Mean swimming velocity was comparable between these two groups, although the physical performance was improved by taurine administration. Probe trials showed that the manner of the rats in finding the platform was comparable. In contrast, no significant differences were found between the intraperitoneally taurine-administered rats and the saline-administered rats. These results indicate that taurine administered directly into the brain ventricle suppresses and delays the ability of learning and memory in rats. In contrast, it is implied that taurine administered peripherally was not involved in learning and memory.

Downregulation of hepatic betaine:homocysteine methyltransferase (BHMT) expression in taurine-deficient mice is reversed by taurine supplementation in vivo

PubMed Central

Jurkowska, Halina; Niewiadomski, Julie; Hirschberger, Lawrence L.; Roman, Heather B.; Mazor, Kevin M.; Liu, Xiaojing; Locasale, Jason W.; Park, Eunkyue

2016-01-01

The cysteine dioxygenase (Cdo1)-null and the cysteine sulfinic acid decarboxylase (Csad)-null mouse are not able to synthesize hypotaurine/taurine by the cysteine/cysteine sulfinate pathway and have very low tissue taurine levels. These mice provide excellent models for studying the effects of taurine on biological processes. Using these mouse models, we identified betaine:homocysteine methyltransferase (BHMT) as a protein whose in vivo expression is robustly regulated by taurine. BHMT levels are low in liver of both Cdo1-null and Csad-null mice, but are restored to wild-type levels by dietary taurine supplementation. A lack of BHMT activity was indicated by an increase in the hepatic betaine level. In contrast to observations in liver of Cdo1-null and Csad-null mice, BHMT was not affected by taurine supplementation of primary hepatocytes from these mice. Likewise, CSAD abundance was not affected by taurine supplementation of primary hepatocytes, although it was robustly upregulated in liver of Cdo1-null and Csad-null mice and lowered to wild-type levels by dietary taurine supplementation. The mechanism by which taurine status affects hepatic CSAD and BHMT expression appears to be complex and to require factors outside of hepatocytes. Within the liver, mRNA abundance for both CSAD and BHMT was upregulated in parallel with protein levels, indicating regulation of BHMT and CSAD mRNA synthesis or degradation. PMID:26481005

Protective role of taurine in developing offspring affected by maternal alcohol consumption

PubMed Central

Ananchaipatana-Auitragoon, Pilant; Ananchaipatana-Auitragoon, Yutthana; Siripornpanich, Vorasith; Kotchabhakdi, Naiphinich

2015-01-01

Maternal alcohol consumption is known to affect offspring growth and development, including growth deficits, physical anomalies, impaired brain functions and behavioral disturbances. Taurine, a sulfur-containing amino acid, is essential during development, and continually found to be protective against neurotoxicity and various tissue damages including those from alcohol exposure. However, it is still unknown whether taurine can exert its protection during development of central nervous system and whether it can reverse alcohol damages on developed brain later in life. This study aims to investigate protective roles of taurine against maternal alcohol consumption on growth and development of offspring. The experimental protocol was conducted using ICR-outbred pregnant mice given 10 % alcohol, with or without maternal taurine supplementation during gestation and lactation. Pregnancy outcomes, offspring mortality and successive bodyweight until adult were monitored. Adult offspring is supplemented taurine to verify its ability to reverse damages on learning and memory through a water maze task performance. Our results demonstrate that offspring of maternal alcohol exposure, together with maternal taurine supplementation show conserved learning and memory, while that of offspring treated taurine later in life are disturbed. Taurine provides neuroprotective effects and preserves learning and memory processes when given together with maternal alcohol consumption, but not shown such effects when given exclusively in offspring. PMID:26648819

Effect of medium osmolarity and taurine on neuritic outgrowth from goldfish retinal explants.

PubMed

Cubillán, Lisbeth; Obregón, Francisco; Lima, Lucimey

2009-01-01

Taurine stimulates outgrowth of goldfish retinal explants in a concentration- and time-dependent manner, an effect related to calcium movement and protein phosphorylation. Since taurine is an osmoregulator in the central nervous system, and osmolality might influence regeneration, the purpose of this work was to evaluate the possible effect of hypo-osmolality on basal outgrowth and on the trophic action of the amino acid. Accordingly, goldfish retinal explants obtained after crushing the optic nerve were cultured in iso- and hypo-osmotic medium, the latter achieved by diluting the medium 10% 24 and 72 h after plating. The length and density of the neurites, measured after 5 days in culture, were significantly lower in the hypo- than in the iso-osmotic medium. Taurine stimulated the outgrowth under both conditions, but the percentage of increase was greater in iso-osmotic medium. Taurine concentration, determined by HPLC, did not significantly change in explants. Co-administration of beta-alanine and taurine impaired the trophic effect of taurine to a greater extent in the iso- than in hypo-osmotic medium, indicating a possible differential interaction with the taurine transporter which could be altered by osmotic stress. The exact mechanism of outgrowth regulation by hypotonicity requires further clarification, taking into considering possible modification of the taurine transporter.

Two complementary liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods to study the excretion and metabolic interaction of edaravone and taurine in rats.

PubMed

Tang, Dao-quan; Zheng, Xiao-xiao; Li, Yin-jie; Bian, Ting-ting; Yu, Yan-yan; Du, Qian; Yang, Dong-zhi; Jiang, Shui-shi

2014-11-01

In this study, two independent and complementary liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods were respectively developed and validated for the determination of edaravone or taurine in rat urine, feces and bile after intravenous administration, using 3-methyl-l-p-tolyl-5-pyrazolone and sulfanilic acid as the internal standards (IS). Edaravone was separated on an Agilent Eclipse Plus C18 column (100×2.1 mm, 3.5 μm) using methanol and water (containing 5 mM ammonium formate and 0.02% formic acid) as mobile phase, while taurine was performed on a Waters Atlantis HILIC Silica column (150×2.1 mm, 3 μm) using acetonitrile and water (containing 5mM ammonium formate and 0.2% formic acid) as mobile phase. The mass analysis was performed in a Triple Quadrupole mass spectrometer via multiple reaction monitoring (MRM) with negative ionization mode. The optimized mass transition ion pairs (m/z) for quantification were 173.1→92.2 and 187.2→106.0 for edaravone and its IS, 124.1→80.0 and 172.0→80.0 for taurine and its IS, respectively. The validated methods have been successfully applied to the excretion and metabolism interaction study of edaravone and taurine in rats after independent intravenous administration and co-administration with a single dose. The results demonstrated that there were no significant alternations on the metabolism and cumulative excretion rate of edaravone and taurine, implying that the proposed combination therapy was pharmacologically viable. Copyright © 2014 Elsevier B.V. All rights reserved.

Influence of fenofibrate treatment on triacylglycerides, diacylglycerides and fatty acids in fructose fed rats.

PubMed

Kopf, Thomas; Schaefer, Hans-Ludwig; Troetzmueller, Martin; Koefeler, Harald; Broenstrup, Mark; Konovalova, Tatiana; Schmitz, Gerd

2014-01-01

Fenofibrate (FF) lowers plasma triglycerides via PPARα activation. Here, we analyzed lipidomic changes upon FF treatment of fructose fed rats. Three groups with 6 animals each were defined as control, fructose-fed and fructose-fed/FF treated. Male Wistar Unilever Rats were subjected to 10% fructose-feeding for 20 days. On day 14, fenofibrate treatment (100 mg/kg p.o.) was initiated and maintained for 7 days. Lipid species in serum were analyzed using mass spectrometry (ESI-MS/MS; LC-FT-MS, GC-MS) on days 0, 14 and 20 in all three groups. In addition, lipid levels in liver and intestine were determined. Short-chain TAGs increased in serum and liver upon fructose-feeding, while almost all TAG-species decreased under FF treatment. Long-chain unsaturated DAG-levels (36:1, 36:2, 36:4, 38:3, 38:4, 38:5) increased upon FF treatment in rat liver and decreased in rat serum. FAs, especially short-chain FAs (12:0, 14:0, 16:0) increased during fructose-challenge. VLDL secretion increased upon fructose-feeding and together with FA-levels decreased to control levels during FF treatment. Fructose challenge of de novo fatty acid synthesis through fatty acid synthase (FAS) may enhance the release of FAs ≤ 16:0 chain length, a process reversed by FF-mediated PPARα-activation.

Assay of free and glycine- and taurine-conjugated bile acids in serum by high-pressure liquid chromatography by using post-column reaction after group separation.

PubMed Central

Onishi, S; Itoh, S; Ishida, Y

1982-01-01

An accurate and sensitive method that involves the group separations of serum bile acids (i.e. free and glycine- and taurine-conjugated bile acid fractions) by ion-exchange chromatography on piperidinohydroxypropyl-Sephadex LH-20 is described. Each group was then analysed by high-pressure liquid chromatography by using the post-column reaction technique with immobilized 3 alpha-hydroxy steroid dehydrogenase. The bile acid patterns in the umbilical venous serum samples were analysed by this method. Taurochenodeoxycholate predominated in the umbilical blood. PMID:6956336

[Influence of oral contraceptive agents on the concentration of amino acids in leukocytes of supposedly healthy women (author's transl)].

PubMed

Tarallo, P; Houpert, Y; Siest, G

1977-12-15

The concentration of amino acids has been measured in leukocytes of women taking oral contraceptive agents and also in controls. These assays were made by means of ion exchange chromatography. The amino acid pool in leukocytes was found to be smaller in those patients taking the "pill". Each amino acid concentration decreased except for taurine and glutamine. Taurine represented 64.1 percent of the pool in treated women and only 23.5 percent in controls. Glutamine represented 9.5 percent of the pool in patients and 3.7 percent in controls.

[Taurine as a regulator of fluid-electrolyte balance and arterial pressure].

PubMed

Ciechanowska, B

1997-01-01

Taurine is a sulfonic beta-amino acid which occurs in the highest concentration in the brain, the retina and in the myocardium. In cardiomyocytes it presents about 50% of free amino acids and plays a role as an osmoregulator, an inotropic factor and has an antiarrhythmic property. Moreover, taurine lowers arterial pressure by extension of diuresis and by vasodilatation. Similar effect on the vascular system and arterial pressure is exerted by atrial natriuretic peptide (ANP). Increase of both ANP secretion and myocardial taurine concentration is present in the same diseases as congestive cardiac failure, hypertension and hypernatremia. The aim of the study was the evaluation of general taurine depletion, caused by making the rats drink guanidinoethyl sulfonate (GES)--an inhibitor of taurine transport affecting fluid balance and arterial pressure as well as plasma ANP concentration under normal conditions and after increase of sodium load. The 103 male Wistar rats weighing 250-300 g were used. The animals were separated into 5 groups. Control group received tap water to drink. Group II was sodium-loaded by drinking 171 mmol/l NaCl. In group III depletion of taurine was obtained by the intake of 60 mmol/l GES. Rats in group IV were drinking 60 mmol/l GES in 171 mmol/l NaCl. Group V was made to drink 200 mmol/l taurine in 171 mmol/l NaCl. All animals had standard food and were able at any time to drink. Duration of the experiment was 20 days. At the onset and after 10 and 20 days the rats were weighed and their systolic blood pressure was measured by tail plethysmography. After 10 and 20 days of the study, plasma and myocardium taurine concentration, ANP, hematocrit, plasma osmolity, natremia, kalemia, urea and creatinine concentrations were determined. Taking GES for 20 days led to 43% decrease of plasma taurine and its myocardium content about 50% as compared to control group (Tab. 2). High, statistically significant correlation (r = 0.50, p < 0.001) between myocardium taurine and plasma ANP was found. The animals with taurine depletion had significantly lower (about 30%) plasma ANP concentration (Tab. 3), higher natremia (Tab. 4) and their arterial pressure increased due to sodium load. Systolic pressure was 11 mm Hg higher in that group in comparison to control and other groups (Tab. 1). However, the sodium-loading of the rats that drank taurine solution led to an increase of hematocrit, plasma osmolity, urea concentration and body mass gain as compared to control group, but without any arterial pressure increase. The sodium-loaded rats with normal plasma and myocardium taurine concentration were affected in a similar manner. The rats with higher myocardium taurine concentration had lower heart mass index. Results of this work lead to the following conclusions: 1. Depletion of taurine in hearts of examined rats leads to a decrease of plasma atrial natriuretic peptide (ANP) concentration in plasma. 2. ANP secretion caused by salt loading is lower in animals with taurine depletion than in normal animals. 3. Sodium-loading of animals with taurine depletion leads to hypernatremia and to an increase of arterial pressure. 4. Addition of taurine to animals loaded with sodium may lead to their dehydration.

Beneficial effects of high dose taurine treatment in juvenile dystrophic mdx mice are offset by growth restriction.

PubMed

Terrill, Jessica R; Pinniger, Gavin J; Nair, Keshav V; Grounds, Miranda D; Arthur, Peter G

2017-01-01

Duchenne Muscular Dystrophy (DMD) is a fatal muscle wasting disease manifested in young boys, for which there is no current cure. We have shown that the amino acid taurine is safe and effective at preventing dystropathology in the mdx mouse model for DMD. This study aimed to establish if treating growing mdx mice with a higher dose of taurine was more effective at improving strength and reducing inflammation and oxidative stress. Mice were treated with a dose of taurine estimated to be 16 g/kg/day, in drinking water from 1-6 weeks of age, after which in vivo and ex vivo muscle strength was assessed, as were measures of inflammation, oxidative stress and taurine metabolism. While the dose did decrease inflammation and protein oxidation in dystrophic muscles, there was no improvement in muscle strength (in contrast with benefits observed with the lower dose) and growth of the young mice was significantly restricted. We present novel data that a high taurine dose increases the cysteine content of both mdx liver and plasma, a possible result of down regulation of the taurine synthesis pathway in the liver (which functions to dispose of excess cysteine, which is toxic). These data caution that a high dose of taurine can have adverse effects and may be less efficacious than lower taurine doses. Therefore, monitoring of taurine dosage needs to be considered in future pre-clinical trials, in anticipation of using taurine as a clinical therapy for growing DMD boys (and other conditions).

Beneficial effects of high dose taurine treatment in juvenile dystrophic mdx mice are offset by growth restriction

PubMed Central

Pinniger, Gavin J.; Nair, Keshav V.; Grounds, Miranda D.; Arthur, Peter G.

2017-01-01

Duchenne Muscular Dystrophy (DMD) is a fatal muscle wasting disease manifested in young boys, for which there is no current cure. We have shown that the amino acid taurine is safe and effective at preventing dystropathology in the mdx mouse model for DMD. This study aimed to establish if treating growing mdx mice with a higher dose of taurine was more effective at improving strength and reducing inflammation and oxidative stress. Mice were treated with a dose of taurine estimated to be 16 g/kg/day, in drinking water from 1–6 weeks of age, after which in vivo and ex vivo muscle strength was assessed, as were measures of inflammation, oxidative stress and taurine metabolism. While the dose did decrease inflammation and protein oxidation in dystrophic muscles, there was no improvement in muscle strength (in contrast with benefits observed with the lower dose) and growth of the young mice was significantly restricted. We present novel data that a high taurine dose increases the cysteine content of both mdx liver and plasma, a possible result of down regulation of the taurine synthesis pathway in the liver (which functions to dispose of excess cysteine, which is toxic). These data caution that a high dose of taurine can have adverse effects and may be less efficacious than lower taurine doses. Therefore, monitoring of taurine dosage needs to be considered in future pre-clinical trials, in anticipation of using taurine as a clinical therapy for growing DMD boys (and other conditions). PMID:29095865

Taurine Supplementation Improves Functional Capacity, Myocardial Oxygen Consumption, and Electrical Activity in Heart Failure.

PubMed

Ahmadian, Mehdi; Dabidi Roshan, Valiollah; Ashourpore, Eadeh

2017-07-04

Taurine is an amino acid found abundantly in the heart in very high concentrations. It is assumed that taurine contributes to several physiological functions of mammalian cells, such as osmoregulation, anti-inflammation, membrane stabilization, ion transport modulation, and regulation of oxidative stress and mitochondrial protein synthesis. The objective of the current study was to evaluate the effectiveness of taurine supplementation on functional capacity, myocardial oxygen consumption, and electrical activity in patients with heart failure. In a double-blind and randomly designed study, 16 patients with heart failure were assigned to two groups: taurine (TG, n = 8) and placebo (PG, n = 8). TG received 500-mg taurine supplementation three times per day for two weeks. Significant decrease in the values of Q-T segments (p < 0.01) and significant increase in the values of P-R segments (p < 0.01) were detected following exercise post-supplementation in TG rather than in PG. Significantly higher values of taurine concentration, T wave, Q-T segment, physical capacities, and lower values of cardiovascular capacities were detected post-supplementation in TG as compared with PG (all p values <0.01). Taurine significantly enhanced the physical function and significantly reduced the cardiovascular function parameters following exercise. Our results also suggest that the short-term taurine supplementation is an effective strategy for improving some selected hemodynamic parameters in heart failure patients. Together, these findings support the view that taurine improves cardiac function and functional capacity in patients with heart failure. This idea warrants further study.

Neuroprotective Mechanisms of Taurine against Ischemic Stroke.

PubMed

Menzie, Janet; Prentice, Howard; Wu, Jang-Yen

2013-06-03

Ischemic stroke exhibits a multiplicity of pathophysiological mechanisms. To address the diverse pathophysiological mechanisms observed in ischemic stroke investigators seek to find therapeutic strategies that are multifaceted in their action by either investigating multipotential compounds or by using a combination of compounds. Taurine, an endogenous amino acid, exhibits a plethora of physiological functions. It exhibits antioxidative properties, stabilizes membrane, functions as an osmoregulator, modulates ionic movements, reduces the level of pro-inflammators, regulates intracellular calcium concentration; all of which contributes to its neuroprotective effect. Data are accumulating that show the neuroprotective mechanisms of taurine against stroke pathophysiology. In this review, we describe the neuroprotective mechanisms employed by taurine against ischemic stroke and its use in clinical trial for ischemic stroke.

Taurine is absent from amino components in fruits of Opuntia ficus-indica.

PubMed

Ali, Hatem Salama Mohamed; Al-Khalifa, Abdulrahman Saleh; Brückner, Hans

2014-01-01

Juices of edible fruits from Opuntia ficus-indica (L.) Miller, commonly named prickly pears or Indian figs, were analysed for amino acids using an automated amino acid analyser run in the high-resolution physiological mode. Emphasis was put on the detection of free taurine (Tau), but Tau could be detected neither in different cultivars of prickly pears from Italy, South Africa and the Near East nor in commercially available prickly pear juices from the market.

Effect of starvation on free histidine and amino acids in white muscle of milkfish Chanos chanos.

PubMed

Shiau, C Y; Pong, Y P; Chiou, T K; Tin, Y Y

2001-03-01

Milkfish (Chanos chanos) decreased their body weight from 47 to 28 g over the 60-day period of starvation. Starvation also resulted in the reduction of muscle lipid and protein, and hepatosomatic index. The predominant free amino acid (FAA) in white muscle of milkfish was histidine, followed by taurine and glycine. In the first 25 days of starvation, no significant change in histidine was found. After 40 days of starvation, however, the histidine concentration was significantly decreased by 46%, and remained unchanged thereafter. As compared to control group fish, the 60-day-starved fish possessed only half the amount of histidine. Taurine and glycine, on the other hand, showed no significant changes throughout starvation. Taurine became the most predominant in the FAA pool after 40 days of starvation, and the concentration of 60-day-starved fish was two times higher than that of control group fish without starvation. The ratios of histidine, taurine, and glycine to total FAAs remained approximately the same although the individual contributions varied considerably to the total FAAs during starvation. The results of this study suggested that a good strategy would be to keep taurine and glycine in milkfish muscle at relatively high levels for physiological function as histidine decreased drastically for energy source under conditions of food deprivation.

Effects of taurine and housing density on renal function in laying hens*

PubMed Central

Ma, Zi-li; Gao, Yang; Ma, Hai-tian; Zheng, Liu-hai; Dai, Bin; Miao, Jin-feng; Zhang, Yuan-shu

2016-01-01

This study investigated the putative protective effects of supplemental 2-aminoethane sulfonic acid (taurine) and reduced housing density on renal function in laying hens. We randomly assigned fifteen thousand green-shell laying hens into three groups: a free range group, a low-density caged group, and a high-density caged group. Each group was further divided equally into a control group (C) and a taurine treatment group (T). After 15 d, we analyzed histological changes in kidney cells, inflammatory mediator levels, oxidation and anti-oxidation levels. Experimental data revealed taurine supplementation, and rearing free range or in low-density housing can lessen morphological renal damage, inflammatory mediator levels, and oxidation levels and increase anti-oxidation levels. Our data demonstrate that taurine supplementation and a reduction in housing density can ameliorate renal impairment, increase productivity, enhance health, and promote welfare in laying hens. PMID:27921400

Enhancement of the dissolution rate and bioavailability of fenofibrate by a melt-adsorption method using supercritical carbon dioxide

PubMed Central

Cha, Kwang-Ho; Cho, Kyung-Jin; Kim, Min-Soo; Kim, Jeong-Soo; Park, Hee Jun; Park, Junsung; Cho, Wonkyung; Park, Jeong-Sook; Hwang, Sung-Joo

2012-01-01

Background: The aim of this study was to enhance the bioavailability of fenofibrate, a poorly water-soluble drug, using a melt-adsorption method with supercritical CO2. Methods: Fenofibrate was loaded onto Neusilin® UFL2 at different weight ratios of fenofibrate to Neusilin UFL2 by melt-adsorption using supercritical CO2. For comparison, fenofibrate-loaded Neusilin UFL2 was prepared by solvent evaporation and hot melt-adsorption methods. The fenofibrate formulations prepared were characterized by differential scanning calorimetry, powder x-ray diffractometry, specific surface area, pore size distribution, scanning electron microscopy, and energy-dispersive x-ray spectrometry. In vitro dissolution and in vivo bioavailability were also investigated. Results: Fenofibrate was distributed into the pores of Neusilin UFL2 and showed reduced crystal formation following adsorption. Supercritical CO2 facilitated the introduction of fenofibrate into the pores of Neusilin UFL2. Compared with raw fenofibrate, fenofibrate from the prepared powders showed a significantly increased dissolution rate and better bioavailability. In particular, the area under the drug concentration-time curve and maximal serum concentration of the powders prepared using supercritical CO2 were 4.62-fold and 4.52-fold greater than the corresponding values for raw fenofibrate. Conclusion: The results of this study highlight the usefulness of the melt-adsorption method using supercritical CO2 for improving the bioavailability of fenofibrate. PMID:23118538

Forced swimming and imipramine modify plasma and brain amino acid concentrations in mice.

PubMed

Murakami, Tatsuro; Yamane, Haruka; Tomonaga, Shozo; Furuse, Mitsuhiro

2009-01-05

The relationships between monoamine metabolism and forced swimming or antidepressants have been well studied, however information is lacking regarding amino acid metabolism under these conditions. Therefore, the aim of the present study was to investigate the effects of forced swimming and imipramine on amino acid concentrations in plasma, the cerebral cortex and the hypothalamus in mice. Forced swimming caused cerebral cortex concentrations of L-glutamine, L-alanine, and taurine to be increased, while imipramine treatment caused decreased concentrations of L-glutamate, L-alanine, L-tyrosine, L-methionine, and L-ornithine. In the hypothalamus, forced swimming decreased the concentration of L-serine while imipramine treatment caused increased concentration of beta-alanine. Forced swimming caused increased plasma concentration of taurine, while concentrations of L-serine, L-asparagine, L-glutamine and beta-alanine were decreased. Imipramine treatment caused increased plasma concentration of all amino acid, except for L-aspartate and taurine. In conclusion, forced swimming and imipramine treatment modify central and peripheral amino acid metabolism. These results may aid in the identification of amino acids that have antidepressant-like effects, or may help to refine the dosages of antidepressant drugs.

Osmoregulated taurine transport in H4IIE hepatoma cells and perfused rat liver.

PubMed Central

Warskulat, U; Wettstein, M; Häussinger, D

1997-01-01

The effects of aniso-osmotic exposure on taurine transport were studied in H4IIE rat hepatoma cells. Hyperosmotic (405 mosmol/l) exposure of H4IIE cells stimulated Na+-dependent taurine uptake and led to an increase in taurine transporter (TAUT) mRNA levels, whereas hypo-osmotic (205 mosmol/l) exposure diminished both taurine uptake and TAUT mRNA levels when compared with normo-osmotic (305 mosmol/l) control incubations. Taurine uptake increased 30-40-fold upon raising the ambient osmolarity from 205 to 405 mosmol/l. When H4IIE cells and perfused livers were preloaded with taurine, hypo-osmotic cell swelling led to a rapid release of taurine from the cells. The taurine efflux, but not taurine uptake, was sensitive to 4,4'-di-isothiocyanatostilbene-2,2'-disulphonic acid (DIDS), suggestive of an involvement of DIDS-sensitive channels in mediating volume-regulatory taurine efflux. Whereas in both H4IIE rat hepatoma cells and primary hepatocytes TAUT mRNA levels were strongly dependent upon ambient osmolarity, mRNAs for other osmolyte transporters, i.e. the betaine transporter BGT-1 and the Na+/myo-inositol transporter SMIT, were not detectable. In line with this, myo-inositol uptake by H4IIE hepatoma cells was low and was not stimulated by hyperosmolarity. However, despite the absence of BGT-1 mRNA, a slight osmosensitive uptake of betaine was observed, but the rate was less than 10% of that of taurine transport. This study identifies a constitutively expressed and osmosensitive TAUT in H4IIE cells and the use of taurine as a main osmolyte, whereas betaine and myo-inositol play little or no role in the osmolyte strategy in these cells. This is in contrast with rat liver macrophages, in which betaine has been shown to be a major osmolyte. PMID:9032454

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jazrawi, R.P.; Ferraris, R.; Bridges, C.

The apparent fractional turnover rate of the gamma-labeled bile acid analogue 75-selenohomocholic acid-taurine (75-SeHCAT) was assessed from decline in radioactivity over the gallbladder area on 4 successive days using a gamma-camera, and was compared in the same subjects with the fractional turnover rate of the corresponding natural bile acid, cholic acid-taurine, labeled with 14C ((14C)CAT) using the classical Lindstedt technique. Very similar results were obtained in 5 healthy individuals (coefficient of variation 4.8%, medians 0.35 and 0.34, respectively). By contrast, the fractional deconjugation rate assessed from zonal scanning of glycine- and taurine-conjugated bile acids on thin-layer chromatography was much lessmore » for 75-SeHCAT than for (14C)CAT (0.02 and 0.13, respectively; p less than 0.05). The fractional rate for deconjugation plus dehydroxylation was also determined by zonal scanning, and gave lower values for 75-SeHCAT than for (14C)CAT (0.02 and 0.12, respectively; p less than 0.05). There was a striking similarity between the fractional rate for deconjugation alone and that for deconjugation plus dehydroxylation for both bile acids in individual samples (r = 0.999, p less than 0.001), suggesting that these two processes might occur simultaneously and probably involve the same bacteria. We conclude that our scintiscanning technique provides an accurate, noninvasive method of measuring fractional turnover rate of a bile acid in humans, and that the finding that 75SeHCAT remains conjugated with taurine during enterohepatic recycling means that absorption should be specific for the ileal active transport site, thus rendering it an ideal substance for assessing ileal function.« less

Modulation of taurine release by glutamate receptors and nitric oxide.

PubMed

Oja, S S; Saransaari, P

2000-11-01

Taurine is held to function as a modulator and osmoregulator in the central nervous system, being of particular importance in the immature brain. In view of the possible involvement of excitatory pathways in the regulation of taurine function in the brain, the interference of glutamate receptors with taurine release from different tissue preparations in vitro and from the brain in vivo is of special interest. The release of taurine from the brain is enhanced by glutamate receptor agonists. This enhancement is inhibited by the respective receptor antagonists both in vitro and in vivo. The ionotropic N-methyl-D-aspartate (NMDA) and 2-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor agonists appear to be the most effective in enhancing taurine release, their effects being receptor-mediated. Kainate is less effective, particularly in adults. Of the glutamate receptors, the NMDA class seems to be the most susceptible to modulation by nitric oxide. Nitric oxide also modulates taurine release, enhancing the basal release in both immature and mature hippocampus, whereas the K(+)-stimulated release is generally inhibited. Metabotropic glutamate receptors also participate in the regulation of taurine release, group I metabotropic glutamate receptors potentiating the release in the developing hippocampus, while group III receptors may be involved in the adult. Under various cell-damaging conditions, including ischemia, hypoxia and hypoglycemia, taurine release is enhanced, together with an enhanced release of excitatory amino acids. The increase in extracellular taurine upon excessive stimulation of glutamate receptors and under cell-damaging conditions may serve as an important protective mechanism against excitotoxicity, being particularly effective in the immature brain.

Combined administration of taurine and monoisoamyl DMSA protects arsenic induced oxidative injury in rats

PubMed Central

Chouhan, Swapnila; Kannan, Gurusamy M; Mittal, Megha; Swarnkar, Harimohan

2008-01-01

Arsenic is a naturally occurring element that is ubiquitously present in the environment. High concentration of naturally occurring arsenic in drinking water is a major health problem in different parts of the world. Despite arsenic being a health hazard and a well documented carcinogen, no safe, effective and specific preventive or therapeutic measures are available. Among various recent strategies adopted, administration of an antioxidant has been reported to be the most effective. The present study was designed to evaluate the therapeutic efficacy of monoisoamyl dimercaptosuccinic acid (MiADMSA), administered either individually or in combination with taurine post chronic arsenic exposure in rats. Arsenic exposed male rats (25 ppm, sodium arsenite in drinking water for 24 weeks) were treated with taurine (100 mg/kg, i.p., once daily), monoisoamyl dimercaptosuccinic acid (MiADMSA) (50 mg/kg, oral, once daily) either individually or in combination for 5 consecutive days. Biochemical variables indicative of oxidative stress along-with arsenic concentration in blood, liver and kidney were measured. Arsenic exposure significantly reduced blood δ-aminolevulinic acid dehydratase (ALAD) activity, a key enzyme involved in the heme biosynthesis and enhanced zinc protoporphyrin (ZPP) level. Clinical hematological variables like white blood cells (WBC), mean cell hemoglobin (MCH), and mean cell hemoglobin concentration (MCHC) showed significant decrease with a significant elevation in platelet (PLT) count. These changes were accompanied by significant decrease in superoxide dismutase (SOD) activity and increased catalase activity. Arsenic exposure caused a significant decrease in hepatic and renal glutathione (GSH) level and an increase in oxidized glutathione (GSSG). These biochemical changes were correlated with an increased uptake of arsenic in blood, liver and kidney. Administration of taurine significantly reduced hepatic oxidative stress however co-administration of a higher dose of taurine (100 mg/kg) and MiADMSA provided more pronounced effects in improving the antioxidant status of liver and kidney and reducing body arsenic burden compared to the individual treatment of MiADMSA or taurine. The results suggest that in order to achieve better effects of chelation therapy, co-administration of taurine with MiADMSA might be preferred. PMID:19794907

Neuroprotective Mechanisms of Taurine against Ischemic Stroke

PubMed Central

Menzie, Janet; Prentice, Howard; Wu, Jang-Yen

2013-01-01

Ischemic stroke exhibits a multiplicity of pathophysiological mechanisms. To address the diverse pathophysiological mechanisms observed in ischemic stroke investigators seek to find therapeutic strategies that are multifaceted in their action by either investigating multipotential compounds or by using a combination of compounds. Taurine, an endogenous amino acid, exhibits a plethora of physiological functions. It exhibits antioxidative properties, stabilizes membrane, functions as an osmoregulator, modulates ionic movements, reduces the level of pro-inflammators, regulates intracellular calcium concentration; all of which contributes to its neuroprotective effect. Data are accumulating that show the neuroprotective mechanisms of taurine against stroke pathophysiology. In this review, we describe the neuroprotective mechanisms employed by taurine against ischemic stroke and its use in clinical trial for ischemic stroke. PMID:24961429

Effects of ω-Amino Acids and Related Compounds on Staphylococcal Infections in Mice: a Combined Prophylactic-Therapeutic Procedure 1

PubMed Central

Tsuchiya, Yoshiki; Tanaka, Kinji; Cook, Elton S.; Nutini, Leo G.

1970-01-01

By a short-term combined prophylactic-therapeutic procedure, the following compounds were found to be active against staphylococcal infections in Swiss mice: γ-aminobutyric acid, γ-amino-β-hydroxybutyric acid (GABOB), δ-amino-valeric acid (DAVA), ε-aminocaproic acid (EACA), trans-4-aminomethylcyclohexanecarboxylic acid (trans-AMCHA), taurine, and cysteic acid. Many of these compounds had displayed limited or no activity by a previously used prophylactic procedure. Although DAVA and GABOB were the most potent of the straight-chain ω-amino acids, trans-AMCHA displayed the greatest antistaphylococcic activity of the ω-amino acids thus far investigated. Homocarnosine (γ-aminobutyrl histidine, which also was active by the prophylactic procedure) equalled trans-AMCHA in activity. Taurine was similar in potency to DAVA, and the activity of cysteic acid approximated that of EACA. PMID:5422309

Comparative Analysis of Microbicidal and Anti-inflammatory Properties of Novel Taurine Bromamine Derivatives and Bromamine T.

PubMed

Walczewska, M; Peruń, A; Białecka, A; Śróttek, M; Jamróz, W; Dorożyński, P; Jachowicz, R; Kulinowski, P; Nagl, M; Gottardi, W; Marcinkiewicz, J

2017-01-01

Taurine, the most abundant free amino acid in leukocyte cytosol traps hypohalous acids (HOCl and HOBr) to produce N-chlorotaurine (taurine chloramine, NCT and N-bromotaurine (taurine bromamine, Tau-NHBr,) respectively. Both haloamines show anti-inflammatory and antimicrobial properties. However, the therapeutic applicability of Tau-NHBr is limited due to its relatively poor stability. To overcome this disadvantage, we have synthesized the stable N-bromotaurine compounds N-monobromo-2,2-dimethyltaurine (Br-612) and N-dibromo-2,2-dimethyltaurine (Br-422). The aim of this study was to compare anti-inflammatory and microbicidal properties of Br-612 and Br-422 with that of Tau-NHBr and bromamine T (BAT). We have shown that all the tested compounds show similar anti-inflammatory properties. Importantly, the stable N-bromotaurine compounds exerted even stronger microbicidal activity than Tau-NHBr. Finally, for the purpose of topical application of these compounds we have developed a carbomer-based bioadhesive solid dosage form of BAT and Br-612, featuring sustained release of the active substance.

Taurine chloramine: a possible oxidant reservoir.

PubMed

Ogino, Tetsuya; Than, Tin Aung; Hosako, Mutsumi; Ozaki, Michitaka; Omori, Masako; Okada, Shigeru

2009-01-01

Taurine is abundant in polymorphonuclear leukocytes (PMNs) where it reacts with PMN-derived hypochlorous acid to form taurine chloramine (Tau-NHCl), a substance that does not readily cross the cell membrane. When PMNs were stimulated in PBS lacking taurine, extracellular oxidant concentration was low, but the concentration increased 3-4 fold when 15 mM taurine was added, indicating that taurine lowers oxidant levels inside the cell. When Tau-NHCl was added to Jurkat cells in suspension, its half life was about 75 min. In contrast, membrane-permeable ammonia mono-chloramine (NH2Cl) has a half life of only 6 min. Accordingly, NH2Cl oxidizes cytosolic proteins, such as IkappaB, and inhibits NF-kappaB activation, whereas Tau-NHCl exhibits no comparable effect. However, when NH4+ was added to the medium, Tau-NHCl oxidizes IkappaB and inhibits NF-kappaB activation, probably through oxidant transfer to NH4+ leading to NH2Cl formation. These results indicate that Tau-NHCl can serve as an oxidant reservoir, exhibiting either delayed oxidant effects or acting as an oxidant at a distant site.

[Correlations of bile acids in the bile of rats in conditions of alloxan induced diabetes melitus].

PubMed

Danchenko, N M; Vesel'skyĭ, S P; Tsudzevych, B O

2014-01-01

The ratio of bile acids in the bile of rats with alloxan diabetes was investigated using the method of thin-layer chromatography. Changes of coefficients of conjugation and hydroxylation of bile acids were calculated and analyzed in half-hour samples of bile obtained during the 3-hour experiment. It has been found that the processes of conjugation of cholic acid with glycine and taurine are inhibited in alloxan diabetes. At the same time a significant increase of free threehydroxycholic and dixydroxycholic bile acids and conjugates of the latter ones with taurine has been registered. Coefficients of hydroxylation in alloxan diabetes show the domination of "acidic" pathway in bile acid biosynthesis that is tightly connected with the activity of mitochondrial enzymes.

K(+)- and temperature-evoked taurine efflux from hypothalamic astrocytes.

PubMed

Tigges, G A; Philibert, R A; Dutton, G R

1990-10-30

Hypothalamic astrocytes in culture released taurine, a suspected inhibitory amino acid neurotransmitter/neuromodulator/osmoregulator, in response to isoosmotically increasing extracellular K+ in a dose-dependent fashion. In the absence of added Ca2+, basal release levels rose to approach those obtained after exposure to 60 mM K+ in the presence of 2.5 mM Ca2+, and were only partially lowered by the addition of 10 mM Mg2+. Stimulation with K+ (60 mM) did not further increase taurine efflux above the high basal levels seen in the absence of Ca2+. Under standard conditions complete replacement of Na+ with choline Cl had little effect on basal taurine release, but reduced K(+)-evoked (60 mM) efflux by 60%. The temperature dependence of the basal levels of taurine released from hypothalamic astrocytes was similar to that seen for cultured cerebellar astrocytes and neurons over the range 5-50 degrees C. Taurine release increased from 5 to 15 degrees C, remained constant between 15 and 33 degrees C, decreased between 33 and 37 degrees C and increased thereafter. The infection point of increased basal taurine release seen around 37 degrees C (most prominent in astrocytes), may be of physiological significance. Results presented also show that the ion (Na+, Ca2+ and K+) sensitivities of taurine efflux for cultured hypothalamic astrocytes are similar to those previously reported for cultured astrocytes from the cerebellum.

Taurine protects HK-2 cells from oxidized LDL-induced cytotoxicity via the ROS-mediated mitochondrial and p53-related apoptotic pathways

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chang, Chun-Yu; Shen, Chao-Yu; Department of Medical Imaging, Chung Shan Medical University Hospital, Taichung, Taiwan

Oxidized LDL (oxLDL) induces a pro-oxidative environment and promotes apoptosis, causing the progression of renal diseases in humans. Taurine is a semi-essential amino acid in mammals and has been shown to be a potent endogenous antioxidant. The kidney plays a pivotal role in maintaining the balance of taurine. However, the mechanisms underlying the protective effects of taurine against oxLDL-induced injury in renal epithelial cells have not been clarified. In the present study, we investigated the anti-apoptotic effects of taurine on human proximal tubular epithelial (HK-2) cells exposed to oxLDL and explored the related mechanisms. We observed that oxLDL increased themore » contents of ROS and of malondialdehyde (MDA), which is a lipid peroxidation by-product that acts as an indicator of the cellular oxidation status. In addition, oxLDL induced cell death and apoptosis in HK-2 cells. Pretreatment with taurine at 100 μM significantly attenuated the oxLDL-induced cytotoxicity. We determined that oxLDL triggered the phosphorylation of ERK and, in turn, the activation of p53 and other apoptosis-related events, including calcium accumulation, destabilization of the mitochondrial permeability and disruption of the balance between pro-apoptotic Bax and anti-apoptotic Bcl-2 proteins. The malfunctions induced by oxLDL were effectively blocked by taurine. Thus, our results suggested that taurine exhibits potential therapeutic activity by preventing oxLDL-induced nephrotoxicity. The inhibition of oxLDL-induced epithelial apoptosis by taurine was at least partially due to its anti-oxidant activity and its ability to modulate the ERK and p53 apoptotic pathways. - Highlights: • Oxidized LDL induced cytotoxicity and apoptosis in HK-2 cells. • Pretreatment with taurine attenuated oxLDL-induced nephrotoxicity. • Taurine protected against renal damages through inhibition of ROS generation. • Taurine prevented apoptosis through modulation of the p53 phosphorylation.« less

Isolation and Total Synthesis of Stolonines A–C, Unique Taurine Amides from the Australian Marine Tunicate Cnemidocarpa stolonifera

PubMed Central

Tran, Trong D.; Pham, Ngoc B.; Ekins, Merrick; Hooper, John N. A.; Quinn, Ronald J.

2015-01-01

Cnemidocarpa stolonifera is an underexplored marine tunicate that only occurs on the tropical to subtropical East Coast of Australia, with only two pyridoacridine compounds reported previously. Qualitative analysis of the lead-like enhanced fractions of C. stolonifera by LC-MS dual electrospray ionization coupled with PDA and ELSD detectors led to the identification of three new natural products, stolonines A–C (1–3), belonging to the taurine amide structure class. Structures of the new compounds were determined by NMR and MS analyses and later verified by total synthesis. This is the first time that the conjugates of taurine with 3-indoleglyoxylic acid, quinoline-2-carboxylic acid and β-carboline-3-carboxylic acid present in stolonines A–C (1–3), respectively, have been reported. An immunofluorescence assay on PC3 cells indicated that compounds 1 and 3 increased cell size, induced mitochondrial texture elongation, and caused apoptosis in PC3 cells. PMID:26204949

Increasing taurine intake and taurine synthesis improves skeletal muscle function in the mdx mouse model for Duchenne muscular dystrophy

PubMed Central

Pinniger, Gavin J.; Graves, Jamie A.; Grounds, Miranda D.; Arthur, Peter G.

2016-01-01

Key points Duchenne muscular dystrophy (DMD) is a fatal muscle wasting disease associated with increased inflammation, oxidative stress and myofibre necrosis.Cysteine precursor antioxidants such as N‐acetyl cysteine (NAC) and l‐2‐oxothiazolidine‐4‐carboxylate (OTC) reduce dystropathology in the mdx mouse model for DMD, and we propose this is via increased synthesis of the amino acid taurine.We compared the capacity of OTC and taurine treatment to increase taurine content of mdx muscle, as well as effects on in vivo and ex vivo muscle function, inflammation and oxidative stress.Both treatments increased taurine in muscles, and improved many aspects of muscle function and reduced inflammation. Taurine treatment also reduced protein thiol oxidation and was overall more effective, as OTC treatment reduced body and muscle weight, suggesting some adverse effects of this drug.These data suggest that increasing dietary taurine is a better candidate for a therapeutic intervention for DMD. Abstract Duchenne muscular dystrophy (DMD) is a fatal muscle wasting disease for which there is no widely available cure. Whilst the mechanism of loss of muscle function in DMD and the mdx mouse model are not fully understood, disruptions in intracellular calcium homeostasis, inflammation and oxidative stress are implicated. We have shown that protein thiol oxidation is increased in mdx muscle, and that the indirect thiol antioxidant l‐2‐oxothiazolidine‐4‐carboxylate (OTC), which increases cysteine availability, decreases pathology and increases in vivo strength. We propose that the protective effects of OTC are a consequence of conversion of cysteine to taurine, which has itself been shown to be beneficial to mdx pathology. This study compares the efficacy of taurine with OTC in decreasing dystropathology in mdx mice by measuring in vivo and ex vivo contractile function and measurements of inflammation and protein thiol oxidation. Increasing the taurine content of mdx muscle improved both in vivo and ex vivo muscle strength and function, potentially via anti‐inflammatory and antioxidant effects of taurine. OTC treatment increased taurine synthesis in the liver and taurine content of mdx muscle, improved muscle function and decreased inflammation. However, OTC was less effective than taurine treatment, with OTC also decreasing body and EDL muscle weights, suggesting that OTC had some detrimental effects. These data support continued research into the use of taurine as a therapeutic intervention for DMD, and suggest that increasing dietary taurine is the better strategy for increasing taurine content and decreasing severity of dystropathology. PMID:26659826

Increasing taurine intake and taurine synthesis improves skeletal muscle function in the mdx mouse model for Duchenne muscular dystrophy.

PubMed

Terrill, Jessica R; Pinniger, Gavin J; Graves, Jamie A; Grounds, Miranda D; Arthur, Peter G

2016-06-01

Duchenne muscular dystrophy (DMD) is a fatal muscle wasting disease associated with increased inflammation, oxidative stress and myofibre necrosis. Cysteine precursor antioxidants such as N-acetyl cysteine (NAC) and l-2-oxothiazolidine-4-carboxylate (OTC) reduce dystropathology in the mdx mouse model for DMD, and we propose this is via increased synthesis of the amino acid taurine. We compared the capacity of OTC and taurine treatment to increase taurine content of mdx muscle, as well as effects on in vivo and ex vivo muscle function, inflammation and oxidative stress. Both treatments increased taurine in muscles, and improved many aspects of muscle function and reduced inflammation. Taurine treatment also reduced protein thiol oxidation and was overall more effective, as OTC treatment reduced body and muscle weight, suggesting some adverse effects of this drug. These data suggest that increasing dietary taurine is a better candidate for a therapeutic intervention for DMD. Duchenne muscular dystrophy (DMD) is a fatal muscle wasting disease for which there is no widely available cure. Whilst the mechanism of loss of muscle function in DMD and the mdx mouse model are not fully understood, disruptions in intracellular calcium homeostasis, inflammation and oxidative stress are implicated. We have shown that protein thiol oxidation is increased in mdx muscle, and that the indirect thiol antioxidant l-2-oxothiazolidine-4-carboxylate (OTC), which increases cysteine availability, decreases pathology and increases in vivo strength. We propose that the protective effects of OTC are a consequence of conversion of cysteine to taurine, which has itself been shown to be beneficial to mdx pathology. This study compares the efficacy of taurine with OTC in decreasing dystropathology in mdx mice by measuring in vivo and ex vivo contractile function and measurements of inflammation and protein thiol oxidation. Increasing the taurine content of mdx muscle improved both in vivo and ex vivo muscle strength and function, potentially via anti-inflammatory and antioxidant effects of taurine. OTC treatment increased taurine synthesis in the liver and taurine content of mdx muscle, improved muscle function and decreased inflammation. However, OTC was less effective than taurine treatment, with OTC also decreasing body and EDL muscle weights, suggesting that OTC had some detrimental effects. These data support continued research into the use of taurine as a therapeutic intervention for DMD, and suggest that increasing dietary taurine is the better strategy for increasing taurine content and decreasing severity of dystropathology. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

PPARα agonist fenofibrate attenuates TNF-α-induced CD40 expression in 3T3-L1 adipocytes via the SIRT1-dependent signaling pathway

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Weirong; Lin, Qinqin; Lin, Rong, E-mail: linrong63@yahoo.com.cn

2013-06-10

The ligand-activated transcription factor peroxisome proliferator-activated receptor-α (PPARα) participates in the regulation of cellular inflammation. More recent studies indicated that sirtuin1 (SIRT1), a NAD{sup +}-dependent deacetylase, regulates the inflammatory response in adipocytes. However, whether the role of PPARα in inflammation is mediated by SIRT1 remains unclear. In this study, we aimed to determine the effect of PPARα agonist fenofibrate on the expressions of SIRT1 and pro-inflammatory cytokine CD40 and underlying mechanisms in 3T3-L1 adipocytes. We found that fenofibrate inhibited CD40 expression and up-regulated SIRT1 expression in tumor necrosis factor-α (TNF-α)-stimulated adipocytes, and these effects of fenofibrate were reversed by PPARαmore » antagonist GW6471. Moreover, SIRT1 inhibitors sirtinol/nicotinamide (NAM) or knockdown of SIRT1 could attenuate the effect of fenofibrate on TNF-α-induced CD40 expression in adipocytes. Importantly, NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC) augmented the effect of fenofibrate on CD40 expression in adipocytes. Further study found that fenofibrate decreased the expression of acetylated-NF-κB p65 (Ac-NF-κB p65) in TNF-α-stimulated adipocytes, and the effect of fenofibrate was abolished by SIRT1 inhibition. In addition, fenofibrate up-regulated SIRT1 expression through AMPK in TNF-α-stimulated adipocytes. Taken together, these findings indicate that PPARα agonist fenofibrate inhibits TNF-α-induced CD40 expression in 3T3-L1 adipocytes via the SIRT1-dependent signaling pathway. -- Highlights: • Fenofibrate up-regulates SIRT1 expression in TNF-α-stimulated adipocytes. • Fenofibrate inhibits CD40 expression through SIRT1 in adipocytes. • The effects of fenofibrate on CD40 and SIRT1 expressions are dependent on PPARα. • Fenofibrate inhibits CD40 expression via SIRT1-dependent deacetylation of NF-κB. • Fenofibrate increases SIRT1 expression through PPARα and AMPK in adipocytes.« less

Amino acid neurotransmitter release and learning: a study of visual imprinting.

PubMed

Meredith, R M; McCabe, B J; Kendrick, K M; Horn, G

2004-01-01

The intermediate and medial part of the hyperstriatum ventrale (IMHV) is an area of the domestic chick forebrain that stores information acquired through the learning process of imprinting. The effects of visual imprinting on the release of the amino acids aspartate, arginine, citrulline, gamma-aminobutyric acid (GABA), glutamate, glycine and taurine from the left and right IMHVs in vitro were measured at 3.5, 10 and 24 h after training. Chicks were exposed to an imprinting stimulus for 1 h, their preferences measured 10 min afterward and a preference score calculated as a measure of the strength of learning. Potassium stimulation was used to evoke amino acid release from the IMHVs of trained and untrained chicks in the presence and absence of extracellular Ca2+. Ca2+-dependent, K+-evoked release of glutamate was significantly (34.4%) higher in trained than in untrained chicks. This effect was not influenced by time after training or by side (left or right IMHV). Training influenced the evoked release of GABA and taurine from the left IMHV at both 3.5 and 10 h. The training effects at the two times were statistically homogeneous so data (< or = 10 h group) were combined for each amino acid respectively. For this < or = 10 h group, evoked release increased significantly with preference score. In contrast, for the 24 h group, evoked release of GABA and taurine was not significantly correlated with preference score. There were no significant correlations between preference score and GABA or taurine release in the right IMHV at any time, nor in the absence of extracellular calcium. No significant effects of training condition, time or side were observed for any other amino acid in the study. The present findings suggest that soon after chicks have been exposed to an imprinting stimulus glutamatergic excitatory transmission in IMHV is enhanced, and remains enhanced for at least 24 h. In contrast, the learning-related elevations in taurine and GABA release are not sustained over this period. The change in GABA release may reflect a transient increase in inhibitory transmission in the left IMHV. Copyright 2004 IBRO

Amelioration of nandrolone decanoate-induced testicular and sperm toxicity in rats by taurine: effects on steroidogenesis, redox and inflammatory cascades, and intrinsic apoptotic pathway.

PubMed

Ahmed, Maha A E

2015-02-01

The wide abuse of the anabolic steroid nandrolone decanoate by athletes and adolescents for enhancement of sporting performance and physical appearance may be associated with testicular toxicity and infertility. On the other hand, taurine; a free β-amino acid with remarkable antioxidant activity, is used in taurine-enriched beverages to boost the muscular power of athletes. Therefore, the purpose of this study was to investigate the mechanisms of the possible protective effects of taurine on nandrolone decanoate-induced testicular and sperm toxicity in rats. To achieve this aim, male Wistar rats were randomly distributed into four groups and administered either vehicle, nandrolone decanoate (10mg/kg/week, I.M.), taurine (100mg/kg/day, p.o.) or combination of taurine and nandrolone decanoate, for 8 successive weeks. Results of the present study showed that taurine reversed nandrolone decanoate-induced perturbations in sperm characteristics, normalized serum testosterone level, and restored the activities of the key steroidogenic enzymes; 3β-HSD, and 17β-HSD. Moreover, taurine prevented nandrolone decanoate-induced testicular toxicity and DNA damage by virtue of its antioxidant, anti-inflammatory, and anti-apoptotic effects. This was evidenced by taurine-induced modulation of testicular LDH-x activity, redox markers (MDA, NO, GSH contents, and SOD activity), inflammatory indices (TNF-α, ICAM-1 levels, and MMP-9 gene expression), intrinsic apoptotic pathway (cytochrome c gene expression and caspase-3 content), and oxidative DNA damage markers (8-OHdG level and comet assay). In conclusion, at the biochemical and histological levels, taurine attenuated nandrolone decanoate-induced poor sperm quality and testicular toxicity in rats. Copyright © 2014 Elsevier Inc. All rights reserved.

Conversion of taurine into N-chlorotaurine (taurine chloramine) and sulphoacetaldehyde in response to oxidative stress.

PubMed

Cunningham, C; Tipton, K F; Dixon, H B

1998-03-01

N-Chlorotaurine (taurine chloramine), formed by treating taurine with hypochlorous acid, was shown to decompose to sulphoacetaldehyde with a first-order rate constant of 9.9+/-0.5 x 10(-4).h-1 at 37 degrees C in 0.1 M phosphate buffer, pH 7.4. Rat liver homogenates accelerated this decay in a process that was proportional to tissue-protein concentration and saturable, with maximum velocity (Vmax) and Km values of 0.28+/-0.01 nmol/min per mg of protein and 37+/-9 microM respectively. This activity was found to be lost on heat denaturation, but retained after dialysis. There was no detectable formation of sulphoacetaldehyde when taurine itself was incubated with the tissue homogenates under the same conditions. Activation of human neutrophils (1.67 x 10(6) cells/ml) with latex beads resulted in a respiratory burst of oxygen-radical production, the products of which were partially sequestered by 12.5 mM taurine. Under these conditions sulphoacetaldehyde was generated at a constant rate of 637+/-18 pmol/h per ml for over 7 h. A non-activated neutrophil suspension contained constant levels of 1.42+/-0.02 nmol/ml sulphoacetaldehyde, as did activated cells incubated in the absence of taurine, a basal level which may indicate a steady turnover of taurine in these cells. Such formation of chlorotaurine and its decay to the aldehyde may be the first steps in the metabolism of taurine to isethionate (2-hydroxyethanesulphonate) that has been demonstrated by various authors to occur in vivo.

Amelioration of nandrolone decanoate-induced testicular and sperm toxicity in rats by taurine: Effects on steroidogenesis, redox and inflammatory cascades, and intrinsic apoptotic pathway

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ahmed, Maha A.E., E-mail: mahapharm@yahoo.com

The wide abuse of the anabolic steroid nandrolone decanoate by athletes and adolescents for enhancement of sporting performance and physical appearance may be associated with testicular toxicity and infertility. On the other hand, taurine; a free β-amino acid with remarkable antioxidant activity, is used in taurine-enriched beverages to boost the muscular power of athletes. Therefore, the purpose of this study was to investigate the mechanisms of the possible protective effects of taurine on nandrolone decanoate-induced testicular and sperm toxicity in rats. To achieve this aim, male Wistar rats were randomly distributed into four groups and administered either vehicle, nandrolone decanoatemore » (10 mg/kg/week, I.M.), taurine (100 mg/kg/day, p.o.) or combination of taurine and nandrolone decanoate, for 8 successive weeks. Results of the present study showed that taurine reversed nandrolone decanoate-induced perturbations in sperm characteristics, normalized serum testosterone level, and restored the activities of the key steroidogenic enzymes; 3β-HSD, and 17β-HSD. Moreover, taurine prevented nandrolone decanoate-induced testicular toxicity and DNA damage by virtue of its antioxidant, anti-inflammatory, and anti-apoptotic effects. This was evidenced by taurine-induced modulation of testicular LDH-x activity, redox markers (MDA, NO, GSH contents, and SOD activity), inflammatory indices (TNF-α, ICAM-1 levels, and MMP-9 gene expression), intrinsic apoptotic pathway (cytochrome c gene expression and caspase-3 content), and oxidative DNA damage markers (8-OHdG level and comet assay). In conclusion, at the biochemical and histological levels, taurine attenuated nandrolone decanoate-induced poor sperm quality and testicular toxicity in rats. - Highlights: • Nandrolone decanoate (ND) disrupts sperm profile and steroidogenesis in rats. • ND upregulates gene expression of inflammatory and apoptotic markers. • Taurine normalizes sperm profile and serum testosterone level in ND-treated rats. • Taurine prevents ND-induced testicular toxicity and DNA damage. • Taurine shows antioxidant, anti-inflammatory, and anti-apoptotic effects.« less

Gemfibrozil and fenofibrate, Food and Drug Administration-approved lipid-lowering drugs, up-regulate tripeptidyl-peptidase 1 in brain cells via peroxisome proliferator-activated receptor α: implications for late infantile Batten disease therapy.

PubMed

Ghosh, Arunava; Corbett, Grant T; Gonzalez, Frank J; Pahan, Kalipada

2012-11-09

The classical late infantile neuronal ceroid lipofuscinosis (LINCLs) is an autosomal recessive disease, where the defective gene is Cln2, encoding tripeptidyl-peptidase I (TPP1). At the molecular level, LINCL is caused by accumulation of autofluorescent storage materials in neurons and other cell types. Currently, there is no established treatment for this fatal disease. This study reveals a novel use of gemfibrozil and fenofibrate, Food and Drug Administration-approved lipid-lowering drugs, in up-regulating TPP1 in brain cells. Both gemfibrozil and fenofibrate up-regulated mRNA, protein, and enzymatic activity of TPP1 in primary mouse neurons and astrocytes as well as human astrocytes and neuronal cells. Because gemfibrozil and fenofibrate are known to activate peroxisome proliferator-activated receptor-α (PPARα), the role of PPARα in gemfibrozil- and fenofibrate-mediated up-regulation of TPP1 was investigated revealing that both drugs up-regulated TPP1 mRNA, protein, and enzymatic activity both in vitro and in vivo in wild type (WT) and PPARβ(-/-), but not PPARα(-/-), mice. In an attempt to delineate the mechanism of TPP1 up-regulation, it was found that the effects of the fibrate drugs were abrogated in the absence of retinoid X receptor-α (RXRα), a molecule known to form a heterodimer with PPARα. Accordingly, all-trans-retinoic acid, alone or together with gemfibrozil, up-regulated TPP1. Co-immunoprecipitation and ChIP studies revealed the formation of a PPARα/RXRα heterodimer and binding of the heterodimer to an RXR-binding site on the Cln2 promoter. Together, this study demonstrates a unique mechanism for the up-regulation of TPP1 by fibrate drugs via PPARα/RXRα pathway.

Gemfibrozil and Fenofibrate, Food and Drug Administration-approved Lipid-lowering Drugs, Up-regulate Tripeptidyl-peptidase 1 in Brain Cells via Peroxisome Proliferator-activated Receptor α

PubMed Central

Ghosh, Arunava; Corbett, Grant T.; Gonzalez, Frank J.; Pahan, Kalipada

2012-01-01

The classical late infantile neuronal ceroid lipofuscinosis (LINCLs) is an autosomal recessive disease, where the defective gene is Cln2, encoding tripeptidyl-peptidase I (TPP1). At the molecular level, LINCL is caused by accumulation of autofluorescent storage materials in neurons and other cell types. Currently, there is no established treatment for this fatal disease. This study reveals a novel use of gemfibrozil and fenofibrate, Food and Drug Administration-approved lipid-lowering drugs, in up-regulating TPP1 in brain cells. Both gemfibrozil and fenofibrate up-regulated mRNA, protein, and enzymatic activity of TPP1 in primary mouse neurons and astrocytes as well as human astrocytes and neuronal cells. Because gemfibrozil and fenofibrate are known to activate peroxisome proliferator-activated receptor-α (PPARα), the role of PPARα in gemfibrozil- and fenofibrate-mediated up-regulation of TPP1 was investigated revealing that both drugs up-regulated TPP1 mRNA, protein, and enzymatic activity both in vitro and in vivo in wild type (WT) and PPARβ−/−, but not PPARα−/−, mice. In an attempt to delineate the mechanism of TPP1 up-regulation, it was found that the effects of the fibrate drugs were abrogated in the absence of retinoid X receptor-α (RXRα), a molecule known to form a heterodimer with PPARα. Accordingly, all-trans-retinoic acid, alone or together with gemfibrozil, up-regulated TPP1. Co-immunoprecipitation and ChIP studies revealed the formation of a PPARα/RXRα heterodimer and binding of the heterodimer to an RXR-binding site on the Cln2 promoter. Together, this study demonstrates a unique mechanism for the up-regulation of TPP1 by fibrate drugs via PPARα/RXRα pathway. PMID:22989886

Selection of nutrients for prevention or amelioration of lead-induced learning and memory impairment in rats.

PubMed

Fan, Guangqin; Feng, Chang; Li, Yu; Wang, Chunhong; Yan, Ji; Li, Wei; Feng, Jiangao; Shi, Xianglin; Bi, Yongyi

2009-06-01

We carried out animal experiments based on the orthogonal design L(8)(2(7)) setting seven factors with two different levels of each and 10 groups of rats. The nutrients tested were tyrosine, glycine, methionine, taurine, ascorbic acid, thiamine and zinc. The objective of this study was to explore the optimal combinations of nutrients for prevention or amelioration of lead-induced learning and memory impairment. Rats were supplemented with nutrients by gavage once a day in two experiments: one was simultaneous nutrient supplementation with lead acetate administration (800 mg l(-1)) for 8 weeks (prophylactic supplementation) and the other was nutrient supplementation for 4 weeks after the cessation of 4 weeks of lead administration (remedial supplementation). Morris water maze was initiated at ninth week. Rats were terminated for assays of levels of Pb in blood, activities of superoxide dismutase (SOD) and nitric oxide synthase (NOS) in hippocampus, levels of nitric oxide (NO) in hippocampus and expressions of Ca2+/calmodulin-dependent protein kinase II (CaMKII) and cyclic adenosine monophosphate (cAMP) response element-binding protein messenger RNA in hippocampus. Results showed that in prophylactic supplementation, methionine, taurine, zinc, ascorbic acid and glycine were the effective preventive factors for decreasing prolonged escape latency, increasing SOD and NOS activities and NO levels in the hippocampus, respectively. On the other hand, in remedial supplementation, taurine was the effective factor for reversing Pb-induced decrease in activities of SOD, NOS and levels of NO. In conclusion, the optimum combinations of nutrients appear to be methionine, taurine, zinc, ascorbic acid and glycine for the prevention of learning and memory impairment, while taurine and thiamine appear to be the effective factors for reversing Pb neurotoxicity.

Investigating the correlation between in vivo absorption and in vitro release of fenofibrate from lipid matrix particles in biorelevant medium.

PubMed

Borkar, Nrupa; Xia, Dengning; Holm, René; Gan, Yong; Müllertz, Anette; Yang, Mingshi; Mu, Huiling

2014-01-23

Lipid matrix particles (LMP) may be used as better carriers for poorly water-soluble drugs than liquid lipid carriers because of reduced drug mobilization in the formulations. However, the digestion process of solid lipid particles and their effect on the absorption of poorly water-soluble drugs are not fully understood. This study aimed at investigating the effect of particle size of LMP on drug release in vitro as well as absorption in vivo in order to get a better understanding on the effect of degradation of lipid particles on drug solubilisation and absorption. Fenofibrate, a model poorly water-soluble drug, was incorporated into LMP in this study using probe ultrasound sonication. The resultant LMP were characterised in terms of particle size, size distribution, zeta potential, entrapment efficiency, in vitro lipolysis and in vivo absorption in rat model. LMP of three different particle sizes i.e. approximately 100 nm, 400 nm, and 10 μm (microparticles) were produced with high entrapment efficiencies. The in vitro lipolysis study showed that the recovery of fenofibrate in the aqueous phase for 100 nm and 400 nm LMP was significantly higher (p<0.05) than that of microparticles after 30 min of lipolysis, suggesting that nano-sized LMP were digested to a larger extent due to greater specific surface area. The 100 nm LMP showed faster initial digestion followed by 400 nm LMP and microparticles. The area under the plasma concentration-time curve (AUC) following oral administration of 100 nm LMP was significantly higher (p<0.01) than that of microparticles and fenofibrate crystalline suspension (control). However, no significant difference was observed between the AUCs of 100 nm and 400 nm LMP. The same rank order on the in vivo absorption and the in vitro response was observed. The recovery (%) of fenofibrate partitioning into the aqueous phase during in vitro lipolysis and the AUC of plasma concentration-time curve of fenofibric acid was in the order of 100 nm LMP>microparticles>control. In summary, the present study demonstrated the particle size dependence of bioavailability of fenofibrate loaded LMP in rat model which correlates well with the in vitro drug release performed in the biorelevant medium. Copyright © 2013 Elsevier B.V. All rights reserved.

Volume-activated trimethylamine oxide efflux in red blood cells of spiny dogfish (Squalus acanthias).

PubMed

Koomoa, D L; Musch, M W; MacLean, A V; Goldstein, L

2001-09-01

The aims of this study were to determine the pathway of swelling-activated trimethylamine oxide (TMAO) efflux and its regulation in spiny dogfish (Squalus acanthias) red blood cells and compare the characteristics of this efflux pathway with the volume-activated osmolyte (taurine) channel present in erythrocytes of fishes. The characteristics of the TMAO efflux pathway were similar to those of the taurine efflux pathway. The swelling-activated effluxes of both TMAO and taurine were significantly inhibited by known anion transport inhibitors (DIDS and niflumic acid) and by the general channel inhibitor quinine. Volume expansion by hypotonicity, ethylene glycol, and diethyl urea activated both TMAO and taurine effluxes similarly. Volume expansion by hypotonicity, ethylene glycol, and diethyl urea also stimulated the activity of tyrosine kinases p72syk and p56lyn, although the stimulations by the latter two treatments were less than by hypotonicity. The volume activations of both TMAO and taurine effluxes were inhibited by tyrosine kinase inhibitors, suggesting that activation of tyrosine kinases may play a role in activating the osmolyte effluxes. These results indicate that the volume-activated TMAO efflux occurs via the organic osmolyte (taurine) channel and may be regulated by the volume activation of tyrosine kinases.

New Fixed-Dose Combinations of Fenofibrate/Simvastatin Therapy Significantly Improve the Lipid Profile of High-Risk Patients with Mixed Dyslipidemia Versus Monotherapies.

PubMed

Foucher, Christelle; Aubonnet, Patrick; Reichert, Petr; Berli, Mario; Schaeffer, Axel; Calvo Vargas, Cesar Gonzalo; Lochocka, Anna; Belenky, Dmitry; Koch, Hans-Friedrich

2015-12-01

Guidelines propose additional therapy to statin to treat elevated triglycerides (TG) and low high-density lipoprotein cholesterol (HDLC) in dyslipidemic patients. We evaluated the effects of new fixed-dose combinations (FDC) of fenofibrate/simvastatin on plasma lipids versus simvastatin or fenofibrate monotherapies. Subjects with mixed dyslipidemia at high or very high cardiovascular risk on stable statin therapy for at least 3 months were included in a randomized, double-blind, active-control, parallel-group study. Patients were treated with FDC fenofibrate/simvastatin 145/20 mg or 145/40 mg, simvastatin 20 mg or 40 mg, or fenofibrate 145 mg for 12 weeks. Plasma lipids, C-reactive protein, and cystatin C were measured before and after treatments. Differences in % changes were compared between FDC fenofibrate/simvastatin and monotherapies. Significant differences between FDC fenofibrate/simvastatin and simvastatin monotherapies were observed for the % change of TG (LS mean difference [two-sided 95% CI]: -32.2% [-38.6%, -25.8%], P < 0.001) and HDL-C (7.5% [4.7%, 10.2%], P < 0.001). A significant difference between the FDC fenofibrate/simvastatin and fenofibrate was observed for LDLC % changes (-34.7% [-40.8%, -28.5%], P < 0.001). Significant differences between FDC fenofibrate/simvastatin and their respective monotherapies were also observed for Apo B and non-HDLC % changes. The FDC were well tolerated with a similar safety profile compared with monotherapies. FDC fenofibrate/simvastatin are effective and well-tolerated therapies to improve the TG and HDLC profile in high-risk patients with mixed dyslipidemia. © 2015 John Wiley & Sons Ltd.

Release of endogenous amino acids from the hippocampus and brain stem from developing and adult mice in ischemia.

PubMed

Oja, Simo S; Saransaari, Pirjo

2009-09-01

The release of neurotransmitters and modulators has been studied mostly using labeled preloaded compounds. For several reasons, however, the estimated release may not reliably reflect the release of endogenous compounds. The basal and K(+)-evoked release of the neuroactive endogenous amino acids GABA, glycine, taurine, L-glutamate and L-aspartate was now studied in slices from the hippocampus and brain stem from 7-day-old and 3-month-old mice under control and ischemic conditions. The release of synaptically not active L-glutamine, L-alanine, L-threonine and L-serine was assessed for comparison. The estimates for the hippocampus and brainstem were markedly different and also different in developing and adult mice. GABA release was much greater in 3-month-old than in 7-day-old mice, whereas with taurine the situation was the opposite, in the hippocampus in particular. K(+) stimulation enhanced glycine release more in the mature than immature brain stem while in the hippocampus the converse was observed. Ischemia enhanced the release of all neuroactive amino acids in both brain regions, the effects being relatively most pronounced in the case of GABA, aspartate and glutamate in the hippocampus in 3-month-old mice, and taurine in 7-day-old and glycine in 3-month-old mice in the brain stem. These results are qualitatively similar to those obtained on earlier experiments with labeled preloaded amino acids. However, the magnitudes of the release cannot be quite correctly estimated using radioactive labels. In developing mice only taurine release may counteract the harmful effects of excitatory amino acids in ischemia in both hippocampus and brain stem.

Taurine protects HK-2 cells from oxidized LDL-induced cytotoxicity via the ROS-mediated mitochondrial and p53-related apoptotic pathways.

PubMed

Chang, Chun-Yu; Shen, Chao-Yu; Kang, Chao-Kai; Sher, Yuh-Pyng; Sheu, Wayne H-H; Chang, Chia-Che; Lee, Tsung-Han

2014-09-15

Oxidized LDL (oxLDL) induces a pro-oxidative environment and promotes apoptosis, causing the progression of renal diseases in humans. Taurine is a semi-essential amino acid in mammals and has been shown to be a potent endogenous antioxidant. The kidney plays a pivotal role in maintaining the balance of taurine. However, the mechanisms underlying the protective effects of taurine against oxLDL-induced injury in renal epithelial cells have not been clarified. In the present study, we investigated the anti-apoptotic effects of taurine on human proximal tubular epithelial (HK-2) cells exposed to oxLDL and explored the related mechanisms. We observed that oxLDL increased the contents of ROS and of malondialdehyde (MDA), which is a lipid peroxidation by-product that acts as an indicator of the cellular oxidation status. In addition, oxLDL induced cell death and apoptosis in HK-2 cells. Pretreatment with taurine at 100 μM significantly attenuated the oxLDL-induced cytotoxicity. We determined that oxLDL triggered the phosphorylation of ERK and, in turn, the activation of p53 and other apoptosis-related events, including calcium accumulation, destabilization of the mitochondrial permeability and disruption of the balance between pro-apoptotic Bax and anti-apoptotic Bcl-2 proteins. The malfunctions induced by oxLDL were effectively blocked by taurine. Thus, our results suggested that taurine exhibits potential therapeutic activity by preventing oxLDL-induced nephrotoxicity. The inhibition of oxLDL-induced epithelial apoptosis by taurine was at least partially due to its anti-oxidant activity and its ability to modulate the ERK and p53 apoptotic pathways. Copyright © 2014 Elsevier Inc. All rights reserved.

Involvement of metabotropic glutamate receptors in taurine release in the adult and developing mouse hippocampus.

PubMed

Saransaari, P; Oja, S S

1999-01-01

The inhibitory amino acid taurine has been held to function as an osmoregulator and modulator of neural activity, being particularly important in the immature brain. Ionotropic glutamate receptor agonists are known markedly to potentiate taurine release. The effects of different metabotropic glutamate receptor (mGluR) agonists and antagonists on the basal and K(+)-stimulated release of [3H]taurine from hippocampal slices from 3-month-old (adult) and 7-day-old mice were now investigated using a superfusion system. Of group I metabotropic glutamate receptor agonists, quisqualate potentiated basal taurine release in both age groups, more markedly in the immature hippocampus. This action was not antagonized by the specific antagonists of group I but by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and 6-nitro-7-sulphamoylbenzo[f]quinoxaline-2,3-dione (NBQX), which would suggest an involvement of ionotropic glutamate receptors. (S)-3,5-dihydroxyphenylglycine (DHPG) potentiated the basal release by a receptor-mediated mechanism in the immature hippocampus. The group II agonist (2S, 2'R, 3'R)-2-(2',3'-dicarboxycyclopropyl)glycine (DCG IV) markedly potentiated basal taurine release at both ages. These effects were antagonized by dizocilpine, indicating again the participation of ionotropic receptors. Group III agonists slightly potentiated basal taurine release, as did several antagonists of the three metabotropic receptor groups. Potassium-stimulated (50 mM K+) taurine release was generally significantly reduced by mGluR agents, mainly by group I and II compounds. This may be harmful to neurons in hyperexcitatory states. On the other hand, the potentiation by mGluRs of basal taurine release, particularly in the immature hippocampus, together with the earlier demonstrated pronounced enhancement by activation of ionotropic glutamate receptors, may protect neurons against excitotoxicity.

Quantification of taurine in energy drinks using ¹H NMR.

PubMed

Hohmann, Monika; Felbinger, Christine; Christoph, Norbert; Wachter, Helmut; Wiest, Johannes; Holzgrabe, Ulrike

2014-05-01

The consumption of so called energy drinks is increasing, especially among adolescents. These beverages commonly contain considerable amounts of the amino sulfonic acid taurine, which is related to a magnitude of various physiological effects. The customary method to control the legal limit of taurine in energy drinks is LC-UV/vis with postcolumn derivatization using ninhydrin. In this paper we describe the quantification of taurine in energy drinks by (1)H NMR as an alternative to existing methods of quantification. Variation of pH values revealed the separation of a distinct taurine signal in (1)H NMR spectra, which was applied for integration and quantification. Quantification was performed using external calibration (R(2)>0.9999; linearity verified by Mandel's fitting test with a 95% confidence level) and PULCON. Taurine concentrations in 20 different energy drinks were analyzed by both using (1)H NMR and LC-UV/vis. The deviation between (1)H NMR and LC-UV/vis results was always below the expanded measurement uncertainty of 12.2% for the LC-UV/vis method (95% confidence level) and at worst 10.4%. Due to the high accordance to LC-UV/vis data and adequate recovery rates (ranging between 97.1% and 108.2%), (1)H NMR measurement presents a suitable method to quantify taurine in energy drinks. Copyright © 2013 Elsevier B.V. All rights reserved.

Lack of effect of bezafibrate and fenofibrate on the pharmacokinetics and pharmacodynamics of repaglinide

PubMed Central

Kajosaari, Lauri I; Backman, Janne T; Neuvonen, Mikko; Laitila, Jouko; Neuvonen, Pertti J

2004-01-01

Aims Gemfibrozil markedly increases the plasma concentrations and blood glucose-lowering effects of repaglinide, but the effects of other fibrates on repaglinide pharmacokinetics are not known. Our aim was to investigate the effects of bezafibrate and fenofibrate on the pharmacokinetics and pharmacodynamics of repaglinide. Methods In a randomized, three-phase cross-over study, 12 healthy subjects received 400 mg bezafibrate, 200 mg fenofibrate or placebo once daily for 5 days. On day 5, a single 0.25 mg dose of repaglinide was ingested 1 h after the last pretreatment dose. The concentrations of plasma repaglinide, bezafibrate and fenofibrate and blood glucose were measured up to 7 h postdose. Results During the bezafibrate and fenofibrate phases, the total area under the concentration-time curve [AUC(0,∞)] of repaglinide was 99% (95% confidence interval of the ratio to the control phase 73, 143%) and 99% (85, 127%) of the corresponding value during the placebo (control) phase, respectively. Bezafibrate and fenofibrate had no significant effect on the peak concentration (Cmax) of repaglinide. The mean half-life of repaglinide was 1.3 h in all phases. The blood glucose-lowering effect of repaglinide was not affected by bezafibrate or fenofibrate. The AUC(0,8 h) values for bezafibrate and fenofibrate varied 3.0-fold and 4.4-fold between individual subjects, respectively. Neither bezafibrate nor fenofibrate affected the pharmacokinetic variables of repaglinide. Conclusions Bezafibrate and fenofibrate do not affect the pharmacokinetics or pharmacodynamics of repaglinide. PMID:15373931

Extracellular levels of amino acids and choline in human high grade gliomas: an intraoperative microdialysis study.

PubMed

Bianchi, L; De Micheli, E; Bricolo, A; Ballini, C; Fattori, M; Venturi, C; Pedata, F; Tipton, K F; Della Corte, L

2004-01-01

The concentrations of endogenous amino acids and choline in the extracellular fluid of human cerebral gliomas have been measured, for the first time, by in vivo microdialysis. Glioblastoma growth was associated with increased concentrations of choline, GABA, isoleucine, leucine, lysine, phenylalanine, taurine, tyrosine, and valine. There was no difference between grade III and grade IV tumors in the concentrations of phenylalanine, isoleucine, tyrosine, valine, and lysine, whereas the concentrations of choline, aspartate, taurine, GABA, leucine, and glutamate were significantly different in the two tumor-grade subgroups. In contrast to the other compounds, the concentration of glutamate was decreased in glioma. The parenchyma adjacent to the tumor showed significant changes only in the extracellular concentration of glutamate, isoleucine, and valine. The concentrations of choline and the amino acids, glutamate, leucine, taurine, and tyrosine showed significant positive correlations with the degree of cell proliferation. Epilepsy, which is relatively common in subjects with gliomas, was shown to be a significant confounding variable when the extracellular concentrations of aspartate, glutamate and GABA were considered.

Characterization of N-methyl-D-aspartate-evoked taurine release in the developing and adult mouse hippocampus.

PubMed

Saransaari, P; Oja, S S

2003-01-01

Taurine is an inhibitory amino acid acting as an osmoregulator and neuroromodulator in the brain, with neuroprotective properties. The ionotropic glutamate receptor agonist N-methyl-D-aspartate (NMDA) greatly potentiates taurine release from brain preparations in both normal and ischemic conditions, the effect being particularly marked in the developing hippocampus. We now characterized the regulation of NMDA-stimulated taurine release from hippocampal slices from adult (3-month-old) and developing (7-day-old) mouse using a superfusion system. The NMDA-stimulated taurine release was receptor-mediated in both adult and developing mouse hippocampus. In adults, only NO-generating compounds, sodium nitroprusside, S-nitroso-N-acetylpenicillamine and hydroxylamine reduced the release, as did also NO synthase inhibitors, 7-nitroindazole and nitroarginine, indicating that the release is mediated by the NO/cGMP pathway. On the other hand, the regulation of the NMDA-evoked taurine release proved to be somewhat complex in the immature hippocampus. It was not affected by the NOergic compounds, but enhanced by the protein kinase C activator 4 beta-phorbol 12-myristate 13-acetate and adenosine receptor A(1) agonists, N(6)-cyclohexyladenosine and R(-)N(6)-(2-phenylisopropyl)adenosine in a receptor-mediated manner. The activation of both ionotropic 2-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors and metabotropic glutamate group I receptors also enhanced the evoked release. The NMDA-receptor-stimulated taurine release could be a part of the neuroprotective properties of taurine, being important particularly under cell-damaging conditions in the developing hippocampus and hence preventing excitotoxicity.

Taurine ameliorated thyroid function in rats co-administered with chlorpyrifos and lead.

PubMed

Akande, Motunrayo Ganiyat; Shittu, Muftau; Uchendu, Chidiebere; Yaqub, Lukuman Surakat

2016-12-01

Chlorpyrifos is a widely used organophosphate insecticide for domestic, agricultural and industrial purposes. Lead is a toxic heavy metal and it is used for domestic and industrial purposes. Taurine is a semi essential amino acid with bioprotective properties. The aim of this study was to investigate the effects of taurine on thyroid function in Wistar rats co-administered with chlorpyrifos and lead. The rats were divided into 5 groups of 10 rats each. The first two groups were administered with distilled water and soya oil (1 ml/kg) respectively. The other groups received taurine (50 mg/kg), chlorpyrifos + lead [chlorpyrifos (4.25 mg/kg, 1/20 median lethal dose] and lead (233.25 mg/kg, 1/20 median lethal dose) and taurine + chlorpyrifos + lead respectively. The treatments were administered once daily by oral gavage for 16 weeks. The rats were euthanized after the completion of the study and the thyroid function and thyroid histoarchitecture were evaluated. The results revealed that co-administration of chlorpyrifos and lead to the rats induced perturbations in thyroid function and this was manifested by reductions in the concentrations of triiodothyronine and thyroxine, increased thyroid stimulating hormone concentration and degeneration of the follicular epithelia of the thyroid gland. Taurine alleviated the perturbations in thyroid function and improved thyroid gland histoarchitecture. The beneficial effects of taurine may be attributed to its ability to protect the body from toxicity and oxidative stress. Taurine may be useful for prophylaxis against disruptions in thyroid function in animals that are exposed to environmental chlorpyrifos and lead.

Taurine supplementation of plant derived protein 1 and n-3 fatty acids are critical for optimal growth and development of cobia, rachycentron canadum

USDA-ARS?s Scientific Manuscript database

We examined growth performance and lipid content in juvenile cobia, Rachycentron canadum, fed a taurine supplemented (1.5%), plant protein based diet with two fish oil replacements. The first fish oil replacement was a thraustochytrid meal (TM+SOY) plus soybean oil (~9% CL) and the second was a cano...

Formulation and Solid State Characterization of Nicotinamide-based Co-crystals of Fenofibrate

PubMed Central

Shewale, Sheetal; Shete, A. S.; Doijad, R. C.; Kadam, S. S.; Patil, V. A.; Yadav, A. V.

2015-01-01

The present investigation deals with formulation of nicotinamide-based co-crystals of fenofibrate by different methods and solid-state characterization of the prepared co-crystals. Fenofibrate and nicotinamide as a coformer in 1:1 molar ratio were used to formulate molecular complexes by kneading, solution crystallization, antisolvent addition and solvent drop grinding methods. The prepared molecular complexes were characterized by powder X-ray diffractometry, differential scanning calorimetry, Fourier transform infrared spectroscopy, nuclear magnetic resonance spectroscopy and in vitro dissolution study. Considerable improvement in the dissolution rate of fenofibrate from optimized co-crystal formulation was due to an increased solubility that is attributed to the super saturation from the fine co-crystals is faster because of large specific surface area of small particles and prevention of phase transformation to pure fenofibrate. In vitro dissolution study showed that the formation of co-crystals improves the dissolution rate of fenofibrate. Nicotinamide forms the co-crystals with fenofibrate, theoretically and practically. PMID:26180279

Indications and contraindications for infusing specific amino acids (leucine, glutamine, arginine, citrulline, and taurine) in critical illness.

PubMed

Ginguay, Antonin; De Bandt, Jean-Pascal; Cynober, Luc

2016-03-01

The review assesses the utility of supplementing parenteral or enteral nutrition of ICU patients with each of five specific amino acids that display pharmacological properties. Specifying indications implies also stating contraindications.Combined supplementation of amino acids with ω3-fatty acids and/or trace elements (immune-enhancing diets) will not be considered in this review because these mixtures do not allow the role of amino acids in the effect (positive or negative) of the mixture to be isolated, and so cannot show whether or not supplementation of a given amino acid is indicated. After decades of unbridled use of glutamine (GLN) supplementation in critically ill patients, recent large trials have brought a note of caution, indicating for example that GLN should not be used in patients with multiple organ failure. Yet these large trials do not change the conclusions of recent meta-analyses. Arginine (ARG), as a single dietary supplement, is probably not harmful in critical illness, in particular in a situation of ARG deficiency syndrome with low nitric oxide production. Citrulline supplementation strongly improves microcirculation in animal models with gut injury, but clinical studies are lacking. Taurine has a potent protective effect against ischemic reperfusion injury. Amino acid-based pharmaconutrition has displayed familiar 'big project' stages: enthusiasm (citrulline and taurine), doubt (GLN), hunt for the guilty (ARG), and backpedalling (leucine). Progress in this field is very slow, and sometimes gives way to retreat, as demonstrated by recent large trials on GLN supplementation.

Study on the interaction of plasma protein binding rate between edaravone and taurine in human plasma based on HPLC analysis coupled with ultrafiltration technique.

PubMed

Tang, Dao-quan; Li, Yin-jie; Li, Zheng; Bian, Ting-ting; Chen, Kai; Zheng, Xiao-xiao; Yu, Yan-yan; Jiang, Shui-shi

2015-08-01

In this work, two high-performance liquid chromatography (HPLC) assays were developed and validated for the independent determination of edaravone and taurine using 3-methyl-1-p-tolyl-5-pyrazolone and L-glutamine as internal standards. In in vitro experiments, human plasma was separately spiked with a mixture of edaravone and taurine, edaravone or taurine alone. Plasma was precipitated with acetonitrile containing 0.1% formic acid. Ultrafiltration was employed to obtain the unbound ingredients of the two drugs. The factors that might influence the ultrafiltration effiency were elaborately optimized. Plasma supernatant and ultrafiltrate containing taurine were derivated with o-phthalaldehyde and ethanethiol in the presence of 40 mmol/L sodium borate buffer (pH 10.2) at room temperature within 1 min. Chromatographic separations were achieved on an InertSustain C18 column (250 × 4.6 mm, 5 µm). Isocratic 50 mmol/L ammonium acetate-acetonitrile and gradient 50 mmol/L sodium acetate (pH 5.3)-methanol were respectively selected as the mobile phase for the determination of edaravone and taurine. All of the validation data including linearity, extraction recovery, precision, accuracy and stability conformed to the requirements. Results showed that there were no significant alterations in the plasma protein binding rate of taurine and edaravone, implying that the proposed combination therapy was pharmacologically feasible. Copyright © 2014 John Wiley & Sons, Ltd.

Impact of taurine depletion on glucose control and insulin secretion in mice.

PubMed

Ito, Takashi; Yoshikawa, Natsumi; Ito, Hiromi; Schaffer, Stephen W

2015-09-01

Taurine, an endogenous sulfur-containing amino acid, is found in millimolar concentrations in mammalian tissue, and its tissue content is altered by diet, disease and aging. The effectiveness of taurine administration against obesity and its related diseases, including type 2 diabetes, has been well documented. However, the impact of taurine depletion on glucose metabolism and fat deposition has not been elucidated. In this study, we investigated the effect of taurine depletion (in the taurine transporter (TauT) knockout mouse model) on blood glucose control and high fat diet-induced obesity. TauT-knockout (TauTKO) mice exhibited lower body weight and abdominal fat mass when maintained on normal chow than wild-type (WT) mice. Blood glucose disposal after an intraperitoneal glucose injection was faster in TauTKO mice than in WT mice despite lower serum insulin levels. Islet beta-cells (insulin positive area) were also decreased in TauTKO mice compared to WT mice. Meanwhile, overnutrition by high fat (60% fat)-diet could lead to obesity in TauTKO mice despite lower body weight under normal chow diet condition, indicating nutrition in normal diet is not enough for TauTKO mice to maintain body weight comparable to WT mice. In conclusion, taurine depletion causes enhanced glucose disposal despite lowering insulin levels and lower body weight, implying deterioration in tissue energy metabolism. Copyright © 2015 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Discovery of peroxisome proliferator-activated receptor α (PPARα) activators with a ligand-screening system using a human PPARα-expressing cell line.

PubMed

Tachibana, Keisuke; Yuzuriha, Tomohiro; Tabata, Ryotaro; Fukuda, Syohei; Maegawa, Takashi; Takahashi, Rika; Tanimoto, Keiichi; Tsujino, Hirofumi; Nunomura, Kazuto; Lin, Bangzhong; Matsuura, Yoshiharu; Tanaka, Toshiya; Hamakubo, Takao; Sakai, Juro Js; Kodama, Tatsuhiko; Kobayashi, Tadayuki; Ishimoto, Kenji; Miyachi, Hiroyuki; Doi, Takefumi

2018-05-15

Peroxisome proliferator-activated receptor alpha (PPARα) is a ligand-activated transcription factor that belongs to the superfamily of nuclear hormone receptors. PPARα is mainly expressed in the liver, where it activates fatty acid oxidation and lipoprotein metabolism and improves plasma lipid profiles. Therefore, PPARα activators are often used to treat patients with dyslipidemia. To discover additional PPARα activators as potential compounds for use in hypolipidemic drugs, here we established human hepatoblastoma cell lines with luciferase reporter expression from the promoters containing peroxisome proliferator responsive elements (PPRE) and tetracycline-regulated expression of full-length human PPARα to quantify the effects of chemical ligands on PPARα activity. Using the established cell-based PPARα-activator screening system to screen a library of > 12,000 chemical compounds, we identified several hit compounds with basic chemical skeletons different from those of known PPARα agonists. One of the hit compounds, a 1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid derivative we termed compound 3, selectively up-regulated PPARα transcriptional activity, leading to PPARα target gene expression both in vitro and in vivo. Of note, the half-maximal effective concentrations of the hit compounds were lower than that of the known PPARα ligand fenofibrate. Finally, fenofibrate or compound 3 treatment of high fructose-fed rats having elevated plasma triglyceride levels for 14 days indicated that compound 3 reduces plasma triglyceride levels with similar efficiency as fenofibrate. These observations raise the possibility that 1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid derivatives might be effective drug candidates for selective targeting of PPARα to manage dyslipidemia. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

Activation of PPAR alpha by fenofibrate inhibits apoptosis in vascular adventitial fibroblasts partly through SIRT1-mediated deacetylation of FoxO1.

PubMed

Wang, Wei-Rong; Liu, En-Qi; Zhang, Ji-Ye; Li, Yan-Xiang; Yang, Xiao-Feng; He, Yan-Hao; Zhang, Wei; Jing, Ting; Lin, Rong

2015-10-15

Recent studies demonstrated that the ligand-activated transcription factor peroxisome proliferator-activated receptorα (PPARα) acts in association with histone deacetylase sirtuin 1 (SIRT1) in the regulation of metabolism and inflammation involved in cardiovascular diseases. PPARα activation also participates in the modulation of cell apoptosis. Our previous study found that SIRT1 inhibits the apoptosis of vascular adventitial fibroblasts (VAFs). However, whether the role of PPARα in apoptosis of VAFs is mediated by SIRT1 remains unknown. In this study, we aimed to determine the effect of PPARα agonist fenofibrate on cell apoptosis and SIRT1 expression and related mechanisms in ApoE(-/-) mice and VAFs in vitro. We found that fenofibrate inhibited cell apoptosis in vascular adventitia and up-regulated SIRT1 expression in aorta of ApoE(-/-) mice. Moreover, SIRT1 activator resveratrol (RSV) further enhanced these effects of fenofibrate. In vitro study showed that activation of PPARα by fenofibrate inhibited TNF-α-induced cell apoptosis and cell cycle arrest in VAFs. Meanwhile, fenofibrate up-regulated SIRT1 expression and inhibited SIRT1 translocation from nucleus to cytoplasm in VAFs stimulated with TNF-α. Moreover, the effects of fenofibrate on cell apoptosis and SIRT1 expression in VAFs were reversed by PPARα antagonist GW6471. Importantly, treatment of VAFs with SIRT1 siRNA or pcDNA3.1(+)-SIRT1 showed that the inhibitory effect of fenofibrate on cell apoptosis in VAFs through SIRT1. On the other hand, knockdown of FoxO1 decreased cell apoptosis of VAFs compared with fenofibrate group. Overexpression of FoxO1 increased cell apoptosis of VAFs compared with fenofibrate group. Further study found that fenofibrate decreased the expression of acetylated-FoxO1 in TNF-α-stimulated VAFs, which was abolished by SIRT1 knockdown. Taken together, these findings indicate that activation of PPARα by fenofibrate inhibits cell apoptosis in VAFs partly through the SIRT1-mediated deacetylation of FoxO1. Copyright © 2015 Elsevier Inc. All rights reserved.

Fenofibrate suppressed proliferation and migration of human neuroblastoma cells via oxidative stress dependent of TXNIP upregulation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Su, Cunjin; Shi, Aiming; Cao, Guowen

2015-05-15

There are no appropriate drugs for metastatic neuroblastoma (NB), which is the most common extra-cranial solid tumor for childhood. Thioredoxin binding protein (TXNIP), the endogenous inhibitor of ROS elimination, has been identified as a tumor suppressor in various solid tumors. It reported that fenofibrate exerts anti-tumor effects in several human cancer cell lines. However, its detail mechanisms remain unclear. The present study assessed the effects of fenofibrate on NB cells and investigated TXNIP role in its anti-tumor mechanisms. We used MTT assay to detect cells proliferation, starch wound test to investigate cells migration, H{sub 2}DCF-DA to detect intracellular ROS, siRNAmore » to interfere TXNIP and peroxisome proliferator-androgen receptor-alpha (PPAR-α) expression, western blot to determine protein levels, flow cytometry to analyze apoptosis. Fenofibrate suppressed proliferation and migration of NB cells, remarkably increased intracellular ROS, upregulated TXNIP expression, promoted cell apoptosis. Furthermore, inhibition of TXNIP expression attenuated anti-tumor effects of fenofibrate, while inhibition of PPAR-α had no influences. Our results indicated the anti-tumor role of fenofibrate on NB cells by exacerbating oxidative stress and inducing apoptosis was dependent on the upregulation of TXNIP. - Highlights: • We found that fenofibrate suppressed proliferation and migration of NB cells. • We found that fenofibrate remarkably increased intracellular ROS, upregulated TXNIP expression, and promoted cell apoptosis. • Inhibition of TXNIP expression attenuated anti-tumor effects of fenofibrate, while inhibition of PPAR-α had no influences. • Our results indicated the anti-tumor role of fenofibrate on NB cells was dependent on the upregulation of TXNIP.« less

Fenofibrate inhibits atrial metabolic remodelling in atrial fibrillation through PPAR-α/sirtuin 1/PGC-1α pathway.

PubMed

Liu, Guang-Zhong; Hou, Ting-Ting; Yuan, Yue; Hang, Peng-Zhou; Zhao, Jing-Jing; Sun, Li; Zhao, Guan-Qi; Zhao, Jing; Dong, Jing-Mei; Wang, Xiao-Bing; Shi, Hang; Liu, Yong-Wu; Zhou, Jing-Hua; Dong, Zeng-Xiang; Liu, Yang; Zhan, Cheng-Chuang; Li, Yue; Li, Wei-Min

2016-03-01

Atrial metabolic remodelling is critical for the process of atrial fibrillation (AF). The PPAR-α/sirtuin 1 /PPAR co-activator α (PGC-1α) pathway plays an important role in maintaining energy metabolism. However, the effect of the PPAR-α agonist fenofibrate on AF is unclear. Therefore, the aim of this study was to determine the effect of fenofibrate on atrial metabolic remodelling in AF and explore its possible mechanisms of action. The expression of metabolic proteins was examined in the left atria of AF patients. Thirty-two rabbits were divided into sham, AF (pacing with 600 beats·min(-1) for 1 week), fenofibrate treated (pretreated with fenofibrate before pacing) and fenofibrate alone treated (for 2 weeks) groups. HL-1 cells were subjected to rapid pacing in the presence or absence of fenofibrate, the PPAR-α antagonist GW6471 or sirtuin 1-specific inhibitor EX527. Metabolic factors, circulating biochemical metabolites, atrial electrophysiology, adenine nucleotide levels and accumulation of glycogen and lipid droplets were assessed. The PPAR-α/sirtuin 1/PGC-1α pathway was significantly inhibited in AF patients and in the rabbit/HL-1 cell models, resulting in a reduction of key downstream metabolic factors; this effect was significantly restored by fenofibrate. Fenofibrate prevented the alterations in circulating biochemical metabolites, reduced the level of adenine nucleotides and accumulation of glycogen and lipid droplets, reversed the shortened atrial effective refractory period and increased risk of AF. Fenofibrate inhibited atrial metabolic remodelling in AF by regulating the PPAR-α/sirtuin 1/PGC-1α pathway. The present study may provide a novel therapeutic strategy for AF. © 2016 The British Pharmacological Society.

Efficacy and Safety of Long-term Coadministration of Fenofibrate and Ezetimibe in Patients with Combined Hyperlipidemia: Results of the EFECTL Study

PubMed Central

Yamashita, Shizuya; Nakaya, Noriaki; Sasaki, Jun; Kono, Suminori

2017-01-01

Aim: We investigated the safety and efficacy of a long-term combination therapy with fenofibrate and ezetimibe in Japanese patients with combined hyperlipidemia, in comparison with fenofibrate or ezetimibe alone. Methods: The study was a three-arm parallel-group, open-label randomized trial. Eligible patients were assigned to a combination therapy with fenofibrate (200 mg/day in capsule form or 160 mg/day in tablet form) and ezetimibe (10 mg/day), the fenofibrate monotherapy, or the ezetimibe monotherapy, which lasted for 52 weeks. The changes in serum low-density lipoprotein (LDL) cholesterol and triglycerides were the primary outcomes. Results: A total of 236 patients were assigned to one of the three treatments, and the number of patients included in the final analysis was 107 in the combination therapy, 52 in the fenofibrate monotherapy, and 51 in the ezetimibe monotherapy. Mean ± SD changes in LDL cholesterol were −24.2% ± 14.7% with combination therapy, −16.0% ± 16.0% with fenofibrate alone, and −17.4% ± 10.1% with ezetimibe alone. The combination therapy resulted in a significantly greater reduction in LDL cholesterol as compared with each monotherapy (p < 0.01 for each). The corresponding values for triglycerides were −40.0% ± 29.5%, −40.1% ± 28.7%, and −3.4% ± 32.6%, respectively. Fenofibrate use was associated with some changes in laboratory measurements, but there was no differential adverse effect between the combination therapy and fenofibrate monotherapy. Conclusion: The combination therapy with fenofibrate and ezetimibe substantially reduces concentrations of LDL cholesterol and triglycerides and is safe in a long-term treatment in Japanese patients with combined hyperlipidemia. PMID:27397061

Efficacy and Safety of Long-term Coadministration of Fenofibrate and Ezetimibe in Patients with Combined Hyperlipidemia: Results of the EFECTL Study.

PubMed

Oikawa, Shinichi; Yamashita, Shizuya; Nakaya, Noriaki; Sasaki, Jun; Kono, Suminori

2017-01-01

We investigated the safety and efficacy of a long-term combination therapy with fenofibrate and ezetimibe in Japanese patients with combined hyperlipidemia, in comparison with fenofibrate or ezetimibe alone. The study was a three-arm parallel-group, open-label randomized trial. Eligible patients were assigned to a combination therapy with fenofibrate (200 mg/day in capsule form or 160 mg/day in tablet form) and ezetimibe (10 mg/day), the fenofibrate monotherapy, or the ezetimibe monotherapy, which lasted for 52 weeks. The changes in serum low-density lipoprotein (LDL) cholesterol and triglycerides were the primary outcomes. A total of 236 patients were assigned to one of the three treatments, and the number of patients included in the final analysis was 107 in the combination therapy, 52 in the fenofibrate monotherapy, and 51 in the ezetimibe monotherapy. Mean±SD changes in LDL cholesterol were -24.2%±14.7% with combination therapy, -16.0%±16.0% with fenofibrate alone, and -17.4%± 10.1% with ezetimibe alone. The combination therapy resulted in a significantly greater reduction in LDL cholesterol as compared with each monotherapy (p＜0.01 for each). The corresponding values for triglycerides were -40.0%±29.5%, -40.1%±28.7%, and -3.4%±32.6%, respectively. Fenofibrate use was associated with some changes in laboratory measurements, but there was no differential adverse effect between the combination therapy and fenofibrate monotherapy. The combination therapy with fenofibrate and ezetimibe substantially reduces concentrations of LDL cholesterol and triglycerides and is safe in a long-term treatment in Japanese patients with combined hyperlipidemia.

Fenofibrate inhibited pancreatic cancer cells proliferation via activation of p53 mediated by upregulation of LncRNA MEG3

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hu, Duanmin; Su, Cunjin; Jiang, Min

There is still no suitable drug for pancreatic cancer treatment, which is one of the most aggressive human tumors. Maternally expressed gene 3 (MEG3), a LncRNA, has been suggested as a tumor suppressor in a range of human tumors. Studies found fenofibrate exerted anti-tumor roles in various human cancer cell lines. However, its role in pancreatic cancer remains unknown. The present study aimed to explore the impacts of fenofibrate on pancreatic cancer cell lines, and to investigate MEG3 role in its anti-tumor mechanisms. We used MTT assay to determine cells proliferation, genome-wide LncRNA microarray analysis to identify differently expressed LncRNAs,more » siRNA or pCDNA-MEG3 transfection to interfere or upregulate MEG3 expression, western blot to detect protein levels, real-time PCR to determine MEG3 level. Fenofibrate significantly inhibited proliferation of pancreatic cancer cells, increased MEG3 expression and p53 levels. Moreover, knockdown of MEG3 attenuated cytotoxicity induced by fenofibrate. Furthermore, overexpression of MEG3 induced cells death and increased p53 expression. Our results indicated fenofibrate inhibited pancreatic cancer cells proliferation via activation of p53 mediated by upregulation of MEG3. - Highlights: • We found that fenofibrate suppressed proliferation of pancreatic cancer cells. • We found fenofibrate increased LncRNA-MEG3 expression and p53 level in PANC-1 cells. • Inhibition of MEG3 expression attenuated anti-tumor effects of fenofibrate.« less

Chlorine transfer between glycine, taurine, and histamine: reaction rates and impact on cellular reactivity.

PubMed

Peskin, Alexander V; Midwinter, Robyn G; Harwood, David T; Winterbourn, Christine C

2005-02-01

Hypochlorous acid formed by activated neutrophils reacts with amines to produce chloramines. Chloramines vary in stability, reactivity, and cell permeability. We have examined whether chloramine exchange occurs between physiologically important amines or amino acids and if this affects interactions of chloramines with cells. We have demonstrated transchlorination reactions between histamine, glycine, and taurine chloramines by measuring chloramine decay rates with mixtures as well as by mass spectrometry. Kinetic analysis suggested the formation of an intermediate complex with a high Km. Apparent second-order rate constants, determined for concentrations

Chlorine transfer between glycine, taurine, and histamine: reaction rates and impact on cellular reactivity.

PubMed

Peskin, Alexander V; Midwinter, Robyn G; Harwood, David T; Winterbourn, Christine C

2004-11-15

Hypochlorous acid formed by activated neutrophils reacts with amines to produce chloramines. Chloramines vary in stability, reactivity, and cell permeability. We have examined whether chloramine exchange occurs between physiologically important amines or amino acids and if this affects interactions of chloramines with cells. We have demonstrated transchlorination reactions between histamine, glycine, and taurine chloramines by measuring chloramine decay rates with mixtures as well as by mass spectrometry. Kinetic analysis suggested the formation of an intermediate complex with a high K(m). Apparent second-order rate constants, determined for concentrations

A taurine-supplemented vegan diet may blunt the contribution of neutrophil activation to acute coronary events.

PubMed

McCarty, Mark F

2004-01-01

Neutrophils are activated in the coronary circulation during acute coronary events (unstable angina and myocardial infarction), often prior to the onset of ischemic damage. Moreover, neutrophils infiltrate coronary plaque in these circumstances, and may contribute to the rupture or erosion of this plaque, triggering thrombosis. Activated neutrophils secrete proteolytic enzymes in latent forms which are activated by the hypochlorous acid (HOCl) generated by myeloperoxidase. These phenomena may help to explain why an elevated white cell count has been found to be an independent coronary risk factor. Low-fat vegan diets can decrease circulating leukocytes--neutrophils and monocytes--possibly owing to down-regulation of systemic IGF-I activity. Thus, a relative neutropenia may contribute to the coronary protection afforded by such diets. However, vegetarian diets are devoid of taurine - the physiological antagonist of HOCl--and tissue levels of this nutrient are relatively low in vegetarians. Taurine has anti-atherosclerotic activity in animal models, possibly reflecting a role for macrophage-derived myeloperoxidase in the atherogenic process. Taurine also has platelet-stabilizing and anti-hypertensive effects that presumably could reduce coronary risk. Thus, it is proposed that a taurine-supplemented low-fat vegan diet represents a rational strategy for diminishing the contribution of activated neutrophils to acute coronary events; moreover, such a regimen would work in a number of other complementary ways to promote cardiovascular health. Moderate alcohol consumption, the well-tolerated drug pentoxifylline, and 5-lipoxygenase inhibitors--zileuton, boswellic acids, fish oil--may also have potential in this regard. Copyright 2004 Elsevier Ltd.

RP-HPLC method for simultaneous estimation of vigabatrin, gamma-aminobutyric acid and taurine in biological samples.

PubMed

Police, Anitha; Shankar, Vijay Kumar; Narasimha Murthy, S

2018-02-15

Vigabatrin is used as first line drug in treatment of infantile spasms for its potential benefit overweighing risk of causing permanent peripheral visual field defects and retinal damage. Chronic administration of vigabatrin in rats has demonstrated these ocular events are result of GABA accumulation and depletion of taurine levels in retinal tissues. In vigabatrin clinical studies taurine plasma level is considered as biomarker for studying structure and function of retina. The analytical method is essential to monitor taurine levels along with vigabatrin and GABA. A RP-HPLC method has been developed and validated for simultaneous estimation of vigabatrin, GABA and taurine using surrogate matrix. Analytes were extracted from human plasma, rat plasma, retina and brain by simple protein precipitation method and derivatized by naphthalene 2, 3‑dicarboxaldehyde to produce stable fluorescent active isoindole derivatives. The chromatographic analysis was performed on Zorbax Eclipse AAA column using gradient elution profile and eluent was monitored using fluorescence detector. A linear plot of calibration curve was observed in concentration range of 64.6 to 6458, 51.5 to 5150 and 62.5 to 6258 ng/mL for vigabatrin, GABA and taurine, respectively with r 2  ≥ 0.997 for all analytes. The method was successfully applied for estimating levels of vigabatrin and its modulator effect on GABA and taurine levels in rat plasma, brain and retinal tissue. This RP-HPLC method can be applied in clinical and preclinical studies to explore the effect of taurine deficiency and to investigate novel approaches for alleviating vigabatrin induced ocular toxicity. Copyright © 2018. Published by Elsevier B.V.

Effects of glutamine, taurine and their association on inflammatory pathway markers in macrophages.

PubMed

Sartori, Talita; Galvão Dos Santos, Guilherme; Nogueira-Pedro, Amanda; Makiyama, Edson; Rogero, Marcelo Macedo; Borelli, Primavera; Fock, Ricardo Ambrósio

2018-06-01

The immune system is essential for the control and elimination of infections, and macrophages are cells that act as important players in orchestrating the various parts of the inflammatory/immune response. Amino acids play important role in mediating functionality of the inflammatory response, especially mediating macrophages functions and cytokines production. We investigated the influence of glutamine, taurine and their association on the modulation of inflammatory pathway markers in macrophages. The RAW 264.7 macrophage cell line was cultivated in the presence of glutamine and taurine and proliferation rates, cell viability, cell cycle phases, IL-1α, IL-6, IL-10 and TNF-α as well as H 2 O 2 production and the expression of the transcription factor, NFκB, and its inhibitor, IκBα, were evaluated. Our results showed an increase in viable cells and increased proliferation rates of cells treated with glutamine concentrations over 2 mM, as well as cells treated with both glutamine and taurine. The cell cycle showed a higher percentage of cells in the phases S, G2 and M when they were treated with 2 or 10 mM glutamine, or with glutamine and taurine in cells stimulated with lipopolysaccharide. The pNFκB/NFκB showed reduced ratio expression when cells were treated with 10 mM of glutamine or with glutamine in association with taurine. These conditions also resulted in reduced TNF-α, IL-1α and H 2 O 2 production, and higher production of IL-10. These findings demonstrate that glutamine and taurine are able to modulate macrophages inflammatory pathways, and that taurine can potentiate the effects of glutamine, illustrating their immunomodulatory properties.

Modulation of fatty acid metabolism is involved in the alleviation of isoproterenol-induced rat heart failure by fenofibrate

PubMed Central

LI, PING; LUO, SHIKE; PAN, CHUNJI; CHENG, XIAOSHU

2015-01-01

Heart failure is a disease predominantly caused by an energy metabolic disorder in cardiomyocytes. The present study investigated the inhibitory effects of fenofibrate (FF) on isoproterenol (ISO)-induced hear failure in rats, and examined the underlying mechanisms. The rats were divided into CON, ISO (HF model), FF and FF+ISO (HF animals pretreated with FF) groups. The cardiac structure and function of the rats were assessed, and contents of free fatty acids and glucose metabolic products were determined. In addition, myocardial cells were isolated from neonatal rats and used in vitro to investigate the mechanisms by which FF relieves heart failure. Western blot analysis was performed to quantify the expression levels of peroxisome proliferator-activated receptor (PPAR)α and uncoupling protein 2 (UCP2). FF effectively alleviated the ISO-induced cardiac structural damage, functional decline, and fatty acid and carbohydrate metabolic abnormalities. Compared with the ISO group, the serum levels of brain natriuretic peptide (BNP), free fatty acids, lactic acid and pyruvic acid were decreased in the FF animals. In the cultured myocardial cells, lactic acid and pyruvic acid contents were lower in the supernatants obtained from the FF animals, with lower levels of mitochondrial ROS production and cell necrosis, compared with the ISO group, whereas PPARα upregulation and UCP2 downregulation occurred in the FF+ISO group. The results demonstrated that FF efficiently alleviated heart failure in the ISO-induced rat model, possibly via promoting fatty acid oxidation. PMID:26497978

Free amino acids in spider hemolymph.

PubMed

Tillinghast, Edward K; Townley, Mark A

2008-11-01

We examined the free amino acid composition of hemolymph from representatives of five spider families with an interest in knowing if the amino acid profile in the hemolymph of orb-web-building spiders reflects the high demands for small organic compounds in the sticky droplets of their webs. In nearly all analyses, on both orb and non-orb builders, glutamine was the most abundant free amino acid. Glycine, taurine, proline, histidine, and alanine also tended to be well-represented in orb and non-orb builders. While indications of taxon-specific differences in amino acid composition were observed, it was not apparent that two presumptive precursors (glutamine, taurine) of orb web sticky droplet compounds were uniquely enriched in araneids (orb builders). However, total amino acid concentrations were invariably highest in the araneids and especially so in overwintering juveniles, even as several of the essential amino acids declined during this winter diapause. Comparing the data from this study with those from earlier studies revealed a number of discrepancies. The possible origins of these differences are discussed.

Efficacy and safety of coadministration of fenofibrate and ezetimibe compared with each as monotherapy in patients with type IIb dyslipidemia and features of the metabolic syndrome: a prospective, randomized, double-blind, three-parallel arm, multicenter, comparative study.

PubMed

Ansquer, Jean-Claude; Bekaert, Ivan; Guy, Martine; Hanefeld, Markolf; Simon, Alain

2009-01-01

Patients with type IIb, or mixed, dyslipidemia have high levels of low-density lipoprotein cholesterol (LDL-C) with predominance of small dense LDL particles, high levels of triglycerides (TG), and low levels of high-density lipoprotein cholesterol (HDL-C). Fenofibrate significantly reduces TG and, more moderately, LDL-C, increases HDL-C and produces a shift from small to large LDL particle size; the main effect of ezetimibe is a reduction in LDL-C levels. Combined treatment with fenofibrate and ezetimibe may correct all the abnormalities of type IIb dyslipidemia. To assess the efficacy and safety of coadministration of fenofibrate (NanoCrystal(R)) and ezetimibe in patients with type IIb dyslipidemia and the metabolic syndrome compared with administration of fenofibrate and ezetimibe alone (ClinicalTrials.gov Identifier: NCT00349284; Study ID: CLF178P 04 01). This was a prospective, randomized, double-blind, three-parallel arm, multicenter, comparative study. Sixty ambulatory patients (mean age 56 years; 50% women, 50% men) were treated in each group. For inclusion in the study, patients were required to have LDL-C >or=4.13 mmol/L (>or=160 mg/dL), TG >or=1.71 mmol/L and or=150 mg/dL and

Taurine, caffeine, and energy drinks: Reviewing the risks to the adolescent brain.

PubMed

Curran, Christine Perdan; Marczinski, Cecile A

2017-12-01

Energy drinks are emerging as a major component of the beverage market with sales projected to top $60 billion globally in the next five years. Energy drinks contain a variety of ingredients, but many of the top-selling brands include high doses of caffeine and the amino acid taurine. Energy drink consumption by children has raised concerns, due to potential caffeine toxicity. An additional risk has been noted among college-aged consumers of energy drinks who appear at higher risk of over-consumption of alcohol when the two drinks are consumed together. The differential and combinatorial effects of caffeine and taurine on the developing brain are reviewed here with an emphasis on the adolescent brain, which is still maturing. Key data from animal studies are summarized to highlight both reported benefits and adverse effects reported following acute and chronic exposures. The data suggest that age is an important factor in both caffeine and taurine toxicity. Although the aged or diseased brain might benefit from taurine or caffeine supplementation, it appears that adolescents are not likely to benefit from supplementation and may, in fact, suffer ill effects from chronic ingestion of high doses. Additional work is needed though to address gaps in our understanding of how taurine affects females, since the majority of animal studies focused exclusively on male subjects. © 2017 Wiley Periodicals, Inc.

Cerebral Taurine Levels are Associated with Brain Edema and Delayed Cerebral Infarction in Patients with Aneurysmal Subarachnoid Hemorrhage.

PubMed

Kofler, Mario; Schiefecker, Alois; Ferger, Boris; Beer, Ronny; Sohm, Florian; Broessner, Gregor; Hackl, Werner; Rhomberg, Paul; Lackner, Peter; Pfausler, Bettina; Thomé, Claudius; Schmutzhard, Erich; Helbok, Raimund

2015-12-01

Cerebral edema and delayed cerebral infarction (DCI) are common complications after aneurysmal subarachnoid hemorrhage (aSAH) and associated with poor functional outcome. Experimental data suggest that the amino acid taurine is released into the brain extracellular space secondary to cytotoxic edema and brain tissue hypoxia, and therefore may serve as a biomarker for secondary brain injury after aSAH. On the other hand, neuroprotective mechanisms of taurine treatment have been described in the experimental setting. We analyzed cerebral taurine levels using high-performance liquid chromatography in the brain extracellular fluid of 25 consecutive aSAH patients with multimodal neuromonitoring including cerebral microdialysis (CMD). Patient characteristics and clinical course were prospectively recorded. Associations with CMD-taurine levels were analyzed using generalized estimating equations with an autoregressive process to handle repeated observations within subjects. CMD-taurine levels were highest in the first days after aSAH (11.2 ± 3.2 µM/l) and significantly decreased over time (p < 0.001). Patients with brain edema on admission or during hospitalization (N = 20; 80 %) and patients developing DCI (N = 5; 20 %) had higher brain extracellular taurine levels compared to those without (Wald = 7.3, df = 1, p < 0.01; Wald = 10.1, df = 1, p = 0.001, respectively) even after adjusting for disease severity and CMD-probe location. There was no correlation between parenteral taurine supplementation and brain extracellular taurine (p = 0.6). Moreover, a significant correlation with brain extracellular glutamate (r = 0.82, p < 0.001), lactate (r = 0.56, p < 0.02), pyruvate (r = 0.39, p < 0.01), potassium (r = 0.37, p = 0.01), and lactate-to-pyruvate ratio (r = 0.24, p = 0.02) was found. Significantly higher CMD-taurine levels were found in patients with brain edema or DCI after aneurysmal subarachnoid hemorrhage. Its value as a potential biomarker deserves further investigation.

Concentrations in beef and lamb of taurine, carnosine, coenzyme Q(10), and creatine.

PubMed

Purchas, R W; Rutherfurd, S M; Pearce, P D; Vather, R; Wilkinson, B H P

2004-03-01

Levels of taurine, carnosine, coenzyme Q(10), and creatine were measured in beef liver and several muscles of beef and lamb and in cooked and uncooked meat. The amino acid taurine has numerous biological functions, the dipeptide carnosine is a buffer as well as an antioxidant, coenzyme Q(10) is also an antioxidant present within mitochondria, and creatine along with creatine phosphate is involved with energy metabolism in muscle. Large differences were shown for all compounds between beef cheek muscle (predominantly red fibres) and beef semitendinosus muscle (mainly white fibres), with cheek muscle containing 9.9 times as much taurine, and 3.2 times as much coenzyme Q(10), but only 65% as much creatine and 9% as much carnosine. Levels in lamb relative to beef semitendinosus muscles were higher for taurine but slightly lower for carnosine, coenzyme Q(10) and creatine. Values for all the compounds varied significantly between eight lamb muscles, possibly due in part to differences in the proportion of muscle fibre types. Slow cooking (90 min at 70 °C) of lamb longissimus and semimembranosus muscles led to significant reductions in the content of taurine, carnosine, and creatine (P<0.001), but a slight increase in coenzyme Q(10). There was also a four-fold increase in creatinine, presumably due to its formation from creatine. It is concluded that biologically, and possibly nutritionally, significant levels of taurine, carnosine, coenzyme Q(10), and creatine are present in beef and lamb, but that these levels vary between muscles, between animals, and with cooking.

Therapeutic Effects of PPARα Agonists on Diabetic Retinopathy in Type 1 Diabetes Models

PubMed Central

Chen, Ying; Hu, Yang; Lin, Mingkai; Jenkins, Alicia J.; Keech, Anthony C.; Mott, Robert; Lyons, Timothy J.; Ma, Jian-xing

2013-01-01

Retinal vascular leakage, inflammation, and neovascularization (NV) are features of diabetic retinopathy (DR). Fenofibrate, a peroxisome proliferator–activated receptor α (PPARα) agonist, has shown robust protective effects against DR in type 2 diabetic patients, but its effects on DR in type 1 diabetes have not been reported. This study evaluated the efficacy of fenofibrate on DR in type 1 diabetes models and determined if the effect is PPARα dependent. Oral administration of fenofibrate significantly ameliorated retinal vascular leakage and leukostasis in streptozotocin-induced diabetic rats and in Akita mice. Favorable effects on DR were also achieved by intravitreal injection of fenofibrate or another specific PPARα agonist. Fenofibrate also ameliorated retinal NV in the oxygen-induced retinopathy (OIR) model and inhibited tube formation and migration in cultured endothelial cells. Fenofibrate also attenuated overexpression of intercellular adhesion molecule-1, monocyte chemoattractant protein-1, and vascular endothelial growth factor (VEGF) and blocked activation of hypoxia-inducible factor-1 and nuclear factor-κB in the retinas of OIR and diabetic models. Fenofibrate’s beneficial effects were blocked by a specific PPARα antagonist. Furthermore, Pparα knockout abolished the fenofibrate-induced downregulation of VEGF and reduction of retinal vascular leakage in DR models. These results demonstrate therapeutic effects of fenofibrate on DR in type 1 diabetes and support the existence of the drug target in ocular tissues and via a PPARα-dependent mechanism. PMID:23043158

Rationale for an adjunctive therapy with fenofibrate in pharmacoresistant nocturnal frontal lobe epilepsy.

PubMed

Puligheddu, Monica; Melis, Miriam; Pillolla, Giuliano; Milioli, Giulia; Parrino, Liborio; Terzano, Giovanni Mario; Aroni, Sonia; Sagheddu, Claudia; Marrosu, Francesco; Pistis, Marco; Muntoni, Anna Lisa

2017-10-01

Nocturnal frontal lobe epilepsy (NFLE) is an idiopathic partial epilepsy with a family history in about 25% of cases, with autosomal dominant inheritance (autosomal dominant NFLE [ADNFLE]). Traditional antiepileptic drugs are effective in about 55% of patients, whereas the rest remains refractory. One of the key pathogenetic mechanisms is a gain of function of neuronal nicotinic acetylcholine receptors (nAChRs) containing the mutated α4 or β2 subunits. Fenofibrate, a common lipid-regulating drug, is an agonist at peroxisome proliferator-activated receptor alpha (PPARα) that is a ligand-activated transcription factor, which negatively modulates the function of β2-containing nAChR. To test clinical efficacy of adjunctive therapy with fenofibrate in pharmacoresistant ADNFLE\\NFLE patients, we first demonstrated the effectiveness of fenofibrate in a mutated mouse model displaying both disease genotype and phenotype. We first tested the efficacy of fenofibrate in transgenic mice carrying the mutation in the α4-nAChR subunit (Chrna4S252F) homologous to that found in humans. Subsequently, an add-on protocol was implemented in a clinical setting and fenofibrate was administered to pharmacoresistant NFLE patients. Here, we show that a chronic fenofibrate diet markedly reduced the frequency of large inhibitory postsynaptic currents (IPSCs) recorded from cortical pyramidal neurons in Chrna4S252F mice, and prevented nicotine-induced increase of IPSC frequency. Moreover, fenofibrate abolished differences between genotypes in the frequency of sleep-related movements observed under basal conditions. Patients affected by NFLE, nonresponders to traditional therapy, by means of adjunctive therapy with fenofibrate displayed a reduction of seizure frequency. Furthermore, digital video-polysomnographic recordings acquired in NFLE subjects after 6 months of adjunctive fenofibrate substantiated the significant effects on control of motor-behavioral seizures. Our preclinical and clinical studies suggest PPARα as a novel disease-modifying target for antiepileptic drugs due to its ability to regulate dysfunctional nAChRs. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

How Abbott’s Fenofibrate Franchise Avoided Generic Competition

PubMed Central

Downing, Nicholas S.; Ross, Joseph S.; Jackevicius, Cynthia A.; Krumholz, Harlan M.

2013-01-01

The ongoing debate concerning the efficacy of fenofibrate has overshadowed an important aspect of the drug’s history: Abbott, the maker of branded fenofibrate, has produced several bioequivalent reformulations, which dominate the market even though generic fenofibrate has been available for almost a decade. This continued use of branded formulations, which cost twice as much as generic versions of fenofibrate, imposes an annual cost of approximately $700 million on our healthcare system. Abbott maintained its dominance of the fenofibrate market, in part, through a complex switching strategy involving the sequential launch of branded reformulations that had not been shown to be superior to the first generation product and patent litigation that delayed the approval of generic formulations. The small differences in dose of the newer branded formulations prevented substitution with generics of older generation products. As soon as direct generic competition seemed likely at the new dose level where substitution would be allowed, Abbott would launch another reformulation and the cycle would repeat. Our objective, using the fenofibrate example, is to describe how current policy can allow pharmaceutical companies to maintain market share using reformulations of branded medications without demonstrating the superiority of next generation products. PMID:22493409

Avoidance of generic competition by Abbott Laboratories' fenofibrate franchise.

PubMed

Downing, Nicholas S; Ross, Joseph S; Jackevicius, Cynthia A; Krumholz, Harlan M

2012-05-14

The ongoing debate concerning the efficacy of fenofibrate has overshadowed an important aspect of the drug's history: Abbott Laboratories, the maker of branded fenofibrate, has produced several bioequivalent reformulations that dominate the market, although generic fenofibrate has been available for almost a decade. This continued use of branded formulations, which cost twice as much as generic versions of fenofibrate, imposes an annual cost of approximately $700 million on the US health care system. Abbott Laboratories maintained its dominance of the fenofibrate market in part through a complex switching strategy involving the sequential launch of branded reformulations that had not been shown to be superior to the first-generation product and patent litigation that delayed the approval of generic formulations. The small differences in dose of the newer branded formulations prevented their substitution with generics of older-generation products. As soon as direct generic competition seemed likely at the new dose level, where substitution would be allowed, Abbott would launch another reformulation, and the cycle would repeat. Based on the fenofibrate example, our objective is to describe how current policy can allow pharmaceutical companies to maintain market share using reformulations of branded medications, without demonstrating the superiority of next-generation products.

β-Alanine and taurine as endogenous agonists at glycine receptors in rat hippocampus in vitro

PubMed Central

Mori, Masahiro; Gähwiler, Beat H; Gerber, Urs

2002-01-01

Electrophysiological and pharmacological properties of glycine receptors were characterized in hippocampal organotypic slice cultures. In the presence of ionotropic glutamate and GABAB receptor antagonists, pressure-application of glycine onto CA3 pyramidal cells induced a current associated with increased chloride conductance, which was inhibited by strychnine. Similar chloride currents could also be induced with β-alanine or taurine. Whole-cell glycine responses were significantly greater in CA3 pyramidal cells than in CA1 pyramidal cells and dentate granule cells, while responses to GABA were similar among these three cell types. Although these results demonstrate the presence of functional glycine receptors in the hippocampus, no evidence for their activation during synaptic stimulation was found. Gabazine, a selective GABAA receptor antagonist, totally blocked evoked IPSCs in CA3 pyramidal cells. Glycine receptor activation is not dependent on transporter-controlled levels of extracellular glycine, as no chloride current was observed in response to sarcosine, an inhibitor of glycine transporters. In contrast, application of guanidinoethanesulfonic acid, an uptake inhibitor of β-alanine and taurine, induced strychnine-sensitive chloride current in the presence of gabazine. These data indicate that modulation of transporters for the endogenous amino acids, β-alanine and taurine, can regulate tonic activation of glycine receptors, which may function in maintenance of inhibitory tone in the hippocampus. PMID:11850512

Monthly changes of glycogen, lipid and free amino acid of oyster

NASA Astrophysics Data System (ADS)

Zhicui, Zhang; Changhu, Xue; Xin, Gao; Zhaojie, Li; Qi, Wang

2006-07-01

Monthly difference of the chemical composition of oyster cultured along the eastern coast of Shandong Province was analyzed. The components analyzed included glycogen, fatty acid and free amino acid (FAA). The content of glycogen was high in January and March (2.89 and 2.82 g(100g)-1 on average, respectively) and low in October (2.07 g(100g)-1 on avarage). The low content of neutral lipids in October reflected a relatively poor nutritional value of oyster (1.42 g(100 g)-1 on average). The main fatty acids of oyster were palmitic acid (16:0), oleic acid (18:1), eicosapentaenoic acid (EPA, 20: 5ω-3) and docosahexaenoic acid (DHA, 22:6ω-3). The major FAAs of oyster were Taurine, Glutamicacid, Glycin, Alanine, Arginine and Proline. Taurine was the most abundant FAA with its content ranging from 603 mg (100g)-1 to 1139 mg(100g)-1. The high contents of glycogen, polyunsaturated fatty acid and FAA showed that oyster cultured along the eastern coast of Shandong Province was nutritionally good in January and March.

Additive Renoprotection by Pioglitazone and Fenofibrate against Inflammatory, Oxidative and Apoptotic Manifestations of Cisplatin Nephrotoxicity: Modulation by PPARs

PubMed Central

Helmy, Mai M.; Helmy, Maged W.; El-Mas, Mahmoud M.

2015-01-01

Nephrotoxicity is a major side effect for the antineoplastic drug cisplatin. Here, we employed pharmacological, biochemical, and molecular studies to investigate the role of peroxisome proliferator-activated receptors (PPARs) in cisplatin nephrotoxicity. Rats were treated with a single i.p. dose of cisplatin (5 mg/kg) alone or combined with pioglitazone (PPARγ agonist), fenofibrate (PPARα agonist), pioglitazone plus fenofibrate, or thalidomide (Tumor necrosis factor-α inhibitor; TNF-α). Cisplatin nephrotoxicity was evidenced by rises in renal indices of functional (blood urea nitrogen, BUN, and creatinine), inflammatory (TNF-α, interleukin 6, IL-6), oxidative (increased malondialdehyde, MDA, and decreased superoxide dismutase, SOD and nitric oxide metabolites, NOx), apoptotic (caspase 3), and histological (glomerular atrophy, acute tubular necrosis and vacuolation) profiles. Cisplatin effects were partly abolished upon concurrent exposure to pioglitazone, fenofibrate, or thalidomide; more renoprotection was observed in rats treated with pioglitazaone plus fenofibrate. Immunostaining showed that renal expressions of PPARα and PPARγ were reduced by cisplatin and restored to vehicle-treated values after simultaneous treatment with pioglitazone or fenofibrate. Fenofibrate or pioglitazone renoprotection remained unaltered after concurrent blockade of PPARα (GW6471) and PPARγ (GW9662), respectively. To complement the rat studies, we also report that in human embryonic kidney cells (HEK293 cells), increases caused by cisplatin in inflammatory, apoptotic, and oxidative biomarkers were (i) partly improved after exposure to pioglitazone, fenofibrate, or thalidomide, and (ii) completely disappeared in cells treated with a combination of all three drugs. These data establish that the combined use of pioglitazone and fenofibrate additively improved manifestations of cisplatin nephrotoxicity through perhaps GW6471/GW9662-insensitive mechanisms. PMID:26536032

Amino acids as central synaptic transmitters or modulators in mammalian thermoregulation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bligh, J.

1981-11-01

Of the amino acids that affect the activity of central neurons, aspartate and glutamate (which exert generally excitatory influences) and glycine, taurine, and ..gamma..-aminobutyric acid (GABA) (which generally exert inhibitory influences) are the strongest neurotransmitter candidates. As with other putative transmitter substances, their effects on body temperature when injected into the cerebral ventricles or the preoptic hypothalamus tend to vary within and between species. These effects are uninterpretable without accompanying information regarding effector activity changes and the influences of dose and ambient temperature. Observations necessary for analysis of apparent action have been made in studies of the effects of intracerebroventricularmore » injections of these amino acids into sheep. Aspartate and glutamate have similar excitatory effects on the pathway from cold sensors, whereas taurine and GABA exert inhibitory influences on the neural pathways that activate both heat production and heat loss effectors. Glycine appears to be without effect.« less

Merging Photoredox and Nickel Catalysis: The Direct Synthesis of Ketones via the Decarboxylative Arylation of α-Oxo Acids**

PubMed Central

Chu, Lingling; Lipshultz, Jeffrey M.

2015-01-01

The direct decarboxylative arylation of α-oxo acids has been achieved via synergistic visible light-mediated photoredox and nickel catalyses. This method offers rapid entry to aryl and alkyl ketone architectures from simple α-oxo acid precursors via an acyl radical intermediate. Significant substrate scope is observed with respect to both the oxo acid and arene coupling partners. This mild decarboxylative arylation can also be utilized to efficiently access medicinal agents, as demonstrated by the rapid synthesis of fenofibrate. PMID:26014029

The Peroxisome Proliferator-Activated Receptor Alpha Agonist Fenofibrate Attenuates Alcohol Self-administration in Rats

PubMed Central

Haile, Colin N.; Kosten, Therese A.

2017-01-01

Fibrates are a class of medications used to treat hypercholesterolemia and dyslipidemia that target nuclear peroxisome proliferator-activated receptors (PPARs). Studies have shown the PPARα agonist fenofibrate decreases voluntary EtOH consumption however its impact on the reinforcing and motivational effects of EtOH is unknown. We evaluated the ability of fenofibrate (25, 50 and 100mg/kg), to alter EtOH (10%, w/v) and sucrose (2%, w/v) operant self-administration in rats under a FR2 schedule of reinforcement over four days and under a progressive ratio (PR) schedule on day five of treatment. Results showed fenofibrate dose-dependently decreased EtOH self-administration under both schedules of reinforcement with the greatest effects seen after four to five days of treatment. Fenofibrate decreased responding for sucrose only under the PR schedule of reinforcement and this effect was not dose-dependent. These findings provide further evidence for fenofibrate as a potential treatment for alcohol use disorder in humans. PMID:28088358

Peroxisome proliferator-activated receptor {alpha} agonist-induced down-regulation of hepatic glucocorticoid receptor expression in SD rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen Xiang; Li Ming; Sun Weiping

2008-04-18

It was reported that glucocorticoid production was inhibited by fenofibrate through suppression of type-1 11{beta}-hydroxysteroid dehydrogenase gene expression in liver. The inhibition might be a negative-feedback regulation of glucocorticoid receptor (GR) activity by peroxisome proliferator-activated receptor alpha (PPAR{alpha}), which is quickly induced by glucocorticoid in the liver. However, it is not clear if GR expression is changed by fenofibrate-induced PPAR{alpha} activation. In this study, we tested this possibility in the liver of Sprague-Dawley rats. GR expression was reduced by fenofibrate in a time- and does-dependent manner. The inhibition was observed in liver, but not in fat and muscle. The corticosteronemore » level in the blood was increased significantly by fenofibrate. These effects of fenofibrate were abolished by PPAR{alpha} inhibitor MK886, suggesting that fenofibrate activated through PPAR{alpha}. In conclusion, inhibition of GR expression may represent a new molecular mechanism for the negative feedback regulation of GR activity by PPAR{alpha}.« less

Genetic risk scores associated with baseline lipoprotein subfraction concentrations do not associate with their responses to fenofibrate

USDA-ARS?s Scientific Manuscript database

Lipoprotein subclass concentrations are modifiable markers of cardiovascular disease risk. Fenofibrate is known to show beneficial effects on lipoprotein subclasses, but little is known about the role of genetics in mediating the responses of lipoprotein subclasses to fenofibrate. A recent genomewid...

Taurine restores the exploratory behavior following alcohol withdrawal and decreases BDNF mRNA expression in the frontal cortex of chronic alcohol-treated rats.

PubMed

Hansen, Alana Witt; Almeida, Felipe Borges; Bandiera, Solange; Pulcinelli, Rianne Remus; Fragoso, Ana Luiza Rodrigues; Schneider, Ricardo; Barros, Helena Maria Tannhauser; Gomez, Rosane

2017-10-01

Alcohol use disorder is an alarming health problem, and the withdrawal symptoms increase the risk of relapse. We have hypothesized that taurine, a multitarget substance acting as a gamma-aminobutyric acid A receptor (GABA A R) positive modulator and a partial inhibitor of N-methyl-d-aspartate (NMDA) glutamate receptors, may reduce the withdrawal symptoms or modify behaviors when combined with alcohol. Therefore, we investigated the effects of taurine on behavior in the open field test (OFT), the GABA A R α 2 subunit and BDNF mRNA expression in the frontal cortex of rats after chronic alcohol treatment or upon withdrawal. Rats received alcohol 2g/kg (alcohol and withdrawal groups) or water (control group) twice daily by oral gavage for 28days. On day 29, the withdrawal rats received water instead of alcohol, and all groups were reallocated to receive 100mg/kg taurine or vehicle intraperitoneally, once a day for 5days. On day 33, the rats were exposed to OFT; 18h later, they were euthanized, and the frontal cortex was dissected for GABA A R α 2 subunit detection and BDNF mRNA expression determination by real-time quantitative PCR. Taurine administration restored rearing behavior to the control levels in the withdrawal rats. Taurine also showed anxiolytic-like effects in control rats and did not change the behaviors in the chronic alcohol group. Chronic alcohol treatment or withdrawal did not change the GABA A R α 2 subunit or BDNF mRNA expression in the frontal cortex, but taurine decreased the α 2 subunit level in control rats and to the BDNF levels in the alcohol rat group. We conclude that taurine restored exploratory behavior after alcohol withdrawal but that this effect was not related to the GABA A R α 2 subunit or BDNF mRNA expression in the frontal cortex of the rats. Copyright © 2017 Elsevier Inc. All rights reserved.

Effect of combination of taurine and azelaic acid on antimelanogenesis in murine melanoma cells

PubMed Central

2010-01-01

Background Pigmentation in human skin is an important defense mechanism against sunlight or oxidative stress. Despite the protective role of melanin, abnormal hyperpigmentation such as freckles and chloasma sometimes can be serious aesthetic problems. Because of these effects of hyperpigmentation, people have considered the effect of depigmentation. Azelaic acid (AZ) is a saturated dicarboxylic acid found naturally in wheat, rye, and barley. Previously, we showed that AZ inhibited melanogenesis. In this study, we investigated the antimelanogenic activity of combination of AZ and taurine (Tau) in B16F10 mouse melanoma cells. Methods The mouse melanoma cell line B16F10 was used in the study. We measured melanin contents and tyrosinase activity. To gain the change of protein expression, we carried out western blotting. Results We investigated that AZ combined with taurine (Tau) show more inhibitory effects in melanocytes than the treatment of AZ alone. AZ combined with Tau inhibited the melanin production and tyrosinase activity of B16F10 melanoma cells without significant cytotoxicity. Also inhibitory effects after treatment with these combined chemical are stronger than AZ alone on melanogenesis. Conclusions These findings indicate that AZ with Tau might play an important role in the regulation of melanin formation and be useful as effective ingredients in antimelanogesis. PMID:20804622

Effect of combination of taurine and azelaic acid on antimelanogenesis in murine melanoma cells.

PubMed

Yu, Ji Sun; Kim, An Keun

2010-08-24

Pigmentation in human skin is an important defense mechanism against sunlight or oxidative stress. Despite the protective role of melanin, abnormal hyperpigmentation such as freckles and chloasma sometimes can be serious aesthetic problems. Because of these effects of hyperpigmentation, people have considered the effect of depigmentation. Azelaic acid (AZ) is a saturated dicarboxylic acid found naturally in wheat, rye, and barley. Previously, we showed that AZ inhibited melanogenesis. In this study, we investigated the antimelanogenic activity of combination of AZ and taurine (Tau) in B16F10 mouse melanoma cells. The mouse melanoma cell line B16F10 was used in the study. We measured melanin contents and tyrosinase activity. To gain the change of protein expression, we carried out western blotting. We investigated that AZ combined with taurine (Tau) show more inhibitory effects in melanocytes than the treatment of AZ alone. AZ combined with Tau inhibited the melanin production and tyrosinase activity of B16F10 melanoma cells without significant cytotoxicity. Also inhibitory effects after treatment with these combined chemical are stronger than AZ alone on melanogenesis. These findings indicate that AZ with Tau might play an important role in the regulation of melanin formation and be useful as effective ingredients in antimelanogesis.

A simple and sensitive method for the determination of fibric acids in the liver by liquid chromatography.

PubMed

Karahashi, Minako; Fukuhara, Hiroto; Hoshina, Miki; Sakamoto, Takeshi; Yamazaki, Tohru; Mitsumoto, Atsushi; Kawashima, Yoichi; Kudo, Naomi

2014-01-01

Fibrates are used in biochemical and pharmacological studies as bioactive tools. Nevertheless, most studies have lacked information concerning the concentrations of fibric acids working inside tissues because a simple and sensitive method is not available for their quantitation. This study aimed to develop a simple and sensitive bioanalytical method for the quantitation of clofibric, bezafibric and fenofibric acids in samples of very small portions of tissues. Fibric acids were extracted into n-hexane-ethyl acetate from tissue homogenates (10 mg of liver, kidney or muscle) or serum (100 µL) and were derivatized with 4-bromomethyl-6,7-dimethoxycoumarin, followed by HPLC with fluorescence detection. These compounds were separated isocratically on a reversed phase with acetonitrile-water. Standard analytical curves were linear over the concentration range of 0.2-20 nmol/10 mg of liver. Precision and accuracy were within acceptable limits. Recovery from liver homogenates ranged from 93.03 to 112.29%. This method enabled the quantitation of fibric acids in 10 mg of liver from rats treated with clofibric acid, bezafibric acid or fenofibrate. From these analytical data, it became clear that there was no large difference in ratio of acyl-CoA oxidase 1 (Acox1) mRNA level to fibric acid content in the liver among the three fibric acids, suggesting that these three fibric acids have similar potency to increase expression of the Acox1 gene, which is a target of peroxisome proliferator-activated receptor α. Thus, the proposed method is a simple, sensitive and reliable tool for the quantitation of fibric acids working in vivo inside livers.

Update on the clinical utility of fenofibrate in mixed dyslipidemias: mechanisms of action and rational prescribing

PubMed Central

Farnier, Michel

2008-01-01

Mixed dyslipidemia is a common lipid disorder characterized by the presence of an atherogenic lipoprotein phenotype due to abnormalities in various atherogenic and anti-atherogenic lipoproteins. Despite the link between the decrease of LDL-cholesterol by statin treatment and the prevention of cardiovascular disease, a high residual risk is observed in statin trials. This residual risk is partly explained by lipoprotein abnormalities other than LDL. Fenofibrate exerts a favorable effect on the atherogenic lipid profile of mixed dyslipidemia and can effectively reduce cardiovascular disease in patients with mixed dyslipidemia. Fenofibrate may offer important treatment alternatives as a second-line therapy in several circumstances: in combination with a statin for patients with mixed dyslipidemias not at goals on statin mono-therapy; in monotherapy for patients intolerant or with contraindication to statin therapy; and in combination with other drugs (ezetimibe, colesevelam) for patients with mixed dyslipidemias, known intolerance, or contraindication to statin and not at goals on fenofibrate monotherapy. However, the role of fenofibrate-statin therapy and of other therapies involving fenofibrate in cardiovascular risk reduction strategies remains to be established. PMID:19183747

Fasting Serum Taurine-Conjugated Bile Acids Are Elevated in Type 2 Diabetes and Do Not Change With Intensification of Insulin

PubMed Central

Wewalka, Marlene; Patti, Mary-Elizabeth; Barbato, Corinne; Houten, Sander M.

2014-01-01

Context: Bile acids (BAs) are newly recognized signaling molecules in glucose and energy homeostasis. Differences in BA profiles with type 2 diabetes mellitus (T2D) remain incompletely understood. Objective: The objective of the study was to assess serum BA composition in impaired glucose-tolerant, T2D, and normal glucose-tolerant persons and to monitor the effects of improving glycemia on serum BA composition in T2D patients. Design and Setting: This was a cross-sectional cohort study in a general population (cohort 1) and nonrandomized intervention (cohort 2). Patients and Interventions: Ninety-nine volunteers underwent oral glucose tolerance testing, and 12 persons with T2D and hyperglycemia underwent 8 weeks of intensification of treatment. Main Outcome Measures: Serum free BA and respective taurine and glycine conjugates were measured by HPLC tandem mass spectrometry. Results: Oral glucose tolerance testing identified 62 normal-, 25 impaired glucose-tolerant, and 12 T2D persons. Concentrations of total taurine-conjugated BA were higher in T2D and intermediate in impaired- compared with normal glucose-tolerant persons (P = .009). Univariate regression revealed a positive association between total taurine-BA and fasting glucose (R = 0.37, P < .001), postload glucose (R = 0.31, P < .002), hemoglobin A1c (R = 0.26, P < .001), fasting insulin (R = 0.21, P = .03), and homeostatic model assessment-estimated insulin resistance (R = 0.26, P = .01) and an inverse association with oral disposition index (R = −0.36, P < .001). Insulin-mediated glycemic improvement in T2D patients did not change fasting serum total BA or BA composition. Conclusion: Fasting taurine-conjugated BA concentrations are higher in T2D and intermediate in impaired compared with normal glucose-tolerant persons and are associated with fasting and postload glucose. Serum BAs are not altered in T2D in response to improved glycemia. Further study may elucidate whether this pattern of taurine-BA conjugation can be targeted to provide novel therapeutic approaches to treat T2D. PMID:24432996

Efficacy and Safety of Pemafibrate Versus Fenofibrate in Patients with High Triglyceride and Low HDL Cholesterol Levels: A Multicenter, Placebo-Controlled, Double-Blind, Randomized Trial.

PubMed

Arai, Hidenori; Yamashita, Shizuya; Yokote, Koutaro; Araki, Eiichi; Suganami, Hideki; Ishibashi, Shun

2018-06-01

To verify the superiority of pemafibrate over placebo and the non-inferiority of pemafibrate to the maximum dose of fenofibrate for determining the percent change in fasting serum triglyceride (TG) levels and to investigate safety by assessing the incidence of adverse events (AEs) and adverse drug reactions (ADRs). This phase III, placebo/active drug-controlled, randomized, double-blind, parallel group comparison study enrolled patients with high TG and low high-density lipoprotein cholesterol levels. Patients were randomly assigned to receive placebo; pemafibrate 0.1 mg/day, 0.2 mg/day, or 0.4 mg/day; or fenofibrate 100 mg/day or 200 mg/day for 12 weeks. Among 526 randomized patients, 489 completed the study, with drop-out rates of 0%, 6.7%, 5.5%, 5.9%, 8.2%, and 10.7% in the placebo; pemafibrate 0.1 mg/day, 0.2 mg/day, and 0.4 mg/day; and fenofibrate 100 mg/day and 200 mg/day groups. The study showed the non-inferiority of pemafibrate 0.4 mg/day and 0.2 mg/day to fenofibrate 200 mg/day as well the non-inferiority and superiority of all pemafibrate doses to fenofibrate 100 mg/day for reducing TG levels. No dose-dependent increase in the incidence of AEs or ADRs was observed among the pemafibrate dose groups. The incidence of AEs and ADRs for all pemafibrate doses was similar to that for placebo and fenofibrate 100 mg/day and significantly lower than that for fenofibrate 200 mg/day (P＜0.05). The favorable safety profile of pemafibrate, with fewer adverse effects on kidney/liver-related laboratory tests and fewer AEs/ADRs, including those leading to treatment discontinuation, over fenofibrate 200 mg/day may justify the use of this novel and potent treatment option for reducing TG levels in a broader range of patients.

A new, major C27 biliary bile acid in the Red-winged tinamou (Rhynchotus rufescens):(25R)-1β,3α,7α-trihydroxy-5β-cholestan-27-oic acid*

PubMed Central

Hagey, Lee R.; Kakiyama, Genta; Muto, Akina; Iida, Takashi; Mushiake, Kumiko; Goto, Takaaki; Mano, Nariyasu; Goto, Junichi; Oliveira, Cleida A.; Hofmann, Alan F.

2009-01-01

The chemical structures of the three major bile acids present in the gallbladder bile of the Red-winged tinamou (Rhynchotus rufescens), an early evolving, ground-living bird related to ratites, were determined. Bile acids were isolated by preparative reversed-phase HPLC. Two of the compounds were identified as the taurine N-acylamidates of (25R)-3α,7α-dihydroxy-5β-cholestan-27-oic acid (constituting 22% of biliary bile acids) and (25R)-3α,7α,12α-trihydroxy-5β-cholestan-27-oic acid (constituting 51%). The remaining compound, constituting 21% of biliary bile acids, was an unknown C27 bile acid. Its structure was elucidated by LC/ESI-MS/MS and NMR and shown to be the taurine conjugate of (25R)-1β,3α,7α-trihydroxy-5β-cholestan-27-oic acid, a C27 trihydroxy bile acid not previously reported. Although C27 bile acids with a 1β-hydroxyl group have been identified as trace bile acids in the alligator, this is the first report of a major biliary C27 bile acid possessing a 1β-hydroxyl group. PMID:19011113

Taurine elevates dopamine levels in the rat nucleus accumbens; antagonism by strychnine.

PubMed

Ericson, Mia; Molander, Anna; Stomberg, Rosita; Söderpalm, Bo

2006-06-01

The mesolimbic dopamine (DA) system, projecting from the ventral tegmental area (VTA) to the nucleus accumbens (nAcc), is involved in reward-related behaviours and addictive processes, such as alcoholism and drug addiction. It was recently suggested that strychnine-sensitive glycine receptors (GlyR) in the nAcc regulate both basal and ethanol-induced mesolimbic DA activity via a neuronal loop involving endogenous activation of nicotinic acetylcholine receptors (nAChR) in the VTA. However, as the nAcc appears to contain few glycine-immunoreactive cell bodies or fibres, the question as to what may be the endogenous ligand for GlyRs in this brain region remains open. Here we have investigated whether the amino acid taurine could serve this purpose using in vivo microdialysis in awake, freely moving male Wistar rats. Local perfusion of taurine (1, 10 or 100 mm in the perfusate) increased DA levels in the nAcc. The taurine (10 mm)-induced DA increase was, similarly to that previously observed after ethanol, completely blocked by (i) perfusion of the competitive GlyR antagonist strychnine in the nAcc, (ii) perfusion of the nAChR antagonist mecamylamine (100 microm) in the VTA, and (iii) systemic administration of the acetylcholine-depleting drug vesamicol (0.4 mg/kg, i.p). The present results suggest that taurine may be an endogenous ligand for GlyRs in the nAcc and that the taurine-induced elevation of DA levels in this area, similarly to that observed after local ethanol, is mediated via a neuronal loop involving endogenous activation of nAChRs in the VTA.

NF-κB/RelA-PKM2 mediates inhibition of glycolysis by fenofibrate in glioblastoma cells

PubMed Central

Wang, Yingyi; Zhang, Junxia; Wang, Xiefeng; Yu, Tianfu; Hu, Qi; Liu, Ning; You, Yongping

2015-01-01

Aerobic glycolysis (production of lactate from glucose in the presence of oxygen) is a hallmark of cancer. Fenofibrate is a lipid-lowering drug and an agonist of the peroxisome proliferator-activated receptor alpha (PPARα). We found that FF inhibited glycolysis in a PPARα-dependent manner in glioblastoma cells. Fenofibrate inhibited the transcriptional activity of NF-κB/RelA and also disrupted its association with hypoxia inducible factor1 alpha (HIF1α), which is required for the binding of NF-κB/RelA to the PKM promoter and PKM2 expression. High ratios of PKM2/PKM1 promote glycolysis and inhibit oxidative phosphorylation, thus favoring aerobic glycolysis. Fenofibrate decreased the PKM2/PKM1 ratio and caused mitochondrial damage. Given that fenofibrate is a widely used non-toxic drug, we suggest its use in patients with glioblastoma multiforme (GBM). PMID:26172294

NF-κB/RelA-PKM2 mediates inhibition of glycolysis by fenofibrate in glioblastoma cells.

PubMed

Han, Dongfeng; Wei, Wenjin; Chen, Xincheng; Zhang, Yaxuan; Wang, Yingyi; Zhang, Junxia; Wang, Xiefeng; Yu, Tianfu; Hu, Qi; Liu, Ning; You, Yongping

2015-09-22

Aerobic glycolysis (production of lactate from glucose in the presence of oxygen) is a hallmark of cancer. Fenofibrate is a lipid-lowering drug and an agonist of the peroxisome proliferator-activated receptor alpha (PPARα). We found that FF inhibited glycolysis in a PPARα-dependent manner in glioblastoma cells. Fenofibrate inhibited the transcriptional activity of NF-κB/RelA and also disrupted its association with hypoxia inducible factor1 alpha (HIF1α), which is required for the binding of NF-κB/RelA to the PKM promoter and PKM2 expression. High ratios of PKM2/PKM1 promote glycolysis and inhibit oxidative phosphorylation, thus favoring aerobic glycolysis. Fenofibrate decreased the PKM2/PKM1 ratio and caused mitochondrial damage. Given that fenofibrate is a widely used non-toxic drug, we suggest its use in patients with glioblastoma multiforme (GBM).

The protective effects of taurine on acute ammonia toxicity in grass carp Ctenopharynodon idellus.

PubMed

Xing, Xiaodan; Li, Ming; Yuan, Lixia; Song, Meize; Ren, Qianyan; Shi, Ge; Meng, Fanxing; Wang, Rixin

2016-09-01

The four experimental groups were carried out to test the response of grass carp Ctenopharyngodon idella to ammonia toxicity and taurine: group 1 was injected with NaCl, group 2 was injected with ammonium acetate, group 3 was injected with ammonium acetate and taurine, and group 4 was injected taurine. Fish in group 2 had the highest ammonia content in the liver and brain, and alanine, arginine, glutamine, glutamate and glycine contents in liver. Brain alanine and glutamate of fish in group 2 were significantly higher than those of fish in group 1. Malondialdehyde content of fish in group 2 was the highest, but superoxide dismutase and glutathione activities were the lowest. Although fish in group 2 had the lowest red cell count and hemoglobin, the highest alkaline phosphatase, complement C3, C4 and total immunoglobulin contents appeared in this group. In addition, superoxide dismutase and glutathione activities, red cell count and hemoglobin of fish in group 3 were significantly higher than those of fish in group 2, but malondialdehyde content is the opposite. This study indicates that ammonia exerts its toxic effects by interfering with amino acid transport, inducing reactive oxygen species generation and malondialdehyde accumulation, leading to blood deterioration and over-activation of immune response. The exogenous taurine could mitigate the adverse effect of high ammonia level on fish physiological disorder. Copyright © 2016 Elsevier Ltd. All rights reserved.

Differential effects of gemfibrozil and fenofibrate on reverse cholesterol transport from macrophages to feces in vivo.

PubMed

Rotllan, Noemí; Llaverías, Gemma; Julve, Josep; Jauhiainen, Matti; Calpe-Berdiel, Laura; Hernández, Cristina; Simó, Rafael; Blanco-Vaca, Francisco; Escolà-Gil, Joan Carles

2011-02-01

Gemfibrozil and fenofibrate, two of the fibrates most used in clinical practice, raise HDL cholesterol (HDLc) and are thought to reduce the risk of atherosclerotic cardiovascular disease. These drugs act as PPARα agonists and upregulate the expression of genes crucial in reverse cholesterol transport (RCT). In the present study, we determined the effects of these two fibrates on RCT from macrophages to feces in vivo in human apoA-I transgenic (hApoA-ITg) mice. [(3)H]cholesterol-labeled mouse macrophages were injected intraperitoneally into hApoA-ITg mice treated with intragastric doses of fenofibrate, gemfibrozil or a vehicle solution for 17days, and radioactivity was determined in plasma, liver and feces. Fenofibrate, but not gemfibrozil, enhanced [(3)H]cholesterol flux to plasma and feces of female hApoA-ITg mice. Fenofibrate significantly increased plasma HDLc, HDL phospholipids, hApoA-I levels and phospholipid transfer protein activity, whereas these parameters were not altered by gemfibrozil treatment. Unlike gemfibrozil, fenofibrate also induced the generation of larger HDL particles, which were more enriched in cholesteryl esters, together with higher potential to generate preβ-HDL formation and caused a significant increase in [(3)H]cholesterol efflux to plasma. Our findings demonstrate that fenofibrate promotes RCT from macrophages to feces in vivo and, thus, highlight a differential action of this fibrate on HDL. Copyright © 2010 Elsevier B.V. All rights reserved.

Rickets in lion cubs at the London Zoo in 1889: some new insights.

PubMed

Chesney, Russell W; Hedberg, Gail

2009-05-01

In 1889, when Dr John Bland-Sutton, a prominent surgeon in London, England, was consulted concerning fatal rickets in more than 20 successive litters of lion cubs at the London Zoo, he evaluated the role of diet relative to the development of rickets. He prescribed goat meat and bones and cod-liver oil to be added to the lean horse-meat diet of the cubs and their mothers. Rickets reversed, the cubs survived, and litters were reared successfully. In classic controlled studies conducted in puppies and young rats 3 decades later, the crucial role of calcium, phosphate, and vitamin D in both prevention and therapy of rickets was elucidated. Later studies led to the identification of the structural features of vitamin D. Although the Bland-Sutton interventional diet obviously provides calcium and phosphate from bones and vitamin D from cod-liver oil, other benefits of this diet were not initially recognized. Chewing bones promotes tooth and gum health and removes bacteria-laden tartar. Cod-liver oil also contains vitamin A, which is essential for the prevention of infection and for epithelial cell health. Taurine-conjugated bile salts are also necessary for the intestinal absorption of fat-soluble vitamins, including A and D. Moreover, unlike dogs and rats, all feline species are unable to synthesize taurine yet can only conjugate bile acids with taurine. This sulfur-containing beta-amino acid must be provided in the carnivorous diet of a large cat. Taurine-conjugated bile salts were provided in the oil cold-pressed from cod liver. The now famous Bland-Sutton "experiment of nature," namely, fatal rickets in lion cubs, was cured by the addition of minerals and vitamin D. However, gum health and the presence of taurine-conjugated bile salts undoubtedly permitted absorption of vitamin A and D, the latter promoting the cure of rickets.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Galatola, G.; Jazrawi, R.P.; Bridges, C.

The purpose of this study was to develop and validate a method of directly measuring ileal bile acid absorption efficiency during a single enterohepatic cycle (first-pass ileal clearance). This has become feasible for the first time because of the availability of the synthetic gamma-labeled bile acid 75Selena-homocholic acid-taurine (75SeHCAT). Together with the corresponding natural bile acid cholic acid-taurine (labeled with 14C), SeHCAT was infused distal to an occluding balloon situated beyond the ampulla of Vater in six healthy subjects. Completion of a single enterohepatic cycle was assessed by obtaining a plateau for 75SeHCAT activity proximal to the occluding balloon, whichmore » prevented further cycles. Unabsorbed 75SeHCAT was collected after total gut washout, which was administered distal to the occluding balloon. 75SeHCAT activity in the rectal effluent measured by gamma counter was compared with that of absorbed 75SeHCAT level measured by gamma camera and was used to calculate first-pass ileal clearance. This was very efficient (mean value, 96%) and showed very little variation in the six subjects studied (range, 95%-97%). A parallel time-activity course in hepatic bile for 14C and 75Se during a single enterohepatic cycle, together with a ratio of unity for 14C/75Se in samples obtained at different time intervals, suggests that 75SeHCAT is handled by the ileum like the natural bile acid cholic acid-taurine. Extrapolation of 75SeHCAT first-pass ileal clearance to that of the natural bile acid therefore seems justifiable. In a subsidiary experiment, ileal absorption efficiency per day for 75SeHCAT was also measured by scanning the gallbladder area on 5 successive days after the measurement of first-pass ileal clearance. In contrast with absorption efficiency per cycle, absorption efficiency per day varied widely (49%-86%).« less

The osmotic/calcium stress theory of brain damage: are free radicals involved?

PubMed

Pazdernik, T L; Layton, M; Nelson, S R; Samson, F E

1992-01-01

This overview presents data showing that glucose use increases and that excitatory amino acids (i.e., glutamate, aspartate), taurine and ascorbate increase in the extracellular fluid during seizures. During the cellular hyperactive state taurine appears to serve as an osmoregulator and ascorbate may serve as either an antioxidant or as a pro-oxidant. Finally, a unifying hypothesis is given for seizure-induced brain damage. This unifying hypothesis states that during seizures there is a release of excitatory amino acids which act on glutamatergic receptors, increasing neuronal activity and thereby increasing glucose use. This hyperactivity of cells causes an influx of calcium (i.e., calcium stress) and water movements (i.e., osmotic stress) into the cells that culminate in brain damage mediated by reactive oxygen species.

Two Major Bile Acids in the Hornbills, (24R,25S)-3α,7α,24-Trihydroxy-5β-cholestan-27-oyl Taurine and Its 12α-Hydroxy Derivative.

PubMed

Satoh, Rika; Ogata, Hiroaki; Saito, Tetsuya; Zhou, Biao; Omura, Kaoru; Kurabuchi, Satoshi; Mitamura, Kuniko; Ikegawa, Shigeo; Hagey, Lee R; Hofmann, Alan F; Iida, Takashi

2016-06-01

Two major bile acids were isolated from the gallbladder bile of two hornbill species from the Bucerotidae family of the avian order Bucerotiformes Buceros bicornis (great hornbill) and Penelopides panini (Visayan tarictic hornbill). Their structures were determined to be 3α,7α,24-dihydroxy-5β-cholestan-27-oic acid and its 12α-hydroxy derivative, 3α,7α,12α,24-tetrahydroxy-5β-cholestan-27-oic acid (varanic acid, VA), both present in bile as their corresponding taurine amidates. The four diastereomers of varanic acid were synthesized and their assigned structures were confirmed by X-ray crystallographic analysis. VA and its 12-deoxy derivative were found to have a (24R,25S)-configuration. 13 additional hornbill species were also analyzed by HPLC and showed similar bile acid patterns to B. bicornis and P. panini. The previous stereochemical assignment for (24R,25S)-VA isolated from the bile of varanid lizards and the Gila monster should now be revised to the (24S,25S)-configuration.

Development and validation of a hydrophilic interaction chromatography-mass spectrometry assay for taurine and methionine in matrices rich in carbohydrates.

PubMed

de Person, Marine; Hazotte, Aurélie; Elfakir, Claire; Lafosse, Michel

2005-07-22

A new procedure based on hydrophilic interaction chromatography coupled to tandem mass spectrometry (ionisation process by pneumatically assisted electrospray in negative ion mode), is developed and validated for the simultaneous determination of underivatised taurine and methionine in beverages rich in carbohydrates such as energy drinks. No initial clean-up procedure and no sample derivatisation are required. Satisfactory analysis was obtained on an Astec apHera NH2 (150 mm x 4.6 mm; 5 microm) column with methanol-water (60/40) as mobile phase. The method was validated in terms of specificity, detection limits, linearity, accuracy, precision and stability, using threonine as internal standard. The potential effects of matrix and endogenous amino acid content were also examined. The limits of detection in the beverage varied from 20 microg L(-1) for taurine to 50 micro L(-1) for methionine.

Taurine supplementation of plant derived protein and n-3 fatty acids are critical for optimal growth and development of cobia, Rachycentron canadum.

PubMed

Watson, Aaron M; Barrows, Frederic T; Place, Allen R

2013-09-01

We examined growth performance and the lipid content in juvenile cobia, Rachycentron canadum, fed a taurine supplemented (1.5 %), plant protein based diet with two fish oil replacements. The first fish oil replacement was a thraustochytrid meal (TM + SOY) plus soybean oil (~9 % CL) and the second was a canola oil supplemented with the essential fatty acids (EFA) docosahexaenoic acid (DHA) and arachidonic acid (ARA) (~8 % CL). The diet using the thraustochytrid meal plus soybean oil performed equivalently to the fish oil diet; both resulting in significantly higher growth rates, lower feed conversion ratios, and higher survival than the supplemented canola oil diet, even though all three diets were similar in overall energy and met known protein and lipid requirements for cobia. The poor performance of the canola oil diet was attributed to insufficient addition of EFA in the supplemented canola oil source. Increasing levels of EFA in the supplemented canola oil above 0.5 g EFA kg(-1) would likely improve results with cobia. When fish fed either of the fish oil replacement diets were switched to the fish oil control diet, fatty acid profiles of the fillets were observed to transition toward that of the fish oil diet and could be predicted based on a standard dilution model. Based on these findings, a formulated diet for cobia can be produced without fish products providing 100 % survivorship, specific growth rates greater than 2.45 and feed conversion ratios less than 1.5, as long as taurine is added and EFA levels are above 0.5 g EFA kg(-1).

Parental prey selection affects risk-taking behaviour and spatial learning in avian offspring

PubMed Central

Arnold, Kathryn E; Ramsay, Scot L; Donaldson, Christine; Adam, Aileen

2007-01-01

Early nutrition shapes life history. Parents should, therefore, provide a diet that will optimize the nutrient intake of their offspring. In a number of passerines, there is an often observed, but unexplained, peak in spider provisioning during chick development. We show that the proportion of spiders in the diet of nestling blue tits, Cyanistes caeruleus, varies significantly with the age of chicks but is unrelated to the timing of breeding or spider availability. Moreover, this parental prey selection supplies nestlings with high levels of taurine particularly at younger ages. This amino acid is known to be both vital and limiting for mammalian development and consequently found in high concentrations in placenta and milk. Based on the known roles of taurine in mammalian brain development and function, we then asked whether by supplying taurine-rich spiders, avian parents influence the stress responsiveness and cognitive function of their offspring. To test this, we provided wild blue tit nestlings with either a taurine supplement or control treatment once daily from the ages of 2–14 days. Then pairs of size- and sex-matched siblings were brought into captivity for behavioural testing. We found that juveniles that had received additional taurine as neonates took significantly greater risks when investigating novel objects than controls. Taurine birds were also more successful at a spatial learning task than controls. Additionally, those individuals that succeeded at a spatial learning task had shown intermediate levels of risk taking. Non-learners were generally very risk-averse controls. Early diet therefore has downstream impacts on behavioural characteristics that could affect fitness via foraging and competitive performance. Fine-scale prey selection is a mechanism by which parents can manipulate the behavioural phenotype of offspring. PMID:17698490

Parental prey selection affects risk-taking behaviour and spatial learning in avian offspring.

PubMed

Arnold, Kathryn E; Ramsay, Scot L; Donaldson, Christine; Adam, Aileen

2007-10-22

Early nutrition shapes life history. Parents should, therefore, provide a diet that will optimize the nutrient intake of their offspring. In a number of passerines, there is an often observed, but unexplained, peak in spider provisioning during chick development. We show that the proportion of spiders in the diet of nestling blue tits, Cyanistes caeruleus, varies significantly with the age of chicks but is unrelated to the timing of breeding or spider availability. Moreover, this parental prey selection supplies nestlings with high levels of taurine particularly at younger ages. This amino acid is known to be both vital and limiting for mammalian development and consequently found in high concentrations in placenta and milk. Based on the known roles of taurine in mammalian brain development and function, we then asked whether by supplying taurine-rich spiders, avian parents influence the stress responsiveness and cognitive function of their offspring. To test this, we provided wild blue tit nestlings with either a taurine supplement or control treatment once daily from the ages of 2-14 days. Then pairs of size- and sex-matched siblings were brought into captivity for behavioural testing. We found that juveniles that had received additional taurine as neonates took significantly greater risks when investigating novel objects than controls. Taurine birds were also more successful at a spatial learning task than controls. Additionally, those individuals that succeeded at a spatial learning task had shown intermediate levels of risk taking. Non-learners were generally very risk-averse controls. Early diet therefore has downstream impacts on behavioural characteristics that could affect fitness via foraging and competitive performance. Fine-scale prey selection is a mechanism by which parents can manipulate the behavioural phenotype of offspring.

Taurine ameliorated homocysteine-induced H9C2 cardiomyocyte apoptosis by modulating endoplasmic reticulum stress.

PubMed

Zhang, Zhimin; Zhao, Lianyou; Zhou, Yanfen; Lu, Xuanhao; Wang, Zhengqiang; Wang, Jipeng; Li, Wei

2017-05-01

Homocysteine (Hcy)-triggered endoplasmic reticulum (ER) stress-mediated endothelial cell apoptosis has been suggested as a cause of Hcy-dependent vascular injury. However, whether ER stress is the molecular mechanism linking Hcy and cardiomyocytes death is unclear. Taurine has been reported to exert cardioprotective effects via various mechanisms. However, whether taurine protects against Hcy-induced cardiomyocyte death by attenuating ER stress is unknown. This study aimed to evaluate the opposite effects of taurine on Hcy-induced cardiomyocyte apoptosis and their underlying mechanisms. Our results demonstrated that low-dose or short-term Hcy treatment increased the expression of glucose-regulated protein 78 (GRP78) and activated protein kinase RNA-like ER kinase (PERK), inositol-requiring enzyme 1 (IRE1), and activating transcription factor 6 (ATF6), which in turn prevented apoptotic cell death. High-dose Hcy or prolonged Hcy treatment duration significantly up-regulated levels of C/EBP homologous protein (CHOP), cleaved caspase-12, p-c-Jun N-terminal kinase (JNK), and then triggered apoptotic events. High-dose Hcy also resulted in a decrease in mitochondrial membrane potential (Δψm) and an increase in cytoplasmic cytochrome C and the expression of cleaved caspase-9. Pretreatment of cardiomyocytes with sodium 4-phenylbutyric acid (an ER stress inhibitor) significantly inhibited Hcy-induced apoptosis. Furthermore, blocking the PERK pathway partly alleviated Hcy-induced ER stress-modulated cardiomyocyte apoptosis, and down-regulated the levels of Bax and cleaved caspase-3. Experimental taurine pretreatment inhibited the expression of ER stress-related proteins, and protected against apoptotic events triggered by Hcy-induced ER stress. Taken together, our results suggest that Hcy triggered ER stress in cardiomyocytes, which was the crucial molecular mechanism mediating Hcy-induced cardiomyocyte apoptosis, and the adverse effect of Hcy could be prevented by taurine.

Expression patterns of regulatory RNAs, including lncRNAs and tRNAs, during postnatal growth of normal and dystrophic (mdx) mouse muscles, and their response to taurine treatment.

PubMed

Butchart, Lauren C; Terrill, Jessica R; Rossetti, Giulia; White, Robert; Filipovska, Aleksandra; Grounds, Miranda D

2018-06-01

Post-natal skeletal muscle growth in mice is very rapid and involves complex changes in many cells types over the first 6 weeks of life. The acute onset of dystropathology also occurs around 3 weeks of age in the mdx mouse model of the human disease Duchenne Muscular Dystrophy (DMD). This study investigated (i) alterations in expression patterns of regulatory non-coding RNAs (ncRNAs) in vivo, including miRNAs, lncRNAs and tRNAs, during early growth of skeletal muscles in normal control C57Bl/10Scsn (C57) compared with dystrophic mdx mice from 2 to 6 weeks of postnatal age, and revealed inherent differences in vivo for levels of 3 ncRNAs between C57 and mdx muscles before the onset of dystropathology. Since the amino acid taurine has many benefits and reduces disease severity in mdx mice, this study also (ii) determined the impact of taurine treatment on these expression patterns in mdx muscles at the onset of dystropathology (3 weeks) and after several bouts of myonecrosis and regeneration (6 weeks). Taurine treatment of mdx mice only altered ncRNA levels when administered from 18 days to 6 weeks of age, but a deficiency in tRNA levels was rectified earlier in mdx skeletal muscles treated from 14 days to 3 weeks. Myogenesis in tissue culture was also used to (iii) compare ncRNA expression patterns for both strains, and (iv) the response to taurine treatment. These analyses revealed intrinsic differences in ncRNA expression patterns during myogenesis between strains, as well as increased sensitivity of mdx ncRNA levels to taurine treatment. Copyright © 2018 Elsevier Ltd. All rights reserved.

Changes in urinary amino acids excretion in relationship with muscle activity markers over a professional cycling stage race: in search of fatigue markers.

PubMed

Corsetti, Roberto; Barassi, Alessandra; Perego, Silvia; Sansoni, Veronica; Rossi, Alessandra; Damele, Clara Anna Linda; Melzi D'Eril, Gianlodovico; Banfi, Giuseppe; Lombardi, Giovanni

2016-01-01

The aim of this study was to identify the relationship between metabolic effort, muscular damage/activity indices, and urinary amino acids profile over the course of a strenuous prolonged endurance activity, as a cycling stage race is, in order to identify possible fatigue markers. Nine professional cyclists belonging to a single team, competing in the Giro d'Italia cycling stage race, were anthropometrically characterized and sampled for blood and urine the day before the race started, and on days 12 and 23 of the race. Diet was kept the same over the race, and power output and energy expenditure were recorded. Sera were assayed for muscle markers (lactate dehydrogenase, aspartate aminotransferase, and creatine kinase activities, and blood urea nitrogen), and creatinine, all corrected for plasma volume changes. Urines were profiled for amino acid concentrations, normalized on creatinine excretion. Renal function, in terms of glomerular filtration rate, was monitored by MDRD equation corrected on body surface area. Creatine kinase activity and blood urea were increased during the race as did serum creatinine while kidney function remained stable. Among the amino acids, taurine, glycine, cysteine, leucine, carnosine, 1-methyl histidine, and 3-methyl histidine showed a net decreased, while homocysteine was increased. Taurine and the dipeptide carnosine (β-alanyl-L-histidine) were significantly correlated with the muscle activity markers and the indices of effort. In conclusion, the metabolic profile is modified strikingly due to the effort. Urinary taurine and carnosine seem useful tools to evaluate the muscle damage and possibly the fatigue status on a long-term basis.

Fish oil and fenofibrate for the treatment of hypertriglyceridemia in HIV-infected subjects on antiretroviral therapy: results of ACTG A5186.

PubMed

Gerber, John G; Kitch, Douglas W; Fichtenbaum, Carl J; Zackin, Robert A; Charles, Stéphannie; Hogg, Evelyn; Acosta, Edward P; Connick, Elizabeth; Wohl, David; Kojic, E Milu; Benson, Constance A; Aberg, Judith A

2008-04-01

Fish oil has been shown to reduce serum triglyceride (TG) concentrations. In HIV-infected patients on antiretroviral therapy, high TG concentrations likely contribute to increased risk of cardiovascular disease. AIDS Clinical Trials Group A5186 examined the safety and efficacy of fish oil plus fenofibrate in subjects not achieving serum TG levels < or =200 mg/dL with either agent alone. One hundred subjects on highly active antiretroviral therapy with serum TG concentrations > or =400 mg/dL and low-density lipoprotein cholesterol < or =160 mg/dL were randomized to 3 g of fish oil twice daily or 160 mg of fenofibrate daily for 8 weeks. Subjects with a fasting TG level >200 mg/dL at week 8 received a combination of fish oil and fenofibrate in the same doses from week 10 to week 18. Median baseline TG was 662 mg/dL in the fish oil group and 694 mg/dL in the fenofibrate group (P = not significant). Fish oil reduced TG levels by a median of 283 mg/dL (46%), fenofibrate reduced them by 367 mg/dL (58%), and combination therapy reduced them by 65.5%. Combination therapy achieved TG levels of < or =200 mg/dL in 22.7% subjects. Fish oil had no measurable effect on immunologic parameters or the pharmacokinetics of lopinavir. Fish oil was safe when administered alone or combined with fenofibrate and significantly reduced TG levels in HIV-infected subjects with hypertriglyceridemia.

Fish Oil and Fenofibrate for the Treatment of Hypertriglyceridemia in HIV-Infected Subjects on Antiretroviral Therapy

PubMed Central

Gerber, John G.; Kitch, Douglas W.; Fichtenbaum, Carl J.; Zackin, Robert A.; Charles, Stéphannie; Hogg, Evelyn; Acosta, Edward P.; Connick, Elizabeth; Wohl, David; Kojic, E. Milu; Benson, Constance A.; Aberg, Judith A.

2009-01-01

Introduction Fish oil has been shown to reduce serum triglyceride (TG) concentrations. In HIV-infected patients on antiretroviral therapy, high TG concentrations likely contribute to increased risk of cardiovascular disease. AIDS Clinical Trials Group A5186 examined the safety and efficacy of fish oil plus fenofibrate in subjects not achieving serum TG levels ≤200 mg/dL with either agent alone. Methods One hundred subjects on highly active antiretroviral therapy with serum TG concentrations ≥400 mg/dL and low-density lipoprotein cholesterol ≤160 mg/dL were randomized to 3 g of fish oil twice daily or 160 mg of fenofibrate daily for 8 weeks. Subjects with a fasting TG level >200 mg/dL at week 8 received a combination of fish oil and fenofibrate in the same doses from week 10 to week 18. Results Median baseline TG was 662 mg/dL in the fish oil group and 694 mg/dL in the fenofibrate group (P = not significant). Fish oil reduced TG levels by a median of 283 mg/dL (46%), fenofibrate reduced them by 367 mg/dL (58%), and combination therapy reduced them by 65.5%. Combination therapy achieved TG levels of ≤200 mg/dL in 22.7% subjects. Fish oil had no measurable effect on immunologic parameters or the pharmacokinetics of lopinavir. Conclusions Fish oil was safe when administered alone or combined with fenofibrate and significantly reduced TG levels in HIV-infected subjects with hypertriglyceridemia. PMID:17971707

Probable fenofibrate-induced acute generalized exanthematous pustulosis.

PubMed

Power, Anna E; Graudins, Linda V; McLean, Catriona A; Hopper, Ingrid

2015-12-01

The case of a patient who experienced a severe adverse reaction requiring emergency treatment after a single dose of fenofibrate is described. A 58-year-old woman with type 1 diabetes was hospitalized for treatment of an extensive blistering rash on the buttocks and trunk accompanied by fever, hypotension, tachycardia, neutrophilia, impaired renal function, and liver enzyme abnormalities. She reported that two days previously she had developed fever and vomiting four hours after taking her first dose of fenofibrate (145 mg). The patient required vasopressor support and was initially treated with broad-spectrum antibiotics for 3 days and a course of immune globulin. On hospital day 4, histopathology returned results consistent with acute generalized exanthematous pustulosis (AGEP), and the patient was subsequently treated with topical steroids. Gradual resolution of AGEP was noted at the time of her discharge from the hospital on day 7 and at one-week follow-up. Analysis of the case using the adverse drug reaction probability scale of Naranjo et al. yielded a score of 5, indicating a probable association between fenofibrate use and AGEP development. AGEP is a predominantly drug-induced condition but is not typically associated with fenofibrate use. Cutaneous eruptions in AGEP are often accompanied by systemic symptoms (e.g., fever, leukocytosis), and the disorder can also be associated with impaired creatinine clearance and elevated aminotransaminase levels. A woman with type 1 diabetes developed AGEP after taking a single dose of fenofibrate. Her cutaneous symptoms began to resolve within days of discontinuation of fenofibrate use. Copyright © 2015 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

Chronic treatment with fibrates elevates superoxide dismutase in adult mouse brain microvessels

PubMed Central

Wang, Guangming; Liu, Xiaowei; Guo, Qingmin; Namura, Shobu

2010-01-01

Fibrates are activators of peroxisome proliferator-activated receptor (PPAR) α. Pretreatment with fibrates has been shown to protect brain against ischemia in mice. We hypothesized that fibrates elevate superoxide dismutase (SOD) levels in the brain microvessels (BMV). BMV were isolated from male C57BL/6 and PPARα null mice that had been treated with fenofibrate or gemfibrozil for 7 days. To examine the effect of discontinuation of fenofibrate, another animal group treated with fenofibrate was examined on post-discontinuation day 3 (D-3). To examine whether SOD elevations attenuate oxidative stress in the ischemic brain, separate animals treated with fenofibrate for 7 days were subjected to 60 minutes focal ischemia on post-discontinuation day 0 (D-0) or D-3. Fenofibrate (30 mg/kg) increased mRNA levels of all three isoforms of SOD and activity level in BMV on D-0 but these effects were not detected on D-3. The elevations were not detected in PPARα null mice. SOD levels were also elevated by gemfibrozil (30 mg/kg). Fenofibrate significantly reduced superoxide production and protein oxidation in the ischemic brain at 30 minutes after reperfusion. Fenofibrate reduced infarct size measured at 24 hours after reperfusion on D-0; however, the infarct reduction was not seen when ischemia was induced on D-3. These findings suggest that fibrates elevate SOD in BMV through PPARα, which contributes to the infarct reduction, at least in part. Further studies are needed to establish the link between the SOD elevations and the brain protection by fibrates against ischemia. PMID:20813100

Amino acid transmitters in patients with headache during the acute phase of cerebrovascular ischemic disease.

PubMed

Castillo, J; Martínez, F; Corredera, E; Aldrey, J M; Noya, M

1995-11-01

The pathophysiology of headache occurring at stroke onset is unknown. Migraine and ischemia share an excessive release of neuroexcitatory amino acids. Inhibitory amino acids also may be implicated in both diseases. We investigated whether fluctuations of these amino acids occur in headache accompanying cerebral infarction. We studied 100 patients with infarction in the territory of the middle cerebral artery. Neurological impairment was assessed using the Canadian Neurological Scale and Barthel Index. Size of infarction was determined with CT. Twenty-eight patients developed headache. Glutamate, aspartate, and taurine were quantified in blood and cerebrospinal fluid (CSF) within 24 hours of stroke onset with cationic exchange chromatography. Stroke subtypes, size of infarct on CT, and clinical scales were similar in patients with and without headache. Plasma glutamate level was 321.14 +/- 149.53 mumol/L in patients with headache and 233 +/- 107.23 mumol/L in those without headache (P < .005). Glutamate in CSF was higher in patients with headache (4.6 +/- 1.49 mumol/L) than in patients without headache (3.11 +/- 1.18 mumol/L) (P < .001). Aspartate concentrations in plasma and CSF were similar in both groups. Taurine concentrations in plasma were 103.10 +/- 52.82 mumol/L and 177.49 +/- 90.92 mumol/L in headache and nonheadache patients, respectively (P < .001). Taurine levels in CSF were 5.42 +/- 2.42 mumol/L in patients with headache and 9.27 +/- 5.31 mumol/L in those without headache (P < .001). No significant correlation was found between amino acid levels in plasma or CSF and size of infarction. Amino acid neurotransmitters play a role in the pathophysiology of headache that occurs at the onset of stroke. The ischemic penumbral area, more than the infarction itself, may cause a state of cortical hyperexcitability that would be responsible for the cortical release of amino acids and the induction of headache by altering pain perception mechanisms.

Crystal structure of choline fenofibrate (Trilipix®), (C5H14NO) (C17H14ClO4)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kaduk, James A.; Zhong, Kai; Gindhart, Amy M.

2016-04-04

The crystal structure of choline fenofibrate has been solved and refined using synchrotron X-ray powder diffraction data, and optimized using density functional techniques. Choline fenofibrate crystallizes in space groupPbca(#61) witha= 12.341 03(2),b= 28.568 70(6),c= 12.025 62(2) Å,V= 4239.84(1) Å 3, andZ= 8. The hydroxyl group of the choline anion makes a strong hydrogen bond to the ionized carboxylate group of the fenofibrate anion. Together with C–H···O hydrogen bonds, these link the cations and anions into layers parallel to theac-plane. The powder pattern has been submitted to ICDD for inclusion in the Powder Diffraction File™.

Proximate composition, amino acid and fatty acid profiles of marine snail Rapana venosa meat, visceral mass and operculum.

PubMed

Luo, Fenglei; Xing, Ronge; Wang, Xueqin; Peng, Quancai; Li, Pengcheng

2017-12-01

Rapana venosa (Rv), an important marine snail, demonstrates an increasing nutritional and economic importance. However, there is still limited information available on their nutritional composition. The present study highlights and provides new information on the proximate composition, amino acid and fatty acid profiles of different body parts of Rv, aiming for its better application and research. The operculum contained a high amount of protein and flavor amino acids. The edible tissues, including meat and visceral mass, were valuable sources of essential amino acids (EAA) apart from methionine and cysteine. In addition, the meat contained high amount of taurine. Fatty acid analysis indicated that the edible tissues contained high amounts of ω3 fatty acids, especially eicosapentaenoic acid (EPA) (C20:5ω3) and docosahexaenoic acid (DHA) (C22:6ω3), and had a low ω6/ω3 fatty acid ratio. Interestingly, significantly higher concentrations of most nutritional elements such as fat, EAA, EPA and DHA, were found in the visceral mass compared to those in the meat. The operculum of Rv may became a very interesting source for some protein and flavor peptide development, and the edible parts of Rv may be utilized for special dietary applications requiring high amounts of taurine, EPA, DHA and a lower ω6/ω3 fatty acid ratio. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Study on the release of fenofibrate nanosuspension in vitro and its correlation with in situ intestinal and in vivo absorption kinetics in rats.

PubMed

Xu, Yuanlong; Wang, Yonglu; Li, Xue Ming; Huang, Qinqin; Chen, Wei; Liu, Ran; Chen, BaoAn; Wei, Ping

2014-07-01

As an oral delivery carrier for poorly water soluble drugs, the nanosuspension was prepared by melt emulsification method combined with high-pressure homogenization. The objective of this study was to clarify the absorption mechanism in rats of fenofibrate nanosuspension using the model of in situ gut perfusion. The release rate of drug from nanosuspension was fast which about 70% of the drug would be released within 5 minutes. The absorption of fenofibrate nanosuspension in the gastrointestinal (GI) tract was studied by the in situ closed loop method in rats. It was found that the absorption process in intestine was first-process with passive diffusion mechanism, and the whole intestine was the major segment for the drug absorption. Additionally, GI absorption in situ studies indicated that the fenofibrate nanosuspension had great success in regard to enhancement of intestinal absorption compared to the fenofibrate suspension of coarse powder. The pharmacokinetic characteristics were studied in rats after oral administration of fenofibrate nanosuspension or suspension at the dosage of 27 mg/kg. The plasma concentration-time curve was fitted to the one-compartment model. The correlation between in vitro dissolution (P), in situ intestinal absorption (F) and in vivo absorption (Fa) in rats was investigated with the results as follows: Fa = 6.2061P-456.38(r = 0.9559), F = 3.6911P-2.2169(r = 0.970), F = 0.5095P + 44.189(r = 0.9609). The highest level A could be obtained from the in vitro--in vivo correlation (IVIVC) between dissolution percentage and intestinal absorption of the fenofibrate nanosuspension in rats. Consequently, the in situ intestinal perfusion model could be used to predict the in vivo pharmacokinetic characteristics in rats.

Fenofibrate inhibits aldosterone-induced apoptosis in adult rat ventricular myocytes via stress-activated kinase-dependent mechanisms

PubMed Central

De Silva, Deepa S.; Wilson, Richard M.; Hutchinson, Christoph; Ip, Peter C.; Garcia, Anthony G.; Lancel, Steve; Ito, Masa; Pimentel, David R.; Sam, Flora

2009-01-01

Aldosterone induces extracellular signal-regulated kinase (ERK)-dependent cardiac remodeling. Fenofibrate improves cardiac remodeling in adult rat ventricular myocytes (ARVM) partly via inhibition of aldosterone-induced ERK1/2 phosphorylation and inhibition of matrix metalloproteinases. We sought to determine whether aldosterone caused apoptosis in cultured ARVM and whether fenofibrate ameliorated the apoptosis. Aldosterone (1 μM) induced apoptosis by increasing terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL)-positive nuclei in ARVM. Spironolactone (100 nM), an aldosterone receptor antagonist, but not RU-486, a glucocorticoid receptor, inhibited aldosterone-mediated apoptosis, indicating that the mineralocorticoid receptor (MR) plays a role. SP-600125 (3 μM)—a selective inhibitor of c-Jun NH2-terminal kinase (JNK)—inhibited aldosterone-induced apoptosis in ARVM. Although aldosterone increased the expression of both stress-activated protein kinases, pretreatment with fenofibrate (10 μM) decreased aldosterone-mediated apoptosis by inhibiting only JNK phosphorylation and the aldosterone-induced increases in Bax, p53, and cleaved caspase-3 and decreases in Bcl-2 protein expression in ARVM. In vivo studies demonstrated that chronic fenofibrate (100 mg·kg body wt−1·day−1) inhibited myocardial Bax and increased Bcl-2 expression in aldosterone-induced cardiac hypertrophy. Similarly, eplerenone, a selective MR inhibitor, used in chronic pressure-overload ascending aortic constriction inhibited myocardial Bax expression but had no effect on Bcl-2 expression. Therefore, involvement of JNK MAPK-dependent mitochondrial death pathway mediates ARVM aldosterone-induced apoptosis and is inhibited by fenofibrate, a peroxisome proliferator-activated receptor (PPAR)α ligand. Fenofibrate mediates beneficial effects in cardiac remodeling by inhibiting programmed cell death and the stress-activated kinases. PMID:19395558

Hypochlorous acid regulates neutrophil extracellular trap release in humans

PubMed Central

Palmer, L J; Cooper, P R; Ling, M R; Wright, H J; Huissoon, A; Chapple, I L C

2012-01-01

Neutrophil extracellular traps (NETs) comprise extracellular chromatin and granule protein complexes that immobilize and kill bacteria. NET release represents a recently discovered, novel anti-microbial strategy regulated non-exclusively by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase generation of reactive oxygen intermediates (ROIs), particularly hydrogen peroxide. This study aimed to characterize the role of ROIs in the process of NET release and to identify the dominant ROI trigger. We employed various enzymes, inhibitors and ROIs to record their effect fluorometrically on in vitro NET release by human peripheral blood neutrophils. Treatment with exogenous superoxide dismutase (SOD) supported the established link between hydrogen peroxide and NET production. However, treatment with myeloperoxidase inhibitors and direct addition of hypochlorous acid (HOCl; generated in situ from sodium hypochlorite) established that HOCl was a necessary and sufficient ROI for NET release. This was confirmed by the ability of HOCl to stimulate NET release in chronic granulomatous disease (CGD) patient neutrophils which, due to the lack of a functional NADPH oxidase, also lack the capacity for NET release in response to classical stimuli. Moreover, the exogenous addition of taurine, abundantly present within the neutrophil cytosol, abrogated NET production stimulated by phorbol myristate acetate (PMA) and HOCl, providing a novel mode of cytoprotection by taurine against oxidative stress by taurine. PMID:22236002

Fenofibrate attenuates diabetic nephropathy in experimental diabetic rat's model via suppression of augmented TGF-β1/Smad3 signaling pathway.

PubMed

Al-Rasheed, Nouf Mohamed; Al-Rasheed, Nawal Mohamed; Al-Amin, Maha Abdelrahman; Hasan, Iman Huesein; Al-Ajmi, Hanaa Najeeb; Mohammad, Raeesa Ahmed; Attia, Hala Aboulfotooh

2016-10-01

Fibrates, the ligands of peroxisome profileferator-activated receptor-α have been shown to have a renal protective action in diabetic nephropathy (DN). This study aimed to elucidate the effect of fenofibrate on renal transforming growth factor-β1 (TGF-β1) and Smad3 in Streptozotocin (STZ)-induced DN. Diabetes was induced in rats by a single intraperitoneal injection of streptozotocin (55 mg/kg). Diabetic rats were given fenofibrate (100 mg/kg, p.o.). After 12 weeks, diabetic nephropathy biomarkers were assessed. The mRNA expression of collage I and III, TGF-β1 and Smad3 and were detected by RT-PCR. Fenofibrate reduced significantly serum creatinine, kidney/body weight ratio, serum albumin excretion Collage I & III, TGF-β1 and Smad3 mRNA expression. Our results give further insights into the mechanisms underlying the protective role of fenofibrate in DN, suggesting that interference with TGF-β1/Smad3 signaling pathway may be a useful therapeutic approach to prevent DN.

Taurine flux in chicken erythrocytes.

PubMed

Porter, D W; Martin, W G

1992-05-01

1. The intracellular taurine concentration in chick erythrocytes increased with age. 2. Erythrocyte taurine influx and efflux rates increased with age. 3. Erythrocyte taurine influx decreased when the extracellular sodium concentration was below normal physiological concentrations. 4. Under hypo-osmotic conditions, taurine efflux from erythrocytes increased. 5. The data suggest that chick erythrocyte taurine metabolism changes during early post-hatch development and that one taurine function may be as an osmoregulator.

Benefits and Safety of Long-Term Fenofibrate Therapy in People With Type 2 Diabetes and Renal Impairment

PubMed Central

Ting, Ru-Dee; Keech, Anthony C.; Drury, Paul L.; Donoghoe, Mark W.; Hedley, John; Jenkins, Alicia J.; Davis, Timothy M.E.; Lehto, Seppo; Celermajer, David; Simes, R. John; Rajamani, Kushwin; Stanton, Kim

2012-01-01

OBJECTIVE Diabetic patients with moderate renal impairment (estimated glomerular filtration rate [eGFR] 30–59 mL/min/1.73 m2) are at particular cardiovascular risk. Fenofibrate’s safety in these patients is an issue because it may elevate plasma creatinine. Furthermore, guidelines regarding fenofibrate dosing in renal impairment vary internationally. We investigated fenofibrate’s effects on cardiovascular and end-stage renal disease (ESRD) events, according to eGFR, in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) Study. RESEARCH DESIGN AND METHODS Type 2 diabetic patients (aged 50–75 years) with eGFR ≥30 mL/min/1.73 m2 were randomly allocated to a fixed dose of fenofibrate (200 mg daily) (n = 4,895) or placebo (n = 4,900) for 5 years. Baseline renal function (Modification of Diet in Renal Disease equation) was grouped by eGFR (30–59, 60–89, and ≥90 mL/min/1.73 m2). The prespecified outcome was total cardiovascular events (composite of cardiovascular death, myocardial infarction, stroke, and coronary/carotid revascularization). Serious adverse events and instances of ESRD (plasma creatinine >400 μmol/L, dialysis, renal transplant, or renal death) were recorded. Analysis was by intention to treat. RESULTS Overall, fenofibrate reduced total cardiovascular events, compared with placebo (hazard ratio 0.89 [95% CI 0.80–0.99]; P = 0.035). This benefit was not statistically different across eGFR groupings (P = 0.2 for interaction) (eGFR 30–59 mL/min/1.73 m2: 0.68 [0.47–0.97], P = 0.035; eGFR ≥90 mL/min/1.73 m2: 0.85 [0.70–1.02], P = 0.08). ESRD rates were similar between treatment arms, without adverse safety signals of fenofibrate use in renal impairment. CONCLUSIONS Patients with type 2 diabetes and moderate renal impairment benefit from long-term fenofibrate, without excess drug-related safety concerns compared with those with no or mild renal impairment. Fenofibrate treatment should not be contraindicated in moderate renal impairment, suggesting that current guidelines may be too restrictive. PMID:22210576

Impact of chronic administration of anabolic androgenic steroids and taurine on blood pressure in rats

PubMed Central

Roşca, A.E.; Stoian, I.; Badiu, C.; Gaman, L.; Popescu, B.O.; Iosif, L.; Mirica, R.; Tivig, I.C.; Stancu, C.S.; Căruntu, C.; Voiculescu, S.E.; Zăgrean, L.

2016-01-01

Supraphysiological administration of anabolic androgenic steroids has been linked to increased blood pressure. The widely distributed amino acid taurine seems to be an effective depressor agent in drug-induced hypertension. The purpose of this study was to assess the impact of chronic high dose administration of nandrolone decanoate (DECA) and taurine on blood pressure in rats and to verify the potentially involved mechanisms. The study was conducted in 4 groups of 8 adult male Wistar rats, aged 14 weeks, treated for 12 weeks with: DECA (A group); vehicle (C group); taurine (T group), or with both drugs (AT group). Systolic blood pressure (SBP) was measured at the beginning of the study (SBP1), 2 (SBP2) and 3 months (SBP3) later. Plasma angiotensin-converting enzyme (ACE) activity and plasma end products of nitric oxide metabolism (NOx) were also determined. SBP3 and SBP2 were significantly increased compared to SBP1 only in the A group (P<0.002 for both). SBP2, SBP3 and ACE activity showed a statistically significant increase in the A vs C (P<0.005), andvs AT groups (P<0.05), while NOx was significantly decreased in the A and AT groups vs controls (P=0.01). ACE activity was strongly correlated with SBP3 in the A group (r=0.71, P=0.04). These findings suggest that oral supplementation of taurine may prevent the increase in SBP induced by DECA, an effect potentially mediated by angiotensin-converting enzyme. PMID:27254659

Low temperature IR spectroscopic study of torsional vibrations of taurine

NASA Astrophysics Data System (ADS)

Bajaj, Naini; Bhatt, Himal; Vishwakarma, S. R.; Thomas, Susy; Murli, C.; Deo, M. N.

2018-04-01

The hydrogen bonding network in amino acids can give information about the structural stability under varying thermodynamic conditions such as temperature and pressure. We have carried out low temperature IR spectroscopic studies on Taurine, an amino acid with various bio-chemical applications in physiology and synthesis, in order to observe the behaviour of torsional modes, i.e. τ(CSH) and τ(NH3), which are very sensitive to the hydrogen bonding interactions. It was observed that the CSH torsional mode showed splitting at low temperature of nearly 250 K and the bandwidth shows linear temperature dependence, which can be attributed to anharmonicity. Another torsional mode, τ(NH3) showed no splitting, but the bandwidth has non-linear temperature dependence. This can be due to orientational changes at low temperature. These observations are strong evidences for a hydrogen bond reorientation induced phase transition at 250 K.

Ursodeoxycholic Acid Ameliorates Fructose-Induced Metabolic Syndrome in Rats

PubMed Central

2014-01-01

The metabolic syndrome (MS) is characterized by insulin resistance, dyslipidemia and hypertension. It is associated with increased risk of cardiovascular diseases and type-2 diabetes. Consumption of fructose is linked to increased prevalence of MS. Ursodeoxycholic acid (UDCA) is a steroid bile acid with antioxidant, anti-inflammatory activities and has been shown to improve insulin resistance. The current study aims to investigate the effect of UDCA (150 mg/kg) on MS induced in rats by fructose administration (10%) in drinking water for 12 weeks. The effects of UDCA were compared to fenofibrate (100 mg/kg), an agonist of PPAR-α receptors. Treatment with UDCA or fenofibrate started from the 6th week after fructose administration once daily. Fructose administration resulted in significant increase in body weight, elevations of blood glucose, serum insulin, cholesterol, triglycerides, advanced glycation end products (AGEs), uric acid levels, insulin resistance index and blood pressure compared to control rats. Moreover, fructose increased oxidative stress in aortic tissues indicated by significant increases of malondialdehyde (MDA), expression of iNOS and reduction of reduced glutathione (GSH) content. These disturbances were associated with decreased eNOS expression, increased infiltration of leukocytes and loss of aortic vascular elasticity. Treatment with UDCA successfully ameliorated the deleterious effects of fructose. The protective effect of UDCA could be attributed to its ability to decrease uric acid level, improve insulin resistance and diminish oxidative stress in vascular tissues. These results might support possible clinical application of UDCA in MS patients especially those present with liver diseases, taking into account its tolerability and safety. However, further investigations on human subjects are needed before the clinical application of UDCA for this indication. PMID:25202970

Pleiotropic effects of fenofibrate therapy on rats with hypertriglycemia.

PubMed

Sun, Bing; Xie, Yuan; Jiang, Jinfa; Wang, Yiping; Xu, Xiaolin; Zhao, Cuimei; Huang, Feifei

2015-04-14

Cardio-protective effect of fibrate therapy is controversial and current research is to evaluate the effect of fenofibrate therapy on rats with hypertriglycemia. Rats with hypertriglycemia were produced by 10% fructose administration (10 ml daily) for 4 weeks. After model has been successfully produced as reflected by increased triglyceride level, different doses of fenofibrate, namely low dose (50 mg/kg body weight) and high dose (100 mg/kg body weight), were orally prescribed for 2 weeks. At baseline, 4 weeks of fructose administration and 2 weeks of fenofibrate therapy, parameters of interest were evaluated and compared. At baseline, no significant differences of parameter were observed between groups. After 4 weeks of fructose prescription, triglyceride level increased in company with high density lipoprotein cholesterol (HDL-C) and apoprotein A1 (ApoA1) decreased. C-reactive protein (CRP) and malondialdehyde (MDA) levels were also elevated. Endothelial function was impaired as reflected by reduced nitric oxide (NO) production and elevated serum asymmetric dimethylarginine (ADMA) level. All these changes were significant as compared to the control group (P<0.05), suggesting that short-term of triglyceride elevation could potently initiate atherosclerosis. With 2 weeks of fenofibrate therapy, in comparison to un-treated group, triglyceride level was significantly reduced in parallel with HDL-C and ApoA1 elevation. Inflammation and oxidation were also profoundly ameliorated as reflected by CRP and MDA reduction. Notably, NO production was enhanced in company with serum ADMA level decrease. Overall, these improvements manifested in a dose-dependent manner, which was supported by multivariate regression analysis showing that after adjusted to other variables, the dose of fenofibrate therapy remained significantly associated with NO production and serum ADMA level, with OR of 1.042 (high-dose versus low-dose, 95% CI 1.028-1.055, P<0.05). Fenofibrate therapy not only could reduce triglyceride level but also confer pleiotropic effects in terms of endothelium-protection and amelioration of inflammation and oxidation in a dose-dependent manner.

Structures with Reconfigurable Circulatory Systems

DTIC Science & Technology

2008-05-16

chemical groups ( cinnamates , etc.) may be explored as they may result in faster kinetics which will facilitate transition between solid and liquid...Cysteine, an amino acid , is a critical substrate in biosynthesis of proteins, glutathione, taurine sulfate and the exceptionally metabolically active

PPAR{alpha} agonist fenofibrate protects the kidney from hypertensive injury in spontaneously hypertensive rats via inhibition of oxidative stress and MAPK activity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hou, Xiaoyang; Division of Cardiothoracic Surgery, The Michael E. DeBakey Department of Surgery, Baylor College of Medicine, BCM 390, One Baylor Plaza, Houston, TX 77030; Shen, Ying H.

2010-04-09

Oxidative stress has been shown to play an important role in the development of hypertensive renal injury. Peroxisome proliferator-activated receptors {alpha} (PPAR{alpha}) has antioxidant effect. In this study, we demonstrated that fenofibrate significantly reduced proteinuria, inflammatory cell recruitment and extracellular matrix (ECM) proteins deposition in the kidney of SHRs without apparent effect on blood pressure. To investigate the mechanisms involved, we found that fenofibrate treatment markedly reduced oxidative stress accompanied by reduced activity of renal NAD(P)H oxidase, increased activity of Cu/Zn SOD, and decreased phosphorylation of p38MAPK and JNK in the kidney of SHRs. Taken together, fenofibrate treatment can protectmore » against hypertensive renal injury without affecting blood pressure by inhibiting inflammation and fibrosis via suppression of oxidative stress and MAPK activity.« less

Neurotransmitter contents in the retina of RCS rat.

PubMed

Okada, M; Okuma, Y; Osumi, Y; Nishihara, M; Yokotani, K; Ueno, H

2000-12-01

Retinitis pigmentosa is a hereditary disease characterized by gradually developing degeneration of photoreceptors. The Royal College of Surgeons (RCS) rat is an experimental model of retinitis pigmentosa. However, there is a paucity of information concerning neurotransmitter contents in the retina of RCS rats. Thus, we determined the retinal contents of neurotransmitters in RCS rats at 4 and 23 weeks postnatally and in age-matched congenic control rats. Dopamine (DA) and acetylcholine (ACh) were electrochemically measured by high-performance liquid chromatography (HPLC). Neuroactive amino acids, including gamma-aminobutyric acid (GABA) and taurine, were determined by means of an HPLC-precolumn derivatization method. Contents of DA, ACh, glutamate, aspartate and GABA in the retina of RCS rats 4 weeks postnatally were within normal ranges. At 23 weeks, the retinal contents of DA, glutamate and aspartate in the RCS rats were significantly lower than in the age-matched control rats, while the contents of ACh and GABA were unaffected even at this later stage. On the other hand, the retinal content of glycine in the RCS rats at 23 weeks was significantly higher than that in the age-matched control rats. It is interesting to note that the content of taurine in the RCS rats had already decreased at 4 weeks postnatally and the decrease was more marked at 23 weeks. The decrease in taurine content is probably the first sign of degeneration revealed by the retinal neurotransmitters of RCS rats.

Enhanced oral bioavailability of fenofibrate using polymeric nanoparticulated systems: physicochemical characterization and in vivo investigation

PubMed Central

Yousaf, Abid Mehmood; Kim, Dong Wuk; Oh, Yu-Kyoung; Yong, Chul Soon; Kim, Jong Oh; Choi, Han-Gon

2015-01-01

Background The intention of this research was to prepare and compare various solubility-enhancing nanoparticulated systems in order to select a nanoparticulated formulation with the most improved oral bioavailability of poorly water-soluble fenofibrate. Methods The most appropriate excipients for different nanoparticulated preparations were selected by determining the drug solubility in 1% (w/v) aqueous solutions of each carrier. The polyvinylpyrrolidone (PVP) nanospheres, hydroxypropyl-β-cyclodextrin (HP-β-CD) nanocorpuscles, and gelatin nanocapsules were formulated as fenofibrate/PVP/sodium lauryl sulfate (SLS), fenofibrate/HP-β-CD, and fenofibrate/gelatin at the optimized weight ratios of 2.5:4.5:1, 1:4, and 1:8, respectively. The three solid-state products were achieved using the solvent-evaporation method through the spray-drying technique. The physicochemical characterization of these nanoparticles was accomplished by powder X-ray diffraction, differential scanning calorimetry, scanning electron microscopy, and Fourier-transform infrared spectroscopy. Their physicochemical properties, aqueous solubility, dissolution rate, and pharmacokinetics in rats were investigated in comparison with the drug powder. Results Among the tested carriers, PVP, HP-β-CD, gelatin, and SLS showed better solubility and were selected as the most appropriate constituents for various nanoparticulated systems. All of the formulations significantly improved the aqueous solubility, dissolution rate, and oral bioavailability of fenofibrate compared to the drug powder. The drug was present in the amorphous form in HP-β-CD nanocorpuscles; however, in other formulations, it existed in the crystalline state with a reduced intensity. The aqueous solubility and dissolution rates of the nanoparticles (after 30 minutes) were not significantly different from one another. Among the nanoparticulated systems tested in this study, the initial dissolution rates (up to 10 minutes) were higher with the PVP nanospheres and HP-β-CD nanocorpuscles; however, neither of them resulted in the highest oral bioavailability. Irrespective of relatively retarded dissolution rate, gelatin nanocapsules showed the highest apparent aqueous solubility and furnished the most improved oral bioavailability of the drug (~5.5-fold), owing to better wetting and diminution in crystallinity. Conclusion Fenofibrate-loaded gelatin nanocapsules prepared using the solvent-evaporation method through the spray-drying technique could be a potential oral pharmaceutical product for administering the poorly water-soluble fenofibrate with an enhanced bioavailability. PMID:25784807

Distinctive metabolite profiles in in-migrating Sockeye salmon suggest sex-linked endocrine perturbation.

PubMed

Benskin, Jonathan P; Ikonomou, Michael G; Liu, Jun; Veldhoen, Nik; Dubetz, Cory; Helbing, Caren C; Cosgrove, John R

2014-10-07

The health of Skeena River Sockeye salmon (Onchorhychus nerka) has been of increasing concern due to declining stock returns over the past decade. In the present work, in-migrating Sockeye from the 2008 run were evaluated using a mass spectrometry-based, targeted metabolomics platform. Our objectives were to (a) investigate natural changes in a subset of the hepatic metabolome arising from migration-associated changes in osmoregulation, locomotion, and gametogenesis, and (b) compare the resultant profiles with animals displaying altered hepatic vitellogenin A (vtg) expression at the spawning grounds, which was previously hypothesized as a marker of xenobiotic exposure. Of 203 metabolites monitored, 95 were consistently observed in Sockeye salmon livers and over half of these changed significantly during in-migration. Among the most dramatic changes in both sexes were a decrease in concentrations of taurine (a major organic osmolyte), carnitine (involved in fatty acid transport), and two major polyunsaturated fatty acids (eicosapentaenoic acid and docosahexaenoic acid). In females, an increase in amino acids was attributed to protein catabolism associated with vitellogenesis. Animals with atypical vtg mRNA expression demonstrated unusual hepatic amino acid, fatty acid, taurine, and carnitine profiles. The cause of these molecular perturbations remains unclear, but may include xenobiotic exposure, natural senescence, and/or interindividual variability. These data provide a benchmark for further investigation into the long-term health of migrating Skeena Sockeye.

Antioxidant activity of methanol extract of Helichrysum foetidum Moench.

PubMed

Tirillini, Bruno; Menghini, Luigi; Leporini, Lidia; Scanu, Nadia; Marino, Stefania; Pintore, Giorgio

2013-01-01

Methanol extract of Helichrysum foetidum Moench (Asteraceae) was investigated for antioxidative properties. The antioxidant activities were investigated by 2,2'-azinobis-3-ethylbenzothiazoline-6-sulphonic acid (ABTS) assay, 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging, ß-carotene/linoleic acid assay, scavenging of hydrogen peroxide (HRPO test), superoxide anion scavenging (S.A.S. test) and hypochlorous acid scavenging (taurine test). The antioxidant activity was reported as IC50 and reveals Trolox-like antioxidative effects.

Attenuation of Diabetes-induced Cardiac and Subcellular Defects by Sulphur-containing Amino Acids.

PubMed

Tappia, Paramjit S; Adameova, Adriana; Dhalla, Naranjan S

2018-01-30

Patients with diabetes mellitus have an increased risk of mortality due to cardiovascular complications. Supplementation with specific sulphur-containing amino acids is rapidly emerging as a possible therapeutic adjuvant for diabetes and associated cardiovascular complications. It is well-known that oxidative stress plays an important role in the pathogenesis of diabetes-induced cardiovascular disease, which is invariably associated with abnormal blood lipid profile, insulin resistance and other symptoms of metabolic syndrome. Cysteine and taurine are among the most common sulphur-containing amino acids and their cellular levels decline during diabetes that may contribute to the development of the cardiomyopathy. Although sulphur-containing agents exert multiple actions on cellular and subcellular functions in the heart, they also exhibit antioxidant properties and thus may exert beneficial effects in different pathophysiological conditions. It is concluded that reduction of oxidative stress by cysteine and taurine may serve as an important mechanism for the attenuation of diabetes-induced subcellular and functional abnormalities in the heart. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Characterization of taurine as inhibitor of sodium glucose transporter.

PubMed

Kim, Ha Won; Lee, Alexander John; You, Seungkwon; Park, Taesun; Lee, Dong Hee

2006-01-01

The most characterized roles of taurine include osmoregulator and membrane-stabilizing activities. However, much remains to be understood about its role in human physiology concerning its anti-hyperglycemic effect. Studies indicate that taurine-supplemented diet helps alleviate hyperglycemia or insulin resistance. This hypoglycemic effect has been postulated as taurine helping to increase the excretion of cholesterol. Alternatively, this study investigated the effect of taurine on glucose transporter using heterologous expression of sodium-glucose transporter-1 (SGLT-1). SGLT-1 was expressed in Xenopus oocytes and the effect of taurine on the expressed SGLT-1 was analyzed utilizing 2-deoxy-D-glucose (2-DOG) uptake and voltage clamp studies. In the oocytes expressing SGLT-1, taurine was shown to inhibit SGLT-1 activity compared to the non-treated controls in a dose-dependent manner. In the presence of taurine, the glucose uptake was greatly inhibited and the glucose-generated current was significantly inhibited. Synthetic taurine analogs were also shown to be effective in inhibiting SGLT-1 activity in a manner comparable to taurine. These effects might offer a promising opportunity in designing functional foods with anti-hyperglycemic potential by supplementing taurine and its analogs to the diet.

Genetic Variants in HSD17B3, SMAD3, and IPO11 Impact Circulating Lipids in Response to Fenofibrate in Individuals With Type 2 Diabetes.

PubMed

Rotroff, Daniel M; Pijut, Sonja S; Marvel, Skylar W; Jack, John R; Havener, Tammy M; Pujol, Aurora; Schluter, Agatha; Graf, Gregory A; Ginsberg, Henry N; Shah, Hetal S; Gao, He; Morieri, Mario-Luca; Doria, Alessandro; Mychaleckyi, Josyf C; McLeod, Howard L; Buse, John B; Wagner, Michael J; Motsinger-Reif, Alison A

2018-04-01

Individuals with type 2 diabetes (T2D) and dyslipidemia are at an increased risk of cardiovascular disease. Fibrates are a class of drugs prescribed to treat dyslipidemia, but variation in response has been observed. To evaluate common and rare genetic variants that impact lipid responses to fenofibrate in statin-treated patients with T2D, we examined lipid changes in response to fenofibrate therapy using a genomewide association study (GWAS). Associations were followed-up using gene expression studies in mice. Common variants in SMAD3 and IPO11 were marginally associated with lipid changes in black subjects (P < 5 × 10 -6 ). Rare variant and gene expression changes were assessed using a false discovery rate approach. AKR7A3 and HSD17B13 were associated with lipid changes in white subjects (q < 0.2). Mice fed fenofibrate displayed reductions in Hsd17b13 gene expression (q < 0.1). Associations of variants in SMAD3, IPO11, and HSD17B13, with gene expression changes in mice indicate that transforming growth factor-beta (TGF-β) and NRF2 signaling pathways may influence fenofibrate effects on dyslipidemia in patients with T2D. © 2017 American Society for Clinical Pharmacology and Therapeutics.

Impregnation of Fenofibrate on mesoporous silica using supercritical carbon dioxide.

PubMed

Bouledjouidja, Abir; Masmoudi, Yasmine; Van Speybroeck, Michiel; Schueller, Laurent; Badens, Elisabeth

2016-02-29

Low oral bioavailability can be circumvented by the formulation of the poorly water soluble drug in ordered mesoporous silica (OMS-L-7). Fenofibrate is an orally administered, poorly water-soluble active pharmaceutical ingredient (API), used clinically to lower lipid levels. Fenofibrate was loaded into silica using two methods: incipient wetness and supercritical impregnation. This study investigates the impact of loading and the impact of varying supercritical carbon dioxide (scCO2) processing conditions. The objective is to enhance Fenofibrate loading into silica while reducing degree of the drug crystallinity, so as to increase the drug's dissolution rate and its bioavailability. The comparison of both impregnation processes was made in terms of impregnation yields and duration as well as physical characterization of the drug. While incipient wetness method led to a Fenofibrate loading up to 300 mgdrug/gsilica in 48 h of impregnation, the supercritical impregnation method yielded loading up to 485 mgdrug/gsilica in 120 min of impregnation duration, at 16 MPa and 308 K, with a low degree of crystallinity (about 1%) comparable to the crystallinity observed via the solvent method. In addition to the enhancement of impregnation efficiency, the supercritical route provides a solvent-free alternative for impregnation. Copyright © 2015 Elsevier B.V. All rights reserved.

IVIVC for fenofibrate immediate release tablets using solubility and permeability as in vitro predictors for pharmacokinetics.

PubMed

Buch, Philipp; Holm, Per; Thomassen, Jesper Qvist; Scherer, Dieter; Branscheid, Robert; Kolb, Ute; Langguth, Peter

2010-10-01

The goal of this study was to investigate the in vitro-in vivo correlation (IVIVC) for fenofibrate immediate release (IR) tablet formulations based on MeltDose-technique. The in vitro determined drug solubility and permeability data were related to the C(max) values observed from two in vivo human studies. Solubility and permeation studies of fenofibrate were conducted in medium simulating the fasted state conditions in the upper jejunum, containing the surfactant compositions of the six formulations at different concentrations. The behavior of all surfactant compositions was characterized by surface tension, dynamic light scattering, and cryo-TEM. The obtained solubility and permeation data were combined and compared with the C(max) values for the fenofibrate formulations, assuming a 50 mL in vivo dissolution volume. A good IVIVC was observed for five fenofibrate formulations (R(2) = 0.94). The in vitro studies revealed that the formulation compositions containing sodium lauryl sulfate (SLS) interfered with the vesicular drug solubilizing system of the biorelevant medium and antagonized its solubilization capacity. The opposing interaction of surfactants with the emulsifying physiological constituents in intestinal juice should be taken into consideration in order to prevent unsatisfactory in vivo performance of orally administered formulations with low soluble active pharmaceutical ingredients.

Mesoporous silica-based dosage forms improve bioavailability of poorly soluble drugs in pigs: case example fenofibrate.

PubMed

O'Shea, Joseph P; Nagarsekar, Kalpa; Wieber, Alena; Witt, Vanessa; Herbert, Elisabeth; O'Driscoll, Caitriona M; Saal, Christoph; Lubda, Dieter; Griffin, Brendan T; Dressman, Jennifer B

2017-10-01

Mesoporous silicas (SLC) have demonstrated considerable potential to improve bioavailability of poorly soluble drugs by facilitating rapid dissolution and generating supersaturation. The addition of certain polymers can further enhance the dissolution of these formulations by preventing drug precipitation. This study uses fenofibrate as a model drug to investigate the performance of an SLC-based formulation, delivered with hydroxypropyl methylcellulose acetate succinate (HPMCAS) as a precipitation inhibitor, in pigs. The ability of biorelevant dissolution testing to predict the in vivo performance was also assessed. Fenofibrate-loaded mesoporous silica (FF-SLC), together with HPMCAS, displayed significant improvements in biorelevant dissolution tests relative to a reference formulation consisting of a physical mixture of crystalline fenofibrate with HPMCAS. In vivo assessment in fasted pigs demonstrated bioavailabilities of 86.69 ± 35.37% with combination of FF-SLC and HPMCAS in capsule form and 75.47 ± 14.58% as a suspension, compared to 19.92 ± 9.89% with the reference formulation. A positive correlation was identified between bioavailability and dissolution efficiency. The substantial improvements in bioavailability of fenofibrate from the SLC-based formulations confirm the ability of this formulation strategy to overcome the dissolution and solubility limitations, further raising the prospects of a future commercially available SLC-based formulation. © 2017 Royal Pharmaceutical Society.

PPARα-dependent increase of mouse urine output by gemfibrozil and fenofibrate.

PubMed

Song, Danjun; Luo, Min; Dai, Manyun; Bu, Shizhong; Wang, Weihua; Zhang, Burong; Gonzalez, Frank J; Liu, Aiming

2017-02-01

While gemfibrozil and fenofibrate are prescribed for anti-dyslipidemia treatment, a rational basis for the use of these drugs for treatment of dyslipidemia with concurrent metabolic syndrome has not been established. In this study, wild-type and Pparα-null mice were fed gemfibrozil- or fenofibrate-containing diets for 14 days. Urine output (24 h) was monitored, and urine, serum, and liver and kidney tissues were subjected to toxicity assessment. A 2-month challenge followed by a 2-week wash-out was performed for gemfibrozil to determine urine output and the potential toxicity. A therapeutically equivalent dose of gemfibrozil was more effective than fenofibrate in increasing urine output. This regulatory effect was not observed in Pparα-null mice. In contrast, hepatomegaly induced by fenofibrate was more pronounced than that of gemfibrozil. No significant toxicity was observed in liver or kidney in the 2-month treatment with gemfibrozil. These data demonstrated PPARα mediates the increased urine output by fibrates. Considering the relative action on hepatomegaly and the regulatory effect on urine output, gemfibrozil may be the preferable drug to increase urine output. These results revealed a new pharmacodynamic effect of clinically prescribed PPARα agonists and suggested the potential value of gemfibrozil in modification of blood pressure.

Thin-layer chromatographic separation of conjugates of ursodeoxycholic acid from those of litho-, chenodeoxy-, deoxy-, and cholic acids.

PubMed

Batta, A K; Shefer, S; Salen, G

1981-05-01

Separation of the glycine and taurine conjugates of ursodeoxycholic acid from those of lithocholic acid, chenodeoxycholic acid, deoxycholic acid, and cholic acid by thin-layer chromatography is described. Thus, on running a silica gel G plate first in a solvent system of n-butanol-water 20:3 and then in a second solvent system of chloroform-isopropanol-acetic acid-water 30:20:4:1, all the above-mentioned conjugated bile acids are separated from one another. The application of this method to study the change in the biliary bile acid conjugation pattern in ursodeoxycholic acid-fed gallstone patients is described.

Novel electrosprayed nanospherules for enhanced aqueous solubility and oral bioavailability of poorly water-soluble fenofibrate

PubMed Central

Yousaf, Abid Mehmood; Mustapha, Omer; Kim, Dong Wuk; Kim, Dong Shik; Kim, Kyeong Soo; Jin, Sung Giu; Yong, Chul Soon; Youn, Yu Seok; Oh, Yu-Kyoung; Kim, Jong Oh; Choi, Han-Gon

2016-01-01

Purpose The purpose of the present research was to develop a novel electrosprayed nanospherule providing the most optimized aqueous solubility and oral bioavailability for poorly water-soluble fenofibrate. Methods Numerous fenofibrate-loaded electrosprayed nanospherules were prepared with polyvinylpyrrolidone (PVP) and Labrafil® M 2125 as carriers using the electrospray technique, and the effect of the carriers on drug solubility and solvation was assessed. The solid state characterization of an optimized formulation was conducted by scanning electron microscopy, powder X-ray diffraction, differential scanning calorimetry, and Fourier transform infrared spectroscopic analyses. Oral bioavailability in rats was also evaluated for the formulation of an optimized nanospherule in comparison with free drug and a conventional fenofibrate-loaded solid dispersion. Results All of the electrosprayed nanospherule formulations had remarkably enhanced aqueous solubility and dissolution compared with free drug. Moreover, Labrafil M 2125, a surfactant, had a positive influence on the solubility and dissolution of the drug in the electrosprayed nanospherule. Increases were observed as the PVP/drug ratio increased to 4:1, but higher ratios gave no significant increases. In particular, an electrosprayed nanospherule composed of fenofibrate, PVP, and Labrafil M 2125 at the weight ratio of 1:4:0.5 resulted in a particle size of <200 nm with the drug present in the amorphous state. It demonstrated the highest solubility (32.51±2.41 μg/mL), an excellent dissolution (~85% in 10 minutes), and an oral bioavailability ~2.5-fold better than that of the free drug. It showed similar oral bioavailability compared to the conventional solid dispersion. Conclusion Electrosprayed nanospherules, which provide improved solubility and bioavailability, are promising drug delivery tools for oral administration of poorly water-soluble fenofibrate. PMID:26834471

Novel electrosprayed nanospherules for enhanced aqueous solubility and oral bioavailability of poorly water-soluble fenofibrate.

PubMed

Yousaf, Abid Mehmood; Mustapha, Omer; Kim, Dong Wuk; Kim, Dong Shik; Kim, Kyeong Soo; Jin, Sung Giu; Yong, Chul Soon; Youn, Yu Seok; Oh, Yu-Kyoung; Kim, Jong Oh; Choi, Han-Gon

2016-01-01

The purpose of the present research was to develop a novel electrosprayed nanospherule providing the most optimized aqueous solubility and oral bioavailability for poorly water-soluble fenofibrate. Numerous fenofibrate-loaded electrosprayed nanospherules were prepared with polyvinylpyrrolidone (PVP) and Labrafil(®) M 2125 as carriers using the electrospray technique, and the effect of the carriers on drug solubility and solvation was assessed. The solid state characterization of an optimized formulation was conducted by scanning electron microscopy, powder X-ray diffraction, differential scanning calorimetry, and Fourier transform infrared spectroscopic analyses. Oral bioavailability in rats was also evaluated for the formulation of an optimized nanospherule in comparison with free drug and a conventional fenofibrate-loaded solid dispersion. All of the electrosprayed nanospherule formulations had remarkably enhanced aqueous solubility and dissolution compared with free drug. Moreover, Labrafil M 2125, a surfactant, had a positive influence on the solubility and dissolution of the drug in the electrosprayed nanospherule. Increases were observed as the PVP/drug ratio increased to 4:1, but higher ratios gave no significant increases. In particular, an electrosprayed nanospherule composed of fenofibrate, PVP, and Labrafil M 2125 at the weight ratio of 1:4:0.5 resulted in a particle size of <200 nm with the drug present in the amorphous state. It demonstrated the highest solubility (32.51±2.41 μg/mL), an excellent dissolution (~85% in 10 minutes), and an oral bioavailability ~2.5-fold better than that of the free drug. It showed similar oral bioavailability compared to the conventional solid dispersion. Electrosprayed nanospherules, which provide improved solubility and bioavailability, are promising drug delivery tools for oral administration of poorly water-soluble fenofibrate.

Use of Fibrates in the United States and Canada

PubMed Central

Jackevicius, Cynthia A.; Tu, Jack V.; Ross, Joseph S.; Ko, Dennis T.; Carreon, Daniel; Krumholz, Harlan M.

2012-01-01

Context Interest in the role of fibrates has intensified with the publication of the negative ACCORD trial with fenofibrate, especially since the evidence for clinical outcomes benefit for fibrates is heavily weighted on older fibrates, gemfibrozil and clofibrate. Objective This study seeks to examine trends in the current use of fibrates, and for fenofibrate, to illuminate the relationship between differences in the availability of proprietary versus generic formulations and use and economic implications in the United States (US) compared with Canada. Design/Setting/Patients Population-level, cohort study using IMS Health data in the United States and Canada of patients prescribed fibrates between 2002 and 2009. Main Outcome Measure(s) Fibrate prescribing and expenditures. Results From 2002–2009, fibrate prescriptions increased 117.1% in the US, by 12,000/month to 2.1 million prescriptions/month, yet only increased by 18.1% in Canada. (p<0.001) Fenofibrate use was relatively constant in Canada, while in the US, it increased by 159.3%, comprising 47.9% of total fibrate prescriptions in 2002 and 65.2% in 2009. The annual ratio of generic:brand fenofibrate use in the US from 2002 to 2008 ranged from 0:1 to 0.09:1, while the ratio in Canada steadily increased from 2005 to 2008 from 0.51:1 to 1.89:1. In the US, crude fenofibrate expenditures rose from $33.2 million/month in 2002 to $129.6 million/month in 2009, while those in Canada declined from $5.6 million/month to $5.1 million/month. Fibrate expenditures per 100,000 population were 3-fold higher in the US compared with Canada in 2009. Conclusions During the past decade, prescriptions for fibrates, particularly, fenofibrate, increased in the United States, while prescriptions for fibrates in Canada remained stable. PMID:21427374

Pharmacoepidemiologic and in vitro evaluation of potential drug–drug interactions of sulfonylureas with fibrates and statins

PubMed Central

Schelleman, H; Han, X; Brensinger, C M; Quinney, S K; Bilker, W B; Flockhart, D A; Li, L; Hennessy, Sean

2014-01-01

Aims To examine whether initiation of fibrates or statins in sulfonylurea users is associated with hypoglycaemia, and examine in vitro inhibition of cytochrome P450 (CYP) enzymes by statins, fenofibrate and glipizide. Methods We used healthcare data to conduct nested case-control studies of serious hypoglycaemia (i.e. resulting in hospital admission or emergency department treatment) in persons taking glipizide or glyburide, and calculated adjusted overall and time-stratified odds ratios (ORs) and 95% confidence intervals (CIs). We also characterized the in vitro inhibition of CYP enzymes by statins, fenofibrate and glipizide using fluorometric CYP450 inhibition assays, and estimated area under the concentration–time curve ratios (AUCRs) for the drug pairs. Results We found elevated adjusted overall ORs for glyburide-fenofibrate (OR 1.84, 95% CI 1.37, 2.47) and glyburide-gemfibrozil (OR 1.57, 95% CI 1.25, 1.96). The apparent risk did decline over time as might be expected from a pharmacokinetic mechanism. Fenofibrate was a potent in vitro inhibitor of CYP2C19 (IC50 = 0.2 μm) and CYP2B6 (IC50 = 0.7 μm) and a moderate inhibitor of CYP2C9 (IC50 = 9.7 μm). The predicted CYP-based AUCRs for fenofibrate-glyburide and gemfibrozil-glyburide interactions were only 1.09 and 1.04, suggesting that CYP inhibition is unlikely to explain such an interaction. Conclusions Use of fenofibrate or gemfibrozil together with glyburide was associated with elevated overall risks of serious hypoglycaemia. CYP inhibition seems unlikely to explain this observation. We speculate that a pharmacodynamic effect of fibrates (e.g. activate peroxisome proliferator-activator receptor alpha) may contribute to these apparent interactions. PMID:24548191

Effects of Taurine Supplementation on Neuronal Excitability and Glucose Homeostasis.

PubMed

El Idrissi, Abdeslem; El Hilali, Fatiha; Rotondo, Salvatore; Sidime, Francoise

2017-01-01

In this study we examined the role of chronic taurine supplementation on plasma glucose homeostasis and brain excitability through activation of the insulin receptor. FVB/NJ male mice were supplemented with taurine in drinking water (0.05% w/v) for 4 weeks and subjected to a glucose tolerance test (7.5 mg/kg BW) after 12 h fasting. We found that taurine-fed mice were slightly hypoglycemic prior to glucose injection and showed significantly reduced plasma glucose at 30 and 60 min post-glucose injection when compared to control mice. Previously, we reported that taurine supplementation induces biochemical changes that target the GABAergic system. Those studies show that taurine-fed mice are hyperexcitable, have reduced GABA A receptors expression and increased GAD and somatostatin expression in the brain. In this study, we found that taurine-fed mice had a significant increase in insulin receptor (IR) immuno-reactivity in the pancreas and all brain regions examined. At the mRNA level, we found that the IR showed differential regional expression. Surprisingly, we found that neurons express the gene for insulin and that taurine had a significant role in regulating insulin gene expression. We propose that increased insulin production and secretion in taurine-fed mice cause an increase activation of the central IR and may be partially responsible for the increased neuronal excitability observed in taurine supplemented mice. Furthermore, the high levels of neuronal insulin expression and its regulation by taurine implicates taurine in the regulation of metabolic homeostasis.

UPLC-QTOFMS-based metabolomic analysis of the serum of hypoxic preconditioning mice

PubMed Central

Liu, Jie; Zhang, Gang; Chen, Dewei; Chen, Jian; Yuan, Zhi-Bin; Zhang, Er-Long; Gao, Yi-Xing; Xu, Gang; Sun, Bing-Da; Liao, Wenting; Gao, Yu-Qi

2017-01-01

Hypoxic preconditioning (HPC) is well-known to exert a protective effect against hypoxic injury; however, the underlying molecular mechanism remains unclear. The present study utilized a serum metabolomics approach to detect the alterations associated with HPC. In the present study, an animal model of HPC was established by exposing adult BALB/c mice to acute repetitive hypoxia four times. The serum samples were collected by orbital blood sampling. Metabolite profiling was performed using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOFMS), in conjunction with univariate and multivariate statistical analyses. The results of the present study confirmed that the HPC mouse model was established and refined, suggesting significant differences between the control and HPC groups at the molecular levels. HPC caused significant metabolic alterations, as represented by the significant upregulation of valine, methionine, tyrosine, isoleucine, phenylalanine, lysophosphatidylcholine (LysoPC; 16:1), LysoPC (22:6), linoelaidylcarnitine, palmitoylcarnitine, octadecenoylcarnitine, taurine, arachidonic acid, linoleic acid, oleic acid and palmitic acid, and the downregulation of acetylcarnitine, malate, citrate and succinate. Using MetaboAnalyst 3.0, a number of key metabolic pathways were observed to be acutely perturbed, including valine, leucine and isoleucine biosynthesis, in addition to taurine, hypotaurine, phenylalanine, linoleic acid and arachidonic acid metabolism. The results of the present study provided novel insights into the mechanisms involved in the acclimatization of organisms to hypoxia, and demonstrated the protective mechanism of HPC. PMID:28901489

Development and validation of a sensitive LC-MS-MS method for the simultaneous determination of multicomponent contents in artificial Calculus Bovis.

PubMed

Peng, Can; Tian, Jixin; Lv, Mengying; Huang, Yin; Tian, Yuan; Zhang, Zunjian

2014-02-01

Artificial Calculus Bovis is a major substitute in clinical treatment for Niuhuang, a widely used, efficacious but rare traditional Chinese medicine. However, its chemical structures and the physicochemical properties of its components are complicated, which causes difficulty in establishing a set of effective and comprehensive methods for its identification and quality control. In this study, a simple, sensitive and reliable liquid chromatography-tandem mass spectrometry method was successfully developed and validated for the simultaneous determination of bilirubin, taurine and major bile acids (including six unconjugated bile acids, two glycine-conjugated bile acids and three taurine-conjugated bile acids) in artificial Calculus Bovis using a Zorbax SB-C18 column with a gradient elution of methanol and 10 mmol/L ammonium acetate in aqueous solution (adjusted to pH 3.0 with formic acid). The mass spectra were obtained in the negative ion mode using dehydrocholic acid as the internal standard. The content of each analyte in artificial Calculus Bovis was determined by monitoring specific ion pairs in the selected reaction monitoring mode. All analytes demonstrated perfect linearity (r(2) > 0.994) in a wide dynamic range, and 10 batches of samples from different sources were further analyzed. This study provided a comprehensive method for the quality control of artificial Calculus Bovis.

Temporal changes in concentrations of amino acids in plasma and whole blood of healthy neonatal foals from birth to two days of age.

PubMed

Zicker, S C; Rogers, Q R

1994-07-01

Temporal changes, as well as differences in distribution, in concentrations of 24 amino acids in plasma and whole blood of neonatal foals were determined from birth to 2 days of age. In addition, differences in concentrations of amino acids in plasma between mare and foal pairs were determined at birth. Significant (P < 0.05) hypoaminoacidemia existed for 15 amino acids in plasma of foals at birth, compared with mares (paired t-test). Concentrations of 7 amino acids (aspartate, glutamate, glutamine, glycine, hydroxyproline, phenylalanine, proline) in plasma of foals were higher (P < 0.05) at birth than in mares, and concentrations of 2 (taurine, tryptophan) were not different (P > 0.05). Significant (P < 0.05) temporal changes for concentrations of 19 of 24 amino acids in plasma were observed during the 48-hour period. Concentrations of 13 of the 19 amino acids in plasma that had significant changes were higher (P < 0.05) at 48 hours. Significant (P > 0.05) effect of time on concentration of 5 amino acids (alanine, methionine, phenylalanine, taurine, threonine) in plasma was not found after birth. Temporal changes in concentrations of 7 amino acids (alanine, asparagine, glutamine, histidine, hydroxyproline, methionine, and threonine) in whole blood were not significantly (P > 0.05) different from those in plasma. Temporal changes for concentrations of the remaining 17 amino acids in whole blood were significantly (P < 0.05) different, compared with plasma. Distribution of the concentrations of 18 amino acids between whole blood and plasma was significantly (P < 0.05) different.(ABSTRACT TRUNCATED AT 250 WORDS)

In vitro studies on the putative function of N-acetylaspartate as an osmoregulator.

PubMed

Tranberg, Mattias; Abbas, Abdul-Karim; Sandberg, Mats

2007-07-01

Efflux and tissue content of N-acetylaspartate (NAA) and amino acids were evaluated from cultured and acutely prepared hippocampal slices in response to changes in osmolarity. The osmoregulator taurine, but not NAA, was lost from both types of slices after moderate reductions in extracellular osmolarity (-60 mOsm) for 10-48 h. Hypoosmotic shock (-166 mOsm) for 5 min resulted in unselective efflux of several amino acids from acutely prepared slices. Notably, the efflux of taurine, but not NAA, was prominent also after the shock. Efflux of NAA was markedly enhanced by NMDA and high K(+), in particular after the stimulation period. The high K(+)-mediated efflux was decreased by high extracellular osmolarity and a NMDA-receptor antagonist. The results indicate that NAA efflux can be induced by a sudden non-physiological decrease in extracellular osmolarity but not by prolonged more moderate changes in osmolarity. The mechanisms behind the efflux of NAA by high K(+) are complex and may involve both swelling and activation of NMDA-receptors.

Physiological and chemical analysis of neurotransmitter candidates at a fast excitatory synapse in the jellyfish Cyanea capillata (Cnidaria, Scyphozoa).

PubMed

Anderson, Peter A V; Trapido-Rosenthal, H G

2009-12-01

Motor nerve net (MNN) neurons in the jellyfish Cyanea capillata communicate with one another by way of fast, bidirectional excitatory chemical synapses. As is the case with almost all identified chemical synapses in cnidarians, the identity of the neurotransmitter at these synapses is unclear. MNN neurons are large enough for stable intracellular recordings. This, together with the fact that they can be exposed, providing unlimited access to them and to their synapses, prompted a study of the action of a variety of neurotransmitter candidates, including those typically associated with fast synapses in higher animals. Only the amino acids taurine and beta-alanine produced physiological responses consistent with those of the normal EPSP in these cells. Moreover, chemical analysis revealed that both taurine and beta-alanine are present in the neurons and released by depolarization. These various findings strongly suggest that either or both of these amino acids, or a closely related compound is the neurotransmitter at the fast chemical synapses between MNN neurons.

HIGH GLUCOSE POTENTIATES L-FABP MEDIATED FIBRATE INDUCTION OF PPARα IN MOUSE HEPATOCYTES

PubMed Central

Petrescu, Anca D.; McIntosh, Avery L.; Storey, Stephen M.; Huang, Huan; Martin, Gregory G.; Landrock, Danilo; Kier, Ann B.; Schroeder, Friedhelm

2013-01-01

Although liver fatty acid binding protein (L-FABP) binds fibrates and PPARα in vitro and enhances fibrate induction of PPARα in transformed cells, the functional significance of these findings is unclear, especially in normal hepatocytes. Studies with cultured primary mouse hepatocytes show that: 1) At physiological (6 mM) glucose, fibrates (bezafibrate, fenofibrate) only weakly activated PPARα transcription of genes in LCFA β-oxidation; 2) High (11–20 mM) glucose, but not maltose (osmotic control), significantly potentiated fibrate-induction of mRNA of these and other PPARα target genes to increase LCFA β-oxidation. These effects were associated with fibrate-mediated redistribution of L-FABP into nuclei—an effect prolonged by high glucose—but not with increased de novo fatty acid synthesis from glucose; 3) Potentiation of bezafibrate action by high glucose required an intact L-FABP/PPARα signaling pathway as shown with L-FABP null, PPARα null, PPARα inhibitor-treated WT, or PPARα-specific fenofibrate-treated WT hepatocytes. High glucose alone in the absence of fibrate was ineffective. Thus, high glucose potentiation of PPARα occurred through FABP/PPARα rather than indirectly through other PPARs or glucose induced signaling pathways. These data indicated L-FABP’s importance in fibrate-induction of hepatic PPARα LCFA β-oxidative genes, especially in the context of high glucose levels. PMID:23747828

The effect of taurine and β-alanine supplementation on taurine transporter protein and fatigue resistance in skeletal muscle from mdx mice.

PubMed

Horvath, Deanna M; Murphy, Robyn M; Mollica, Janelle P; Hayes, Alan; Goodman, Craig A

2016-11-01

This study investigated the effect of taurine and β-alanine supplementation on muscle function and muscle taurine transporter (TauT) protein expression in mdx mice. Wild-type (WT) and mdx mice (5 months) were supplemented with taurine or β-alanine for 4 weeks, after which in vitro contractile properties, fatigue resistance and force recovery, and the expression of the TauT protein and proteins involved in excitation-contraction (E-C) coupling were examined in fast-twitch muscle. There was no difference in basal TauT protein expression or basal taurine content between mdx than WT muscle. Supplementation with taurine and β-alanine increased and reduced taurine content, respectively, in muscle from WT and mdx mice but had no effect of TauT protein. Taurine supplementation reduced body and muscle mass, and enhanced fatigue resistance and force recovery in mdx muscle. β-Alanine supplementation enhanced fatigue resistance in WT and mdx muscle. There was no difference in the basal expression of key E-C coupling proteins [ryanodine receptor 1 (RyR1), dihydropyridine receptor (DHPR), sarco(endo)plasmic reticulum Ca 2+ -ATPase 1 (SERCA1) or calsequestrin 1 (CSQ1)] between WT and mdx mice, and the expression of these proteins was not altered by taurine or β-alanine supplementation. These findings suggest that TauT protein expression is relatively insensitive to changes in muscle taurine content in WT and mdx mice, and that taurine and β-alanine supplementation may be viable therapeutic strategies to improve fatigue resistance of dystrophic skeletal muscle.

Stimulation of glucose utilization and inhibition of protein glycation and AGE products by taurine.

PubMed

Nandhini, A T A; Thirunavukkarasu, V; Anuradha, C V

2004-07-01

Pathological effects of the process of non-enzymatic glycation of proteins are reflected in chronic complications of diabetes mellitus. We investigated the antiglycating effect of taurine in high fructose fed rats in vivo and the inhibiting potency of taurine in the process of in vitro glycation. Additionally, we investigated whether taurine enhances glucose utilization in the rat diaphragm. Rats fed a high fructose diet (60% total calories) were provided 2% taurine solution for 30 days. The effects of taurine on plasma glucose, fructosamine, protein glycation and glycosylated haemoglobin in high fructose rats were determined. For in vitro glycation a mixture of 25 mm glucose and 25 mm fructose was used as glycating agent, bovine serum albumin as the model protein and taurine as the inhibitor. Incubations were carried out in a constant temperature bath at 37 degrees C for 3-30 days. Amadori products and advanced glycation end products (AGEs) formed were measured. In vitro utilization of glucose was carried out in the rat diaphragm in the presence and absence of insulin in which taurine was used as an additive. The contents of glucose, glycated protein, glycosylated haemoglobin and fructosamine were significantly lowered by taurine treatment to high fructose rats. Taurine prevented in vitro glycation and the accumulation of AGEs. Furthermore, taurine enhanced glucose utilization in the rat diaphragm. This effect was additive to that of insulin and did not interfere with the action of insulin. These results underline the potential use of taurine as a therapeutic supplement for the prevention of diabetic pathology.

Myeloperoxidase-hydrogen peroxide-chloride antimicrobial system: effect of exogenous amines on antibacterial action against Escherichia coli.

PubMed

Thomas, E L

1979-07-01

Exogenous ammonium ions (NH(4) (+)) and amine compounds had a profound influence on the antibacterial activity of the myeloperoxidase-hydrogen peroxide-chloride system against Escherichia coli. The rate of killing increased in the presence of NH(4) (+) and certain guanidino compounds and decreased in the presence of alpha-amino acids, polylysine, taurine, or tris (hydroxymethyl) aminomethane. Myeloperoxidase catalyzed the oxidation of chloride to hypochlorous acid, which reacted either with bacterial amine or amide components or both or with the exogenous compounds to yield chloramine or chloramide derivatives or both. These nitrogen-chlorine derivatives could oxidize bacterial components. Killing was correlated with oxidation of bacterial components. The rate of oxidation of bacterial sulfhydryls increased in the presence of the compounds that increased the rate of killing and decreased in the presence of the other compounds. The reaction of HOCl with NH(4) (+) yielded monochloramine (NH(2)Cl), which could be extracted into organic solvents. The N-Cl derivatives of bacterial components or of polylysine, taurine, or tris(hydroxymethyl)aminomethane could not be extracted. The effect of NH(4) (+) on killing is attributed to the ability of NH(2)Cl to penetrate the hydrophobic cell membrane and thus to oxidize intracellular components. Polylysine, taurine, and tris(hydroxymethyl)aminomethane formed high-molecular-weight, charged, or polar N-Cl derivatives that would be unable to penetrate the cell membrane. These results suggest an important role for leukocyte amine components in myeloperoxidase-catalyzed antimicrobial activity in vivo.

Changes in the faecal bile acid profile in dogs fed dry food vs high content of beef: a pilot study.

PubMed

Herstad, Kristin Marie Valand; Rønning, Helene Thorsen; Bakke, Anne Marie; Moe, Lars; Skancke, Ellen

2018-05-11

Dogs are fed various diets, which also include components of animal origin. In humans, a high-fat/low-fibre diet is associated with higher faecal levels of bile acids, which can influence intestinal health. It is unknown how an animal-based diet high in fat and low in fibre influences the faecal bile acid levels and intestinal health in dogs. This study investigated the effects of high intake of minced beef on the faecal bile acid profile in healthy, adult, client-owned dogs (n = 8) in a 7-week trial. Dogs were initially adapted to the same commercial dry food. Thereafter, incremental substitution of the dry food by boiled minced beef over 3 weeks resulted in a diet in which 75% of each dog's total energy requirement was provided as minced beef during week 5. Dogs were subsequently reintroduced to the dry food for the last 2 weeks of the study. The total taurine and glycine-conjugated bile acids, the primary bile acids chenodeoxycholic acid and cholic acid, and the secondary bile acids lithocholic acid, deoxycholic acid (DCA) and ursodeoxycholic acid (UDCA) were analysed, using liquid chromatography-tandem mass spectrometry. The faecal quantities of DCA were significantly higher in dogs fed the high minced beef diet. These levels reversed when dogs were reintroduced to the dry food diet. The faecal levels of UDCA and taurine-conjugated bile acids had also increased in response to the beef diet, but this was only significant when compared to the last dry food period. These results suggest that an animal-based diet with high-fat/low-fibre content can influence the faecal bile acids levels. The consequences of this for canine colonic health will require further investigation.

Potential mechanism of corpus-predominant gastritis after PPI therapy in Helicobacter pylori-positive patients with GERD.

PubMed

Mukaisho, Ken-ichi; Hagiwara, Tadashi; Nakayama, Takahisa; Hattori, Takanori; Sugihara, Hiroyuki

2014-09-14

The long-term use of proton pump inhibitors (PPIs) exacerbates corpus atrophic gastritis in patients with Helicobacter pylori (H. pylori) infection. To identify a potential mechanism for this change, we discuss interactions between pH, bile acids, and H. pylori. Duodenogastric reflux, which includes bile, occurs in healthy individuals, and bile reflux is increased in patients with gastroesophageal reflux disease (GERD). Diluted human plasma and bile acids have been found to be significant chemoattractants and chemorepellents, respectively, for the bacillus H. pylori. Although only taurine conjugates, with a pKa of 1.8-1.9, are soluble in an acidic environment, glycine conjugates, with a pKa of 4.3-5.2, as well as taurine-conjugated bile acids are soluble in the presence of PPI therapy. Thus, the soluble bile acid concentrations in the gastric contents of patients with GERD after continuous PPI therapy are considerably higher than that in those with intact acid production. In the distal stomach, the high concentration of soluble bile acids is likely to act as a bactericide or chemorepellent for H. pylori. In contrast, the mucous layer in the proximal stomach has an optimal bile concentration that forms chemotactic gradients with plasma components required to direct H. pylori to the epithelial surface. H. pylori may then colonize in the stomach body rather than in the pyloric antrum, which may explain the occurrence of corpus-predominant gastritis after PPI therapy in H. pylori-positive patients with GERD.

Association of gene variants with lipid levels in response to fenofibrate is influenced by metabolic syndrome status

USDA-ARS?s Scientific Manuscript database

Fenofibrate therapy reduces serum triglycerides (TG) and increases high-density lipoprotein-cholesterol (HDL-C) and thus addresses the atherogenic dyslipidemia associated with metabolic syndrome (MetS). Our hypothesis is that genetic factors contribute to the variability of lipid response to fenofib...

Genome-wide association study indicates variants associated with insulin signaling and inflammation mediate lipoprotein responses to fenofibrate

USDA-ARS?s Scientific Manuscript database

A shift towards overall larger very low-density lipoprotein (VLDL), and smaller low-density lipoprotein and high-density lipoprotein (HDL) diameters occurs in insulin resistance (IR), which reflects shifts in the distribution of the subfraction concentrations. Fenofibrate, indicated for hypertriglyc...

Taurine uptake by human retinal pigment epithelium: implications for the transport of small solutes between the choroid and the outer retina.

PubMed

Hillenkamp, Jost; Hussain, Ali A; Jackson, Timothy L; Cunningham, Joanna R; Marshall, John

2004-12-01

To characterize the Michaelis-Menten kinetics of the taurine transporter (TT) in retinal pigment epithelium (RPE) freshly isolated from human donor eyes. To identify the rate limiting compartment in the pathway of taurine delivery from the choroidal blood supply to the outer retina composed by Bruch's-choroid (BC) and the RPE in the human older age group. In human donor samples (4 melanoma-affected eyes, and 14 control eyes; age range, 62-93 years), radiochemical techniques were used to determine the RPE taurine accumulation at various exogenous concentrations. The transport capability of human RPE was obtained from a kinetic analysis of the high-affinity carrier over a substrate concentration of 1 to 60 microM taurine. Uptake of taurine into human RPE at a taurine concentration of 1 microM was independent of donor age (P > 0.05) and averaged at 2.83 +/- 0.27 (SEM) pmol/10 minutes per 6-mm trephine. Taurine transport by human RPE was mediated by a high-affinity carrier of K(m) 50 microM and V(max) of 267 pmol/10 minutes per 5-mm disc. In human donor RPE, uptake of taurine remained viable in the age range 62 to 93 years. Taurine transport rates in the RPE were lower than across the isolated BC complex, and thus the data suggest that the former compartment houses the rate-limiting step in the delivery of taurine to the outer retina.

Sulfur in Distillers Grains for Dairy Cattle

USDA-ARS?s Scientific Manuscript database

Sulfur is an essential element needed by animals for many functions. About 0.15% of the body weight is sulfur. It is found in the amino acids methionine, cysteine, cystine, homocysteine, and taurine; in chondroitin sulfate of cartilage; and in the B-vitamins, thiamin and biotin. Methionine, thiam...

Effects of taurine on plasma glucose concentration and active glucose transport in the small intestine.

PubMed

Tsuchiya, Yo; Kawamata, Koichi

2017-11-01

Taurine lowers blood glucose levels and improves hyperglycemia. However, its effects on glucose transport in the small intestine have not been investigated. Here, we elucidated the effect of taurine on glucose absorption in the small intestine. In the oral glucose tolerance test, addition of 10 mmol/L taurine suppressed the increase in hepatic portal glucose concentrations. To investigate whether the suppressive effect of taurine occurs via down-regulation of active glucose transport in the small intestine, we performed an assay using the everted sac of the rat jejunum. Addition of taurine to the mucosal side of the jejunum suppressed active glucose transport via sodium-glucose cotransporter 1 (SGLT1). After elimination of chloride ions from the mucosal solution, taurine did not show suppressive effects on active glucose transport. These results suggest that taurine suppressed the increase in hepatic portal glucose concentrations via suppression of SGLT1 activity in the rat jejunum, depending on chloride ions. © 2017 Japanese Society of Animal Science.

Estimates of genetic parameters for chemical traits of meat quality in Japanese black cattle

PubMed Central

Sakuma, Hironori; Saito, Kaoru; Kohira, Kimiko; Ohhashi, Fumie; Shoji, Noriaki

2016-01-01

Abstract Genetic parameters for 54 carcass and chemical traits, such as general composition (moisture, crude fat and crude protein), fatty acid composition and water‐soluble compounds (free amino acids, peptides, nucleotides and sugars) of 587 commercial Japanese Black cattle were assessed. Heritability estimates for carcass traits and general composition ranged between 0.19–0.28, whereas those for fatty acid composition ranged between 0.11–0.85. Most heritability estimates for water‐soluble compounds were lower than 0.30; these traits were affected by aging period. Moderate heritability was observed for glutamine, alanine, taurine, anserine, inosine 5′‐monophosphate (IMP), inosine and myo‐inositol. In particular, heritability estimates were the highest (0.66) for taurine. Traits with moderate heritability were unaffected by aging period, with the exception of IMP, which was affected by aging period but exhibited moderate heritability (0.47). Although phenotypic correlations of water‐soluble compounds with carcass weight (CW), beef marbling standard (BMS) and monounsaturated fatty acid were generally low, genetic correlations between these traits were low to high. At the genetic level, most of the water‐soluble compounds were positively correlated with monounsaturated fatty acid but negatively correlated with CW and BMS. Thus, our results indicate that genetic variance and correlations could exist and be captured for some of the water‐soluble compounds. PMID:27146072

Does taurine deficiency cause metabolic bone disease and rickets in polar bear cubs raised in captivity?

PubMed

Chesney, Russell W; Hedberg, Gail E; Rogers, Quinton R; Dierenfeld, Ellen S; Hollis, Bruce E; Derocher, Andrew; Andersen, Magnus

2009-01-01

Rickets and fractures have been reported in captive polar bears. Taurine (TAU) is key for the conjugation of ursodeoxycholic acid (UDCA), a bile acid unique to bears. Since TAU-conjugated UDCA optimizes fat and fat-soluble vitamin absorption, we asked if TAU deficiency could cause vitamin D malabsorption and lead to metabolic bone disease in captive polar bears. We measured TAU levels in plasma (P) and whole blood (WB) from captive and free-ranging cubs and adults, and vitamin D3 and TAU concentrations in milk samples from lactating sows. Plasma and WB TAU levels were significantly higher in cubs vs captive and free-ranging adult bears. Vitamin D in polar bear milk was 649.2 +/- 569.2 IU/L, similar to that found in formula. The amount of TAU in polar bear milk is 3166.4 +/- 771 nmol/ml, 26-fold higher than in formula. Levels of vitamin D in bear milk and formula as well as in plasma do not indicate classical nutritional vitamin D deficiency. Higher dietary intake of TAU by free-ranging cubs may influence bile acid conjugation and improve vitamin D absorption.

Taurine zinc solid dispersions attenuate doxorubicin-induced hepatotoxicity and cardiotoxicity in rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Yu; Mei, Xueting; Yuan, Jingquan

2015-11-15

The clinical efficacy of anthracycline anti-neoplastic agents is limited by cardiac and hepatic toxicities. The aim of this study was to assess the hepatoprotective and cardioprotective effects of taurine zinc solid dispersions, which is a newly-synthesized taurine zinc compound, against doxorubicin-induced toxicity in Sprague–Dawley rats intraperitoneally injected with doxorubicin hydrochloride (3 mg/kg) three times a week (seven injections) over 28 days. Hemodynamic parameters, levels of liver toxicity markers and oxidative stress were assessed. Taurine zinc significantly attenuated the reductions in blood pressure, left ventricular pressure and ± dp/dtmax, increases in serum alanine aminotransferase and aspartate aminotransferase activities, and reductions inmore » serum Zn{sup 2+} and albumin levels (P < 0.05 or 0.01) induced by doxorubicin. In rats treated with doxorubicin, taurine zinc dose-dependently increased liver superoxide dismutase activity and glutathione concentration, and decreased malondialdehyde level (P < 0.01). qBase{sup +} was used to evaluate the stability of eight candidate reference genes for real-time quantitative reverse-transcription PCR. Taurine zinc dose-dependently increased liver heme oxygenase-1 and UDP-glucuronyl transferase mRNA and protein expression (P < 0.01). Western blotting demonstrated that taurine zinc inhibited c-Jun N-terminal kinase phosphorylation by upregulating dual-specificity phosphoprotein phosphatase-1. Additionally, taurine zinc inhibited cardiomyocyte apoptosis as there was decreased TUNEL/DAPI positivity and protein expression of caspase-3. These results indicate that taurine zinc solid dispersions prevent the side-effects of anthracycline-based anticancer therapy. The mechanisms might be associated with the enhancement of antioxidant defense system partly through activating transcription to synthesize endogenous phase II medicine enzymes and anti-apoptosis through inhibiting JNK phosphorylation. - Highlights: • Dissolution of taurine zinc complex can be increased by solid dispersions (SDs). • Taurine zinc SDs blocked doxorubicin-induced hepatotoxicity and cardiotoxicity. • Taurine zinc SDs can alleviate oxidative stress and dampen JNK phosphorylation. • Taurine zinc SDs increased the expression of UGT, HO-1 at mRNA and protein level. • Taurine zinc SDs revealed greater hepatoprotective effects than silymarin.« less

The PPAR alpha gene is associated with triglyceride, low-density cholesterol and inflammation marker response to fenofibrate intervention: the GOLDN study

USDA-ARS?s Scientific Manuscript database

As a peroxisome proliferator-activated receptor alpha (PPAR Alpha) agonist, fenofibrate favorably modulates dyslipidemia and inflammation markers, which are associated with cardiovascular risk. To determine whether variation in the PPAR Alpha receptor gene was associated with lipid and inflammatory ...

Simultaneous determination of atorvastatin calcium, ezetimibe, and fenofibrate in a tablet formulation by HPLC.

PubMed

Patel, Archita; Macwana, Chhaya; Parmar, Vishal; Patel, Samir

2012-01-01

An accurate, simple, reproducible, and sensitive HPLC method was developed and validated for the simultaneous determination of atorvastatin calcium, ezetimibe, and fenofibrate in a tablet formulation. The analyses were performed on an RP C18 column, 150 x 4.60 mm id, 5 pm particle size. The mobile phase methanol-acetonitrile-water (76 + 13 + 11, v/v/v), was pumped at a constant flow rate of 1 mL/min. UV detection was performed at 253 nm. Retention times of atorvastatin calcium, ezetimibe, and fenofibrate were found to be 2.25, 3.68, and 6.41 min, respectively. The method was validated in terms of linearity, precision, accuracy, LOD, LOQ, and robustness. The response was linear in the range 2-10 microg/mL (r2 = 0.998) for atorvastatin calcium, 2-10 microg/mL (r2 = 0.998) for ezetimibe, and 40-120 microg/mL (r2 = 0.998) for fenofibrate. The developed method can be used for routine quality analysis of the drugs in the tablet formulation.

Taurine Ameliorates Renal Oxidative Damage and Thyroid Dysfunction in Rats Chronically Exposed to Fluoride.

PubMed

Adedara, Isaac A; Ojuade, Temini Jesu D; Olabiyi, Bolanle F; Idris, Umar F; Onibiyo, Esther M; Ajeigbe, Olufunke F; Farombi, Ebenezer O

2017-02-01

Excessive exposure to fluoride poses several detrimental effects to human health particularly the kidney which is a major organ involved in its elimination from the body. The influence of taurine on fluoride-induced renal toxicity was investigated in a co-exposure paradigm for 45 days using five groups of eight rats each. Group I rats received normal drinking water alone, group II rats were exposed to sodium fluoride (NaF) in drinking water at 15 mg/L alone, group III received taurine alone at a dose of 200 mg/kg group IV rats were co-administered with NaF and taurine (100 mg/kg), while group V rats were co-administered with NaF and taurine (200 mg/kg). Administration of taurine significantly reversed the fluoride-mediated decrease in absolute weight and organo-somatic index of the kidney in the exposed rats. Taurine significantly prevented fluoride-induced elevation in plasma urea and creatinine levels in the exposed rats. Moreover, taurine restored fluoride-mediated decrease in the circulatory concentrations of triiodothyronine, thyroxine, and the ratio of triiodothyronine to thyroxine. Taurine ameliorated fluoride-mediated decrease in renal antioxidant status by significantly enhancing the antioxidant enzyme activities as well as glutathione level in the exposed rats. Additionally, taurine inhibited fluoride-induced renal oxidative damage by markedly decreasing the hydrogen peroxide and malondialdehyde levels as well as improved the kidney architecture in the treated rats. Collectively, taurine protected against fluoride-induced renal toxicity via enhancement of thyroid gland function, renal antioxidant status, and histology in rats.

Intestinal absorption of the bile acid analogue 75Se-homocholic acid-taurine is increased in primary biliary cirrhosis, and reverts to normal during ursodeoxycholic acid administration.

PubMed

Lanzini, A; De Tavonatti, M G; Panarotto, B; Scalia, S; Mora, A; Benini, F; Baisini, O; Lanzarotto, F

2003-09-01

Whether ileal absorption of bile acid is up or downregulated in chronic cholestasis is still debated, and most evidence has come from animal studies. To compare ileal bile acid absorption in patients with primary biliary cirrhosis (PBC) and in healthy control subjects, and to assess the effect of ursodeoxycholic acid (UDCA). We studied 14 PBC patients before and during (n=11) UDCA administration, 14 healthy control subjects, and 14 Crohn's disease patients (as disease controls). We used cholescintigraphy to measure retention in the enterohepatic circulation over five successive days of the bile acid analogue (75)Se-homocholic acid-taurine ((75)SeHCAT) as an index of ileal bile acid absorption. Results were expressed as (75)SeHCAT fractional turnover rate (FTR) and t(1/2)12. (75)SeHCAT FTR was 0.19 (0.11)/day, 0.34 (0.11)/day (p<0.001), and 0.83 (0.32)/day in PBC patients, healthy controls (p<0.0001), and Crohn's patients (p<0.001), respectively, which increased to 0.36 (0.16)/day in PBC patients during UDCA treatment (p<0.005). (75)SeHCAT t(1/2)12 was 4.8 (2.1) days in PBC patients, 2.2 (0.5) days (p<0.001) in healthy controls, and 1.0 (0.5) days (p<0.001) in Crohn's disease patients. (75)SeHCAT t(1/2)12 decreased to 2.2 (0.93) days (p< 0.001) in PBC patients during UDCA treatment. Our results support the concept that ileal bile acid absorption is upregulated in PBC patients, and that this effect may contribute towards damaging the cholestatic liver. This upregulation of bile acid absorption is abolished by UDCA.

Preference of Conjugated Bile Acids over Unconjugated Bile Acids as Substrates for OATP1B1 and OATP1B3

PubMed Central

Suga, Takahiro; Sato, Toshihiro; Maekawa, Masamitsu; Goto, Junichi; Mano, Nariyasu

2017-01-01

Bile acids, the metabolites of cholesterol, are signaling molecules that play critical role in many physiological functions. They undergo enterohepatic circulation through various transporters expressed in intestine and liver. Human organic anion-transporting polypeptides (OATP) 1B1 and OATP1B3 contribute to hepatic uptake of bile acids such as taurocholic acid. However, the transport properties of individual bile acids are not well understood. Therefore, we selected HEK293 cells overexpressing OATP1B1 and OATP1B3 to evaluate the transport of five major human bile acids (cholic acid, chenodeoxycholic acid, deoxycholic acid, ursodeoxycholic acid, lithocholic acid) together withtheir glycine and taurine conjugates via OATP1B1 and OATP1B3. The bile acids were quantified by liquid chromatography-tandem mass spectrometry. The present study revealed that cholic acid, chenodeoxyxcholic acid, and deoxycholic acid were transported by OATP1B1 and OATP1B3, while ursodeoxycholic acid and lithocholic acid were not significantly transported by OATPs. However, all the conjugated bile acids were taken up rapidly by OATP1B1 and OATP1B3. Kinetic analyses revealed the involvement of saturable OATP1B1- and OATP1B3-mediated transport of bile acids. The apparent Km values for OATP1B1 and OATP1B3 of the conjugated bile acids were similar (0.74–14.7 μM for OATP1B1 and 0.47–15.3 μM for OATP1B3). They exhibited higher affinity than cholic acid (47.1 μM for OATP1B1 and 42.2 μM for OATP1B3). Our results suggest that conjugated bile acids (glycine and taurine) are preferred to unconjugated bile acids as substrates for OATP1B1 and OATP1B3. PMID:28060902

Carbohydrate-lipid profile and use of metformin with micronized fenofibrate in reducing metabolic consequences of craniopharyngioma treatment in children: single institution experience.

PubMed

Kalina, Maria Aleksandra; Wilczek, Marta; Kalina-Faska, Barbara; Skała-Zamorowska, Eliza; Mandera, Marek; Małecka Tendera, Ewa

2015-01-01

To evaluate auxology and metabolic disturbances in children with craniopharyngioma, and to present observational results of treatment of metabolic sequels with metformin and micronized fenofibrate. The studied group comprised 22 children [median age at diagnosis 10.5 (0.17-16.75) years; median follow-up 5.1 years]. Assessment included height standard deviations (SDS), body mass index (BMI) SDS, concentrations of lipids, glucose and insulin (fasting or oral glucose tolerance test) and homeostatic model assessment of insulin resistance (HOMA-IR) index. Ten adolescents with hyperinsulinemia and dyslipidemia received therapy with metformin (500-1500 mg/daily) and micronized fenofibrate (160 mg/daily). At diagnosis, median hSDS was -1.66 (range: -4.08; +0.1). Nine (40.9%) children were growth hormone-treated. There was gradual increase of BMI SDS, 18 (81.8%) patients being overweight at the final assessment. Dyslipidaemia was found in 19 patients (86.4%), hyperinsulinaemia in 11 patients (50%) and elevated HOMA-IR in 15 patients (68.2%). Decrease of triglycerides [median 263.5 (171-362) mg/dL vs. 154 (102-183) mg/dL] and HOMA-IR [8.64 (5.08-12.65) vs. 4.68 (0.7-7.9)] was significant in the group treated with metformin and fenofibrate for 6 months. Significant auxologic changes and metabolic abnormalities were found in children treated for craniopharyngioma. The use of metformin and fenofibrate seemed to attenuate these disturbances in a short-term observation.

Catalytic effect of different reactor materials under subcritical water conditions: decarboxylation of cysteic acid into taurine

NASA Astrophysics Data System (ADS)

Faisal, M.

2018-03-01

In order to understand the influence of reactor materials on the catalytic effect for a particular reaction, the decomposition of cysteic acid from Ni/Fe-based alloy reactors under subcritical water conditions was examined. Experiments were carried out in three batch reactors made of Inconel 625, Hastelloy C-22 and SUS 316 over temperatures of 200 to 300 °C. The highest amount of eluted metals was found for SUS 316. The results demonstrated that reactor materials contribute to the resulting product. Under the tested conditions, cysteic acid decomposes readily with SUS 316. However, the Ni-based materials (Inconel 625 and Hastelloy C-22) show better resistance to metal elution. It was found that among the materials used in this work, SUS 316 gave the highest reaction rate constant of 0.1934 s‑1. The same results were obtained at temperatures of 260 and 300 °C. Investigation of the Arrhenius activation energy revealed that the highest activation energy was for Hastelloy C-22 (109 kJ/mol), followed by Inconel 625 (90 kJ/mol) and SUS 316 (70 kJ/mol). The decomposition rate of cysteic acid was found to follow the results for the trend of the eluted metals. Therefore, it can be concluded that the decomposition of cysteic acid was catalyzed by the elution of heavy metals from the surface of the reactor. The highest amount of taurine from the decarboxylation of cysteic acid was obtained from SUS 316.

Atorvastatin or fenofibrate on post-prandial lipaemia in type 2 diabetic patients with hyperlipidaemia.

PubMed

Iovine, C; Lilli, S; Gentile, A; Patti, L; Di Marino, L; Cipriano, P; Riccardi, G; Rivellese, A A

2006-08-01

Post-prandial lipid abnormalities might contribute to the excess of cardiovascular risk typical of type 2 diabetic patients. The study evaluated the effects of atorvastatin (20 mg d(-1)) vs. fenofibrate (200 mg d(-1)) on post-prandial lipids in type 2 diabetic patients with mixed hyperlipidaemia. Eight type 2 diabetic patients, male/female (M/F) 6/2, age 58 +/- 5 years, body mass index (BMI) 28 +/- 3 kg m(-2) with cholesterol of low-density lipoprotein (LDL) between 100-160 mg dL(-1) and triglycerides between 150-400 mg dL(-1), participated in a randomized, cross-over study (3 months on atorvastatin and 3 months on fenofibrate). At baseline and at the end of the two treatments, the patients were given a standard fat meal; blood samples were taken before the meal and every 2 h after for the assay of cholesterol, triglycerides, apoB-48 and apoB-100 (determined by sodium dodecyl sulphate-polyacrylamide gel electrophoresis) in plasma lipoproteins and very low-density lipoprotein (VLDL) subfractions (large and small VLDL), separated by density gradient ultracentrifugation. Data on fasting lipids confirmed that atorvastatin was more effective on the reduction of LDL-cholesterol, whereas fenofibrate was a better triglyceride-lowering agent. Concerning the post-prandial phase, the incremental areas under the curve (IAUC) for chylomicrons and large VLDL were reduced after both treatments, reaching statistical significance for cholesterol, triglyceride and apoB-100 content of chylomicrons only after fenofibrate administration [IAUC, (5.2 +/- 4.6 vs. 10.7 +/- 9.3) mg dL(-1) h(-1), P = 0.03; (131.3 +/- 95.1 vs. 259.1 +/- 201.5) mg dL(-1) h(-1), P = 0.02; (0.46 +/- 1 vs. 3 +/- 3.7) mg dL(-1) h(-1), P = 0.025, all respectively]. During the post-prandial state fenofibrate appeared to be more effective than atorvastatin in reducing the chylomicron response.

Effects of combination lipid therapy in type 2 diabetes mellitus.

PubMed

Ginsberg, Henry N; Elam, Marshall B; Lovato, Laura C; Crouse, John R; Leiter, Lawrence A; Linz, Peter; Friedewald, William T; Buse, John B; Gerstein, Hertzel C; Probstfield, Jeffrey; Grimm, Richard H; Ismail-Beigi, Faramarz; Bigger, J Thomas; Goff, David C; Cushman, William C; Simons-Morton, Denise G; Byington, Robert P

2010-04-29

We investigated whether combination therapy with a statin plus a fibrate, as compared with statin monotherapy, would reduce the risk of cardiovascular disease in patients with type 2 diabetes mellitus who were at high risk for cardiovascular disease. We randomly assigned 5518 patients with type 2 diabetes who were being treated with open-label simvastatin to receive either masked fenofibrate or placebo. The primary outcome was the first occurrence of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes. The mean follow-up was 4.7 years. The annual rate of the primary outcome was 2.2% in the fenofibrate group and 2.4% in the placebo group (hazard ratio in the fenofibrate group, 0.92; 95% confidence interval [CI], 0.79 to 1.08; P=0.32). There were also no significant differences between the two study groups with respect to any secondary outcome. Annual rates of death were 1.5% in the fenofibrate group and 1.6% in the placebo group (hazard ratio, 0.91; 95% CI, 0.75 to 1.10; P=0.33). Prespecified subgroup analyses suggested heterogeneity in treatment effect according to sex, with a benefit for men and possible harm for women (P=0.01 for interaction), and a possible interaction according to lipid subgroup, with a possible benefit for patients with both a high baseline triglyceride level and a low baseline level of high-density lipoprotein cholesterol (P=0.057 for interaction). The combination of fenofibrate and simvastatin did not reduce the rate of fatal cardiovascular events, nonfatal myocardial infarction, or nonfatal stroke, as compared with simvastatin alone. These results do not support the routine use of combination therapy with fenofibrate and simvastatin to reduce cardiovascular risk in the majority of high-risk patients with type 2 diabetes. (ClinicalTrials.gov number, NCT00000620.) 2010 Massachusetts Medical Society

Composition, disintegrative properties, and labeling compliance of commercially available taurine and carnitine dietary products.

PubMed

Bragg, Rebecca R; Freeman, Lisa M; Fascetti, Andrea J; Yu, Zengshou

2009-01-15

To test the quality, disintegration properties, and compliance with labeling regulations for representative commercially available taurine and carnitine dietary products. Evaluation study. 11 commercially available taurine and 10 commercially available carnitine products. For each product, the amount of taurine or carnitine was determined and compared with the label claim. All products were evaluated for concentrations of mercury, arsenic, and selenium. Disintegration properties of 5 taurine and 8 carnitine products were determined in vitro. Labels were evaluated for compliance with FDA guidelines. 10 of 11 taurine and 10 of 10 carnitine products were within 10% of the stated label claim. Three of 11 taurine and 6 of 10 carnitine products were within 5% of the stated label claim. The median percentage difference between laboratory analysis and label claim was -5.7% (range, -26.3% to 2.5%) for taurine and 3.6% (range, -2.6% to 8.8%) for carnitine. No substantial amount of contamination with mercury, arsenic, or selenium was found in any of the products. During disintegration testing, 1 of 5 taurine products and 5 of 8 carnitine products did not disintegrate within 45 minutes during at least 1 test. Disintegration time for those that did disintegrate ranged from 1.7 to 37.0 minutes. All product labels conformed with FDA regulations. Taurine and carnitine products evaluated in this study closely adhered to manufacturer claims and labeling guidelines. However, disintegration testing suggested high variability in some products, possibly limiting uptake and use by animals that receive them.

Imaging Taurine in the Central Nervous System Using Chemically Specific X-ray Fluorescence Imaging at the Sulfur K-Edge

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hackett, Mark J.; Paterson, Phyllis G.; Pickering, Ingrid J.

A method to image taurine distributions within the central nervous system and other organs has long been sought. Since taurine is small and mobile, it cannot be chemically “tagged” and imaged using conventional immuno-histochemistry methods. Combining numerous indirect measurements, taurine is known to play critical roles in brain function during health and disease and is proposed to act as a neuro-osmolyte, neuro-modulator, and possibly a neuro-transmitter. Elucidation of taurine’s neurochemical roles and importance would be substantially enhanced by a direct method to visualize alterations, due to physiological and pathological events in the brain, in the local concentration of taurine atmore » or near cellular spatial resolution in vivo or in situ in tissue sections. We thus have developed chemically specific X-ray fluorescence imaging (XFI) at the sulfur K-edge to image the sulfonate group in taurine in situ in ex vivo tissue sections. To our knowledge, this represents the first undistorted imaging of taurine distribution in brain at 20 μm resolution. We report quantitative technique validation by imaging taurine in the cerebellum and hippocampus regions of the rat brain. Further, we apply the technique to image taurine loss from the vulnerable CA1 (cornus ammonis 1) sector of the rat hippocampus following global brain ischemia. The location-specific loss of taurine from CA1 but not CA3 neurons following ischemia reveals osmotic stress may be a key factor in delayed neurodegeneration after a cerebral ischemic insult and highlights the significant potential of chemically specific XFI to study the role of taurine in brain disease.« less

Evaluation of taurine as an osmotic agent for peritoneal dialysis solution.

PubMed

Nishimura, Hideki; Ikehara, Osamu; Naito, Takashi; Higuchi, Chieko; Sanaka, Tsutomu

2009-01-01

The development of a glucose-free peritoneal dialysis (PD) solution is important because glucose has been associated with functional and morphological damage to the peritoneal membrane. The ultrafiltration (UF) and biocompatibility of new PD solutions containing taurine (PD-taurine) instead of glucose as an osmolite were tested in a rat PD model. To determine the solution's UF ability, different concentrations of taurine in PD solutions were compared to glucose-based PD solutions (PD-glucose) by giving single intraperitoneal injections for 2, 4, and 6 hours. To examine the biocompatibility of PD-taurine, the rats were divided into 3 groups: a 3.86% PD-glucose group, a 3.5% PD-taurine group and a not dialyzed group. The rats were given 10-mL injections of PD fluids intraperitoneally 3 times daily for 7 days. A peritoneal equilibration test (PET) was performed using a 1.9% xylitol solution at the time the rats were sacrificed. Mesothelial cell monolayers were obtained from the animals and studied based on a population analysis. The net UF of PD-taurine increased in a dose-dependent manner; the 3.5% PD-taurine solution was equivalent to the 3.86% PD-glucose solution after 4 hours. The PET showed that the drainage volume and the D(4)/D(0) ratio for xylitol after 4 hours with PD-taurine solution were significantly greater than with the PD-glucose solution (p < 0.001 and p < 0.001 respectively). Mesothelial and fibroblast-like cell proliferation was significantly less with PD-taurine than with PD-glucose (p < 0.01). These results indicate that PD-taurine resulted in net UF equivalent to that of PD-glucose and was more biocompatible than PD-glucose with respect to the peritoneal membrane.

Revisiting AFLP fingerprinting for an unbiased assessment of genetic structure and differentiation of taurine and zebu cattle

PubMed Central

2014-01-01

Background Descendants from the extinct aurochs (Bos primigenius), taurine (Bos taurus) and zebu cattle (Bos indicus) were domesticated 10,000 years ago in Southwestern and Southern Asia, respectively, and colonized the world undergoing complex events of admixture and selection. Molecular data, in particular genome-wide single nucleotide polymorphism (SNP) markers, can complement historic and archaeological records to elucidate these past events. However, SNP ascertainment in cattle has been optimized for taurine breeds, imposing limitations to the study of diversity in zebu cattle. As amplified fragment length polymorphism (AFLP) markers are discovered and genotyped as the samples are assayed, this type of marker is free of ascertainment bias. In order to obtain unbiased assessments of genetic differentiation and structure in taurine and zebu cattle, we analyzed a dataset of 135 AFLP markers in 1,593 samples from 13 zebu and 58 taurine breeds, representing nine continental areas. Results We found a geographical pattern of expected heterozygosity in European taurine breeds decreasing with the distance from the domestication centre, arguing against a large-scale introgression from European or African aurochs. Zebu cattle were found to be at least as diverse as taurine cattle. Western African zebu cattle were found to have diverged more from Indian zebu than South American zebu. Model-based clustering and ancestry informative markers analyses suggested that this is due to taurine introgression. Although a large part of South American zebu cattle also descend from taurine cows, we did not detect significant levels of taurine ancestry in these breeds, probably because of systematic backcrossing with zebu bulls. Furthermore, limited zebu introgression was found in Podolian taurine breeds in Italy. Conclusions The assessment of cattle diversity reported here contributes an unbiased global view to genetic differentiation and structure of taurine and zebu cattle populations, which is essential for an effective conservation of the bovine genetic resources. PMID:24739206

Past Taurine Intake Has a Positive Effect on Present Cognitive Function in the Elderly.

PubMed

Bae, Mi Ae; Gao, Ranran; Kim, Sung Hoon; Chang, Kyung Ja

2017-01-01

This study investigated the associations between dietary history of past taurine intake and cognitive function in the elderly. Subjects of this study were 40 elderly persons with dementia (men 14, women 26) and 37 normal elderly persons (men 5, women 32). Data were collected using questionnaires by investigator-based interview to the elderly and family caregivers. We examined their general characteristics, anthropometric data, cognitive function, and taurine index. Cognitive function was measured using MMSE-DS and higher score means better cognitive function. As dietary history of past taurine intake, taurine index was evaluated by scoring the intake frequency of 41 kinds of taurine-containing foods. Part correlation analysis (sex, age, and school educational period correction) was used to analyze associations between taurine index and cognitive function. The analysis of all data was carried out by the SPSS 20.0 program for windows. The age, height, weight, and BMI of elderly with dementia showed no statistical significance compared to normal elderly. The elderly with dementia had significantly higher school education period (7.4 years) than the normal elderly (4.8 years) (p < 0.01). Nevertheless, the average total score of cognitive function (MMSE-DS) of the elderly with dementia (18.1 points) was significantly lower than score of the normal elderly (21.7 points) (p < 0.05). The average taurine index of the elderly with dementia (104.7 points) was significantly lower than average taurine index of the normal elderly (123.7 points) (p < 0.01). There were positive correlations between total taurine index and total score of cognitive function in all the elderly subjects (p < 0.05). In particular, as taurine index was higher, there were significantly higher scores of cognitive function such as 'time orientation' and 'judgement and abstract thinking' (p < 0.01). In conclusion, these results suggest that past taurine intake may have a positive effect on present cognitive function in the elderly.

Effect of dietary taurine supplementation on growth, feed efficiency, and nutrient composition of juvenile sablefish (Anoplopoma fimbria)

USDA-ARS?s Scientific Manuscript database

Juvenile sablefish were fed a low taurine, basal feed with seven graded levels of supplemental taurine to determine taurine requirements for growth and feed efficiency. The basal feed was plant based, formulated primarily with soy and corn proteins with a minimal (9%) amount of fishmeal. The unsuppl...

Taurine as osmoregulator and neuromodulator in the brain.

PubMed

Oja, S S; Saransaari, P

1996-06-01

Taurine has been assumed to function as an osmoregulator and neuromodulator in the brain. The pertinent studies are now reviewed in an attempt to formulate a unifying hypothesis as to how taurine could simultaneously act in both roles. Neuromodulatory actions of taurine may also underlie its protective effects against neuronal overexcitation and glutamate agonist-induced neurotoxicity.

Toward the establishment of standardized in vitro tests for lipid-based formulations, part 3: understanding supersaturation versus precipitation potential during the in vitro digestion of type I, II, IIIA, IIIB and IV lipid-based formulations.

PubMed

Williams, Hywel D; Sassene, Philip; Kleberg, Karen; Calderone, Marilyn; Igonin, Annabel; Jule, Eduardo; Vertommen, Jan; Blundell, Ross; Benameur, Hassan; Müllertz, Anette; Pouton, Colin W; Porter, Christopher J H

2013-12-01

Recent studies have shown that digestion of lipid-based formulations (LBFs) can stimulate both supersaturation and precipitation. The current study has evaluated the drug, formulation and dose-dependence of the supersaturation - precipitation balance for a range of LBFs. Type I, II, IIIA/B LBFs containing medium-chain (MC) or long-chain (LC) lipids, and lipid-free Type IV LBF incorporating different doses of fenofibrate or tolfenamic acid were digested in vitro in a simulated intestinal medium. The degree of supersaturation was assessed through comparison of drug concentrations in aqueous digestion phases (APDIGEST) during LBF digestion and the equilibrium drug solubility in the same phases. Increasing fenofibrate or tolfenamic acid drug loads (i.e., dose) had negligible effects on LC LBF performance during digestion, but promoted drug crystallization (confirmed by XRPD) from MC and Type IV LBF. Drug crystallization was only evident in instances when the calculated maximum supersaturation ratio (SR(M)) was >3. This threshold SR(M) value was remarkably consistent across all LBF and was also consistent with previous studies with danazol. The maximum supersaturation ratio (SR(M)) provides an indication of the supersaturation 'pressure' exerted by formulation digestion and is strongly predictive of the likelihood of drug precipitation in vitro. This may also prove effective in discriminating the in vivo performance of LBFs.

Gateways to clinical trials.

PubMed

Tomillero, A; Moral, M A

2009-03-01

ABT-869, Acadesine, Acetylsalicylic acid/omeprazole, Adefovir, Adefovir dipivoxil, AEG-35156, Agatolimod sodium, Albiglutide, Alemtuzumab, Alipogene tiparvovec, Alogliptin benzoate, AMG-386, Amrubicin hydrochloride, Apremilast, Aripiprazole, Asoprisnil, Atorvastatin/fenofibrate, AVN-944, Axitinib; Belinostat, Bevacizumab, BHT-3021, BI-2536, Biapenem, Bilastine, Biphasic insulin aspart, Blinatumomab, Bortezomib, Bosentan; Catumaxomab, CD-NP, Cediranib, Certolizumab pegol, Cetuximab, Choline fenofibrate, Ciclesonide, CK-1827452,Clevudine, Clofarabine, CSL-360, CYT-997; Dapagliflozin, Darinaparsin, Denosumab, Densiron 68, Desloratadine, Dulanermin; Edoxaban tosilate, Emtricitabine, Entecavir, Erlotinib hydrochloride, Everolimus, Exenatide, Ezetimibe, Ezetimibe/simvastatin; Fidaxomicintiacumiv, Fulvestrant; G-207, GCR-8015, Gefitinib, Ghrelin (human), Glufosfamide; HPV16L1E7CVLP; Ibutamoren mesilate, Imatinib mesylate, Insulin detemir, Insulin glargine, Iodine (I131) tositumomab, Istaroxime, ITMN-191, Ixabepilone; JZP-4, Lenalidomide; Levetiracetam, Linaclotide acetate, Liposomal cytarabine/daunorubicin, Liposomal doxorubicin, Liraglutide, LY-518674; Milatuzumab, MMR-V, Motesanib diphosphate, Mycophenolic acid sodium salt; Niacin/simvastatin; Obatoclax mesylate, Odanacatib; Paclitaxel nanoparticles, Paclitaxel-eluting stent, Pazufloxacin, PBT-2, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b, Peginterferon alfa-2b/ribavirin, Pemetrexed disodium, Perampanel, PfCP2.9, Pitavastatin calcium, Poly I:CLC, Pomalidomide, Pralatrexate, Pramlintide acetate, Prucalopride; rhGAD65, Roflumilast; RTS,S/AS02D; SCH-530348, Semagacestat, Sirolimus-eluting coronary stent, Sirolimus-Eluting Stent, SIR-Spheres, Sivelestat sodium hydrate, Sorafenib, Sunitinib malate; Tadalafil, Tafluprost, Tanespimycin, Teduglutide, Telaprevir, Telbivudine, Tenofovir disoproxil fumarate, Tiotropium bromide, TMC-435350, Tositumomab/iodine (I131) tositumomab, Travoprost/timolol, Triciribine phosphate; Vandetanib, VIA-2291, Vinflunine, Vorinostat; XL-019; Yttrium 90 (90Y) ibritumomab tiuxetan. Copyright 2009 Prous Science, S.A.U. or its licensors. All rights reserved.

Interaction between gemfibrozil and warfarin: case report and review of the literature.

PubMed

Dixon, Dave L; Williams, Virginia G

2009-06-01

Possible procoagulant effects can occur when lipid-lowering fibric acid derivatives, such as gemfibrozil and fenofibrate, are taken concomitantly with warfarin. Although there are several detailed reports of fenofibrate potentiating the anticoagulant effects of warfarin, few case reports have been published regarding an interaction between gemfibrozil and warfarin. We describe a 62-year-old man who was taking warfarin for paroxysmal atrial fibrillation and came to the anticoagulation clinic for a routine follow-up. For 9 months, the patient's international normalized ratio (INR) had been stable (target range 2.0-3.0) with warfarin 45 mg/week. At this clinic visit, however, his INR was supratherapeutic at 5.8; the only identified change in his drug therapy was the addition of gemfibrozil 600 mg twice/day, started 3 weeks earlier. The patient denied any changes in his dietary intake of vitamin K, alcohol use, or addition of nonprescription or herbal agents. Recent laboratory tests revealed no signs of thyroid abnormalities and only an insignificant elevation in his alanine aminotransferase level. His warfarin dose was decreased to 35-37.5 mg/week (a 22% reduction), and a therapeutic INR was maintained until gemfibrozil was later discontinued because of myalgia. After consecutive subtherapeutic INRs, his warfarin dose was increased to 45 mg/week and a therapeutic INR was maintained. Use of the Drug Interaction Probability Scale indicated that the likelihood of the gemfibrozil-warfarin interaction was probable. The exact mechanism of the proposed interactions between fibric acid derivatives and warfarin remains unknown but may be multifactorial through inhibition of cytochrome P450 isoenzymes, displacement from protein binding sites, or changes in coagulation factor synthesis. Regardless of the fibric acid derivative chosen, an empiric dosage reduction of 20% and close INR monitoring are warranted in patients receiving warfarin.

Effect of ursodeoxycholic acid on bile acid profiles and intestinal detoxification machinery in primary biliary cirrhosis and health.

PubMed

Dilger, Karin; Hohenester, Simon; Winkler-Budenhofer, Ursula; Bastiaansen, Barbara A J; Schaap, Frank G; Rust, Christian; Beuers, Ulrich

2012-07-01

Ursodeoxycholic acid (UDCA) exerts anticholestatic, antifibrotic and antiproliferative effects in primary biliary cirrhosis (PBC) via mechanisms not yet fully understood. Its adequate biliary enrichment is considered mandatory for therapeutic efficacy. However, precise determination of biliary enrichment of UDCA is not possible in clinical practice. Therefore, we investigated (i) the relationship between biliary enrichment and plasma pharmacokinetics of UDCA, (ii) the effect of UDCA on plasma and biliary bile acid composition and conjugation patterns, and (iii) on the intestinal detoxification machinery in patients with PBC and healthy controls. In 11 PBC patients and 11 matched healthy subjects, cystic bile and duodenal tissue were collected before and after 3 weeks of administration of UDCA (15 mg/kg/day). Extensive pharmacokinetic profiling of bile acids was performed. The effect of UDCA on the intestinal detoxification machinery was studied by quantitative PCR and Western blotting. The relative fraction of UDCA and its conjugates in plasma at trough level[x] correlated with their biliary enrichment[y] (r=0.73, p=0.0001, y=3.65+0.49x). Taurine conjugates of the major hydrophobic bile acid, chenodeoxycholic acid, were more prominent in bile of PBC patients than in that of healthy controls. Biliary bile acid conjugation patterns normalized after treatment with UDCA. UDCA induced duodenal expression of key export pumps, BCRP and P-glycoprotein. Biliary and trough plasma enrichment of UDCA are closely correlated in PBC and health. Taurine conjugation may represent an adaptive mechanism in PBC against chenodeoxycholic acid-mediated bile duct damage. UDCA may stabilize small intestinal detoxification by upregulation of efflux pumps. Copyright © 2012. Published by Elsevier B.V.

Taurine Protects Mouse Spermatocytes from Ionizing Radiation-Induced Damage Through Activation of Nrf2/HO-1 Signaling.

PubMed

Yang, Wenjun; Huang, Jinfeng; Xiao, Bang; Liu, Yan; Zhu, Yiqing; Wang, Fang; Sun, Shuhan

2017-01-01

The increasing prevalence of ionizing radiation exposure has inevitably raised public concern over the potential detrimental effects of ionizing radiation on male reproductive system function. The detection of drug candidates to prevent reproductive system from damage caused by ionizing radiation is urgent. We aimed to investigate the protective role of taurine on the injury of mouse spermatocyte-derived cells (GC-2) subjected to ionizing radiation. mouse spermatocytes (GC-2 cells) were exposed to ionizing radiation with or without treatment of Taurine. The effect of ionizing radiation and Taurine treatment on GC-2 cells were evaluated by cell viability assay (CCK8), cell cycle and apoptosis. The relative protein abundance change was determined by Western blotting. The siRNA was used to explore whether Nrf2 signaling was involved in the cytoprotection of Taurine. Taurine significantly inhibited the decrease of cell viability, percentage of apoptotic cells and cell cycle arrest induced by ionizing radiation. Western blot analysis showed that taurine significantly limited the ionizing radiation-induced down-regulation of CyclinB1 and CDK1, and suppressed activation of Fas/FasL system pathway. In addition, taurine treatment significantly increased the expression of Nrf2 and HO-1 in GC-2 cells exposed to ionizing radiation, two components in antioxidant pathway. The above cytoprotection of Taurine was blocked by siNrf2. Our results demonstrate that taurine has the potential to effectively protect GC-2 cells from ionizing radiation- triggered damage via upregulation of Nrf2/HO-1 signaling. © 2017 The Author(s). Published by S. Karger AG, Basel.

Taurine protects methamphetamine-induced developmental angiogenesis defect through antioxidant mechanism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shao, Xue; Hu, Zhengtao; Hu, Chunyan

Investigations have characterized addictive drug-induced developmental cardiovascular malformation in human, non-human primate and rodent. However, the underlying mechanism of malformation caused by drugs during pregnancy is still largely unknown, and preventive and therapeutic measures have been lacking. Using {sup 1}H NMR spectroscopy, we profiled the metabolites from human embryo endothelial cells exposed to methamphetamine (METH) and quantified a total of 226 peaks. We identified 11 metabolites modified robustly and found that taurine markedly increased. We then validated the hypothesis that this dramatic increase in taurine could attribute to its effect in inhibiting METH-induced developmental angiogenesis defect. Taurine supplement showed amore » more significant potential than other metabolites in protecting against METH-induced injury in endothelial cells. Taurine strongly attenuated METH-induced inhibition of proliferation and migration in endothelial cells. Furthermore, death rate and vessel abnormality of zebrafish embryos treated with METH were greatly reversed by taurine. In addition, taurine supplement caused a rapid decrease in reactive oxygen species generation and strongly attenuated the excitable arise of antioxidase activities in the beginning of METH exposure prophase. Dysregulations of NF-κB, p-ERK as well as Bax, which reflect apoptosis, cell cycle arrest and oxidative stress in vascular endothelium, were blocked by taurine. Our results provide the first evidence that taurine prevents METH-caused developmental angiogenesis defect through antioxidant mechanism. Taurine could serve as a potential therapeutic or preventive intervention of developmental vascular malformation for the pregnant women with drug use. Highlights: ► Metabonomics findings. ► Abnormal development. ► Dysregulations of key proteins.« less

Arachidonic acid with taurine enhances pulmonary absorption of macromolecules without any serious histopathological damages.

PubMed

Miyake, Masateru; Minami, Takanori; Yamazaki, Hiroyuki; Emoto, Chie; Mukai, Tadashi; Toguchi, Hajime

2017-05-01

Therapeutic peptides and protein are being used in several indications; however, their poor permeability still remains to be solved. This study focused on the pulmonary route of macromolecules. First, the effects of arachidonic acid (AA) as an absorption enhancer on drug serum concentration, after intratracheal administration, were investigated in rats. Second, the safety of AA was assessed in rats in an acute toxicity study for 7days. AA enhanced the exposure of both interferon-α (IFN-α) and fluorescein isothiocyanate 4000 (FD-4). In addition, the histopathological analysis indicated that AA caused alveolitis and bronchitis in rats. In combination with Taurine (Tau), these lung injuries were prevented through the histopathological analysis. The combined use of Tau with AA did not show any changes in the pharmacokinetics of FD-4. From these results, we suggest the combined use of AA with Tau as a novel formulation on the pulmonary route of macromolecule drugs. This formulation could improve the bioavailability of macromolecule drugs without any serious local damage to the lungs. Copyright © 2017 Elsevier B.V. All rights reserved.

Cysteic Acid in Dietary Keratin is Metabolized to Glutathione and Liver Taurine in a Rat Model of Human Digestion

PubMed Central

Wolber, Frances M.; McGrath, Michelle; Jackson, Felicity; Wylie, Kim; Broomfield, Anne

2016-01-01

Poultry feathers, consisting largely of keratin, are a low-value product of the poultry industry. The safety and digestibility of a dietary protein produced from keratin (KER) was compared to a cysteine-supplemented casein-based diet in a growing rat model for four weeks. KER proved to be an effective substitute for casein at 50% of the total dietary protein, with no changes in the rats’ food intake, weight gain, organ weight, bone mineral density, white blood cell counts, liver glutathione, or blood glutathione. Inclusion of KER in the diet reduced total protein digestibility from 94% to 86% but significantly increased total dietary cysteine uptake and subsequent liver taurine levels. The KER diet also significantly increased caecum weight and significantly decreased fat digestibility, resulting in a lower proportion of body fat, and induced a significant increase in blood haemoglobin. KER is therefore a safe and suitable protein substitute for casein, and the cysteic acid in keratin is metabolised to maintain normal liver and blood glutathione levels. PMID:26907334

The effects of bisphosphonates on taurine transport in retinal capillary endothelial cells under high glucose conditions.

PubMed

Lee, Na-Young; Kang, Young-Sook

2013-01-01

Diabetic retinopathy (DR) is a major cause of blindness in diabetic patients. Elevated glucose and vascular endothelial growth factor (VEGF) in retina can trigger many of the retinal vascular changes caused by diabetes and DR. Recently, bisphosphonates, antiosteoporosis drugs, have been reported to have anti-angiogenic effect by decreasing VEGF. Taurine has several biological processes such as osmoregulation and antioxidation in retina. Therefore, the purpose of this study is to clarify the regulation of taurine transport activity by high glucose concentration and the effect of inhibitors for VEGF function, bisphosphonates, on taurine transport under high glucose condition using TR-iBRB cell lines as an in vitro model of inner blood-retinal barrier (iBRB). As a result, by exposing TR-iBRB cells to high glucose for 48 h, [(3)H]taurine uptake was decreased continuously. [(3)H]Taurine uptake was increased significantly by pretreatment of alendronate and pamidronate compared with the values for high glucose. Increased [(3)H]taurine uptake by pretreatment of alendronate and pamidronate was significantly reduced by mevalonate pathway intermediates, geranylgeraniol (GGOH). In conclusion, taurine transport through the iBRB under high glucose condition can be regulated by bisphosphonates via mevalonate pathway. Therefore, we suggest that bisphosphonates could have the beneficial effects on DR by regulation of taurine contents in retina.

PPAR-α Agonist Fenofibrate Decreased Serum Irisin Levels in Type 2 Diabetes Patients with Hypertriglyceridemia

PubMed Central

Feng, Xiaomeng; Gao, Xia; Jia, Yumei; Zhang, Heng; Pan, Qingrong; Yao, Zhi; Yang, Ning; Liu, Jia; Xu, Yuan; Wang, Guang; Yang, Xinchun

2015-01-01

Irisin is related to insulin resistance and metabolic disorders. The physiologic effects of irisin are partially mediated through peroxisome proliferator-activated receptor-α (PPAR-α). We investigated the effect of fenofibrate, a PPAR-α agonist, on serum irisin in type 2 diabetes patients with hypertriglyceridemia. This study evaluated cross-sectional and interventional studies of 25 type 2 diabetes patients with hypertriglyceridemia (group A) and 40 controls (group B). Group A was treated with fenofibrate (200 mg/day) for 8 weeks. Serum irisin and clinical characteristics were examined. Serum irisin was significantly higher in group A compared with group B (45.15 ± 10.48 versus 35.38 ± 9.97 ng/ml, P < 0.001) and correlated with body mass index (r = 0.314, P = 0.011), fasting blood glucose (r = 0.399, P = 0.001), total cholesterol (r = 0.256, P = 0.040), and high-density lipoprotein cholesterol (r = 0.247, P = 0.047). In multiple regression analysis after controlling for confounders, only fasting blood glucose (β = 5.615, P < 0.001) and high-density lipoprotein cholesterol (β = 19.483, P < 0.001) were independently related to serum irisin. After 8 weeks of fenofibrate treatment, serum irisin significantly decreased in group A compared with baseline (45.15 ± 10.48 versus 38.74 ± 12.54 ng/ml, P = 0.011). Conclusively, fenofibrate decreased serum irisin in type 2 diabetes patients with hypertriglyceridemia, indicating that PPAR-α agonists may protect against metabolic disorders by improving irisin resistance. PMID:26693220

Effect of Cordyceps sinensis and taurine either alone or in combination on streptozotocin induced diabetes.

PubMed

El Zahraa Z El Ashry, Fatma; Mahmoud, Mona F; El Maraghy, Nabila N; Ahmed, Ahmed F

2012-03-01

The present study aimed to investigate the antidiabetic effects of Cordyceps sinensis, taurine and their combination in comparison with glibenclamide both in vivo and in vitro using streptozotocin rat model. The diabetic rats were orally given glibenclamide, C. sinensis, taurine or Cordyceps and taurine combination for 21 days. Their effects were studied both in vivo and in vitro. Oral administration of Cordyceps, taurine and their combination decreased serum glucose, fructosamine, total cholesterol, triglycerides levels, insulin resistance index and pancreatic malondialdehyde content. Cordyceps significantly increased serum insulin, HDL-cholesterol, total antioxidant capacity levels, β cell function percent, and pancreatic reduced glutathione (GSH) content. However, taurine was unable to elevate pancreatic GSH level to a significant level. These natural products and their combinations were more effective than glibenclamide in reducing insulin resistance index and they had stronger antioxidant properties. Cordyceps and taurine significantly enhanced glucose uptake by diaphragms of normal and diabetic rats in absence and presence of insulin. In conclusion, Cordyceps and taurine either alone or in combination have less potent hypoglycemic effects than glibenclamide; however, they have more ability to reduce insulin resistance and stronger antioxidant properties. Copyright © 2011 Elsevier Ltd. All rights reserved.

Effect of Brain Tumor Presence During Radiation on Tissue Toxicity: Transcriptomic and Metabolic Changes.

PubMed

Zawaski, Janice A; Sabek, Omaima M; Voicu, Horatiu; Eastwood Leung, Hon-Chiu; Gaber, M Waleed

2017-11-15

Radiation therapy (RT) causes functional and transcriptomic changes in the brain; however, most studies have been carried out in normal rodent brains. Here, the long-term effect of irradiation and tumor presence during radiation was investigated. Male Wistar rats ∼7 weeks old were divided into 3 groups: sham implant, RT+sham implant, and RT+tumor implant (C6 glioma). Hypofractionated irradiation (8 or 6 Gy/day for 5 days) was localized to a 1-cm strip of cranium starting 5 days after implantation, resulting in complete tumor regression and prolonged survival. Biopsy of tissue was performed in the implant area 65 days after implantation. RNA was hybridized to GeneChip Rat Exon 1.0 ST array. Data were analyzed using significant analysis of microarrays and ingenuity pathway analysis. 1 H magnetic resonance spectroscopy ( 1 H-MRS) imaging was performed in the implantation site 65 to 70 days after implantation using a 9.4 T Biospec magnetic resonance imaging scanner with a quadrature rat brain array. Immunohistochemical staining for astrogliosis, HMG-CoA synthase 2, γ-aminobutyric acid (GABA) and taurine was performed at ∼65 days after implantation. Eighty-four genes had a false discovery rate <3.5%. We compared RT+tumor implant with RT+sham implant animals. The tumor presence affected networks associated with cancer/cell morphology/tissue morphology. 1 H-MRS showed significant reduction in taurine levels (P<.04) at the implantation site in both groups. However, the RT+tumor group also showed significant increase in levels of neurotransmitter GABA (P=.02). Hippocampal taurine levels were only significantly reduced in the RT+tumor group (P=.03). HMG-CoA synthase 2, GABA and taurine levels were confirmed using staining. Glial fibrillary acidic protein staining demonstrated a significant increase in inflammation that was heightened in the RT+tumor group. Our data indicate that tumor presence during radiation significantly affects long-term functional transcriptomics landscape and neurotransmitter levels at the tumor implantation site/normal tissue, accompanied by increased inflammation (astrogliosis). Copyright © 2017 Elsevier Inc. All rights reserved.

Effect of taurine feeding on bone mineral density and bone markers in rats.

PubMed

Choi, Mi-Ja; Seo, Ji-Na

2013-01-01

The purpose of this study was to investigate the effect of dietary taurine supplementation on bone mineral density (BMD) and bone mineral content (BMC) in rats. Twenty Sprague-Dawley male rats (body weight 200 ± 10 g) were divided into two groups, control and taurine group (2% taurine-supplemented diet). All rats were fed on experimental diet and deionized water and libitum for 6 weeks. Serum alkaline phosphatase (ALP) activity, osteocalcin, PTH, and urinary deoxypyridinoline cross-links value were measured as markers of bone formation and resorption. BMD and BMC were measured using PIXImus (GE Lunar Co., Wisconsin) in spine and femur. The effect of diet on ALP, osteocalcine, and PTH was not significant. There were no significant differences in ALP, osteocalcine, and PTH concentration. Urinary calcium excretion was lower in taurine group than in control group. Femur BMC/weight of taurine group was significantly higher than control group. The results of this study showed the possible role of taurine in bone metabolism in male rats.

Central effect of taurine and its analogues on fever caused by intravenous leukocytic pyrogen in the rabbit.

PubMed Central

Lipton, J M; Ticknor, C B

1979-01-01

1. Taurine infused I.C.V. after I.V. injection of leukocytic pyrogen (LP) inhibited the initial rise in body temperature and prolonged fever when infusion was stopped. 2. Similar infusion of taurine also inhibited the hypertermic effect of I.C.V. PGE2 (0.5 microgram) but did not cause prolonged hyperthermia. 3. I.C.V. administration of the taurine analogues hypotaurine and beta-alanine, compounds which have been shown previously to compete with taurine for facilitated transport in C.N.S. tissue, also inhibited the initial increase in body temperature and prolonged LP fever. 4. These results suggest that taurine prolongs LP fever by preferentially occupying a carrier system normally required for termination of the effects of endogenous pyrogens or related central mediators of fever. There was no evidence that taurine prolongs fever by blocking inactivation of central PGE2, a substance proposed previously to be a central mediator of fever. PMID:107309

An exome-wide sequencing study of lipid response to high-fat meal and fenofibrate in Caucasians from the GOLDN cohort

USDA-ARS?s Scientific Manuscript database

Our understanding of genetic influences on the response of lipids to specific interventions is limited. In this study, we sought to elucidate effects of rare genetic variants on lipid response to a high-fat meal challenge and fenofibrate (FFB) therapy in the Genetics of Lipid Lowering Drugs and Diet...

Apolipoprotein E polymorphisms and postprandial triglyceridemia before and after fenofibrate treatment in the Genetics of Lipid Lowering and Diet Network (GOLDN) Study

USDA-ARS?s Scientific Manuscript database

Background: While much is known about the effect of Apolipoprotein E (APOE) alleles on fasting lipid concentrations, less is known about the effect of APOE alleles on postprandial triglyceridemia or the triglyceride response to fenofibrate. Methods and Results: We evaluated the effects of the APOE l...

Theoretical and experimental study of fenofibrate and simvastatin

NASA Astrophysics Data System (ADS)

Nicolás Vázquez, Inés; Rodríguez-Núñez, Jesús Rubén; Peña-Caballero, Vicente; Ruvalcaba, Rene Miranda; Aceves-Hernandez, Juan Manuel

2017-12-01

Fenofibrate, an oral fibrate lipid lowering agent, and simvastatin, which reduces plasma levels of low-density lipoprotein cholesterol, are active pharmaceutical ingredients (APIs), currently in the market. We characterized these APIs by thermal analysis and conducted X-ray powder diffraction techniques. Studies should be carried out in the formulation stage before the final composition of a polypill may be established. Thus, it was found in thermochemical studies that both compounds present no chemical interactions in an equimolar mixture of solid samples at room temperature. Theoretical studies were employed to determine possible interactions between fenofibrate and simvastatin. A very weak intramolecular hydrogen bond is formed between the hydroxyl group (O5H5) of the simvastatin with chlorine and carbonyl group (C11O4, C1O2) of the fenofibrate molecule. These weak energy hydrogen bonds have no effect on the chemical stability of the compounds studied. The results were obtained using Density Functional Theory methods; particularly the BPE1BPE and B3LYP functional and 6-31++G** basis set. The values of energy show good approximation when are compared with similar calculations previously reported. Infrared spectra of monomers and dimers were obtained via theoretical calculations.

Gemfibrozil not fenofibrate decreases systemic glucose level via PPARα.

PubMed

Song, Danjun; Chu, Zanbo; Min, Luo; Zhen, Tan; Li, Pengxu; Han, Liyuan; Bu, Shizhong; yang, Julin; Gonzale, F J; Liu, Aiming

2016-04-01

Concurrence of high glucose or diabetes in patients with dyslipidemia is presenting major challenges for clinicians. Although sporadically reported, a rational basis for the use of fibrates for the treatment of dyslipidemia with concurrent metabolic syndrome has not been established. In this study, wild-type (WT) and Ppara-null (KO) mice were fed a serial gemfibrozil- and fenofibrate-containing diet under the same experimental conditions for 14 days. Glucose level in the blood, glycogen storage in the liver tissues, and the potential toxic responses were assayed. Genes involved in glucose metabolism were determined by quantitative polymerase chain reaction analysis. Both the blood glucose level and the glycogen content in the liver were down-regulated by gemfibrozil but not by fenofibrate in WT mice, in a dose-dependent manner. This decrement did not occur in KO mice for either fibrate agent. Secondary regulation on the transcription of pyruvate kinase, and gluconolactonase were observed following gemfibrozil treatment, which was differential between WT mice and KO mice. Gemfibrozil, not fenofibrate, down-regulates systemic glucose level and glycogen storage in the liver dependent on PPARα, suggesting its potential value for treatment of dyslipidemia with concurrent diabetes or high glucose levels.

Effects of taurine supplementation on hepatic markers of inflammation and lipid metabolism in mothers and offspring in the setting of maternal obesity.

PubMed

Li, Minglan; Reynolds, Clare M; Sloboda, Deborah M; Gray, Clint; Vickers, Mark H

2013-01-01

Maternal obesity is associated with obesity and metabolic disorders in offspring. However, intervention strategies to reverse or ameliorate the effects of maternal obesity on offspring health are limited. Following maternal undernutrition, taurine supplementation can improve outcomes in offspring, possibly via effects on glucose homeostasis and insulin secretion. The effects of taurine in mediating inflammatory processes as a protective mechanism has not been investigated. Further, the efficacy of taurine supplementation in the setting of maternal obesity is not known. Using a model of maternal obesity, we examined the effects of maternal taurine supplementation on outcomes related to inflammation and lipid metabolism in mothers and neonates. Time-mated Wistar rats were randomised to either: 1) control : control diet during pregnancy and lactation (CON); 2) CON supplemented with 1.5% taurine in drinking water (CT); 3) maternal obesogenic diet (high fat, high fructose) during pregnancy and lactation (MO); or 4) MO supplemented with taurine (MOT). Maternal and neonatal weights, plasma cytokines and hepatic gene expression were analysed. A MO diet resulted in maternal hyperinsulinemia and hyperleptinemia and increased plasma glucose, glutamate and TNF-α concentrations. Taurine normalised maternal plasma TNF-α and glutamate concentrations in MOT animals. Both MO and MOT mothers displayed evidence of fatty liver accompanied by alterations in key markers of hepatic lipid metabolism. MO neonates displayed a pro-inflammatory hepatic profile which was partially rescued in MOT offspring. Conversely, a pro-inflammatory phenotype was observed in MOT mothers suggesting a possible maternal trade-off to protect the neonate. Despite protective effects of taurine in MOT offspring, neonatal mortality was increased in CT neonates, indicating possible adverse effects of taurine in the setting of normal pregnancy. These data suggest that maternal taurine supplementation may ameliorate the adverse effects observed in offspring following a maternal obesogenic diet but these effects are dependent upon prior maternal nutritional background.

Sulphur-containing Amino Acids: Protective Role Against Free Radicals and Heavy Metals.

PubMed

Colovic, Mirjana B; Vasic, Vesna M; Djuric, Dragan M; Krstic, Danijela Z

2018-01-30

Sulphur is an abundant element in biological systems, which plays an important role in processes essential for life as a constituent of proteins, vitamins and other crucial biomolecules. The major source of sulphur for humans is plants being able to use inorganic sulphur in the purpose of sulphur-containing amino acids synthesis. Sulphur-containing amino acids include methionine, cysteine, homocysteine, and taurine. Methionine and cysteine are classified as proteinogenic, canonic amino acids incorporated in protein structure. Sulphur amino acids are involved in the synthesis of intracellular antioxidants such as glutathione and N-acetyl cysteine. Moreover, naturally occurring sulphur-containing ligands are effective and safe detoxifying agents, often used in order to prevent toxic metal ions effects and their accumulation in human body. Literature search for peer-reviewed articles was performed using PubMed and Scopus databases, and utilizing appropriate keywords. This review is focused on sulphur-containing amino acids - methionine, cysteine, taurine, and their derivatives - glutathione and N-acetylcysteine, and their defense effects as antioxidant agents against free radicals. Additionally, the protective effects of sulphur-containing ligands against the toxic effects of heavy and transition metal ions, and their reactivation role towards the enzyme inhibition are described. Sulphur-containing amino acids represent a powerful part of cell antioxidant system. Thus, they are essential in the maintenance of normal cellular functions and health. In addition to their worthy antioxidant action, sulphur-containing amino acids may offer a chelating site for heavy metals. Accordingly, they may be supplemented during chelating therapy, providing beneficial effects in eliminating toxic metals. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Taurine supplementation has anti-atherogenic and anti-inflammatory effects before and after incremental exercise in heart failure.

PubMed

Ahmadian, Mehdi; Roshan, Valiollah Dabidi; Aslani, Elaheh; Stannard, Stephen R

2017-07-01

The purpose of this study was to examine the anti-atherogenic and anti-inflammatory effect of supplemental taurine prior to and following incremental exercise in patients with heart failure (HF). Patients with HF and left ventricle ejection fraction less than 50%, and placed in functional class II or III according to the New York Heart Association classification, were randomly assigned to two groups: (1) taurine supplementation; or (2) placebo. The taurine group received oral taurine (500 mg) 3 times a day for 2 weeks, and performed exercise before and after the supplementation period. The placebo group followed the same protocol, but with a starch supplement (500 mg) rather than taurine. The incremental multilevel treadmill test was done using a modified Bruce protocol. Our results indicate that inflammatory indices [C-reactive protein (CRP), platelets] decreased in the taurine group in pre-exercise, post-supplementation and post-exercise, post-supplementation as compared with pre-exercise, pre-supplementation ( p < 0.05) whereas these indices increased in pre-exercise, post-supplementation and post-exercise, post-supplementation as compared with pre-exercise, pre-supplementation in the placebo group ( p < 0.05). Our results also show that atherogenic indices [Castelli's Risk Index-I (CRI-I), Castelli's Risk Index-II (CRI-II) and Atherogenic Coefficient (AC)] decreased in the taurine group in pre-exercise, post-supplementation and post-exercise, post-supplementation as compared with pre-exercise, pre-supplementation ( p < 0.05). No such changes were noted in the placebo group ( p > 0.05). our results suggest that 2 weeks of oral taurine supplementation increases the taurine levels and has anti-atherogenic and anti-inflammatory effects prior to and following incremental exercise in HF patients.

The effects of taurine on repeat sprint cycling after low or high cadence exhaustive exercise in females.

PubMed

Waldron, Mark; Knight, Francesca; Tallent, Jamie; Patterson, Stephen; Jeffries, Owen

2018-06-01

This study investigated the effects of taurine on repeated sprint exercise, performed after fixed incremental ramp exercise to exhaustion at isokinetic high (90 r/min) or low (50 r/min) cadences. In a double-blind, repeated measures design, nine females completed an incremental ramp test to volitional exhaustion, followed by 2 min active recovery and 6 × 10 s sprints on a cycle ergometer, in one of four conditions: high cadence (90 r/min) + taurine (50 mg/kg body mass); high cadence + placebo (3 mg/kg body mass maltodextrin); low cadence (50 r/min) + taurine; low cadence + placebo. Heart rate (HR) and blood lactate concentration B[La] were measured before and after the ramp test and after the sprints. Taurine lowered HR vs. placebo prior to the ramp test (P = 0.004; d = 2.1). There was an effect of condition on ramp performance (P < 0.001), with higher end-test power (d = 3.7) in taurine conditions. During repeated sprints, there was a condition × time interaction (P = 0.002), with higher peak sprint power in the placebo conditions compared to taurine (sprint 2-6; P < 0.05). B[La] was higher in taurine compared to placebo post-ramp (P = 0.004; d = 4.7). Taurine-lowered pre-exercise HR and improved incremental end-test power output, with subsequent detrimental effects on sprint performance, independent of cadence. Short endurance performance can be acutely enhanced after taurine ingestion but this effect might not be maintained across longer periods of exercise or induce the need for longer recovery periods.

Taurine zinc solid dispersions enhance bile-incubated L02 cell viability and improve liver function by inhibiting ERK2 and JNK phosphorylation during cholestasis.

PubMed

Wang, Yu; Mei, Xueting; Yuan, Jingquan; Lai, Xiaofang; Xu, Donghui

2016-07-29

Dietary intakes of taurine and zinc are associated with decreased risk of liver disease. In this study, solid dispersions (SDs) of a taurine zinc complex on hepatic injury were examined in vitro using the immortalized human hepatocyte cell line L02 and in a rat model of bile duct ligation. Sham-operated and bile duct ligated Sprague-Dawley rats were treated with the vehicle alone or taurine zinc (40, 80, 160mg/kg) for 17days. Bile duct ligation significantly increased blood lipid levels, and promoted hepatocyte apoptosis, inflammation and compensatory biliary proliferation. In vitro, incubation with bile significantly reduced L02 cell viability; this effect was significantly attenuated by pretreatment with SP600125 (a JNK inhibitor) and enhanced when co-incubated with taurine zinc SDs. In vivo, administration of taurine zinc SDs decreased serum alanine aminotransferase and aspartate aminotransferase activities in a dose-dependent manner and attenuated the increases in serum total bilirubin, total cholesterol and low density lipoprotein cholesterol levels after bile duct ligation. Additionally, taurine zinc SDs downregulated the expression of interleukin-1β and inhibited the phosphorylation of Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase2 (ERK2) in the liver after bile duct ligation. Moreover, taurine zinc SDs had more potent blood lipid regulatory and anti-apoptotic effects than the physical mixture of taurine and zinc acetate. Therefore, we speculate that taurine zinc SDs protect liver function at least in part via a mechanism linked to reduce phosphorylation of JNK and ERK2, which suppresses inflammation, apoptosis and cholangiocyte proliferation during cholestasis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Fenofibrate-associated changes in renal function and relationship to clinical outcomes among individuals with type 2 diabetes: the Action to Control Cardiovascular Risk in Diabetes (ACCORD) experience.

PubMed

Bonds, D E; Craven, T E; Buse, J; Crouse, J R; Cuddihy, R; Elam, M; Ginsberg, H N; Kirchner, K; Marcovina, S; Mychaleckyj, J C; O'Connor, P J; Sperl-Hillen, J-A

2012-06-01

Fenofibrate has been noted to cause an elevation in serum creatinine in some individuals. Participants in the Action to Control Cardiovascular Risk in Diabetes Lipid Study were studied to better characterise who is at risk of an increase in creatinine level and to determine whether those with creatinine elevation have a differential risk of adverse renal or cardiovascular outcomes. A fenofibrate-associated creatinine increase (FACI) was defined as an increase in serum creatinine of at least 20% from baseline to month 4 in participants assigned to fenofibrate. Baseline patient characteristics, and baseline and 4-month drug, clinical, laboratory characteristics and study outcomes were examined by FACI status. Of the sample, 48% of those randomised to receive fenofibrate had at least a 20% increase in serum creatinine within 4 months. In multivariable analysis, participants who were older, male, used an ACE inhibitor at baseline, used a thiazolidinedione (TZD) at 4 months post-randomisation, had baseline CVD, and had lower baseline serum creatinine and LDL-cholesterol levels were all more likely to meet the criteria for FACI. Participants in the FACI group were also more likely to have a decrease in their serum triacylglycerol level from baseline to 4 months. No differences in study outcomes were seen by FACI criteria. Several characteristics predict a rapid rise in serum creatinine upon starting fenofibrate. Participants who met the criteria for FACI also had a greater change in triacylglycerol levels. In the setting of careful renal function surveillance and reduction of fenofibrate dose as indicated, no increase in renal disease or cardiovascular outcome was seen in those individuals demonstrating FACI. ClincalTrials.gov: NCT00000620. The ACCORD Trial was supported by grants (N01-HC-95178, N01-HC-95179, N01-HC-95180, N01-HC-95181, N01-HC-95182, N01-HC-95183, N01-HC-95184, IAA-Y1-HC-9035 and IAA-Y1-HC-1010) from the National Heart, Lung, and Blood Institute; by the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute on Aging, and the National Eye Institute; by the Centers for Disease Control and Prevention; by General Clinical Research Centers and by the Clinical and Translational Science Awards. Abbott Laboratories, Amylin Pharmaceutical, AstraZeneca Pharmaceuticals LP, Bayer HealthCare LLC, Closer Healthcare, GlaxoSmithKline Pharmaceuticals, King Pharmaceuticals, Merck, Novartis Pharmaceuticals, Novo Nordisk, Omron Healthcare, sanofi-aventis US and Takeda Pharmaceuticals provided study medications, equipment or supplies.

Taurine induces anti-anxiety by activating strychnine-sensitive glycine receptor in vivo.

PubMed

Zhang, Cheng Gao; Kim, Sung-Jin

2007-01-01

Taurine has a variety of actions in the body such as cardiotonic, host-defensive, radioprotective and glucose-regulatory effects. However, its action in the central nervous system remains to be characterized. In the present study, we tested to see whether taurine exerts anti-anxiety effects and to explore its mechanism of anti-anxiety activity in vivo. The staircase test and elevated plus maze test were performed to test the anti-anxiety action of taurine. Convulsions induced by strychnine, picrotoxin, yohimbine and isoniazid were tested to explore the mechanism of anti-anxiety activity of taurine. The Rotarod test was performed to test muscle relaxant activity and the passive avoidance test was carried out to test memory activity in response to taurine. Taurine (200 mg/kg, p.o.) significantly reduced rearing numbers in the staircase test while it increased the time spent in the open arms as well as the number of entries to the open arms in the elevated plus maze test, suggesting that it has a significant anti-anxiety activity. Taurine's action could be due to its binding to and activating of strychnine-sensitive glycine receptor in vivo as it inhibited convulsion caused by strychnine; however, it has little effect on picrotoxin-induced convulsion, suggesting its anti-anxiety activity may not be linked to GABA receptor. It did not alter memory function and muscle activity. Taken together, these results suggest that taurine could be beneficial for the control of anxiety in the clinical situations. Copyright (c) 2007 S. Karger AG, Basel.

Effect of taurine on advanced glycation end products-induced hypertrophy in renal tubular epithelial cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang, J.-S.; Chuang, L.-Y.; Guh, J.-Y.

2008-12-01

Mounting evidence indicates that advanced glycation end products (AGE) play a major role in the development of diabetic nephropathy (DN). Taurine is a well documented antioxidant agent. To explore whether taurine was linked to altered AGE-mediated renal tubulointerstitial fibrosis in DN, we examined the molecular mechanisms of taurine responsible for inhibition of AGE-induced hypertrophy in renal tubular epithelial cells. We found that AGE (but not non-glycated BSA) caused inhibition of cellular mitogenesis rather than cell death by either necrosis or apoptosis. There were no changes in caspase 3 activity, bcl-2 protein expression, and mitochondrial cytochrome c release in BSA, AGE,more » or the antioxidant taurine treatments in these cells. AGE-induced the Raf-1/extracellular signal-regulated kinase (ERK) activation was markedly blocked by taurine. Furthermore, taurine, the Raf-1 kinase inhibitor GW5074, and the ERK kinase inhibitor PD98059 may have the ability to induce cellular proliferation and cell cycle progression from AGE-treated cells. The ability of taurine, GW5074, or PD98059 to inhibit AGE-induced hypertrophy was verified by the observation that it significantly decreased cell size, cellular hypertrophy index, and protein levels of RAGE, p27{sup Kip1}, collagen IV, and fibronectin. The results obtained in this study suggest that taurine may serve as the potential anti-fibrotic activity in DN through mechanism dependent of its Raf-1/ERK inactivation in AGE-induced hypertrophy in renal tubular epithelial cells.« less

Caveolin-1 is enriched in the peroxisomal membrane of rat hepatocytes.

PubMed

Woudenberg, Jannes; Rembacz, Krzysztof P; van den Heuvel, Fiona A J; Woudenberg-Vrenken, Titia E; Buist-Homan, Manon; Geuken, Mariska; Hoekstra, Mark; Deelman, Leo E; Enrich, Carlos; Henning, Rob H; Moshage, Han; Faber, Klaas Nico

2010-05-01

Caveolae are a subtype of cholesterol-enriched lipid microdomains/rafts that are routinely detected as vesicles pinching off from the plasma membrane. Caveolin-1 is an essential component of caveolae. Hepatic caveolin-1 plays an important role in liver regeneration and lipid metabolism. Expression of caveolin-1 in hepatocytes is relatively low, and it has been suggested to also reside at other subcellular locations than the plasma membrane. Recently, we found that the peroxisomal membrane contains lipid microdomains. Like caveolin-1, hepatic peroxisomes are involved in lipid metabolism. Here, we analyzed the subcellular location of caveolin-1 in rat hepatocytes. The subcellular location of rat hepatocyte caveolin-1 was analyzed by cell fractionation procedures, immunofluorescence, and immuno-electron microscopy. Green fluorescent protein (GFP)-tagged caveolin-1 was expressed in rat hepatocytes. Lipid rafts were characterized after Triton X-100 or Lubrol WX extraction of purified peroxisomes. Fenofibric acid-dependent regulation of caveolin-1 was analyzed. Peroxisome biogenesis was studied in rat hepatocytes after RNA interference-mediated silencing of caveolin-1 and caveolin-1 knockout mice. Cell fractionation and microscopic analyses reveal that caveolin-1 colocalizes with peroxisomal marker proteins (catalase, the 70 kDa peroxisomal membrane protein PMP70, the adrenoleukodystrophy protein ALDP, Pex14p, and the bile acid-coenzyme A:amino acid N-acyltransferase BAAT) in rat hepatocytes. Artificially expressed GFP-caveolin-1 accumulated in catalase-positive organelles. Peroxisomal caveolin-1 is associated with detergent-resistant microdomains. Caveolin-1 expression is strongly repressed by the peroxisome proliferator-activated receptor-alpha agonist fenofibric acid. Targeting of peroxisomal matrix proteins and peroxisome number and shape were not altered in rat hepatocytes with 70%-80% reduced caveolin-1 levels and in livers of caveolin-1 knockout mice. Caveolin-1 is enriched in peroxisomes of hepatocytes. Caveolin-1 is not required for peroxisome biogenesis, but this unique subcellular location may determine its important role in hepatocyte proliferation and lipid metabolism.

Taurine and its neuroprotective role.

PubMed

Kumari, Neeta; Prentice, Howard; Wu, Jang-Yen

2013-01-01

Taurine plays multiple roles in the CNS including acting as a -neuro-modulator, an osmoregulator, a regulator of cytoplasmic calcium levels, a trophic factor in development, and a neuroprotectant. In neurons taurine has been shown to prevent mitochondrial dysfunction and to protect against endoplasmic reticulum (ER) stress associated with neurological disorders. In cortical neurons in culture taurine protects against excitotoxicity through reversing an increase in levels of key ER signaling components including eIF-2-alpha and cleaved ATF6. The role of communication between the ER and mitochondrion is also important and examples are presented of protection by taurine against ER stress together with prevention of subsequent mitochondrial initiated apoptosis.

1H-NMR and HPLC studies of the changes involved in volume regulation in the muscle fibres of the crab, Hemigrapsus edwardsi.

PubMed

Bedford, J J; Smith, R A; Thomas, M; Leader, J P

1991-01-01

1. The process of cell volume readjustment, during adaptation to salinity changes, in muscle fibres of the euryhaline New Zealand shore crab, Hemigrapsus edwardsi, involve large changes in the amounts of free amino acid. 2. These are taurine, proline, alanine, arginine, glutamic acid, glycine and serine. 3. These changes may be quantified by High Performance Liquid Chromatography, and qualitatively demonstrated by proton nuclear magnetic resonance spectroscopy.

21 CFR 176.210 - Defoaming agents used in the manufacture of paper and paperboard.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Defoaming agents used in the manufacture of paper...). (3) Miscellaneous: Alcohols and ketone alcohols mixture (still-bottom product from C12-C18 alcohol...-hydroxystearate. Methyl taurine-oleic acid condensate, molecular weight 486. a,a′-[Methylenebis[4-(1,1,3,3...

21 CFR 176.210 - Defoaming agents used in the manufacture of paper and paperboard.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Defoaming agents used in the manufacture of paper...). (3) Miscellaneous: Alcohols and ketone alcohols mixture (still-bottom product from C12-C18 alcohol...-hydroxystearate. Methyl taurine-oleic acid condensate, molecular weight 486. a,a′-[Methylenebis[4-(1,1,3,3...

21 CFR 176.210 - Defoaming agents used in the manufacture of paper and paperboard.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Defoaming agents used in the manufacture of paper...). (3) Miscellaneous: Alcohols and ketone alcohols mixture (still-bottom product from C12-C18 alcohol...-hydroxystearate. Methyl taurine-oleic acid condensate, molecular weight 486. a,a′-[Methylenebis[4-(1,1,3,3...

Taurine supplemented plant protein based diets with alternative lipid sources for juvenile sea bream, sparus aurata

USDA-ARS?s Scientific Manuscript database

Two lipid sources were evaluated as fish oil replacements in fishmeal free, plant protein based diets for juvenile gilthead sea bream, Sparus aurata. A twelve week feeding study was undertaken to examine the performance of fish fed the diets with different sources of essential fatty acids (canola o...

Selection of a discriminant and biorelevant in vitro dissolution test for the development of fenofibrate self-emulsifying lipid-based formulations.

PubMed

Pestieau, Aude; Krier, Fabrice; Brouwers, Adeline; Streel, Bruno; Evrard, Brigitte

2016-09-20

Fenofibrate, a BCS class II compound, has a low bioavailability especially when taken orally on an empty stomach. The challenge to find a new formulation for providing bioavailability, independent of food, is still ongoing. If the development of a suitable oral delivery formulation of BCS class II compounds is a frequent and great challenge to formulation scientists, the in vitro evaluation of these new formulations is also a great challenge. The purpose of this study was therefore to select an in vitro dissolution test that would be useful and as biorelevant as possible for the development of fenofibrate self-emulsifying lipid-based formulations. In this context, three different fenofibrate formulations, for which in vivo data are available in the literature, were tested using different dissolution tests until we found the one that was the most suitable. As part of this approach, we started with the simplest in vitro dissolution tests and progressed to tests that were increasingly more complex. The first tests were different single phase dissolution tests: a test under sink conditions based on the USP monograph, and different tests under non-sink conditions in non-biorelevant and biorelevant media. Given the inconclusive results obtained with these tests, biphasic dissolution systems were then tested: one with USP apparatus type II alone and another which combined USP apparatus types II and IV. This last combined test seemed the most suitable in vitro dissolution test for the development of the future fenofibrate lipid-based formulations we intend to develop in our own laboratory. Copyright © 2016 Elsevier B.V. All rights reserved.

Association between glucokinase regulatory protein (GCKR) and apolipoprotein A5 (APOA5) gene polymorphisms and triacylglycerol concentrations in fasting, postprandial, and fenofibrate-treated states.

PubMed

Perez-Martinez, Pablo; Corella, Dolores; Shen, Jian; Arnett, Donna K; Yiannakouris, Nikos; Tai, E Syong; Orho-Melander, Marju; Tucker, Katherine L; Tsai, Michael; Straka, Robert J; Province, Michael; Kai, Chew Suok; Perez-Jimenez, Francisco; Lai, Chao-Qiang; Lopez-Miranda, Jose; Guillen, Marisa; Parnell, Laurence D; Borecki, Ingrid; Kathiresan, Sekar; Ordovas, Jose M

2009-01-01

Hypertriglyceridemia is a risk factor for cardiovascular disease. Variation in the apolipoprotein A5 (APOA5) and glucokinase regulatory protein (GCKR) genes has been associated with fasting plasma triacylglycerol. We investigated the combined effects of the GCKR rs780094C-->T, APOA5 -1131T-->C, and APOA5 56C-->G single nucleotide polymorphisms (SNPs) on fasting triacylglycerol in several independent populations and the response to a high-fat meal and fenofibrate interventions. We used a cross-sectional design to investigate the association with fasting triacylglycerol in 8 populations from America, Asia, and Europe (n = 7,730 men and women) and 2 intervention studies in US whites (n = 1,061) to examine postprandial triacylglycerol after a high-fat meal and the response to fenofibrate. We defined 3 combined genotype groups: 1) protective (homozygous for the wild-type allele for all 3 SNPs); 2) intermediate (any mixed genotype not included in groups 1 and 3); and 3) risk (carriers of the variant alleles at both genes). Subjects within the risk group had significantly higher fasting triacylglycerol and a higher prevalence of hypertriglyceridemia than did subjects in the protective group across all populations. Moreover, subjects in the risk group had a greater postprandial triacylglycerol response to a high-fat meal and greater fenofibrate-induced reduction of fasting triacylglycerol than did the other groups, especially among persons with hypertriglyceridemia. Subjects with the intermediate genotype had intermediate values (P for trend <0.001). SNPs in GCKR and APOA5 have an additive effect on both fasting and postprandial triacylglycerol and contribute to the interindividual variability in response to fenofibrate treatment.

Association between glucokinase regulatory protein (GCKR) and apolipoprotein A5 (APOA5) gene polymorphisms and triacylglycerol concentrations in fasting, postprandial, and fenofibrate-treated states123

PubMed Central

Perez-Martinez, Pablo; Corella, Dolores; Shen, Jian; Arnett, Donna K; Yiannakouris, Nikos; Tai, E Syong; Orho-Melander, Marju; Tucker, Katherine L; Tsai, Michael; Straka, Robert J; Province, Michael; Kai, Chew Suok; Perez-Jimenez, Francisco; Lai, Chao-Qiang; Lopez-Miranda, Jose; Guillen, Marisa; Parnell, Laurence D; Borecki, Ingrid; Kathiresan, Sekar; Ordovas, Jose M

2009-01-01

Background: Hypertriglyceridemia is a risk factor for cardiovascular disease. Variation in the apolipoprotein A5 (APOA5) and glucokinase regulatory protein (GCKR) genes has been associated with fasting plasma triacylglycerol. Objective: We investigated the combined effects of the GCKR rs780094C→T, APOA5 −1131T→C, and APOA5 56C→G single nucleotide polymorphisms (SNPs) on fasting triacylglycerol in several independent populations and the response to a high-fat meal and fenofibrate interventions. Design: We used a cross-sectional design to investigate the association with fasting triacylglycerol in 8 populations from America, Asia, and Europe (n = 7730 men and women) and 2 intervention studies in US whites (n = 1061) to examine postprandial triacylglycerol after a high-fat meal and the response to fenofibrate. We defined 3 combined genotype groups: 1) protective (homozygous for the wild-type allele for all 3 SNPs); 2) intermediate (any mixed genotype not included in groups 1 and 3); and 3) risk (carriers of the variant alleles at both genes). Results: Subjects within the risk group had significantly higher fasting triacylglycerol and a higher prevalence of hypertriglyceridemia than did subjects in the protective group across all populations. Moreover, subjects in the risk group had a greater postprandial triacylglycerol response to a high-fat meal and greater fenofibrate-induced reduction of fasting triacylglycerol than did the other groups, especially among persons with hypertriglyceridemia. Subjects with the intermediate genotype had intermediate values (P for trend <0.001). Conclusions: SNPs in GCKR and APOA5 have an additive effect on both fasting and postprandial triacylglycerol and contribute to the interindividual variability in response to fenofibrate treatment. PMID:19056598

Effects of High Density Lipoprotein Raising Therapies on Cardiovascular Outcomes in Patients with Type 2 Diabetes Mellitus, with or without Renal Impairment: The Action to Control Cardiovascular Risk in Diabetes Study.

PubMed

Papademetriou, Vasilios; Lovato, Laura; Tsioufis, Costas; Cushman, William; Applegate, William B; Mottle, Amy; Punthakee, Zubin; Nylen, Eric; Doumas, Michael

2017-01-01

The role of high density lipoprotein-raising interventions in addition to statin therapy in patients with diabetes remains controversial. Chronic kidney disease (CKD) is a strong modifier of cardiovascular (CV) outcomes. We therefore investigated the impact of CKD status at baseline on outcomes in patients with diabetes randomized to standard statin or statin plus fenofibrate treatment in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) lipid trial. Among 5,464 participants in the ACCORD lipid trial, 3,554 (65%) were free of CKD at baseline, while 1,910 (35%) had mild to moderate CKD. Differences in CV outcomes during follow-up between CKD and non-CKD subgroups were examined. In addition, the effect of fenofibrate as compared to placebo on CV outcomes was examined for both subgroups. All CV outcomes were 1.4-3 times higher among patients with CKD as compared to non-CKD patients. In patients with CKD, the addition of fenofibrate had no effect on any of the primary or secondary outcomes. In patients without CKD, however, the addition of fenofibrate was associated with a significant 36% reduction of CV mortality (hazards ratio [HR] 0.64; 95% CI 0.42-0.97; p value for treatment interaction <0.05) and 44% lower rate of fatal or non-fatal congestive heart failure (CHF; HR 0.56; 95% CI 0.37-0.84; p value treatment interaction <0.03). For patients with type 2 diabetes at high CV risk but no CKD, fenofibrate therapy added to statin reduced the CV mortality and the rate of fatal and non-fatal CHF. © 2016 S. Karger AG, Basel.

Dealing with methionine/homocysteine sulfur: cysteine metabolism to taurine and inorganic sulfur

PubMed Central

Ueki, Iori

2010-01-01

Synthesis of cysteine as a product of the transsulfuration pathway can be viewed as part of methionine or homocysteine degradation, with cysteine being the vehicle for sulfur conversion to end products (sulfate, taurine) that can be excreted in the urine. Transsulfuration is regulated by stimulation of cystathionine β-synthase and inhibition of methylene tetrahydrofolate reductase in response to changes in the level of S-adenosylmethionine, and this promotes homocysteine degradation when methionine availability is high. Cysteine is catabolized by several desulfuration reactions that release sulfur in a reduced oxidation state, generating sulfane sulfur or hydrogen sulfide (H2S), which can be further oxidized to sulfate. Cysteine desulfuration is accomplished by alternate reactions catalyzed by cystathionine β-synthase and cystathionine γ-lyase. Cysteine is also catabolized by pathways that require the initial oxidation of the cysteine thiol by cysteine dioxygenase to form cysteinesulfinate. The oxidative pathway leads to production of taurine and sulfate in a ratio of approximately 2:1. Relative metabolism of cysteine by desulfuration versus oxidative pathways is influenced by cysteine dioxygenase activity, which is low in animals fed low-protein diets and high in animals fed excess sulfur amino acids. Thus, desulfuration reactions dominate when cysteine is deficient, whereas oxidative catabolism dominates when cysteine is in excess. In rats consuming a diet with an adequate level of sulfur amino acids, about two thirds of cysteine catabolism occurs by oxidative pathways and one third by desulfuration pathways. Cysteine dioxygenase is robustly regulated in response to cysteine availability and may function to provide a pathway to siphon cysteine to less toxic metabolites than those produced by cysteine desulfuration reactions. PMID:20162368

A microdialysis study of the novel antiepileptic drug levetiracetam: extracellular pharmacokinetics and effect on taurine in rat brain

PubMed Central

Tong, X; Patsalos, P N

2001-01-01

Using a rat model which allows serial blood sampling and concurrent brain microdialysis sampling, we have investigated the temporal kinetic inter-relationship of levetiracetam in serum and brain extracellular fluid (frontal cortex and hippocampus) following systemic administration of levetiracetam, a new antiepileptic drug. Concurrent extracellular amino acid concentrations were also determined. After administration (40 or 80 mg kg−1), levetiracetam rapidly appeared in both serum (Tmax, 0.4 – 0.7 h) and extracellular fluid (Tmax, 2.0 – 2.5 h) and concentrations rose linearly and dose-dependently, suggesting that transport across the blood-brain barrier is rapid and not rate-limiting. The serum free fraction (free/total serum concentration ratio; mean±s.e.mean range 0.93 – 1.05) was independent of concentration and confirms that levetiracetam is not bound to blood proteins. The kinetic profiles for the hippocampus and frontal cortex were indistinguishable suggesting that levetiracetam distribution in the brain is not brain region specific. However, t1/2 values were significantly larger than those for serum (mean range, 3.0 – 3.3 h vs 2.1 – 2.3 h) and concentrations did not attain equilibrium with respect to serum. Levetiracetam (80 mg kg−1) was associated with a significant reduction in taurine in the hippocampus and frontal cortex. Other amino acids were unaffected by levetiracetam. Levetiracetam readily and rapidly enters the brain without regional specificity. Its prolonged efflux from and slow equilibration within the brain may explain, in part, its long duration of action. The concurrent changes in taurine may contribute to its mechanism of action. PMID:11454660

Dissolution and solubility behavior of fenofibrate in sodium lauryl sulfate solutions.

PubMed

Granero, Gladys E; Ramachandran, Chandrasekharan; Amidon, Gordon L

2005-10-01

The solubility of fenofibrate in pH 6.8 McIlvaine buffers containing varying concentrations of sodium lauryl sulfate was determined. The dissolution behavior of fenofibrate was also examined in the same solutions with rotating disk experiments. It was observed that the enhancement in intrinsic dissolution rate was approximately 500-fold and the enhancement in solubility was approximately 2000-fold in a pH 6.8 buffer containing 2% (w/v) sodium lauryl sulfate compared to that in buffer alone. The micellar solubilization equilibrium coefficient (k*) was estimated from the solubility data and found to be 30884+/-213 L/mol. The diffusivity for the free solute, 7.15x10(-6) cm2/s, was calculated using Schroeder's additive molal volume estimates and Hayduk-Laurie correlation. The diffusivity of the drug-loaded micelle, estimated from the experimental solubility and dissolution data and the calculated value for free solute diffusivity, was 0.86x10(-6) cm2/s. Thus, the much lower enhancement in dissolution of fenofibrate compared to its enhancement in solubility in surfactant solutions appears to be consistent with the contribution to the total transport due to enhanced micellar solubilization as well as a large decrease (approximately 8-fold) in the diffusivity of the drug-loaded micelle.

A 68-year old male presenting with rhabdomyolysis-associated acute kidney injury following concomitant use of elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate and pravastatin/fenofibrate: a case report.

PubMed

Suttels, Veronique; Florence, Eric; Leys, John; Vekemans, Marc; Van den Ende, Jef; Vlieghe, Erika; Kenyon, Chris

2015-09-08

We present what we believe to be the first case in the literature of rhabdomyolysis-induced renal failure caused by a probable drug interaction between elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (EVG/COBI/FTC/TDF) and pravastatin/fenofibrate. A 68-year old Caucasian man presented with progressive pain in both legs two weeks after commencing treatment with EVG/COBI/FTC/TDF. He was found to have biochemical evidence of rhabdomyolysis and acute renal failure. We emphasize the need for post marketing surveillance of adverse effects of new products. Pharmacokinetic studies are necessary to investigate the levels of pravastatin in patients taking COBI and fenofibrate with and without other comorbidities. Meanwhile, we suggest that creatine kinase levels should be monitored and patients advised to report myalgias when using concomitant EVG/COBI/FTC/TDF and pravastatin/fenofibrate. This case serves as an important reminder to use estimated glomerular filtration rates rather than serum creatinine levels when choosing new medications. If potentially nephrotoxic combinations are started in patients with borderline estimated glomerular filtration rates, it may be prudent to check these filtration rates more frequently than usual. In patients with reduced estimated glomerular filtration rates, potentially nephrotoxic combinations should be avoided wherever possible.

Taurine exerts hypoglycemic effect in alloxan-induced diabetic rats, improves insulin-mediated glucose transport signaling pathway in heart and ameliorates cardiac oxidative stress and apoptosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Das, Joydeep; Vasan, Vandana; Sil, Parames C., E-mail: parames@bosemain.boseinst.ac.in

2012-01-15

Hyperlipidemia, inflammation and altered antioxidant profiles are the usual complications in diabetes mellitus. In the present study, we investigated the therapeutic potential of taurine in diabetes associated cardiac complications using a rat model. Rats were made diabetic by alloxan (ALX) (single i.p. dose of 120 mg/kg body weight) and left untreated or treated with taurine (1% w/v, orally, in water) for three weeks either from the day of ALX exposure or after the onset of diabetes. Animals were euthanized after three weeks. ALX-induced diabetes decreased body weight, increased glucose level, decreased insulin content, enhanced the levels of cardiac damage markersmore » and altered lipid profile in the plasma. Moreover, it increased oxidative stress (decreased antioxidant enzyme activities and GSH/GSSG ratio, increased xanthine oxidase enzyme activity, lipid peroxidation, protein carbonylation and ROS generation) and enhanced the proinflammatory cytokines levels, activity of myeloperoxidase and nuclear translocation of NFκB in the cardiac tissue of the experimental animals. Taurine treatment could, however, result to a decrease in the elevated blood glucose and proinflammatory cytokine levels, diabetes-evoked oxidative stress, lipid profiles and NFκB translocation. In addition, taurine increased GLUT 4 translocation to the cardiac membrane by enhanced phosphorylation of IR and IRS1 at tyrosine and Akt at serine residue in the heart. Results also suggest that taurine could protect cardiac tissue from ALX induced apoptosis via the regulation of Bcl2 family and caspase 9/3 proteins. Taken together, taurine supplementation in regular diet could play a beneficial role in regulating diabetes and its associated complications in the heart. Highlights: ► Taurine controls blood glucose via protection of pancreatic β cells in diabetic rat. ► Taurine controls blood glucose via increasing the insulin level in diabetic rat. ► Taurine improves cardiac AKT/GLUT4 signaling pathways in diabetic conditions. ► Taurine exerts antioxidant, antihyperlipidemic and antiinflammatory activities. ► It protects cardiac apoptosis by regulating Bcl2 family and caspase 9/3 proteins.« less

Intestinal absorption of the bile acid analogue 75Se-homocholic acid-taurine is increased in primary biliary cirrhosis, and reverts to normal during ursodeoxycholic acid administration

PubMed Central

Lanzini, A; De Tavonatti, M G; Panarotto, B; Scalia, S; Mora, A; Benini, F; Baisini, O; Lanzarotto, F

2003-01-01

Background: Whether ileal absorption of bile acid is up or downregulated in chronic cholestasis is still debated, and most evidence has come from animal studies. Aims: To compare ileal bile acid absorption in patients with primary biliary cirrhosis (PBC) and in healthy control subjects, and to assess the effect of ursodeoxycholic acid (UDCA). Patients: We studied 14 PBC patients before and during (n=11) UDCA administration, 14 healthy control subjects, and 14 Crohn’s disease patients (as disease controls). Methods: We used cholescintigraphy to measure retention in the enterohepatic circulation over five successive days of the bile acid analogue 75Se-homocholic acid-taurine (75SeHCAT) as an index of ileal bile acid absorption. Results were expressed as 75SeHCAT fractional turnover rate (FTR) and t½12. Results: 75SeHCAT FTR was 0.19 (0.11)/day, 0.34 (0.11)/day (p<0.001), and 0.83 (0.32)/day in PBC patients, healthy controls (p<0.0001), and Crohn’s patients (p<0.001), respectively, which increased to 0.36 (0.16)/day in PBC patients during UDCA treatment (p<0.005). 75SeHCAT t½12 was 4.8 (2.1) days in PBC patients, 2.2 (0.5) days (p<0.001) in healthy controls, and 1.0 (0.5) days (p<0.001) in Crohn’s disease patients. 75SeHCAT t½12 decreased to 2.2 (0.93) days (p< 0.001) in PBC patients during UDCA treatment. Conclusions: Our results support the concept that ileal bile acid absorption is upregulated in PBC patients, and that this effect may contribute towards damaging the cholestatic liver. This upregulation of bile acid absorption is abolished by UDCA. PMID:12912872

Decreased hepatotoxic bile acid composition and altered synthesis in progressive human nonalcoholic fatty liver disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lake, April D.; Novak, Petr; Shipkova, Petia

2013-04-15

Bile acids (BAs) have many physiological roles and exhibit both toxic and protective influences within the liver. Alterations in the BA profile may be the result of disease induced liver injury. Nonalcoholic fatty liver disease (NAFLD) is a prevalent form of chronic liver disease characterized by the pathophysiological progression from simple steatosis to nonalcoholic steatohepatitis (NASH). The hypothesis of this study is that the ‘classical’ (neutral) and ‘alternative’ (acidic) BA synthesis pathways are altered together with hepatic BA composition during progression of human NAFLD. This study employed the use of transcriptomic and metabolomic assays to study the hepatic toxicologic BAmore » profile in progressive human NAFLD. Individual human liver samples diagnosed as normal, steatosis, and NASH were utilized in the assays. The transcriptomic analysis of 70 BA genes revealed an enrichment of downregulated BA metabolism and transcription factor/receptor genes in livers diagnosed as NASH. Increased mRNA expression of BAAT and CYP7B1 was observed in contrast to decreased CYP8B1 expression in NASH samples. The BA metabolomic profile of NASH livers exhibited an increase in taurine together with elevated levels of conjugated BA species, taurocholic acid (TCA) and taurodeoxycholic acid (TDCA). Conversely, cholic acid (CA) and glycodeoxycholic acid (GDCA) were decreased in NASH liver. These findings reveal a potential shift toward the alternative pathway of BA synthesis during NASH, mediated by increased mRNA and protein expression of CYP7B1. Overall, the transcriptomic changes of BA synthesis pathway enzymes together with altered hepatic BA composition signify an attempt by the liver to reduce hepatotoxicity during disease progression to NASH. - Highlights: ► Altered hepatic bile acid composition is observed in progressive NAFLD. ► Bile acid synthesis enzymes are transcriptionally altered in NASH livers. ► Increased levels of taurine and conjugated bile acids are observed in NASH. ► Hepatic bile acid synthesis shifts toward the alternative pathway in NASH.« less

Taurine supplementation for prevention of stroke-like episodes in MELAS: a multicentre, open-label, 52-week phase III trial.

PubMed

Ohsawa, Yutaka; Hagiwara, Hiroki; Nishimatsu, Shin-Ichiro; Hirakawa, Akihiro; Kamimura, Naomi; Ohtsubo, Hideaki; Fukai, Yuta; Murakami, Tatsufumi; Koga, Yasutoshi; Goto, Yu-Ichi; Ohta, Shigeo; Sunada, Yoshihide

2018-04-17

The aim of this study was to evaluate the efficacy and safety of high-dose taurine supplementation for prevention of stroke-like episodes of MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes), a rare genetic disorder caused by point mutations in the mitochondrial DNA that lead to a taurine modification defect at the first anticodon nucleotide of mitochondrial tRNA Leu(UUR) , resulting in failure to decode codons accurately. After the nationwide survey of MELAS, we conducted a multicentre, open-label, phase III trial in which 10 patients with recurrent stroke-like episodes received high-dose taurine (9 g or 12 g per day) for 52 weeks. The primary endpoint was the complete prevention of stroke-like episodes during the evaluation period. The taurine modification rate of mitochondrial tRNA Leu(UUR) was measured before and after the trial. The proportion of patients who reached the primary endpoint (100% responder rate) was 60% (95% CI 26.2% to 87.8%). The 50% responder rate, that is, the number of patients achieving a 50% or greater reduction in frequency of stroke-like episodes, was 80% (95% CI 44.4% to 97.5%). Taurine reduced the annual relapse rate of stroke-like episodes from 2.22 to 0.72 (P=0.001). Five patients showed a significant increase in the taurine modification of mitochondrial tRNA Leu(UUR) from peripheral blood leukocytes (P<0.05). No severe adverse events were associated with taurine. The current study demonstrates that oral taurine supplementation can effectively reduce the recurrence of stroke-like episodes and increase taurine modification in mitochondrial tRNA Leu(UUR) in MELAS. UMIN000011908. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Taurine protects against methotrexate-induced toxicity and inhibits leukocyte death

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cetiner, Mustafa; Sener, Goeksel; Sehirli, A. Ozer

2005-11-15

The efficacy of methotrexate (MTX), a widely used cytotoxic chemotherapeutic agent, is often limited by severe side effects and toxic sequelae. Regarding the mechanisms of these side effects, several hypotheses have been put forward, among which oxidative stress is noticeable. The present study was undertaken to determine whether taurine, a potent free radical scavenger, could ameliorate MTX-induced oxidative injury and modulate immune response. Following a single dose of methotrexate (20 mg/kg), either saline or taurine (50 mg/kg) was administered for 5 days. After decapitation of the rats, trunk blood was obtained and the ileum, liver, and kidney were removed tomore » measure malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity, and collagen content, as well as histological examination. Our results showed that MTX administration increased the MDA, MPO activity, and collagen contents and decreased GSH levels in all tissues (P < 0.001), while these alterations were reversed in taurine-treated group (P < 0.05-0.01). Elevated (P < 0.001) TNF-{alpha} level observed following MTX treatment was depressed with taurine (P < 0.01). Oxidative burst of neutrophils stimulated by phorbol myristate acetate was reduced in saline-treated MTX group (P < 0.001), while taurine abolished this effect. Similarly, flow cytometric measurements revealed that leukocyte apoptosis and cell death were increased in MTX-treated animals, while taurine reversed these effects (P < 0.05). Reduced cellularity in bone marrow samples of MTX-treated group (P < 0.01) was reversed back to control levels in taurine-treated rats. Severe degeneration of the intestinal mucosa, liver parenchyma, glomerular, and tubular epithelium observed in saline-treated group was improved by taurine treatment. In conclusion, it appears that taurine protects against methotrexate-induced oxidant organ injury and inhibits leukocyte apoptosis and may be of therapeutic potential in alleviating the systemic side effects of chemotherapeutics.« less

Haloperidol impairs auditory filial imprinting and modulates monoaminergic neurotransmission in an imprinting-relevant forebrain area of the domestic chick.

PubMed

Gruss, M; Bock, J; Braun, K

2003-11-01

In vivo microdialysis and behavioural studies in the domestic chick have shown that glutamatergic as well as monoaminergic neurotransmission in the medio-rostral neostriatum/hyperstriatum ventrale (MNH) is altered after auditory filial imprinting. In the present study, using pharmaco-behavioural and in vivo microdialysis approaches, the role of dopaminergic neurotransmission in this juvenile learning event was further evaluated. The results revealed that: (i) the systemic application of the potent dopamine receptor antagonist haloperidol (7.5 mg/kg) strongly impairs auditory filial imprinting; (ii) systemic haloperidol induces a tetrodotoxin-sensitive increase of extracellular levels of the dopamine metabolite, homovanillic acid, in the MNH, whereas the levels of glutamate, taurine and the serotonin metabolite, 5-hydroxyindole-3-acetic acid, remain unchanged; (iii) haloperidol (0.01, 0.1, 1 mm) infused locally into the MNH increases glutamate, taurine and 5- hydroxyindole-3-acetic acid levels in a dose-dependent manner, whereas homovanillic acid levels remain unchanged; (iv) systemic haloperidol infusion reinforces the N-methyl-d-aspartate receptor-mediated inhibitory modulation of the dopaminergic neurotransmission within the MNH. These results indicate that the modulation of dopaminergic function and its interaction with other neurotransmitter systems in a higher associative forebrain region of the juvenile avian brain displays similar neurochemical characteristics as the adult mammalian prefrontal cortex. Furthermore, we were able to show that the pharmacological manipulation of monoaminergic regulatory mechanisms interferes with learning and memory formation, events which in a similar fashion might occur in young or adult mammals.

Taurine zinc solid dispersions attenuate doxorubicin-induced hepatotoxicity and cardiotoxicity in rats.

PubMed

Wang, Yu; Mei, Xueting; Yuan, Jingquan; Lu, Wenping; Li, Binglong; Xu, Donghui

2015-11-15

The clinical efficacy of anthracycline anti-neoplastic agents is limited by cardiac and hepatic toxicities. The aim of this study was to assess the hepatoprotective and cardioprotective effects of taurine zinc solid dispersions, which is a newly-synthesized taurine zinc compound, against doxorubicin-induced toxicity in Sprague-Dawley rats intraperitoneally injected with doxorubicin hydrochloride (3mg/kg) three times a week (seven injections) over 28 days. Hemodynamic parameters, levels of liver toxicity markers and oxidative stress were assessed. Taurine zinc significantly attenuated the reductions in blood pressure, left ventricular pressure and ± dp/dtmax, increases in serum alanine aminotransferase and aspartate aminotransferase activities, and reductions in serum Zn(2+) and albumin levels (P<0.05 or 0.01) induced by doxorubicin. In rats treated with doxorubicin, taurine zinc dose-dependently increased liver superoxide dismutase activity and glutathione concentration, and decreased malondialdehyde level (P<0.01). qBase(+) was used to evaluate the stability of eight candidate reference genes for real-time quantitative reverse-transcription PCR. Taurine zinc dose-dependently increased liver heme oxygenase-1 and UDP-glucuronyl transferase mRNA and protein expression (P<0.01). Western blotting demonstrated that taurine zinc inhibited c-Jun N-terminal kinase phosphorylation by upregulating dual-specificity phosphoprotein phosphatase-1. Additionally, taurine zinc inhibited cardiomyocyte apoptosis as there was decreased TUNEL/DAPI positivity and protein expression of caspase-3. These results indicate that taurine zinc solid dispersions prevent the side-effects of anthracycline-based anticancer therapy. The mechanisms might be associated with the enhancement of antioxidant defense system partly through activating transcription to synthesize endogenous phase II medicine enzymes and anti-apoptosis through inhibiting JNK phosphorylation. Copyright © 2015 Elsevier Inc. All rights reserved.

Protective effect of taurine on cardiotoxicity of the bufadienolides derived from toad (Bufo bufo gargarizans Canto) venom in guinea-pigs in vivo and in vitro.

PubMed

Ma, Hongyue; Jiang, Jiejun; Zhang, Junfeng; Zhou, Jing; Ding, Anwei; Lv, Gaohong; Xu, Huiqin; You, Fenqiang; Zhan, Zhen; Duan, Jinao

2012-01-01

In China, toad venom is an anti-inflammatory agent used in small doses for the treatment of various types of inflammation. Bufadienolides are cardioactive steroids responsible for the anti-inflammatory actions of toad venom. We studied the protective effect of taurine on the cardiotoxicity of bufadienolides in guinea-pigs. Bufadienolides (8 mg/kg) caused arrhythmias, cardiac dysfunction and death in guinea-pigs. Pretreatment with taurine (150, 300 mg/kg) significantly prevented bufadienolide-induced cardiotoxicity and reduced the mortality in vivo. Taurine markedly increased the cumulative doses of bufadienolides and resibufogenin required for lethal arrhythmia in ex vivo isolated guinea-pig heart. Taurine did not compromise the anti-inflammatory activity of the bufadienolides on concanavalin-A-stimulated proliferation of guinea-pig splenocytes in vitro. These data indicate that taurine can prevent bufadienolide-induced cardiotoxicity and could be a novel antidote in combination with bufadienolide therapy.

Cerebral taurine release mechanisms in vivo: pharmacological investigations in rats using microdialysis for proof of principle.

PubMed

Scheller, D; Korte, M; Szathmary, S; Tegtmeier, F

2000-06-01

Cerebral taurine acts as neurotransmitter, as neuromodulator, or as osmoregulator. To investigate its release mechanisms in vivo, we combined the microdialysis technique with a variety of experimental paradigms. Taurine release was stimulated by either NMDA, NO or a hypotonic solution locally with or without the addition of the NMDA antagonists APV or Ketamine, or the NO synthase inhibitor L-NAME. Alternatively, the neuroprotective drug lubeluzole was applied i.v. NMDA, NO or the hypotonic solution stimulated the release of taurine. NMDA-mediated taurine release was inhibited by either APV, Ketamine or the NO synthase inhibitor L-NAME. Lubeluzole had no effect. Under the hypotonic conditions only lubeluzole was effective. These data confirm in vivo that the NMDA-induced taurine release is mediated via the NO cascade. By contrast, the release after a hypotonic stimulus is not related to the NO cascade. Instead, Na(+)- and/or Ca(2+)-mediated events might have been attenuated by lubeluzole.

Prospective evaluation of ursodeoxycholic acid withdrawal in patients with primary sclerosing cholangitis.

PubMed

Wunsch, Ewa; Trottier, Jocelyn; Milkiewicz, Malgorzata; Raszeja-Wyszomirska, Joanna; Hirschfield, Gideon M; Barbier, Olivier; Milkiewicz, Piotr

2014-09-01

Ursodeoxycholic acid (UDCA) is no longer recommended for management of adult patients with primary sclerosing cholangitis (PSC). We undertook a prospective evaluation of UDCA withdrawal in a group of consecutive patients with PSC. Twenty six patients, all treated with UDCA (dose range: 10-15 mg/kg/day) were included. Paired blood samples for liver biochemistry, bile acids, and fibroblast growth factor 19 (FGF19) were collected before UDCA withdrawal and 3 months later. Liquid chromatography/tandem mass spectrometry was used for quantification of 29 plasma bile acid metabolites. Pruritus and health-related quality of life (HRQoL) were assessed with a 10-point numeric rating scale, the Medical Outcomes Study Short Form-36 (SF-36), and PBC-40 questionnaires. UDCA withdrawal resulted in a significant deterioration in liver biochemistry (increase of alkaline phosphatase of 75.6%; P<0.0001; gamma-glutamyl transpeptidase of 117.9%, P<0.0001; bilirubin of 50.0%, P<0.001; alanine aminotransferase of 63.9%, P<0.005; and aspartate aminotransferase of 45.0%, P<0.005) and increase of Mayo Risk Score for PSC (change from baseline of +0.5 point; P<0.003). Bile acid analysis revealed a significant decrease in lithocholic acid and its derivatives after UDCA withdrawal, but no effect on concentrations of primary bile acids aside from an increased accumulation of their taurine conjugates. After UDCA removal cholestatic parameters, taurine species of cholic acid and chenodeoxycholic acid correlated with serum FGF19 levels. No significant effect on HRQoL after UDCA withdrawal was observed; however, 42% of patients reported a deterioration in their pruritus. At 3 months, discontinuation of UDCA in patients with PSC causes significant deterioration in liver biochemistry and influences concentrations of bile acid metabolites. A proportion of patients report increased pruritus, but other short-term markers of quality of life are unaffected. © 2014 by the American Association for the Study of Liver Diseases.

Taurine reduces inflammatory responses after spinal cord injury.

PubMed

Nakajima, Yasuhiro; Osuka, Koji; Seki, Yukio; Gupta, Ramesh C; Hara, Masahito; Takayasu, Masakazu; Wakabayashi, Toshihiko

2010-02-01

Taurine has multiple functions in the central nervous system (CNS), serving as an osmoregulator, antioxidant, inhibitory neuromodulator, and regulator of intracellular Ca(2+) flux. Since the role of taurine in traumatic spinal cord injury (SCI) is not fully understood, the present study was conducted with C57 black/6 mice (18-20 g) who underwent severe SCI at the Th-8 level using a weight compression device. Taurine was injected intraperitoneally at doses of 25, 80, 250, and 800 mg/kg within 30 min after SCI. Controls were injected with saline. The contusional cord segments were removed 6 h after SCI, and concentrations of interleukin-6 (IL-6) and myeloperoxidase (MPO) were measured using ELISA kits. Phosphorylation of STAT3, which is activated by IL-6, and expression of inducible cyclooxygenase-2 (COX-2) were also compared between the taurine treatment group (250 mg/kg) and the control group by Western blot analysis. Morphological changes were evaluated with H&E-stained sections. Taurine significantly decreased IL-6 and MPO levels in a dose-dependent manner, significantly reducing the phosphorylation of STAT3 and expression of COX-2 after SCI compared to controls. A reduced accumulation of neutrophils, especially in the subarachnoid spaces, and secondary degenerative changes in gray matter were also noted, and motor disturbances were significantly attenuated with taurine treatment (250 mg/kg). These findings indicate that taurine has anti-inflammatory effects against SCI, and may play a neuroprotective role against secondary damage, and thus it may have therapeutic potential.

Ursodeoxycholic Acid and Its Taurine- or Glycine-Conjugated Species Reduce Colitogenic Dysbiosis and Equally Suppress Experimental Colitis in Mice

PubMed Central

Van den Bossche, Lien; Hindryckx, Pieter; Devisscher, Lindsey; Devriese, Sarah; Van Welden, Sophie; Holvoet, Tom; Vilchez-Vargas, Ramiro; Vital, Marius; Pieper, Dietmar H.; Vanden Bussche, Julie; Vanhaecke, Lynn; Van de Wiele, Tom; De Vos, Martine

2017-01-01

ABSTRACT The promising results seen in studies of secondary bile acids in experimental colitis suggest that they may represent an attractive and safe class of drugs for the treatment of inflammatory bowel diseases (IBD). However, the exact mechanism by which bile acid therapy confers protection from colitogenesis is currently unknown. Since the gut microbiota plays a crucial role in the pathogenesis of IBD, and exogenous bile acid administration may affect the community structure of the microbiota, we examined the impact of the secondary bile acid ursodeoxycholic acid (UDCA) and its taurine or glycine conjugates on the fecal microbial community structure during experimental colitis. Daily oral administration of UDCA, tauroursodeoxycholic acid (TUDCA), or glycoursodeoxycholic acid (GUDCA) equally lowered the severity of dextran sodium sulfate-induced colitis in mice, as evidenced by reduced body weight loss, colonic shortening, and expression of inflammatory cytokines. Illumina sequencing demonstrated that bile acid therapy during colitis did not restore fecal bacterial richness and diversity. However, bile acid therapy normalized the colitis-associated increased ratio of Firmicutes to Bacteroidetes. Interestingly, administration of bile acids prevented the loss of Clostridium cluster XIVa and increased the abundance of Akkermansia muciniphila, bacterial species known to be particularly decreased in IBD patients. We conclude that UDCA, which is an FDA-approved drug for cholestatic liver disorders, could be an attractive treatment option to reduce dysbiosis and ameliorate inflammation in human IBD. IMPORTANCE Secondary bile acids are emerging as attractive candidates for the treatment of inflammatory bowel disease. Although bile acids may affect the intestinal microbial community structure, which significantly contributes to the course of these inflammatory disorders, the impact of bile acid therapy on the fecal microbiota during colitis has not yet been considered. Here, we studied the alterations in the fecal microbial abundance in colitic mice following the administration of secondary bile acids. Our results show that secondary bile acids reduce the severity of colitis and ameliorate colitis-associated fecal dysbiosis at the phylum level. This study indicates that secondary bile acids might act as a safe and effective drug for inflammatory bowel disease. PMID:28115375

Ursodeoxycholic Acid and Its Taurine- or Glycine-Conjugated Species Reduce Colitogenic Dysbiosis and Equally Suppress Experimental Colitis in Mice.

PubMed

Van den Bossche, Lien; Hindryckx, Pieter; Devisscher, Lindsey; Devriese, Sarah; Van Welden, Sophie; Holvoet, Tom; Vilchez-Vargas, Ramiro; Vital, Marius; Pieper, Dietmar H; Vanden Bussche, Julie; Vanhaecke, Lynn; Van de Wiele, Tom; De Vos, Martine; Laukens, Debby

2017-04-01

The promising results seen in studies of secondary bile acids in experimental colitis suggest that they may represent an attractive and safe class of drugs for the treatment of inflammatory bowel diseases (IBD). However, the exact mechanism by which bile acid therapy confers protection from colitogenesis is currently unknown. Since the gut microbiota plays a crucial role in the pathogenesis of IBD, and exogenous bile acid administration may affect the community structure of the microbiota, we examined the impact of the secondary bile acid ursodeoxycholic acid (UDCA) and its taurine or glycine conjugates on the fecal microbial community structure during experimental colitis. Daily oral administration of UDCA, tauroursodeoxycholic acid (TUDCA), or glycoursodeoxycholic acid (GUDCA) equally lowered the severity of dextran sodium sulfate-induced colitis in mice, as evidenced by reduced body weight loss, colonic shortening, and expression of inflammatory cytokines. Illumina sequencing demonstrated that bile acid therapy during colitis did not restore fecal bacterial richness and diversity. However, bile acid therapy normalized the colitis-associated increased ratio of Firmicutes to Bacteroidetes Interestingly, administration of bile acids prevented the loss of Clostridium cluster XIVa and increased the abundance of Akkermansia muciniphila , bacterial species known to be particularly decreased in IBD patients. We conclude that UDCA, which is an FDA-approved drug for cholestatic liver disorders, could be an attractive treatment option to reduce dysbiosis and ameliorate inflammation in human IBD. IMPORTANCE Secondary bile acids are emerging as attractive candidates for the treatment of inflammatory bowel disease. Although bile acids may affect the intestinal microbial community structure, which significantly contributes to the course of these inflammatory disorders, the impact of bile acid therapy on the fecal microbiota during colitis has not yet been considered. Here, we studied the alterations in the fecal microbial abundance in colitic mice following the administration of secondary bile acids. Our results show that secondary bile acids reduce the severity of colitis and ameliorate colitis-associated fecal dysbiosis at the phylum level. This study indicates that secondary bile acids might act as a safe and effective drug for inflammatory bowel disease. Copyright © 2017 American Society for Microbiology.

Serum and Plasma Metabolomic Biomarkers for Lung Cancer.

PubMed

Kumar, Nishith; Shahjaman, Md; Mollah, Md Nurul Haque; Islam, S M Shahinul; Hoque, Md Aminul

2017-01-01

In drug invention and early disease prediction of lung cancer, metabolomic biomarker detection is very important. Mortality rate can be decreased, if cancer is predicted at the earlier stage. Recent diagnostic techniques for lung cancer are not prognosis diagnostic techniques. However, if we know the name of the metabolites, whose intensity levels are considerably changing between cancer subject and control subject, then it will be easy to early diagnosis the disease as well as to discover the drug. Therefore, in this paper we have identified the influential plasma and serum blood sample metabolites for lung cancer and also identified the biomarkers that will be helpful for early disease prediction as well as for drug invention. To identify the influential metabolites, we considered a parametric and a nonparametric test namely student׳s t-test as parametric and Kruskal-Wallis test as non-parametric test. We also categorized the up-regulated and down-regulated metabolites by the heatmap plot and identified the biomarkers by support vector machine (SVM) classifier and pathway analysis. From our analysis, we got 27 influential (p-value<0.05) metabolites from plasma sample and 13 influential (p-value<0.05) metabolites from serum sample. According to the importance plot through SVM classifier, pathway analysis and correlation network analysis, we declared 4 metabolites (taurine, aspertic acid, glutamine and pyruvic acid) as plasma biomarker and 3 metabolites (aspartic acid, taurine and inosine) as serum biomarker.

Polymeric Precipitation Inhibitors Promote Fenofibrate Supersaturation and Enhance Drug Absorption from a Type IV Lipid-Based Formulation.

PubMed

Suys, Estelle J A; Chalmers, David K; Pouton, Colin W; Porter, Christopher J H

2018-06-04

The ability of lipid-based formulations (LBFs) to increase the solubilization, and prolong the supersaturation, of poorly water-soluble drugs (PWSDs) in the gastrointestinal (GI) fluids has generated significant interest in the past decade. One mechanism to enhance the utility of LBFs is to prolong supersaturation via the addition of polymers that inhibit drug precipitation (polymeric precipitation inhibitors or PPIs) to the formulation. In this work, we have evaluated the performance of a range of PPIs and have identified PPIs that are sufficiently soluble in LBF to allow the construction of single phase formulations. An in vitro model was first employed to assess drug (fenofibrate) solubilization and supersaturation on LBF dispersion and digestion. An in vitro-in situ model was subsequently employed to simultaneously evaluate the impact of PPI enhanced drug supersaturation on drug absorption in rats. The stabilizing effect of the polymers was polymer specific and most pronounced at higher drug loads. Polymers that were soluble in LBF allowed simple processing as single phase formulations, while formulations containing more hydrophilic polymers required polymer suspension in the formulation. The lipid-soluble polymers Eudragit (EU) RL100 and poly(propylene glycol) bis(2-aminopropyl ether) (PPGAE) and the water-soluble polymer hydroxypropylmethyl cellulose (HPMC) E4M were identified as the most effective PPIs in delaying fenofibrate precipitation in vitro. An in vitro model of lipid digestion was subsequently coupled directly to an in situ single pass intestinal perfusion assay to evaluate the influence of PPIs on fenofibrate absorption from LBFs in vivo. This coupled model allowed for real-time evaluation of the impact of supersaturation stabilization on absorptive drug flux and provided better discrimination between the different PPIs and formulations. In the presence of the in situ absorption sink, increased fenofibrate supersaturation resulted in increased drug exposure, and a good correlation was found between the degree of in vitro supersaturation and in vivo drug exposure. An improved in vitro-in vivo correlation was apparent when comparing the same formulation under different supersaturation conditions. These observations directly exemplify the potential utility of PPIs in promoting drug absorption from LBF, via stabilization of supersaturation, and further confirm that relatively brief periods of supersaturation may be sufficient to promote drug absorption, at least for highly permeable drugs such as fenofibrate.

Assessment of taurine bioavailability in pelleted and extruded diets with red drum Sciaenops ocellatus

USDA-ARS?s Scientific Manuscript database

Taurine has been reported to be efficacious in supporting growth of carnivorous fish species, particularly when supplemented to diets primarily containing plant feedstuffs. Although taurine may become unavailable to some extent by heat and moisture, and is susceptible to the Maillard reaction with r...

Supplemental effect of different levels of taurine in Modena on boar semen quality during liquid preservation at 17°C.

PubMed

Li, Hao; Zhang, Xiao-Gang; Fang, Qian; Liu, Qi; Du, Ren-Rang; Yang, Gong-She; Wang, Li-Qiang; Hu, Jian-Hong

2017-11-01

Peroxidation damage induces sublethal injury to boar sperm during the storage process. Taurine has already been demonstrated to protect cells effectively from oxidant-induced injury. This study was aimed to evaluate the effect of different concentrations of taurine (0.5, 1, 5 and 10 mmol/L) in Modena diluent on boar sperm quality during liquid storage at 17°C. Ejaculates from sexually mature Duroc pigs were collected, pooled and preserved in the Modena containing different concentrations of taurine. Sperm motility, plasma membrane integrity, acrosome integrity, total antioxidative capacity (T-AOC) activity and malondialdehyde content (MDA) were examined every 24 h. Modena diluent containing taurine suppressed the reduction in sperm qualities during the process of liquid preservation compared with those of the control group. After 5 days of liquid preservation, the addition of taurine at 5 mmol/L had the optimal effect on survival time as well as maintenance of motility, plasma membrane integrity, acrosomal integrity, T-AOC activity and MDA content. These results may suggest the possibility that the proper addition of taurine to the semen extender improves the swine production system using artificial insemination by the suppressing of sperm damage and subsequent dysfunction during liquid preservation. © 2017 Japanese Society of Animal Science.

Ethanol induces taurine release in the amygdala: an in vivo microdialysis study.

PubMed

Quertemont, E; Dahchour, A; Ward, R J; Witte, P

1999-01-01

The effect of acute IP ethanol injections on the extracellular aspartate, glutamate, taurine and GABA content of the basolateral amygdala microdialysate was investigated in relationship with total brain ethanol. Each acute intraperitoneal injection of ethanol, 0.5, 1.0, 2.0 and 3.0 g/kg body weight, induced an immediate increase in microdialysate taurine; both 0.5 and 1.0 g/kg ethanol evoked an increase during the first 20 minutes following injection which returned to baseline value by 40 minutes, despite the fact that ethanol was detectable in the brain until 60 or 120 minutes, respectively. After either 2.0 or 3.0 g/kg ethanol there was an increase in taurine of gradual intensity which gradually declined to reach baseline values by 100 minutes. In contrast, the ethanol concentration for 2.0 g/kg remained elevated at the end of the 120 minutes; approximately 25 mg ethanol/mg protein. The stimulated release of taurine within the amygdala could participate in the regulation of ethanoli-nduced changes in osmolarity, since taurine is postulated to act as an osmoregulator in the brain. Taurine could also mediate or interact with ethanol-induced central nervous system effects, as it exerts a modulatory action on cell excitability and neurotransmitter processes.

Simultaneous and rapid determination of caffeine and taurine in energy drinks by MEKC in a short capillary with dual contactless conductivity/photometry detection.

PubMed

Vochyánová, Blanka; Opekar, František; Tůma, Petr

2014-06-01

A method has been developed for the simultaneous determination of taurine and caffeine using a laboratory-made instrument enabling separation analysis in a short 10.5 cm capillary. The substances are detected using a contactless conductometry/ultraviolet (UV) photometry detector that enables recording both signals at one place in the capillary. The separation of caffeine and taurine was performed using the MEKC technique in a BGE with the composition 40 mM CHES, 15 mM NaOH, and 50 mM SDS, pH 9.36. Under these conditions, the migration time of caffeine is 43 s and of taurine 60 s; LOD for caffeine is 4 mg/L using photometric detection and LOD for taurine is 24 mg/L using contactless conductometric detection. The standard addition method was used for determination in Red Bull energy drink of caffeine 317 mg/L and taurine 3860 mg/L; the contents in Kamikaze drink were 468 mg/L caffeine and 4110 mg/L taurine. The determined values are in good agreement with the declared contents of these substances. RSD does not exceed 3%. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

In-vitro examination of the positive inotropic effect of caffeine and taurine, the two most frequent active ingredients of energy drinks.

PubMed

Chaban, R; Kornberger, A; Branski, N; Buschmann, K; Stumpf, N; Beiras-Fernandez, A; Vahl, C F

2017-08-10

Our study aimed to evaluate changes in the contractile behavior of human myocardium after exposure to caffeine and taurine, the main active ingredients of energy drinks (EDs), and to evaluate whether taurine exhibits any inotropic effect at all in the dosages commonly used in EDs. Myocardial tissue was removed from the right atrial appendages of patients undergoing cardiac surgery and prepared to obtain specimens measuring 4 mm in length. A total of 92 specimens were exposed to electrical impulses at a frequency of 75 bpm for at least 40 min to elicit their maximum contractile force before measuring the isometric contractile force (ICF) and duration of contraction (CD). Following this, each specimen was treated with either taurine (group 1, n = 29), or caffeine (group 2, n = 31) or both (group 3, n = 32). After exposure, ICF and CD measuring were repeated. Post-treatment values were compared with pre-treatments values and indicated as percentages. Exposure to taurine did not alter the contraction behavior of the specimens. Exposure to caffeine, in contrast, led to a significant increase in ICF (118 ± 03%, p < 0.01) und a marginal decrease in CD (95 ± 1.6%, p < 0.01). Exposure to a combination of caffeine and taurine also induced a statistically significant increase in ICF (124 ± 4%, p < 0.01) and a subtle reduction in CD (92 ± 1.4%, p < 0.01). The increase in ICF achieved by administration of caffeine was similar to that achieved by a combination of both caffeine and taurine (p = 0.2). The relative ICF levels achieved by administration of caffeine and a combination of taurine and caffeine, respectively, were both significantly higher (p < 0.01) than the ICF resulting from exposure to taurine only. While caffeine altered the contraction behavior of the specimen significantly in our in-vitro model, taurine did not exhibit a significant effect. Adding taurine to caffeine did not significantly enhance or reduce the effect of caffeine.

Modulation Effect of Peroxisome Proliferator-Activated Receptor Agonists on Lipid Droplet Proteins in Liver.

PubMed

Zhu, Yun-Xia; Zhang, Ming-Liang; Zhong, Yuan; Wang, Chen; Jia, Wei-Ping

2016-01-01

Peroxisome proliferator-activated receptor (PPAR) agonists are used for treating hyperglycemia and type 2 diabetes. However, the mechanism of action of these agonists is still under investigation. The lipid droplet-associated proteins FSP27/CIDEC and LSDP5, regulated directly by PPARγ and PPARα, are associated with hepatic steatosis and insulin sensitivity. Here, we evaluated the expression levels of FSP27/CIDEC and LSDP5 and the regulation of these proteins by consumption of a high-fat diet (HFD) or administration of PPAR agonists. Mice with diet-induced obesity were treated with the PPARγ or PPARα agonist, pioglitazone or fenofibrate, respectively. Liver tissues from db/db diabetic mice and human were also collected. Interestingly, FSP27/CIEDC was expressed in mouse and human livers and was upregulated in obese C57BL/6J mice. Fenofibrate treatment decreased hepatic triglyceride (TG) content and FSP27/CIDEC protein expression in mice fed an HFD diet. In mice, LSDP5 was not detected, even in the context of insulin resistance or treatment with PPAR agonists. However, LSDP5 was highly expressed in humans, with elevated expression observed in the fatty liver. We concluded that fenofibrate greatly decreased hepatic TG content and FSP27/CIDEC protein expression in mice fed an HFD, suggesting a potential regulatory role for fenofibrate in the amelioration of hepatic steatosis.

Retinal degeneration in cats fed casein. IV. The early receptor potential.

PubMed

Berson, E L; Watson, G; Grasse, K L; Szamier, R B

1981-08-01

Electroretinographic studies of casein-fed cats with retinal taurine deficiency revealed that the early receptor potential (ERP) was initially normal in amplitude at a time when the a-wave and b-wave of the electroretinogram were substantially reduced or even nondetectable. The preserved ERP's in these taurine-deficient cats could be correlated with the histologic finding that their outer segments were relatively intact over 90% of the retinal area subtended by the test flash. The sequence of electroretinographic changes in these taurine-deficient cats was also consistent with previous biochemical studies on the normal cat retina that have shown a relatively low concentration of taurine at the level of the outer segments and a higher concentration at the level of the inner segments. The responses in early stages from taurine-deficient cats differed from the responses obtained from vitamin A--deficient cats but resembled those from cats that received an intravitreal injection of ouabain. Similarities and a difference between the responses of taurine-deficient cats and those of patients with early retinitis pigmentosa are considered.

Is fenofibrate a cost-saving treatment for middle-aged individuals with type 2 diabetes? A South African private-sector perspective.

PubMed

Wessels, Francois

2010-01-01

This project was based on the FIELD trial. It is a localisation of the study by Carrington and Stewart. The aim of the original study was to determine the impact of fenofibrate therapy on healthcare costs of middle-aged patients with type 2 diabetes at high risk of future cardiovascular events. The methodology used in the Carrington article was adopted for this study. The clinical foundation for the analysis was derived from the findings of the FIELD study. All costs were sourced from electronic databases obtained from private-sector South African funders of healthcare. Event costs for the cardiovascular events were determined and added to the treatment costs for the individual treatment arms. The cost saving was determined as the difference between the event costs saved and the additional treatment costs associated with fenofibrate treatment. All costs were reported as 2008 ZAR and a discount rate of 10% was used. The study adopted a South African private-sector funder perspective. If the same approach is followed as in the Carrington and Stewart study, a cost saving of 18% results. This is the difference between the total costs associated with the placebo and fenofibrate arms, respectively (R3 480 471 compared to R2 858 598 per 1 000 patient years for the placebo and fenofibrate arms, respectively). The total costs were determined as the sum of associated event costs and treatment costs for each of the comparators. Based on this exploratory analysis, it seems that Lipanthyl treatment in middle-aged patients resulted in a cost saving due to the prevention of cardiovascular events when it was used in the treatment of type 2 diabetics, as in the FIELD study. It should therefore be considered to be cost effective, even when just the cardiovascular risk reduction effect is considered.

Extracellular glutamate and other amino acids in experimental intracerebral hemorrhage: an in vivo microdialysis study.

PubMed

Qureshi, Adnan I; Ali, Zulfiqar; Suri, M Fareed K; Shuaib, Asfhaq; Baker, Glen; Todd, Kathryn; Guterman, Lee R; Hopkins, L Nelson

2003-05-01

To determine whether extracellular concentrations of glutamate and other amino acids are significantly elevated after intracerebral hemorrhage and, if so, the temporal characteristics of these changes. Although the role of excitotoxic amino acids, particularly that of glutamate, has been described in ischemic stroke and head trauma, no information exists regarding their possible contribution to the pathogenesis of neuronal injury in intracerebral hemorrhage. Prospective, controlled, laboratory trial. Animal research laboratory. Sixteen anesthetized New Zealand rabbits. We introduced intracerebral hemorrhage in each of eight anesthetized New Zealand rabbits by injecting 0.4 mL of autologous blood under arterial pressure into the deep gray matter of the cerebrum. Extracellular fluid samples were collected from the perihematoma region and contralateral (right) hemisphere by in vivo microdialysis at 30-min intervals for 6 hrs. Corresponding samples were similarly collected from both hemispheres in each of eight control animals that underwent needle placement without introduction of a hematoma. Concentrations of amino acids (glutamate, aspartate, asparagine, glycine, taurine, and gamma-aminobutyric acid) in the samples were measured by use of high-pressure liquid chromatography with fluorescence detection. Glutamate concentrations (mean +/- sem) were significantly higher in the hemisphere ipsilateral to the hematoma than in the contralateral hemisphere (92 +/- 22 pg/microL vs. 22 +/- 6 pg/microL) at 30 mins after hematoma creation. A significant increase was observed at 30 mins posthematoma creation in the hemisphere ipsilateral to the hematoma compared with the baseline value. A nonsignificant increase in glutamate concentration persisted in the hemisphere ipsilateral to the hematoma, ranging from 134% to 187% of baseline value between 1 and 5 hrs after hematoma creation. In the hemisphere ipsilateral to the hematoma, a three-fold increase in the concentration of glycine was observed at 30 mins after hematoma creation compared with the baseline level (890 +/- 251 pg/microL vs. 291 +/- 73 pg/microL). There was a significant difference between the hemisphere ipsilateral to the hematoma compared with the ipsilateral (corresponding) hemisphere of the control group at 30 mins posthematoma (890 +/- 251 pg/microL vs. 248 +/- 66 pg/microL). A similar transient increase was observed in taurine and asparagine concentrations at 30 mins after hematoma creation, compared with baseline measurements. Taurine concentrations in the hemisphere ipsilateral to the hematoma were significantly higher than the ipsilateral hemisphere of the control group (622 +/- 180 pg/microL vs. 202 +/- 64 pg/microL) at 30 mins after hematoma creation. The present study suggests that glutamate and other amino acids accumulate transiently in extracellular fluids in the perihematoma region during the early period of intracerebral hemorrhage. The exact role of these amino acids in the pathogenesis of neuronal injury observed in intracerebral hemorrhage needs to be defined.

Biliary Bile Acids in Primary Biliary Cirrhosis: Effect of Ursodeoxycholic Acid

PubMed Central

Combes, Burton; Carithers, Robert L.; Maddrey, Willis C.; Munoz, Santiago; Garcia-Tsao, Guadalupe; Bonner, Gregory F.; Boyer, James L.; Luketic, Velimir A.; Shiffman, Mitchell L.; Peters, Marion G.; White, Heather; Zetterman, Rowen K.; Risser, Richard; Rossi, Stephen S.; Hofmann, Alan F.

2014-01-01

Bile acid composition in fasting duodenal bile was assessed at entry and at 2 years in patients with primary biliary cirrhosis (PBC) enrolled in a randomized, double-blind, placebo-controlled trial of ursodeoxycholic acid (UDCA) (10–12 mg/kg/d) taken as a single bedtime dose. Specimens were analyzed by a high-pressure liquid chromatography method that had been validated against gas chromatography. Percent composition in bile (mean ± SD) for 98 patients at entry for cholic (CA), chenodeoxycholic (CDCA), deoxycholic (DCA), lithocholic (LCA), and ursodeoxycholic (UDCA) acids, respectively, were 57.4 ± 18.6, 31.5 ± 15.5, 8.0 ± 9.3, 0.3 ± 1.0, and 0.6 ± 0.9. Values for CA were increased, whereas those for CDCA, DCA, LCA, and UDCA were decreased when compared with values in normal persons. Bile acid composition of the major bile acids did not change after 2 years on placebo medication. By contrast, in patients receiving UDCA for 2 years, bile became enriched with UDCA on average to 40.1%, and significant decreases were noted for CA (to 32.2%) and CDCA (to 19.5%). No change in percent composition was observed for DCA and LCA. Percent composition at entry and changes in composition after 2 years on UDCA were similar in patients with varying severity of PBC. In patients whose bile was not enriched in UDCA (entry and placebo-treated specimens), CA, CDCA, DCA, and the small amount of UDCA found in some of these specimens were conjugated to a greater extent with glycine (52%–64%) than with taurine (36%–48%). Treatment with UDCA caused the proportion of all endogenous bile acids conjugated with glycine to increase to 69% to 78%, while the proportion conjugated with taurine (22%–31%) fell (P < .05). Administered UDCA was also conjugated predominantly with glycine (87%). PMID:10347103

Taurine Protected Against the Impairments of Neural Stem Cell Differentiated Neurons Induced by Oxygen-Glucose Deprivation.

PubMed

Xiao, Bo; Liu, Huazhen; Gu, Zeyun; Liu, Sining; Ji, Cheng

2015-11-01

Cell transplantation of neural stem cells (NSCs) is a promising approach for neurological recovery both structurally and functionally. However, one big obstacle is to promote differentiation of NSCs into neurons and the followed maturation. In the present study, we aimed to investigate the protective effect of taurine on the differentiation of NSCs and subsequent maturation of their neuronal lineage, when exposed to oxygen-glucose deprivation (OGD). The results suggested that taurine (5-20 mM) promoted the viability and proliferation of NSCs, and it protected against 8 h of OGD induced impairments. Furthermore, 20 mM taurine promoted NSCs to differentiate into neurons after 7 days of culture, and it also protected against the suppressive impairments of 8 h of OGD. Consistently, taurine (20 mM) promoted the neurite sprouting and outgrowth of the NSC differentiated neurons after 14 days of differentiation, which were significantly inhibited by OGD (8 h). At D21, the mushroom spines and spine density were promoted or restored by 20 mM taurine. Taken together, the enhanced viability and proliferation of NSCs, more differentiated neurons and the promoted maturation of neurons by 20 mM taurine support its therapeutic application during stem cell therapy to enhance neurological recovery. Moreover, it protected against the impairments induced by OGD, which may highlight its role for a more direct therapeutic application especially in an ischemic stroke environment.

Antioxidant-Mediated Effects in a Gerbil Model of Iron Overload

PubMed Central

Otto-Duessel, Maya; Aguilar, Michelle; Moats, Rex; Wood, John C.

2010-01-01

Introduction Iron cardiomyopathy is a lethal complication of transfusion therapy in thalassemia major. Nutritional supplements decreasing cardiac iron uptake or toxicity would have clinical significance. Murine studies suggest taurine may prevent oxidative damage and inhibit Ca2+-channel-mediated iron transport. We hypothesized that taurine supplementation would decrease cardiac iron-overloaded toxicity by decreasing cardiac iron. Vitamin E and selenium served as antioxidant control. Methods Animals were divided into control, iron, taurine, and vitamin E/selenium groups. Following sacrifice, iron and selenium measurements, histology, and biochemical analyses were performed. Results No significant differences were found in heart and liver iron content between treatment groups, except for higher hepatic dry-weight iron concentrations in taurine-treated animals (p < 0.03). Serum iron increased with iron loading (751 ± 66 vs. 251 ± 54 μg/dl, p < 0.001) and with taurine (903 ± 136 μg/dl, p = 0.03). Conclusion Consistent with oxidative stress, iron overload increased cardiac malondialdehyde levels, decreased heart glutathione peroxidase (GPx) activity, and increased serum aspartate aminotransferase. Taurine ameliorated these changes, but only significantly for liver GPx activity. Selenium and vitamin E supplementation did not improve oxidative markers and worsened cardiac GPx activity. These results suggest that taurine acts primarily as an antioxidant rather than inhibiting iron uptake. Future studies should illuminate the complexity of these results. PMID:17940334

Effect of taurine supplementation on fat and energy absorption in cystic fibrosis.

PubMed

De Curtis, M; Santamaria, F; Ercolini, P; Vittoria, L; De Ritis, G; Garofalo, V; Ciccimarra, F

1992-09-01

In 10 children with cystic fibrosis and persisting steatorrhoea, supplementation with taurine (30-40 mg/kg/day) was given for two months as an adjunct to the usual pancreatic enzyme treatment. A three day fat and energy balance was performed in patients with cystic fibrosis, before and after the supplementation, and in seven healthy controls who did not receive taurine. Faecal fat was measured by a gravimetric method and stool energy was determined using a bomb calorimeter. Patients with cystic fibrosis, before and after taurine, and healthy controls received the same fat and energy intake (calculated by a dietitian). In patients with cystic fibrosis taurine did not produce any improvement of steatorrhoea (mean (SD) faecal fat 8.7 (3.3) v 11.2 (7.0) g/day, respectively before and after the supplementation), of faecal energy loss (0.978 (0.468) v 1.133 (0.539) MJ/day), of faecal fat expressed as percent of fat intake (13.4 (5.6) v 15.1 (9.8)%), and of faecal energy expressed as percent of energy intake (9.9 (3.6) v 11.2 (5.7)%). Healthy controls had significant lower fat (3.5 (2.3) g/day) and energy 0.576 (0.355) MJ/day faecal losses. In conclusion, taurine failed to decrease significantly fat and energy losses. Our study does not support the use of taurine supplementation in the nutritional management of cystic fibrosis.

Plasma glutathione of HIV⁺ patients responded positively and differently to dietary supplementation with cysteine or glutamine.

PubMed

Borges-Santos, Maria Dorotéia; Moreto, Fernando; Pereira, Paulo Câmara Marques; Ming-Yu, Yong; Burini, Roberto Carlos

2012-07-01

Patients with positivity for the human immunodeficiency virus (HIV⁺) present low concentrations of antioxidant nutrients, including total glutathione (GSH) and its precursors. We investigated the responses of the sulfur-containing amino acid pathway to cysteine and glutamine (Gln) dietary supplements in patients with HIV⁺ compared with healthy controls. Twelve treated patients (six men and six women, 22-45 y old) and 20 healthy controls (10 men and 10 women, 20-59 y old) were randomly assigned to 7-d dietary supplements containing N-acetylcysteine (NAC; 1 g/d) or Gln (20 g/d), with a 7-d washout period ingesting their usual diet. Blood samples were drawn after an overnight fast. High-performance liquid chromatographic plasma analysis of sulfur-containing amino acids (methionine, homocysteine, cysteine, and taurine), GSH, oxidized GSH, and serine, glycine, glutamic acid, and Gln was carried out moments before and after 7-d supplementations. Statistical comparisons were undertaken between groups and between dietary supplements (P < 0.05). Patients with HIV⁺ showed higher oxidized GSH and lower concentrations of GSH and all amino acids except homocysteine. The HIV⁺ group responded to the NAC by increased levels of sulfur-containing amino acids and GSH and equalized taurine and GSH levels in the control group. The Gln supplements also equalized the levels of GSH, Gln, and glycine in the control group. An increase in GSH may be attained by NAC or Gln supplementation, with NAC acting by increasing cysteine levels and Gln likely acting by replenishing the glycine pool (trial registered at http://www.clinicaltrials.gov, identifier NCT00910442). Copyright © 2012 Elsevier Inc. All rights reserved.

Effect of three different intensities of infrared laser energy on the levels of amino acid neurotransmitters in the cortex and hippocampus of rat brain.

PubMed

Ahmed, Nawal Abd El Hay; Radwan, Nasr Mahmoud; Ibrahim, Khayria Mansour; Khedr, Mona Emam; El Aziz, Mona A; Khadrawy, Yasser Ashry

2008-10-01

The aim of this study is to investigate the effects of three different intensities of infrared diode laser radiation on amino acid neurotransmitters in the cortex and hippocampus of rat brain. Lasers are known to induce different neurological effects such as pain relief, anesthesia, and neurosuppressive effects; however, the precise mechanisms of these effects are not clearly elucidated. Amino acid neurotransmitters (glutamate, aspartate, glutamine, gamma-aminobutyric acid [GABA], glycine, and taurine) play vital roles in the central nervous system (CNS). The shaved scalp of each rat was exposed to different intensities of infrared laser energy (500, 190, and 90 mW) and then the rats were sacrificed after 1 h, 7 d, and 14 d of daily laser irradiation. The control groups were exposed to the same conditions but without exposure to laser. The concentrations of amino acid neurotransmitters were measured by high-performance liquid chromatography (HPLC). The rats subjected to 500 mW of laser irradiation had a significant decrease in glutamate, aspartate, and taurine in the cortex, and a significant decrease in hippocampal GABA. In the cortices of rats exposed to 190 mW of laser irradiation, an increase in aspartate accompanied by a decrease in glutamine were observed. In the hippocampus, other changes were seen. The rats irradiated with 90 mW showed a decrease in cortical glutamate, aspartate, and glutamine, and an increase in glycine, while in the hippocampus an increase in glutamate, aspartate, and GABA were recorded. We conclude that daily laser irradiation at 90 mW produced the most pronounced inhibitory effect in the cortex after 7 d. This finding may explain the reported neurosuppressive effect of infrared laser energy on axonal conduction of hippocampal and cortical tissues of rat brain.

MALDI Mass Spectral Imaging of Bile Acids Observed as Deprotonated Molecules and Proton-Bound Dimers from Mouse Liver Sections

NASA Astrophysics Data System (ADS)

Rzagalinski, Ignacy; Hainz, Nadine; Meier, Carola; Tschernig, Thomas; Volmer, Dietrich A.

2018-02-01

Bile acids (BAs) play two vital roles in living organisms, as they are involved in (1) the secretion of cholesterol from liver, and (2) the lipid digestion/absorption in the intestine. Abnormal bile acid synthesis or secretion can lead to severe liver disorders. Even though there is extensive literature on the mass spectrometric determination of BAs in biofluids and tissue homogenates, there are no reports on the spatial distribution in the biliary network of the liver. Here, we demonstrate the application of high mass resolution/mass accuracy matrix-assisted laser desorption/ionization (MALDI)-Fourier-transform ion cyclotron resonance (FTICR) to MS imaging (MSI) of BAs at high spatial resolutions (pixel size, 25 μm). The results show chemical heterogeneity of the mouse liver sections with a number of branching biliary and blood ducts. In addition to ion signals from deprotonation of the BA molecules, MALDI-MSI generated several further intense signals at larger m/z for the BAs. These signals were spatially co-localized with the deprotonated molecules and easily misinterpreted as additional products of BA biotransformations. In-depth analysis of accurate mass shifts and additional electrospray ionization and MALDI-FTICR experiments, however, confirmed them as proton-bound dimers. Interestingly, dimers of bile acids, but also unusual mixed dimers of different taurine-conjugated bile acids and free taurine, were identified. Since formation of these complexes will negatively influence signal intensities of the desired [M - H]- ions and significantly complicate mass spectral interpretations, two simple broadband techniques were proposed for non-selective dissociation of dimers that lead to increased signals for the deprotonated BAs. [Figure not available: see fulltext.

Cataracts and strabismus associated with hand rearing using artificial milk formulas in Bengal tiger (Panthera tigris spp tigris) cubs

PubMed Central

Lange, Rogério Ribas; Lima, Leandro; Frühvald, Erika; da Silva, Vera Sônia Nunes; de Souza, Aparecida Sônia; Montiani-Ferreira, Fabiano

2017-01-01

The aim of this investigation is to describe the potential contributing nutritional factors involved in the development of ophthalmic and dermatologic changes in four Bengal tiger (Panthera tigris spp tigris) cubs fed an artificial milk formula. The affected animals were compared with two other tiger cubs that had been nursed by their dam naturally. After the first clinical signs appeared, the tiger cubs underwent ophthalmic evaluation. Severe symmetric generalized alopecia over the trunk, sparing the head and distal portion of the front and rear limbs, bilateral cataracts and strabismus were noticed. Milk and blood from the mother, as well as blood from the healthy and affected cubs were collected in order to evaluate complete blood counts, serum chemistry values, and amino acid levels. The amino acid concentrations in the artificial formula were also evaluated for comparison to the milk from the dam. The concentration of taurine, arginine, phenylalanine, tryptophan and histidine were very low in the artificial formulas as compared to the dam´s milk. The tiger cubs that received the artificial formula had lower levels of the amino acids listed previously as compared to those that nursed from the dam naturally. Taurine, as well as arginine, phenylalanine, tryptophan and histidine deficiency appeared to be possible causes of the development of skin problems, cataracts and strabismus in the tiger cubs fed with these particular artificial milk replacers. In the future, special attention should be given in order to make sure that adequate levels of these amino acids are present in artificial milk for tiger cubs. PMID:28210544

Investigation on the adsorption characteristics of sodium benzoate and taurine on gold nanoparticle film by ATR-FTIR spectroscopy

NASA Astrophysics Data System (ADS)

Kumar, Naveen; Thomas, S.; Tokas, R. B.; Kshirsagar, R. J.

2014-01-01

Fourier transform infrared (FTIR) spectroscopic studies of sodium benzoate and taurine adsorbed on gold nanoparticle (AuNp) film on silanised glass slides have been studied by attenuated total reflection technique (ATR). The surface morphology of the AuNp films has been measured by Atomic Force Microscopy. The ATR spectra of sodium benzoate and taurine deposited on AuNp film are compared with ATR spectra of their powdered bulk samples. A new red-shifted band appeared along with the symmetric and asymmetric stretches of carboxylate group of sodium benzoate leading to a broadening of the above peaks. Similar behavior is also seen in the case of symmetric and asymmetric stretches of sulphonate group of taurine. The results indicate presence of both chemisorbed and physisorbed layers of both sodium benzoate and taurine on the AuNp film with bottom layer chemically bound to AuNp through carboxylate and sulphonate groups respectively.

Rapid and accurate reversed-phase high-performance liquid chromatographic determination of conjugated bile acids in human bile for routine clinical applications. Therapeutic control during gallstone dissolution therapy.

PubMed

Swobodnik, W; Klüppelberg, U; Wechsler, J G; Volz, M; Normandin, G; Ditschuneit, H

1985-05-03

This paper introduces a new method to detect the taurine and glycine conjugates of five different bile acids (cholic acid, deoxycholic acid, chenodeoxycholic acid, ursodeoxycholic acid and lithocholic acid) in human bile. Advantages of this method are sufficient separation of compounds within a short period of time and a high rate of reproducibility. Using a mobile phase gradient of acetonitrile and water, modified with tetrabutylammonium hydrogen sulphate (0.0075 mol/l), we were able to maximize the differentiation between ursodeoxycholic acid and lithocholic acid, which is of primary interest during conservative gallstone dissolution therapy. Use of this gradient reduced analysis time to less than 0.5 h. Recovery rates for this modified method ranged from 94% to 100%, and reproducibility was 98%, sufficient for routine clinical applications.

[Fenofibrate--induced myopathy in a patient with undiagnosed hypothyroidism--case report and a review of the literature].

PubMed

Lukjanowicz, Małgorzata; Trzcińska-Butkiewicz, Beata; Brzosko, Marek

2006-01-01

Hypothyroidism is one of the common causes of the secondary hypercholesterolemia. The prevalence of hypothyroidism in the general population is estimated to be as high as about 1.5%. Frequency of the hypothyroidism in patients with hyperlipidemia is high, and can be observed in 4.2-10% in different populations. Most commonly, there is no need to treat the hypothyroid patients with the hypolipidemic drugs. Substitution treatment with the thyroid hormones usually results in either normalization or significant decreasing of the lipid levels. Hypothyroidism with symptoms of involvement of skeletal muscles is referred as to hypothyroid myopathy in English literature, and can be present in 30-80% patients with deficiency of the thyroid hormones. Hypothyroidism is a risk factor of developing of toxic injury of muscles, what is thought to be related to hypolipidemic drug intake. We report a case of a patient with undiagnosed hypothyroidism with muscle involvement manifestation, who was treated with fenofibrate due to accidentally diagnosed hypercholesterolemia. Hypolipidemic management resulted in rapid exacerbation of previously moderate myopathy. High concentrations of muscle enzymes and moderate increasing of creatinine concentration were detected. Improvement was observed after discontinuation of fenofibrate administration, but muscle symptoms and elevation of muscle enzymes and creatinine persisted. After administration of levothyroxin, muscle weakness and laboratory abnormalities were observed no longer. After several months of follow-up we believe that treatment with fenofibrate in our patient was complicated with muscle tissue damage and exacerbated symptoms of myopathy originally related to decompensated hypothyroidism.

Preferential PPAR-α activation reduces neuroinflammation, and blocks neurodegeneration in vivo

PubMed Central

Esmaeili, Mohammad A.; Yadav, Shilpi; Gupta, Ravi Kr.; Waggoner, Garrett R.; Deloach, Abigail; Calingasan, Noel Y.; Beal, M. Flint; Kiaei, Mahmoud

2016-01-01

Neuroinflammation, immune reactivity and mitochondrial abnormalities are considered as causes and/or contributors to neuronal degeneration. Peroxisome proliferator-activated receptors (PPARs) regulate both inflammatory and multiple other pathways that are implicated in neurodegeneration. In the present study, we investigated the efficacy of fenofibrate (Tricor), a pan-PPAR agonist that activates PPAR-α as well as other PPARs. We administered fenofibrate to superoxide dismutase 1 (SOD1G93A) mice daily prior to any detectable phenotypes and then animal behavior, pathology and longevity were assessed. Treated animals showed a significant slowing of the progression of disease with weight loss attenuation, enhanced motor performance, delayed onset and survival extension. Histopathological analysis of the spinal cords showed that neuronal loss was significantly attenuated in fenofibrate-treated mice. Mitochondria were preserved as indicated by Cytochrome c immunostaining in the spinal cord, which maybe partly due to increased expression of the PPAR-γ co-activator 1-α. The total mRNA analysis revealed that neuroprotective and anti-inflammatory genes were elevated, while neuroinflammatory genes were down-regulated. This study demonstrates that the activation of PPAR-α action via fenofibrate leads to neuroprotection by both reducing neuroinflammation and protecting mitochondria, which leads to a significant increase in survival in SOD1G93A mice. Therefore, the development of therapeutic strategies to activate PPAR-α as well as other PPARs may lead to new therapeutic agents to slow or halt the progression of amyotrophic lateral sclerosis. PMID:26604138

Modulating drug release from gastric-floating microcapsules through spray-coating layers.

PubMed

Lee, Wei Li; Tan, Jun Wei Melvin; Tan, Chaoyang Nicholas; Loo, Say Chye Joachim

2014-01-01

Floating dosage forms with prolonged gastric residence time have garnered much interest in the field of oral delivery. However, studies had shown that slow and incomplete release of hydrophobic drugs during gastric residence period would reduce drug absorption and cause drug wastage. Herein, a spray-coated floating microcapsule system was developed to encapsulate fenofibrate and piroxicam, as model hydrophobic drugs, into the coating layers with the aim of enhancing and tuning drug release rates. Incorporating fenofibrate into rubbery poly(caprolactone) (PCL) coating layer resulted in a complete and sustained release for up to 8 h, with outermost non-drug-holding PCL coating layer serving as a rate-controlling membrane. To realize a multidrug-loaded system, both hydrophilic metformin HCl and hydrophobic fenofibrate were simultaneously incorporated into these spray-coated microcapsules, with metformin HCl and fenofibrate localized within the hollow cavity of the capsule and coating layer, respectively. Both drugs were observed to be completely released from these coated microcapsules in a sustained manner. Through specific tailoring of coating polymers and their configurations, piroxicam loaded in both the outer polyethylene glycol and inner PCL coating layers was released in a double-profile manner (i.e. an immediate burst release as the loading dose, followed by a sustained release as the maintenance dose). The fabricated microcapsules exhibited excellent buoyancy in simulated gastric fluid, and provided controlled and sustained release, thus revealing its potential as a rate-controlled oral drug delivery system.

Anti-inflammatory actions of a taurine analogue, ethane β-sultam, in phagocytic cells, in vivo and in vitro.

PubMed

Ward, Roberta J; Lallemand, Frederic; de Witte, Philippe; Crichton, Robert R; Piette, Jacques; Tipton, Keith; Hemmings, Karl; Pitard, Arnaud; Page, Mike; Della Corte, Laura; Taylor, Deanna; Dexter, David

2011-03-15

The ability of a taurine prodrug, ethane β-sultam, to reduce cellular inflammation has been investigated, in vitro, in primary cultures of alveolar macrophages and an immortilised N9 microglial cell line and in vivo in an animal model of inflammation and control rats. Ethane β-sultam showed enhanced ability to reduce the inflammatory response in alveolar macrophages, as assayed by the lipopolysaccharide-stimulated-nitric oxide release, (LPS stimulated-NO), in comparison to taurine both in vitro (10 nM, 50 nM) and in vivo (0.15 mmol/kg/day by gavage). In addition, ethane β-sultam, (50, 100 and 1000 nM) significantly reduced LPS-stimulated glutamate release from N9 microglial cells to a greater extent than taurine. The anti-inflammatory response of taurine was shown to be mediated via stabilisation of IkBα. The use of a taurine prodrug as therapeutic agents, for the treatment of neurological conditions, such as Parkinson's and Alzheimer's disease and alcoholic brain damage, where activated phagocytic cells contribute to the pathogenesis, may be of great potential. Copyright © 2011 Elsevier Inc. All rights reserved.

GABA, 5-HT and amino acids in the rotifers Brachionus plicatilis and Brachionus rotundiformis.

PubMed

Gallardo, W G; Hagiwara, A; Hara, K; Soyano, K; Snell, T W

2000-11-01

gamma-Aminobutyric acid (GABA) and 5-hydroxytryptamine (5-HT) have been shown to increase the reproduction of the Brachionus plicatilis (NH3L strain). In the present study, the endogenous presence of GABA and 5-HT in the rotifers B. plicatilis (NH3L and Kamiura strains) and Brachionus rotundiformis (Langkawi strain) were confirmed by dot blot immunoassay and high-performance liquid chromatography (HPLC). HPLC showed that GABA and 5-HT concentrations in the three rotifer strains range from 71 to 188 pmol/mg and from 12 to 64 pmol/mg, respectively. A total of 33 amino acids were also detected in B. plicatilis and B. rotundiformis, with glutamic acid, serine, glycine, taurine, threonine, alanine, arginine, proline, valine and isoleucine in high concentrations relative to other amino acids.

Urinary metabonomics study of the hepatoprotective effects of total alkaloids from Corydalis saxicola Bunting on carbon tetrachloride-induced chronic hepatotoxicity in rats using 1H NMR analysis.

PubMed

Wu, Fang; Zheng, Hua; Yang, Zheng-Teng; Cheng, Bang; Wu, Jin-Xia; Liu, Xu-Wen; Tang, Chao-Ling; Lu, Shi-Yin; Chen, Zhao-Ni; Song, Fang-Ming; Ruan, Jun-Xiang; Zhang, Hong-Ye; Liang, Yong-Hong; Song, Hui; Su, Zhi-Heng

2017-06-05

Chronic liver injury has been shown to cause liver fibrosis due to the sustained pathophysiological wound healing response of the liver, and eventually progresses to cirrhosis. The total alkaloids of Corydalis saxicola Bunting (TACS), a collection of important bioactive ingredients derived from the traditional Chinese folk medicine Corydalis saxicola Bunting (CS), have been reported to have protective effects on the liver. However, the underlying molecular mechanisms need further elucidation. In this study, the urinary metabonomics and the biochemical changes in rats with carbon tetrachloride (CCl 4 )-induced chronic liver injury due to treatment TACS or administration of the positive control drug-bifendate were studied via proton nuclear magnetic resonance ( 1 H NMR) analysis. Partial least squares-discriminate analysis (PLS-DA) suggested that metabolic perturbation caused by CCl 4 damage was recovered with TACS and bifendate treatment. A total of seven metabolites including 2-oxoglutarate, citrate, dimethylamine, taurine, phenylacetylglycine, creatinine and hippurate were considered as potential biomarkers involved in the development of CCl 4 -induced chronic liver injury. According to pathway analysis using identified metabolites and correlation network construction, the tricarboxylic acid (TCA) cycle, gut microbiota metabolism and taurine and hypotaurine metabolism were recognized as the most affected metabolic pathways associated with CCl 4 chronic hepatotoxicity. Notably, the changes in 2-oxoglutarate, citrate, taurine and hippurate during the process of CCl 4 -induced chronic liver injury were significantly restored by TACS treatment, which suggested that TACS synergistically mediated the regulation of multiple metabolic pathways including the TCA cycle, gut microbiota metabolism and taurine and hypotaurine metabolism. This study could bring valuable insight to evaluating the efficacy of TACS intervention therapy, help deepen the understanding of the hepatoprotective mechanisms of TACS and enable optimal diagnosis of chronic liver injury. Copyright © 2017 Elsevier B.V. All rights reserved.

Effect of infrared laser irradiation on amino acid neurotransmitters in an epileptic animal model induced by pilocarpine.

PubMed

Radwan, Nasr Mahmoud; El Hay Ahmed, Nawal Abd; Ibrahim, Khayria Mansour; Khedr, Mona Emam; Aziz, Mona A; Khadrawy, Yasser Ashry

2009-06-01

The aim of the present study was to investigate the effect of daily laser irradiation on the levels of amino acid neurotransmitters in the cortex and hippocampus in an epileptic animal model induced by pilocarpine. It has been claimed that at specific wavelengths and energy densities, laser irradiation is a novel and useful tool for the treatment of peripheral and central nervous system injuries and disorders. Adult male albino rats were divided into three groups: control rats, pilocarpinized rats (epileptic animal model), and pilocarpinized rats treated daily with laser irradiation (90 mW at 830 nm) for 7 d. The following parameters were assayed in cortex and hippocampus: amino acid neurotransmitters (excitatory: glutamic acid and aspartate; and inhibitory: gamma-aminobutyric acid [GABA], glycine, and taurine) by high-performance liquid chromatography (HPLC), glucose content, and the activity of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), using a spectrophotometer. Significant increases in the concentrations of glutamic acid, glutamine, glycine, and taurine were recorded in the cortices of pilocarpinized rats, and they returned to initial levels after laser treatment. In the hippocampus, a moderate increase in aspartate accompanied by a significant increase in glycine were observed in the epileptic animal model, and these dropped to near-control values after laser treatment. In addition, a significant increase in cortical AST activity and a significant decrease in ALT activity and glucose content were obtained in the pilocarpinized animals and pilocarpinized rats treated with laser irradiation. In the hippocampus, significant decreases in the activity of AST and ALT and glucose content were recorded in the epileptic animals and in the epileptic animals treated with laser irradiation. Based on the results obtained in this study, it may be suggested that nearinfrared laser irradiation may reverse the neurochemical changes in amino acid neurotransmitters induced by pilocarpine.

Effect of Vitamin E and Polyunsaturated Fatty Acids on Cryopreserved Sperm Quality in Bos taurus Bulls Under Testicular Heat Stress.

PubMed

Losano, João D A; Angrimani, Daniel S R; Dalmazzo, Andressa; Rocha, Carolina C; Brito, Maíra M; Perez, Eduardo G A; Tsunoda, Roberta H; Góes, Paola A A; Mendes, Camilla M; Assumpção, Mayra E O A; Barnabe, Valquiria H; Nichi, Marcilio

2018-04-03

Taurine bulls are highly susceptible to heat stress, leading to increased oxidative stress (OS) and impaired sperm viability. Polyunsaturated fatty acids (PUFAs) supplementation can be an alternative to improve semen quality, which also results in more sperm susceptibility to lipid peroxidation. Moreover, this deleterious effect can be exacerbated in animals affected by heat stress. Vitamin E is a key antioxidant that counteracts lipid peroxidation of sperm membrane caused by OS. Thus, combining PUFAs with vitamin E may improve sperm quality. In this context, this study aimed to evaluate the effect of interaction between PUFAs and vitamin E on sperm quality in Bos taurus bulls under testicular heat stress. Sixteen taurine bulls under testicular heat stress were randomly assigned in four groups: Control, Vitamin E, PUFA, and PUFA + Vitamin E. All groups lasted for 60 days. Samples were cryopreserved/thawed and analyzed for motility variables (CASA), membrane and acrosome integrity, mitochondrial activity, susceptibility to oxidative stress, DNA integrity, and sperm-binding capacity. Results showed that vitamin E had a beneficial effect on some sperm characteristics, whereas PUFA supplementation had an adverse effect when the two treatments were evaluated separately. Finally, the association between PUFAs and vitamin E did not improve sperm quality.

Immune and cell modulation by amino acids.

PubMed

Roth, Erich

2007-10-01

Sir David Cuthbertson was the first to define metabolic alterations in post-aggression syndrome (PAS). From basic measurements of nitrogen loss and total protein synthesis/degradation, the current research has moved to genomics, proteomics and metabolomics. In this respect, first evidence was accumulated for the influence of acute catabolism, immobilisation by bed rest and sarcopenia of old age on the muscle-cell genome and proteome. Moreover, in post-aggression syndrome specific amino acids such as glutamine, arginine, glycine, taurine, tryptophan and cysteine are used for cell and immune modulation. Our laboratory has focused on the regulative capacity of glutamine. Glutamine deficiency as found in post-aggression syndrome reduces lymphocyte proliferation, alters monocyte/macrophage activity, decreases the formation of heat-shock proteins, stimulates cell apoptosis, shifts the cellular redox potential by altering the glutathione synthesis and increases the activity of the AMPK system. Investigating the molecular effect of glutamine on Hsp 70 induction, we tested the glutamine dependence on the formation of transfer-RNA and of heat-shock factor 1 (HSF 1), and on transcription and translation of Hsp 70. We could demonstrate that glutamine stabilises the mRNA of Hsp 70 thereby prolonging its half-life. The lecture also discusses the principal molecular targets of administered arginine, glycine, cysteine, taurine and tryptophan.

The effect of taurine and enriched environment on behaviour, memory and hippocampus of diabetic rats.

PubMed

Rahmeier, Francine Luciano; Zavalhia, Lisiane Silveira; Tortorelli, Lucas Silva; Huf, Fernanda; Géa, Luiza Paul; Meurer, Rosalva Thereza; Machado, Aryadne Cardoso; Gomez, Rosane; Fernandes, Marilda da Cruz

2016-09-06

Diabetes mellitus (DM) has been studied recently as a major cause of cognitive deficits, memory and neurodegenerative damage. Taurine and enriched environment have stood out for presenting neuroprotective and stimulating effects that deserve further study. In this paper, we examined the effects of taurine and enriched environment in the context of diabetes, evaluating effects on behaviour, memory, death and cellular activity. Eighty-eight Wistar rats were divided into 2 groups (E=enriched environment; C=standard housing). Some animals (24/group) underwent induction of diabetes, and within each group, some animals (half of diabetics (D) and half of non-diabetics (ND)/group) were treated for 30days with taurine (T). Untreated animals received saline (S). In total, there were eight subgroups: DTC, DSC, NDTC, NDSC, DTE, DSE, NDTE and NDSE. During the experiment, short-term memory was evaluated. After 30th day of experiment, the animals were euthanized and was made removal of brains used to immunohistochemistry procedures for GFAP and cleaved caspase-3. As a result, we observed that animals treated with taurine showed better performance in behavioural and memory tasks, and the enriched environment had positive effects, especially in non-diabetic animals. Furthermore, taurine and enriched environment seemed to be able to interfere with neuronal apoptosis and loss of glial cells, and in some instances, these two factors seemed to have synergistic effects. From these data, taurine and enriched environment may have important neurostimulant and neuroprotective effects. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Effect of taurine supplementation on fat and energy absorption in cystic fibrosis.

PubMed Central

De Curtis, M; Santamaria, F; Ercolini, P; Vittoria, L; De Ritis, G; Garofalo, V; Ciccimarra, F

1992-01-01

In 10 children with cystic fibrosis and persisting steatorrhoea, supplementation with taurine (30-40 mg/kg/day) was given for two months as an adjunct to the usual pancreatic enzyme treatment. A three day fat and energy balance was performed in patients with cystic fibrosis, before and after the supplementation, and in seven healthy controls who did not receive taurine. Faecal fat was measured by a gravimetric method and stool energy was determined using a bomb calorimeter. Patients with cystic fibrosis, before and after taurine, and healthy controls received the same fat and energy intake (calculated by a dietitian). In patients with cystic fibrosis taurine did not produce any improvement of steatorrhoea (mean (SD) faecal fat 8.7 (3.3) v 11.2 (7.0) g/day, respectively before and after the supplementation), of faecal energy loss (0.978 (0.468) v 1.133 (0.539) MJ/day), of faecal fat expressed as percent of fat intake (13.4 (5.6) v 15.1 (9.8)%), and of faecal energy expressed as percent of energy intake (9.9 (3.6) v 11.2 (5.7)%). Healthy controls had significant lower fat (3.5 (2.3) g/day) and energy 0.576 (0.355) MJ/day faecal losses. In conclusion, taurine failed to decrease significantly fat and energy losses. Our study does not support the use of taurine supplementation in the nutritional management of cystic fibrosis. PMID:1417050

L-Cysteine metabolism and its nutritional implications.

PubMed

Yin, Jie; Ren, Wenkai; Yang, Guan; Duan, Jielin; Huang, Xingguo; Fang, Rejun; Li, Chongyong; Li, Tiejun; Yin, Yulong; Hou, Yongqing; Kim, Sung Woo; Wu, Guoyao

2016-01-01

L-Cysteine is a nutritionally semiessential amino acid and is present mainly in the form of L-cystine in the extracellular space. With the help of a transport system, extracellular L-cystine crosses the plasma membrane and is reduced to L-cysteine within cells by thioredoxin and reduced glutathione (GSH). Intracellular L-cysteine plays an important role in cellular homeostasis as a precursor for protein synthesis, and for production of GSH, hydrogen sulfide (H(2)S), and taurine. L-Cysteine-dependent synthesis of GSH has been investigated in many pathological conditions, while the pathway for L-cysteine metabolism to form H(2)S has received little attention with regard to prevention and treatment of disease in humans. The main objective of this review is to highlight the metabolic pathways of L-cysteine catabolism to GSH, H(2)S, and taurine, with special emphasis on therapeutic and nutritional use of L-cysteine to improve the health and well-being of animals and humans. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Inhibiting the photosensitized oxidation of anthracene and tryptophan by means of natural antioxidants

NASA Astrophysics Data System (ADS)

Aksenova, N. A.; Vyzhlova, E. N.; Malinovskaya, V. V.; Parfenov, V. V.; Solov'eva, A. B.; Timashev, P. S.

2013-08-01

It is shown that model reactions of photosensitized oxidation of anthracene and tryptophan can be used for evaluation and comparison of antioxidant activity of various classes of compounds. Inhibition of the oxidation of substrates in the presence of the familiar antioxidants tocopherol (vitamin E), ascorbic acid (vitamin C), and mixtures of these vitamins with methionine, and in the presence of reputed antioxidants dihydroquercetin and taurine, are considered. It is concluded that all of the above compounds except for taurine have antioxidant properties; i.e., they reduce the rate constants of the photosensitized oxidation of anthracene and tryptophan. It is found that the inhibition of oxidation is associated with the interaction between antioxidants and singlet oxygen. Analysis of the kinetic dependences of the photosensitized oxidation of substrates in the presence of antioxidants reveals that a mixture of vitamins inhibits the process most efficiently, and inhibition occurs at the initial stages due to more active interaction between singlet oxygen and vitamin C

Sulfur in human nutrition and applications in medicine.

PubMed

Parcell, Stephen

2002-02-01

Because the role of elemental sulfur in human nutrition has not been studied extensively, it is the purpose of this article to emphasize the importance of this element in humans and discuss the therapeutic applications of sulfur compounds in medicine. Sulfur is the sixth most abundant macromineral in breast milk and the third most abundant mineral based on percentage of total body weight. The sulfur-containing amino acids (SAAs) are methionine, cysteine, cystine, homocysteine, homocystine, and taurine. Dietary SAA analysis and protein supplementation may be indicated for vegan athletes, children, or patients with HIV, because of an increased risk for SAA deficiency in these groups. Methylsulfonylmethane (MSM), a volatile component in the sulfur cycle, is another source of sulfur found in the human diet. Increases in serum sulfate may explain some of the therapeutic effects of MSM, DMSO, and glucosamine sulfate. Organic sulfur, as SAAs, can be used to increase synthesis of S-adenosylmethionine (SAMe), glutathione (GSH), taurine, and N-acetylcysteine (NAC). MSM may be effective for the treatment of allergy, pain syndromes, athletic injuries, and bladder disorders. Other sulfur compounds such as SAMe, dimethylsulfoxide (DMSO), taurine, glucosamine or chondroitin sulfate, and reduced glutathione may also have clinical applications in the treatment of a number of conditions such as depression, fibromyalgia, arthritis, interstitial cystitis, athletic injuries, congestive heart failure, diabetes, cancer, and AIDS. Dosages, mechanisms of action, and rationales for use are discussed. The low toxicological profiles of these sulfur compounds, combined with promising therapeutic effects, warrant continued human clinical trails.

Investigation on the adsorption characteristics of sodium benzoate and taurine on gold nanoparticle film by ATR-FTIR spectroscopy.

PubMed

Kumar, Naveen; Thomas, S; Tokas, R B; Kshirsagar, R J

2014-01-24

Fourier transform infrared (FTIR) spectroscopic studies of sodium benzoate and taurine adsorbed on gold nanoparticle (AuNp) film on silanised glass slides have been studied by attenuated total reflection technique (ATR). The surface morphology of the AuNp films has been measured by Atomic Force Microscopy. The ATR spectra of sodium benzoate and taurine deposited on AuNp film are compared with ATR spectra of their powdered bulk samples. A new red-shifted band appeared along with the symmetric and asymmetric stretches of carboxylate group of sodium benzoate leading to a broadening of the above peaks. Similar behavior is also seen in the case of symmetric and asymmetric stretches of sulphonate group of taurine. The results indicate presence of both chemisorbed and physisorbed layers of both sodium benzoate and taurine on the AuNp film with bottom layer chemically bound to AuNp through carboxylate and sulphonate groups respectively. Copyright © 2013 Elsevier B.V. All rights reserved.

Na(+)-dependent transport of taurine is found only on the abluminal membrane of the blood-brain barrier.

PubMed

Rasgado-Flores, Hector; Mokashi, Ashwini; Hawkins, Richard A

2012-01-01

Luminal and abluminal plasma membranes were isolated from bovine brain microvessels and used to identify and characterize Na(+)-dependent and facilitative taurine transport. The calculated transmembrane potential was -59 mV at time 0; external Na(+) (or choline under putative zero-trans conditions) was 126 mM (T=25 °C). The apparent affinity constants of the taurine transporters were determined over a range of taurine concentrations from 0.24 μM to 11.4 μM. Abluminal membranes had both Na(+)-dependent taurine transport as well as facilitative transport while luminal membranes only had facilitative transport. The apparent K(m) for facilitative and Na(+)-dependent taurine transport were 0.06±0.02 μM and 0.7±0.1 μM, respectively. The Na(+)-dependent transport of taurine was voltage dependent over the range of voltages studied (-25 to -101 mV). The transport was over 5 times greater at -101 mV compared to when V(m) was -25 mV. The sensitivity to external osmolality of Na(+)-dependent transport was studied over a range of osmolalities (229 to 398 mOsm/kg H(2)O) using mannitol as the osmotic agent to adjust the osmolality. For these experiments the concentration of Na(+) was maintained constant at 50mM, and the calculated transmembrane potential was -59 mV. The Na(+)-dependent transport system was sensitive to osmolality with the greatest rate observed at 229 mOsm/kg H(2)O. Copyright © 2011 Elsevier Inc. All rights reserved.

Effects of S-Adenosylmethionine and Its Combinations With Taurine and/or Betaine on Glutathione Homeostasis in Ethanol-induced Acute Hepatotoxicity

PubMed Central

Lee, Seo Yeon; Ko, Kwang Suk

2016-01-01

Background Exposure to ethanol abuse and severe oxidative stress are risk factors for hepatocarcinoma. The aim of this study was to evaluate the effects of S-adenosylmethionine (SAMe) and its combinations with taurine and/or betaine on the level of glutathione (GSH), a powerful antioxidant in the liver, in acute hepatotoxicity induced by ethanol. Methods To examine the effects of SAMe and its combinations with taurine and/or betaine on ethanol-induced hepatotoxicity, AML12 cells and C57BL/6 mice were pretreated with SAMe, taurine, and/or betaine, followed by ethanol challenge. Cell viability was detected with an MTT assay. GSH concentration and mRNA levels of GSH synthetic enzymes were measured using GSH reductase and quantitative real-time reverse transcriptase-PCR. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities were measured with commercially available kits. Results Pretreatment of SAMe, with or without taurine and/or betaine, attenuated decreases in GSH levels and mRNA expression of the catalytic subunit of glutamate-cysteine ligase (GCL), the rate-limiting enzyme for GSH synthesis, in ethanol-treated cells and mice. mRNA levels of the modifier subunit of GCL and glutathione synthetase were increased in mice treated with SAMe combinations. SAMe, taurine, and/or betaine pretreatment restored serum ALT and AST levels to control levels in the ethanol-treated group. Conclusions Combinations of SAMe with taurine and/or betaine have a hepatoprotective effect against ethanol-induced liver injury by maintaining GSH homeostasis. PMID:27722142

Characteristics of taurine release in slices from adult and developing mouse brain stem.

PubMed

Saransaari, P; Oja, S S

2006-07-01

Taurine has been thought to function as a regulator of neuronal activity, neuromodulator and osmoregulator. Moreover, it is essential for the development and survival of neural cells and protects them under cell-damaging conditions. Taurine is also involved in many vital functions regulated by the brain stem, including cardiovascular control and arterial blood pressure. The release of taurine has been studied both in vivo and in vitro in higher brain areas, whereas the mechanisms of release have not been systematically characterized in the brain stem. The properties of release of preloaded [(3)H]taurine were now characterized in slices prepared from the mouse brain stem from developing (7-day-old) and young adult (3-month-old) mice, using a superfusion system. In general, taurine release was found to be similar to that in other brain areas, consisting of both Ca(2+)-dependent and Ca(2+)-independent components. Moreover, the release was mediated by Na(+)-, Cl(-)-dependent transporters operating outwards, as both Na(+)-free and Cl(-) -free conditions greatly enhanced it. Cl(-) channel antagonists and a Cl(-) transport inhibitor reduced the release at both ages, indicating that a part of the release occurs through ion channels. Protein kinases appeared not to be involved in taurine release in the brain stem, since substances affecting the activity of protein kinase C or tyrosine kinase had no significant effects. The release was modulated by cAMP second messenger systems and phospholipases at both ages. Furthermore, the metabotropic glutamate receptor agonists likewise suppressed the K(+)-stimulated release at both ages. In the immature brain stem, the ionotropic glutamate receptor agonists N-methyl-D-aspartate (NMDA) and 2-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) potentiated taurine release in a receptor-mediated manner. This could constitute an important mechanism against excitotoxicity, protecting the brain stem under cell-damaging conditions.

TRIGLYCERIDES, ATHEROSCLEROSIS, AND CARDIOVASCULAR OUTCOME STUDIES: FOCUS ON OMEGA-3 FATTY ACIDS.

PubMed

Handelsman, Yehuda; Shapiro, Michael D

2017-01-01

To provide an overview of the roles of triglycerides and triglyceride-lowering agents in atherosclerosis in the context of cardiovascular outcomes studies. We reviewed the published literature as well as ClinicalTrials.gov entries for ongoing studies. Despite improved atherosclerotic cardiovascular disease (ASCVD) outcomes with statin therapy, residual risk remains. Epidemiologic data and recent genetic insights provide compelling evidence that triglycerides are in the causal pathway for the development of atherosclerosis, thereby renewing interest in targeting triglycerides to improve ASCVD outcomes. Fibrates, niacin, and omega-3 fatty acids (OM3FAs) are three classes of triglyceride-lowering drugs. Outcome studies with triglyceride-lowering agents have been inconsistent. With regard to OM3FAs, the JELIS study showed that eicosapentaenoic acid (EPA) significantly reduced major coronary events in statin-treated hypercholesterolemic patients. Regarding other agents, extended-release niacin and fenofibrate are no longer recommended as statin add-on therapy (by some guidelines, though not all) because of the lack of convincing evidence from outcome studies. Notably, subgroup analyses from the outcome studies have generated the hypothesis that triglyceride lowering may provide benefit in statin-treated patients with persistent hypertriglyceridemia. Two ongoing OM3FA outcome studies (REDUCE-IT and STRENGTH) are testing this hypothesis in high-risk, statin-treated patients with triglyceride levels of 200 to 500 mg/dL. There is consistent evidence that triglycerides are in the causal pathway of atherosclerosis but inconsistent evidence from cardiovascular outcomes studies as to whether triglyceride-lowering agents reduce cardiovascular risk. Ongoing outcomes studies will determine the role of triglyceride lowering in statin-treated patients with high-dose prescription OM3FAs in terms of improved ASCVD outcomes. AACE = American Association of Clinical Endocrinologists ACCORD = Action to Control Cardiovascular Risk in Diabetes AIM-HIGH = Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides: Impact on Global Health Outcomes apo = apolipoprotein ASCEND = A Study of Cardiovascular Events in Diabetes ASCVD = atherosclerotic cardiovascular disease BIP = Bezafibrate Infarction Prevention CHD = coronary heart disease CI = confidence interval CV = cardiovascular CVD = cardiovascular disease DHA = docosahexaenoic acid DO-IT = Diet and Omega-3 Intervention Trial EPA = eicosapentaenoic acid FIELD = Fenofibrate Intervention and Event Lowering in Diabetes GISSI-HF = GISSI-Heart Failure HDL-C = high-density-lipoprotein cholesterol HPS2-THRIVE = Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events HR = hazard ratio JELIS = Japan Eicosapentaenoic Acid Lipid Intervention Study LDL = low-density lipoprotein LDL-C = low-density-lipoprotein cholesterol MI = myocardial infarction OM3FAs = omega-3 fatty acids VITAL = Vitamin D and Omega-3 Trial.

Design of lipid-based formulations for oral administration of poorly water-soluble drug fenofibrate: effects of digestion.

PubMed

Mohsin, Kazi

2012-06-01

Lipid-based drug carriers are likely to have influence on bioavailability through enhanced solubilization of the drug in the gastrointestinal tract. The study was designed to investigate the lipid formulation digestibility in the simulated gastro intestinal media. Fenofibrate was formulated in representative Type II, IIIA, IIIB and IV self-emulsifying/microemulsifying lipid delivery systems (SEDDS and SMEDDS designed for oral administration) using various medium-chain glyceride components, non-ionic surfactants and cosolvents as excipients. Soybean oil was used only as an example of long-chain triglycerides to compare the effects of formulation with their counterparts. The formulations were subjected to in vitro digestion specifically to predict the fate of the drug in the gastro intestinal tract after exposure of the formulation to pancreatic enzymes and bile. In vitro digestion experiments were carried out using a pH-stat maintained at pH 7.5 for 30 min using intestinal fluids simulating the fed and fasted states. The digestion rate was faster and almost completed in Type II and IIIA systems. Most of the surfactants used in the studies are digestible. However, the high concentration of surfactant and/or cosolvent used in Type IIIB or IV systems lowered the rate of digestion. The digestion of medium-chain triglycerides was faster than long-chain triglycerides, but kept comparatively less drug in the post digestion products. Medium-chain mixed glycerides are good solvents for fenofibrate as rapidly digested but to improve fenofibrate concentration in post digestion products the use of long-chain mixed glycerides are suggested for further investigations.

Atorvastatin and fenofibrate increase apolipoprotein AV and decrease triglycerides by up-regulating peroxisome proliferator-activated receptor-α

PubMed Central

Huang, Xian-sheng; Zhao, Shui-ping; Bai, Lin; Hu, Min; Zhao, Wang; Zhang, Qian

2009-01-01

Background and purpose: Combining statin and fibrate in clinical practice provides a greater reduction of triglycerides than either drug given alone, but the mechanism for this effect is poorly understood. Apolipoprotein AV (apoAV) has been implicated in triglyceride metabolism. This study was designed to investigate the effect of the combination of statin and fibrate on apoAV and the underlying mechanism(s). Experimental approach: Hypertriglyceridaemia was induced in rats by giving them 10% fructose in drinking water for 2 weeks. They were then treated with atorvastatin, fenofibrate or the two agents combined for 4 weeks, and plasma triglyceride and apoAV measured. We also tested the effects of these two agents on triglycerides and apoAV in HepG2 cells in culture. Western blot and reverse transcription polymerase chain reaction was used to measure apoAV and peroxisome proliferator-activated receptor-α (PPARα) expression. Key results: The combination of atorvastatin and fenofibrate resulted in a greater decrease in plasma triglycerides and a greater increase in plasma and hepatic apoAV than either agent given alone. Hepatic expression of the PPARα was also more extensively up-regulated in rats treated with the combination. A similar, greater increase in apoAV and a greater decrease in triglycerides were observed following treatment of HepG2 cells pre-exposed to fructose), with the combination. Adding an inhibitor of PPARα (MK886) abolished the effects of atorvastatin on HepG2 cells. Conclusions and implications: A combination of atorvastatin and fenofibrate increased apoAV and decreased triglycerides through up-regulation of PPARα. PMID:19694729

[Plasma metabonomics study of ischemic cerebral apoplexy rats treated with Tongsaimai pellets].

PubMed

Tu, Jiayu; A, Jiye; Wang, Guangji; Wen, Hongmei; Wang, Aiyun; Di, Liuqing; Cao, Bei; Liu, Linsheng

2012-04-01

To observe abnormal metabolic changes caused by ischemic cerebral apoplexy and the regulating action of Tongsaimai pellets on abnormal metabolism by analyzing the change of small molecules in plasma of ischemic cerebral apoplexy rat. To find the potential biomarkers, and to explore metabolic mechanisms of Tongsaimai pellets. Rat models of middle cerebral artery occlusion was established with electric coagulation, and rats were divided into 4 groups, model group, sham-operation group, Tongsaimai pellets group and positive control group. Tongsaimai pellets and positive control group were orally administrated by 13.2 g x kg(-1) x d(-1) of crude drugs and 32 mg x kg(-1) x d(-1) of Nimodipine respectively, m odel and sham-operation group by equal volume of distilled water for a week. Plasma of model and sham-operation group were collected, and plasma of Tongsaimai pellets and positive control group were collected on the 1st, 3rd , 7th day after administration. Endogenous metabolites of four groups were determined with GC-MS. Partial least squares discriminant analysis (PLS-DA) was applied to analyze multivariate data and set up model, and T-test was used in significant statistical analysis. Compared with sham-operation group rats, pyruvic acid, taurine and hydroxyproline obviously increased in model group rats, while lactic acid, glyceric acid, aminomalonic acid, fructose, tryptophan and leucine significantly decreased, so these metabolites were potential metabolic biomarkers. These endogenous metabolites except taurine got restoration in Tongsaimai group rats. Abnormal metabolite level in plasma can be certainly recovered by Tongsaimai pellets, and the treatment of Tongsaimai pellets can be connected with the regulation of related metabolic pathways.

The metabolic disturbances of isoproterenol induced myocardial infarction in rats based on a tissue targeted metabonomics.

PubMed

Liu, Yue-tao; Jia, Hong-mei; Chang, Xing; Ding, Gang; Zhang, Hong-wu; Zou, Zhong-Mei

2013-11-01

Myocardial infarction (MI) is a leading cause of morbidity and mortality but the precise mechanism of its pathogenesis remains obscure. To achieve the most comprehensive screening of the entire metabolome related to isoproterenol (ISO) induced-MI, we present a tissue targeted metabonomic study using an integrated approach of ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF MS) and proton nuclear magnetic resonance (1H NMR). Twenty-two metabolites were detected as potential biomarkers related to the formation of MI, and the levels of pantothenic acid (), lysoPC(18:0) (), PC(18:4(6Z,9Z,12Z,15Z)/18:0) (), taurine (), lysoPC(20:3(8Z,11Z,14Z)) (), threonine (), alanine (), creatine (), phosphocreatine (), glucose 1-phosphate (), glycine (), xanthosine (), creatinine () and glucose () were decreased significantly, while the concentrations of histamine (), L-palmitoylcarnitine (), GSSG (), inosine (), arachidonic acid (), linoelaidic acid (), 3-methylhistamine () and glycylproline () were increased significantly in the MI rats compared with the control group. The identified potential biomarkers were involved in twelve metabolic pathways and achieved the most entire metabolome contributing to the injury of the myocardial tissue. Five pathways, including taurine and hypotaurine metabolism, glycolysis, arachidonic acid metabolism, glycine, serine and threonine metabolism and histidine metabolism, were significantly influenced by ISO-treatment according to MetPA analysis and suggested that the most prominent changes included inflammation, interference of calcium dynamics, as well as alterations of energy metabolism in the pathophysiologic process of MI. These findings provided a unique perspective on localized metabolic information of ISO induced-MI, which gave us new insights into the pathogenesis of MI, discovery of targets for clinical diagnosis and treatment.

The essential oil of bergamot enhances the levels of amino acid neurotransmitters in the hippocampus of rat: implication of monoterpene hydrocarbons.

PubMed

Morrone, Luigi A; Rombolà, Laura; Pelle, Cinzia; Corasaniti, Maria T; Zappettini, Simona; Paudice, Paolo; Bonanno, Giambattista; Bagetta, Giacinto

2007-04-01

The effects of bergamot essential oil (BEO) on the release of amino acid neurotransmitters in rat hippocampus have been studied by in vivo microdialysis and by in vitro superfusion of isolated nerve terminals. Intraperitoneal administration of BEO (100microl/kg) significantly elevated the extracellular concentration of aspartate, glycine and taurine in a Ca(2+)-dependent manner. A dose-relation study generated a bell-shaped curve. When perfused into the hippocampus via the dialysis probe (20microl/20min), BEO produced a significant increase of extracellular aspartate, glycine, taurine as well as of GABA and glutamate. The augmentation of all amino acids was Ca(2+)-independent. Focally injected 1:1 diluted BEO preferentially caused extracellular increase of glutamate. Interestingly, this release appeared to be strictly Ca(2+)-dependent. BEO concentration-dependently enhanced the release of [(3)H]D-aspartate from superfused hippocampal synaptosomes. Similar results were obtained by monitoring the BEO-evoked release of endogenous glutamate. At relatively high concentrations, the BEO-induced [(3)H]d-aspartate release was almost entirely prevented by the glutamate transporter blocker dl-threo-beta-benzyloxyaspartic acid (DL-TBOA) and was Ca(2+)-independent. At relatively low concentrations the release of [(3)H]D-aspartate was only in part ( approximately 50%) DL-TBOA-sensitive and Ca(2+)-independent; the remaining portion of release was dependent on extracellular Ca(2+). Interestingly, the monoterpene hydrocarbon-free fraction of the essential oil appeared to be inactive while the bergapten-free fraction superimposed the releasing effect of BEO supporting the deduction that psoralens may not be implicated. To conclude, BEO contains into its volatile fraction still unidentified monoterpene hydrocarbons able to stimulate glutamate release by transporter reversal and/or by exocytosis, depending on the dose administered.

Effect of proteolysis index level on instrumental adhesiveness, free amino acids content and volatile compounds profile of dry-cured ham.

PubMed

Pérez-Santaescolástica, C; Carballo, J; Fulladosa, E; Garcia-Perez, José V; Benedito, J; Lorenzo, J M

2018-05-01

Defective textures in dry-cured ham are a common problem that causes important economic losses in the ham industry. An increase of proteolysis during the dry-cured ham processing may lead to high adhesiveness and consumer rejection of the product. Therefore, the influence of proteolysis index (PI) on instrumental adhesiveness, free amino acids and volatile profile of dry-cured ham was assessed. Two hundred Spanish dry-cured ham units were firstly classified according to their PI: low PI (<32%), medium PI (32-36%) and high PI (>36%). Instrumental adhesiveness was affected by PI, showing the lowest values in the batch with low PI. Significant differences (P < 0.05) among groups were found in six amino acids: serine, taurine, cysteine, methionine, isoleucine and leucine. The content of leucine, serine, methionine, and isoleucine significantly (P < 0.05) increased as the proteolysis index rose. However, taurine and cysteine content showed an opposite behaviour, reaching the highest values in the dry-cured hams with low PI. Significant differences (P < 0.001) in the total content of volatile compounds among ham groups were observed, with the highest concentration in the batch with low PI, and decreasing the concentration as the PI increased. Regarding the different chemical families of volatiles, the hydrocarbons (the main family), alcohols, aldehydes, ketones and acids were more abundant in the hams showing the lowest PI. Esters did not show significant differences among the three batches of hams studied. The present study demonstrated that, apart from the effect on the adhesiveness, an excessive proteolysis seems to be associated with negative effects on the taste and aroma of the dry-cured ham. Copyright © 2018 Elsevier Ltd. All rights reserved.

Profiling of Amino Acids and Their Derivatives Biogenic Amines Before and After Antipsychotic Treatment in First-Episode Psychosis.

PubMed

Leppik, Liisa; Kriisa, Kärt; Koido, Kati; Koch, Kadri; Kajalaid, Kärolin; Haring, Liina; Vasar, Eero; Zilmer, Mihkel

2018-01-01

Schizophrenia (SCH) is a heterogeneous disorder, deriving from a potential multitude of etiopathogenetic factors. During the past few years there has been an increasing interest in the role of circulating amino acids (AAs) and biogenic amines (BAs) in the pathophysiology of SCH. In the present study, we aimed to provide an insight into the potential role of alterations in levels of AAs and BAs as well as examine their more specific metabolic shifts in relation to early stage of SCH. We measured 21 AAs and 17 BAs in serum samples of patients with first-episode psychosis (FEP) before and after 7-month antipsychotic treatment in comparison to control subjects (CSs). According to multivariate analysis, antipsychotic-naïve FEP patients had significantly higher levels of taurine and spermine, whereas values of proline (Pro), alpha-aminoadipic acid (alpha-AAA), kynurenine (Kyn), valine (Val), tyrosine (Tyr), citrulline (Citr), tryptophan (Trp), and histidine (His) were diminished compared to CSs. Increased levels of taurine and spermine, as well as reduced levels of alpha-AAA and Kyn probably reflect the compromised function of N -methyl-D-aspartate (NMDA) receptors in patients. The decreased levels of Pro (AA modulating the function of glutamate decarboxylase) likely reflect the imbalanced function of gamma-aminobutyric acid (GABA) system in the brain of FEP patients. The alterations in ratio between Tyr and phenylalanine (Phe) can be taken as a sign of compromised function of dopaminergic system. These metabolic shifts were reinstated by 7-month antipsychotic treatment. Serum metabolic profiles can be regarded as important indicators to investigate clinical course of SCH and treatment response.

[Nutrition and biological value of food parts of a trade bivalve mollusk Anadara broughtoni].

PubMed

Tabakaeva, O V; Tabakaev, A V

2015-01-01

Currently, the human diet includes different new products of seafishing, including non-fish--bivalves and gastropods, holothurias, echinoderms, jellyfishes that demands careful studying of their chemical composition. The purpose of the study was to determine the nutritional and biological value of all soft parts of the burrowing bivalve MOLLUSK Anadara broughtoni from the Far East region. It was established thatfood parts of a bivalve were significantly flooded (water content--73.5-84.2%), with the minimum water content in the adductor and maximum in the mantle. Dry solids are presented by organic (89-93%) and mineral (7-11%) components. Organic components consist of protein (14.6-20.7%), lipids (1.8-2.3%), carbohydrates (2.1-2.6%). The analysis of amino-acid composition of proteins of food parts of the mollusk of Anadara broughtonishowed the presence of all essential amino acids with slight differences in their content depending on the localization of the protein. All edible parts have tryptophan as the limiting amino acid. Muscle proteins have maximum level of lysine, methionine, cysteine, phenylalanine and tyrosine; mantle proteins--leucine, isoleucine and threonine; adductor proteins--valine, phenylalanine, tyrosine, methionine and cysteine. Predominant nonessential amino acids forproteins of all food pieces are glycine, aspartic acid, glutamic acid, arginine. The coefficient of amino-acid score differences of adductor protein (31.7%) is less than the same of cloak by 3.7%. The indicator "biological value" is maximal for adductor (68.3%), but the differenceformuscle is only 0.83%. Mantle proteins are characterized by minimum biological value (64.6%). The coefficient of utility of amino acid composition of protein is maximalfor muscle (57.83%), and values for a cloak and an adductor differ slightly (55.81 and 55.96%). Taurine content in food parts of a mollusk Anadara broughtoni is rather high compared to with other bivalve mollusks of the Far East region. Muscle tissue has maximal content of taurine (569.3 +/- 28.2 mg/100 g wet tissue), adductor occupies an intermediate position (387.9 +/- 18.2 mg/100 g wet tissue) and the minimum content of this amino acid is characteristic for mantle (297.1 +/- 13.4 mg/100 g wet tissue).

Impact of beta-cyclodextrin and resistant starch on bile acid metabolism and fecal steroid excretion in regard to their hypolipidemic action in hamsters.

PubMed

Trautwein, E A; Forgbert, K; Rieckhoff, D; Erbersdobler, H F

1999-01-29

To examine the impact on bile acid metabolism and fecal steroid excretion as a mechanism involved in the lipid-lowering action of beta-cyclodextrin and resistant starch in comparison to cholestyramine, male golden Syrian hamsters were fed 0% (control), 8% or 12% of beta-cyclodextrin or resistant starch or 1% cholestyramine. Resistant starch, beta-cyclodextrin and cholestyramine significantly lowered plasma total cholesterol and triacylglycerol concentrations compared to control. Distinct changes in the bile acid profile of gallbladder bile were caused by resistant starch, beta-cyclodextrin and cholestyramine. While cholestyramine significantly reduced chenodeoxycholate independently of its taurine-glycine conjugation, beta-cyclodextrin and resistant starch decreased especially the percentage of taurochenodeoxycholate by -75% and -44%, respectively. As a result, the cholate:chenodeoxycholate ratio was significantly increased by 100% with beta-cyclodextrin and by 550% with cholestyramine while resistant starch revealed no effect on this ratio. beta-Cyclodextrin and resistant starch, not cholestyramine, significantly increased the glycine:taurine conjugation ratio demonstrating the predominance of glycine conjugated bile acids. Daily fecal excretion of bile acids was 4-times higher with 8% beta-cyclodextrin and 19-times with 1% cholestyramine compared to control. beta-Cyclodextrin and cholestyramine also induced a 2-fold increase in fecal neutral sterol excretion, demonstrating the sterol binding capacity of these two compounds. Resistant starch had only a modest effect on fecal bile acid excretion (80% increase) and no effect on excretion of neutral sterols, suggesting a weak interaction with intestinal steroid absorption. These data demonstrate the lipid-lowering potential of beta-cyclodextrin and resistant starch. An impaired reabsorption of circulating bile acids and intestinal cholesterol absorption leading to an increase in fecal bile acid and neutral sterol excretion is most likely the primary mechanism responsible for the lipid-lowering action of beta-cyclodextrin. In contrast, other mechanisms involving the alterations in the biliary bile acid profile or repressed hepatic lipogenesis, e.g., VLDL production, appear to be involved in the hypolipidemic effect of resistant starch.

Controlling Release of Integral Lipid Nanoparticles Based on Osmotic Pump Technology.

PubMed

Tian, Zhiqiang; Yu, Qin; Xie, Yunchang; Li, Fengqian; Lu, Yi; Dong, Xiaochun; Zhao, Weili; Qi, Jianping; Wu, Wei

2016-08-01

To achieve controlled release of integral nanoparticles by the osmotic pump strategy using nanostructured lipid carriers (NLCs) as model nanoparticles. NLCs was prepared by a hot-homogenization method, transformed into powder by lyophilization, and formulated into osmotic pump tablets (OPTs). Release of integral NLCs was visualized by live imaging after labeling with a water-quenching fluorescent probe. Effects of formulation variables on in vitro release characteristics were evaluated by measuring the model drug fenofibrate. Pharmacokinetics were studied in beagle dogs using the core tablet and a micronized fenofibrate formulation as references. NLCs are released through the release orifices of the OPTs as integral nanoparticles. Near zero-order kinetics can be achieved by optimizing the influencing variables. After oral administration, decreased C max and steady drug levels for as long as over 24 h are observed. NLC-OPTs show an oral bioavailability of the model drug fenofibrate similar to that of the core tablets, which is about 1.75 folds that of a fast-release formulation. Controlled release of integral NLCs is achieved by the osmotic pump strategy.

Body fluid levels of neuroactive amino acids in autism spectrum disorders: a review of the literature.

PubMed

Zheng, Hui-Fei; Wang, Wen-Qiang; Li, Xin-Min; Rauw, Gail; Baker, Glen B

2017-01-01

A review of studies on the body fluid levels of neuroactive amino acids, including glutamate, glutamine, taurine, gamma-aminobutyric acid (GABA), glycine, tryptophan, D-serine, and others, in autism spectrum disorders (ASD) is given. The results reported in the literature are generally inconclusive and contradictory, but there has been considerable variation among the previous studies in terms of factors such as age, gender, number of subjects, intelligence quotient, and psychoactive medication being taken. Future studies should include simultaneous analyses of a large number of amino acids [including D-serine and branched-chain amino acids (BCAAs)] and standardization of the factors mentioned above. It may also be appropriate to use saliva sampling to detect amino acids in ASD patients in the future-this is noninvasive testing that can be done easily more frequently than other sampling, thus providing more dynamic monitoring.

Determination of the prevalence of whole blood taurine in Irish wolfhound dogs with and without echocardiographic evidence of dilated cardiomyopathy.

PubMed

Vollmar, Andrea C; Fox, Philip R; Servet, Eric; Biourge, Vincent

2013-09-01

Taurine plays an important role in maintaining myocardial function. Irish wolfhound dogs (IW) are at risk for dilated cardiomyopathy (DCM), but a relationship between whole blood taurine (WBT) deficiency and DCM has not been established. Our aim was to determine prevalence of WBT deficiency in IW with and without DCM and assess its association with diet. 115 privately owned IW. Whole blood taurine was measured in IW that received cardiovascular examination. Dietary history was recorded; crude protein and energy intake were estimated. Forty-nine (42.6%) had DCM; 66 (57.4%) had no DCM. Dogs with DCM were older ([median; inter-quartile range or IQR] 5.3; 4.3, 6.2 years) than dogs without heart disease (3; 2, 4 years; P < 0.001). There was no significant relationship between WBT concentration and age (P = 0.64). Whole blood taurine was severely reduced (<130 nmol/mL) in 8 dogs (4 with and 4 without DCM) and moderately reduced (130-179.9 nmol/mL) in 32 dogs (12 with DCM and 20 without DCM). Follow up of dogs without DCM revealed that a higher proportion of dogs with any degree of WBT deficiency developed DCM later compared to dogs with normal WBT (P < 0.001). Whole blood taurine deficiency occurred in IW with and without DCM. Based on taurine measurement on a single occasion, there was no clear relationship between low WBT and presence of DCM in this population. Regardless of WBT, DCM affected predominantly older dogs, suggesting a relatively late onset disease in the IW. Copyright © 2013 Elsevier B.V. All rights reserved.

Hypothyroidism is a predisposing factor for fenofibrate-induced rhabdomyolysis--patient report and literature review.

PubMed

Satarasinghe, R L; Ramesh, R; Riyaaz, A A A; Gunarathne, P A K G; de Silva, A P

2007-01-01

A literature survey reveals that both lipid lowering drugs - statins and fibrates--and hypothyroidism are documented causes of muscle disorders including rhabdomyolysis leading to acute renal failure. We describe a case of fenofibrate monotherapy (Lipicard) induced dialysis dependent acute renal failure in an undiagnosed hypothyroid patient which is the first case to be reported from Sri Lanka. We strongly recommend that all patients who are receiving statins and/or fibrates should be screened for occult hypothyroidism which seems to aggravate the muscle damage due to the above drugs, with or without other risk factors.

RNAi screening of subtracted transcriptomes reveals tumor suppression by taurine-activated GABAA receptors involved in volume regulation

PubMed Central

van Nierop, Pim; Vormer, Tinke L.; Foijer, Floris; Verheij, Joanne; Lodder, Johannes C.; Andersen, Jesper B.; Mansvelder, Huibert D.; te Riele, Hein

2018-01-01

To identify coding and non-coding suppressor genes of anchorage-independent proliferation by efficient loss-of-function screening, we have developed a method for enzymatic production of low complexity shRNA libraries from subtracted transcriptomes. We produced and screened two LEGO (Low-complexity by Enrichment for Genes shut Off) shRNA libraries that were enriched for shRNA vectors targeting coding and non-coding polyadenylated transcripts that were reduced in transformed Mouse Embryonic Fibroblasts (MEFs). The LEGO shRNA libraries included ~25 shRNA vectors per transcript which limited off-target artifacts. Our method identified 79 coding and non-coding suppressor transcripts. We found that taurine-responsive GABAA receptor subunits, including GABRA5 and GABRB3, were induced during the arrest of non-transformed anchor-deprived MEFs and prevented anchorless proliferation. We show that taurine activates chloride currents through GABAA receptors on MEFs, causing seclusion of cell volume in large membrane protrusions. Volume seclusion from cells by taurine correlated with reduced proliferation and, conversely, suppression of this pathway allowed anchorage-independent proliferation. In human cholangiocarcinomas, we found that several proteins involved in taurine signaling via GABAA receptors were repressed. Low GABRA5 expression typified hyperproliferative tumors, and loss of taurine signaling correlated with reduced patient survival, suggesting this tumor suppressive mechanism operates in vivo. PMID:29787571

Vitamin B12–dependent taurine synthesis regulates growth and bone mass

PubMed Central

Roman-Garcia, Pablo; Quiros-Gonzalez, Isabel; Mottram, Lynda; Lieben, Liesbet; Sharan, Kunal; Wangwiwatsin, Arporn; Tubio, Jose; Lewis, Kirsty; Wilkinson, Debbie; Santhanam, Balaji; Sarper, Nazan; Clare, Simon; Vassiliou, George S.; Velagapudi, Vidya R.; Dougan, Gordon; Yadav, Vijay K.

2014-01-01

Both maternal and offspring-derived factors contribute to lifelong growth and bone mass accrual, although the specific role of maternal deficiencies in the growth and bone mass of offspring is poorly understood. In the present study, we have shown that vitamin B12 (B12) deficiency in a murine genetic model results in severe postweaning growth retardation and osteoporosis, and the severity and time of onset of this phenotype in the offspring depends on the maternal genotype. Using integrated physiological and metabolomic analysis, we determined that B12 deficiency in the offspring decreases liver taurine production and associates with abrogation of a growth hormone/insulin-like growth factor 1 (GH/IGF1) axis. Taurine increased GH-dependent IGF1 synthesis in the liver, which subsequently enhanced osteoblast function, and in B12-deficient offspring, oral administration of taurine rescued their growth retardation and osteoporosis phenotypes. These results identify B12 as an essential vitamin that positively regulates postweaning growth and bone formation through taurine synthesis and suggests potential therapies to increase bone mass. PMID:24911144

Electronic absorption spectral studies of Pr(III) chelates with some amino acids

NASA Astrophysics Data System (ADS)

Kachhawa, Chanchal; Solanki, Kanika; Bhandari, H. S.

2018-05-01

Investigations on Pr(III) systems with 1:1 metal-ligand stoichiometric ratio have been carried out in different solvents. β - Alanine, Taurine and anthranilic acid have been opted as ligands for the investigations. The Study is based on doped crystal phenomenon. The Slater-Condon, spin-orbit, nephelauxetic, bonding, Racah and Judd-Ofelt parameters have been explored during the study. Four bands for Pr(III) have been observed and recorded in the region 350 nm to 900nm. Partial regression method has been used for calculations. Use of computational chemistry has been explored in order to develop better and easier methods of calculations.

Quantification of 15 bile acids in lake charr feces by ultra-high performance liquid chromatography–tandem mass spectrometry

USGS Publications Warehouse

Li, Ke; Buchinger, Tyler J.; Bussy, Ugo; Fissette, Skye D.; Johnson, Nicholas; Li, Weiming

2015-01-01

Many fishes are hypothesized to use bile acids (BAs) as chemical cues, yet quantification of BAs in biological samples and the required methods remain limited. Here, we present an UHPLC–MS/MS method for simultaneous, sensitive, and rapid quantification of 15 BAs, including free, taurine, and glycine conjugated BAs, and application of the method to fecal samples from lake charr (Salvelinus namaycush). The analytes were separated on a C18 column with acetonitrile–water (containing 7.5 mM ammonium acetate and 0.1% formic acid) as mobile phase at a flow rate of 0.25 mL/min for 12 min. BAs were monitored with a negative electrospray triple quadrupole mass spectrometer (Xevo TQ-S™). Calibration curves of 15 BAs were linear over the concentration range of 1.00–5,000 ng/mL. Validation revealed that the method was specific, accurate, and precise. The method was applied to quantitative analysis of feces extract of fry lake charr and the food they were eating. The concentrations of analytes CA, TCDCA, TCA, and CDCA were 242.3, 81.2, 60.7, and 36.2 ng/mg, respectively. However, other taurine conjugated BAs, TUDCA, TDCA, and THDCA, were not detected in feces of lake charr. Interestingly, TCA and TCDCA were detected at high concentrations in food pellets, at 71.9 and 38.2 ng/mg, respectively. Application of the method to feces samples from lake charr supported a role of BAs as chemical cues, and will enhance further investigation of BAs as chemical cues in other fish species.

Metabolic remodeling of malignant gliomas for enhanced sensitization during radiotherapy: an in vitro study.

PubMed

Colen, Chaim B; Seraji-Bozorgzad, Navid; Marples, Brian; Galloway, Matthew P; Sloan, Andrew E; Mathupala, Saroj P

2006-12-01

To investigate a novel method to enhance radiosensitivity of gliomas via modification of metabolite flux immediately before radiotherapy. Malignant gliomas are highly glycolytic and produce copious amounts of lactic acid, which is effluxed to the tumor microenvironment via lactate transporters. We hypothesized that inhibition of lactic acid efflux would alter glioma metabolite profiles, including those that are radioprotective. H magnetic resonance spectroscopy (MRS) was used to quantify key metabolites, including those most effective for induction of low-dose radiation-induced cell death. We inhibited lactate transport in U87-MG gliomas with alpha-cyano-4-hydroxycinnamic acid (ACCA). Flow cytometry was used to assess induction of cell death in treated cells. Cells were analyzed by MRS after ACCA treatment. Control and treated cells were subjected to low-dose irradiation, and the surviving fractions of cells were determined by clonogenic assays. MRS revealed changes to intracellular lactate on treatment with ACCA. Significant decreases in the metabolites taurine, glutamate, glutathione, alanine, and glycine were observed, along with inversion of the choline/phosphocholine profile. On exposure to low-dose radiation, ACCA-pretreated U-87MG cells underwent rapid morphological changes, which were followed by apoptotic cell death. Inhibition of lactate efflux in malignant gliomas results in alterations of glycolytic metabolism, including decreased levels of the antioxidants taurine and glutathione and enhanced radiosensitivity of ACCA-treated cells. Thus, in situ application of lactate transport inhibitors such as ACCA as a novel adjunctive therapeutic strategy against glial tumors may greatly enhance the level of radiation-induced cell killing during a combined radio- and chemotherapeutic regimen.

[Biological and nutritional role of taurine and its derivatives on cellular and organic physiology].

PubMed

Cañas, P E; Valenzuela, A

1991-06-01

Several aspects about the biological role of taurine and its derivatives has been described in this work, especially in relation to humans. Some aspects related to the structure and function of the molecule in respect to its capacity as an osmoregulator and as an antioxidant are also analyzed. Moreover, the distribution changes on the biosynthesis phenomenon in some development stages as well as changes at the transport level, especially in some tissues where the concentration is increased several times with respect to plasmatic concentrations, are discussed. Some evidences exist as to the possibilities that taurine may be considered as a conditionally essential nutrient, particularly in some cases where it has been demonstrated that taurine and its derivatives have certain clinical and nutritional implications.

The cholesterol, fatty acid and triglyceride synthesis pathways regulated by site 1 protease (S1P) are required for efficient replication of severe fever with thrombocytopenia syndrome virus.

PubMed

Urata, Shuzo; Uno, Yukiko; Kurosaki, Yohei; Yasuda, Jiro

2018-06-12

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by the SFTS virus (SFTSV), which has a high mortality rate. Currently, no licensed vaccines or therapeutic agents have been approved for use against SFTSV infection. Here, we report that the cholesterol, fatty acid, and triglyceride synthesis pathways regulated by S1P is involved in SFTSV replication, using CHO-K1 cell line (SRD-12B) that is deficient in site 1 protease (S1P) enzymatic activity, PF-429242, a small compound targeting S1P enzymatic activity, and Fenofibrate and Lovastatin, which inhibit triglyceride and cholesterol synthesis, respectively. These results enhance our understanding of the SFTSV replication mechanism and may contribute to the development of novel therapies for SFTSV infection. Copyright © 2018. Published by Elsevier Inc.

Non-lipid effects of rosuvastatin-fenofibrate combination therapy in high-risk Asian patients with mixed hyperlipidemia.

PubMed

Lee, Sang-Hak; Cho, Kyoung-Im; Kim, Jang-Young; Ahn, Young Keun; Rha, Seung-Woon; Kim, Yong-Jin; Choi, Yun-Seok; Choi, Si Wan; Jeon, Dong Woon; Min, Pil-Ki; Choi, Dong-Ju; Baek, Sang Hong; Kim, Kwon Sam; Byun, Young Sup; Jang, Yangsoo

2012-03-01

The aim of this study is to compare the non-lipid effects of rosuvastatin-fenofibrate combination therapy with rosuvastatin monotherapy in high-risk Asian patients with mixed hyperlipidemia. A total of 236 patients were initially screened. After six weeks of diet and life style changes, 180 of these patients were randomly assigned to receive one of two regimens: rosuvastatin 10 mg plus fenofibrate 160 mg or rosuvastatin 10 mg. The primary outcome variables were the incidences of muscle or liver enzyme elevation. The patients were followed for 24 weeks during drug treatment and for an additional four weeks after drug discontinuation. The rates of the primary outcome variables were similar between the two groups (2.8% and 3.9% in the combination and the rosuvastatin groups, respectively, p=1.00). The combination group had more, but not significantly, common treatment-related adverse events (AEs) (13.3% and 5.6%, respectively) and drug discontinuation due to AEs (10.0% and 3.3%, respectively) than the rosouvastatin group. Combination therapy was associated with higher elevations in homocysteine, blood urea nitrogen, and serum creatinine, whereas elevation in alanine aminotransferase was greater in the rosuvastatin group. Leukocyte count and hemoglobin level decreased to a greater extent in the combination group. The combination group showed greater reductions in TG and elevation in HDL-cholesterol. In our study population, the rosuvastatin-fenofibrate combination resulted in comparable incidences of myo- or hepatotoxicity as rosuvastatin monotherapy. However, this combination may need to be used with caution in individuals with underlying pathologies such as renal dysfunction (NCT01414803). Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

The peroxisome proliferator-activated receptor alpha agonist fenofibrate has no effect on insulin sensitivity compared to atorvastatin in type 2 diabetes mellitus; a randomised, double-blind controlled trial.

PubMed

Black, R Neil A; Ennis, Cieran N; Young, Ian S; Hunter, Steven J; Atkinson, A Brew; Bell, Patrick M

2014-01-01

Assess insulin sensitivity after treatment with a selective PPAR-alpha agonist compared to an HMG CoA reductase inhibitor in human subjects with type 2 diabetes mellitus. Thirteen subjects with Type 2 diabetes mellitus were studied in a double-blind crossover design with 4-week placebo run-in and washout and 12-week treatment periods, randomised to micronised fenofibrate 267 mg or atorvastatin 10mg daily followed by the alternate drug in the second period. Insulin resistance was measured using the isoglycaemic hyperinsulinaemic clamp method with isotope dilution. Weight, physical activity and other medications did not change. Total cholesterol (mean +/- standard error) was 4.60+/-0.21 versus 3.9+/-0.22 mmol/L after fenofibrate and atorvastatin respectively, p<0.05. LDL was 2.70+/-0.19 versus 1.95+/-0.23 mmol/L, p<0.05 and triglyceride 1.64+/-0.23 versus 1.84+/-0.26 mmol/L, p<0.05. Insulin-stimulated whole-body glucose disposal (35.4+/-3.1 versus 33.2+/-3.0 μmol/kg/min) and nadir endogenous glucose production (6.2+/-1.4 versus 7.0+/-1.1 μmol/kg/min) revealed no significant differences in effects of the treatments. In human subjects with Type 2 diabetes mellitus there were characteristic differences in lipid profile changes but no difference in insulin sensitivity after treatment with micronised fenofibrate compared to atorvastatin. This study finds no evidence of increased insulin sensitivity using this selective PPAR-alpha agonist over a commonly used statin at these doses. Copyright © 2014 Elsevier Inc. All rights reserved.

Fenofibrate lowers atypical sphingolipids in plasma of dyslipidemic patients: A novel approach for treating diabetic neuropathy?

PubMed

Othman, Alaa; Benghozi, Renee; Alecu, Irina; Wei, Yu; Niesor, Eric; von Eckardstein, Arnold; Hornemann, Thorsten

2015-01-01

The condensation of palmitoyl-CoA and L-Serine is the first step in the de novo formation of sphingolipids and catalyzed by the serine-palmitoyltransferase (SPT). Besides other acyl-CoAs the SPT can also metabolize L-alanine and glycine, which forms an atypical category of neurotoxic 1-deoxy-sphingolipids (1-deoxySL). Several mutations in SPT are associated with pathologically increased 1-deoxySL levels, which cause the inherited sensory neuropathy HSAN1. 1-DeoxySL levels are also elevated in individuals with the metabolic syndrome and diabetes mellitus type II and seem to be involved in the pathology of the diabetic neuropathy. In previous studies, we observed a strong correlation between plasma 1-deoxySLs and triglycerides (TGs). We were therefore interested whether lowering plasma TG levels also affects plasma sphingolipid and in particular, 1-deoxySL levels. Sixty-six patients with dyslipidemia were treated for 6 wk with the TG-lowering drug fenofibrate (160 mg/d) or extended-release niacin (0.5 g/d for 3 wk, then 1 g/d) with 4 wk of washout between treatments. The sphingoid base profile was analyzed by liquid chromatography-mass spectrometry (LC-MS) before and after each treatment block. Fenofibrate significantly lowered 1-deoxySLs and other atypical sphingoid bases (P < .001) but had no effect on the typical sphingolipids. In contrast, extended-release niacin had no effect on 1-deoxySL levels although both treatments lowered plasma TG levels. The lowering of plasma 1-deoxySL levels by fenofibrate in dyslipidemic patients might be a novel therapeutic approach in the prevention and treatment of diabetic neuropathy. Copyright © 2015 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Comparative effectiveness of fish oil versus fenofibrate, gemfibrozil, and atorvastatin on lowering triglyceride levels among HIV-infected patients in routine clinical care

PubMed Central

Muñoz, Monica A; Liu, Wei; Delaney, Joseph AC; Brown, Elizabeth; Mugavero, Michael J; Mathews, W Chris; Napravnik, Sonia; Willig, James H; Eron, Joseph J; Hunt, Peter W; Kahn, James O; Saag, Michael S; Kitahata, Mari M; Crane, Heidi M

2014-01-01

Objective The goal of this study was to compare the effectiveness of fish oil, fenofibrate, gemfibrozil, and atorvastatin on reducing triglyceride (TG) levels among a large cohort of HIV-infected patients in clinical care. Design Retrospective observational cohort study Methods The primary endpoint was absolute change in TG levels measured using the last TG value pre-treatment and the first TG value post-treatment. A pre-post quasi-experimental design was used to estimate the change in TG due to initiating fish oil. Linear regression models examined the comparative effectiveness of treatment with fish oil versus gemfibrozil, fenofibrate, or atorvastatin for TG reduction. Models were adjusted for baseline differences in age, sex, race, CD4+ cell count, diabetes, body mass index, protease inhibitor use, and time between TG measures. Results A total of 493 patients (mean age 46 years; 95% male) were included (46 receiving gemfibrozil, 80 fenofibrate, 291 atorvastatin, 76 fish oil) with a mean baseline TG of 347 mg/dL. New use of fish oil decreased TG (ΔTG -45 mg/dL 95% Confidence interval (CI):-80 to -11) in the pre-post study. Compared with fish oil (reference), fibrates were more effective (ΔTG -66; 95% CI:-120 to -12) in reducing TG levels, whereas atorvastatin was not (ΔTG -39; 95% CI:-86 to 9). Conclusion In HIV-infected patients in routine clinical care, fish oil is less effective than fibrates (but not atorvastatin) at lowering triglyceride values. Fish oil may still represent an attractive alternative for patients with moderately elevated triglycerides particularly among patients who may not want or tolerate fibrates. PMID:23892238

Comparative effectiveness of fish oil versus fenofibrate, gemfibrozil, and atorvastatin on lowering triglyceride levels among HIV-infected patients in routine clinical care.

PubMed

Muñoz, Monica A; Liu, Wei; Delaney, Joseph A C; Brown, Elizabeth; Mugavero, Michael J; Mathews, W Chris; Napravnik, Sonia; Willig, James H; Eron, Joseph J; Hunt, Peter W; Kahn, James O; Saag, Michael S; Kitahata, Mari M; Crane, Heidi M

2013-11-01

The goal of this study was to compare the effectiveness of fish oil, fenofibrate, gemfibrozil, and atorvastatin on reducing triglyceride (TG) levels among a large cohort of HIV-infected patients in clinical care. Retrospective observational cohort study. The primary endpoint was absolute change in TG levels measured using the last TG value pretreatment and the first TG value posttreatment. A pre-post quasi-experimental design was used to estimate the change in TG because of initiating fish oil. Linear regression models examined the comparative effectiveness of treatment with fish oil versus gemfibrozil, fenofibrate, or atorvastatin for TG reduction. Models were adjusted for baseline differences in age, sex, race, CD4⁺ cell count, diabetes, body mass index, protease inhibitor use, and time between TG measures. A total of 493 patients (mean age, 46 years; 95% male) were included (46 patients receiving gemfibrozil; 80, fenofibrate; 291, atorvastatin; and 76, fish oil) with a mean baseline TG of 347 mg/dL. New use of fish oil decreased TG [ΔTG, -45 mg/dL; 95% confidence interval (CI): -80 to -11] in the pre-post study. Compared with fish oil (reference), fibrates were more effective (ΔTG, -66; 95% CI: -120 to -12) in reducing TG levels, whereas atorvastatin was not (ΔTG, -39; 95% CI: -86 to 9). In HIV-infected patients in routine clinical care, fish oil is less effective than fibrates (but not atorvastatin) at lowering TG values. Fish oil may still represent an attractive alternative for patients with moderately elevated TGs, particularly among patients who may not want or tolerate fibrates.

Effects of clofibric acid on the biliary excretion of benoxaprofen glucuronide and taurine conjugate in rats.

PubMed

Okada, K; Kanoh, H; Mohri, K

2011-10-01

Benoxaprofen (BOP) is a 2-methyl propionic acid derivative with anti-inflammatory activity. BOP has an asymmetric carbon, and receives chiral inversion from R to S in vivo. BOP is metabolized to glucuronide (BOP-G) and taurine conjugate (BOP-T). The configuration of BOP-G is mainly S, and that of BOP-T is R. Chiral inversion of R to S of the propionic acid moiety and amino acid conjugation of carboxyl compounds proceed via an acyl CoA intermediate. It is known that fibrates, used in hyperlipidemia, induce acyl CoA synthetase and increase CoA concentration. We administered racemic BOP (10 mg/kg body weight) to rats (CFA+) pre-administered clofibric acid (CFA, 280 mg/kg/day), and studied BOP, BOP-G, and BOP-T enantiomer concentrations in plasma and bile up to 12 h after administration. The findings were compared with those in rats (CFA-) that had not received CFA. Furthermore, we studied the amounts of BOP-G enantiomer produced by glucuronidation in vitro using microsomes pretreated with CFA. The amounts of (S)-BOP-G in CFA+ rats were 2.7-fold larger than that in CFA- rats. Although (R)-BOP-T was excreted in CFA- rats, BOP-T could not be detected in CFA+ rats. Plasma clearance values of racemic BOP and (S)-BOP in CFA+ rats were 5-fold and 6-fold larger than those in CFA- rats, respectively. (S)-BOP-G formation activities were higher than (R)-BOP-G formation activities in both CFA+and CFA- microsomes. These findings suggest that CFA increases biliary excretion of (S)-BOP-G and facilitates plasma elimination of BOP, and further suggests that CFA predominantly induces chiral inversion to S rather than metabolic reaction to (R)-BOP-T, resulting in an increase of (S)-BOP-G.

Worldwide Patterns of Ancestry, Divergence, and Admixture in Domesticated Cattle

PubMed Central

Decker, Jared E.; McKay, Stephanie D.; Rolf, Megan M.; Kim, JaeWoo; Molina Alcalá, Antonio; Sonstegard, Tad S.; Hanotte, Olivier; Götherström, Anders; Seabury, Christopher M.; Praharani, Lisa; Babar, Masroor Ellahi; Correia de Almeida Regitano, Luciana; Yildiz, Mehmet Ali; Heaton, Michael P.; Liu, Wan-Sheng; Lei, Chu-Zhao; Reecy, James M.; Saif-Ur-Rehman, Muhammad; Schnabel, Robert D.; Taylor, Jeremy F.

2014-01-01

The domestication and development of cattle has considerably impacted human societies, but the histories of cattle breeds and populations have been poorly understood especially for African, Asian, and American breeds. Using genotypes from 43,043 autosomal single nucleotide polymorphism markers scored in 1,543 animals, we evaluate the population structure of 134 domesticated bovid breeds. Regardless of the analytical method or sample subset, the three major groups of Asian indicine, Eurasian taurine, and African taurine were consistently observed. Patterns of geographic dispersal resulting from co-migration with humans and exportation are recognizable in phylogenetic networks. All analytical methods reveal patterns of hybridization which occurred after divergence. Using 19 breeds, we map the cline of indicine introgression into Africa. We infer that African taurine possess a large portion of wild African auroch ancestry, causing their divergence from Eurasian taurine. We detect exportation patterns in Asia and identify a cline of Eurasian taurine/indicine hybridization in Asia. We also identify the influence of species other than Bos taurus taurus and B. t. indicus in the formation of Asian breeds. We detect the pronounced influence of Shorthorn cattle in the formation of European breeds. Iberian and Italian cattle possess introgression from African taurine. American Criollo cattle originate from Iberia, and not directly from Africa with African ancestry inherited via Iberian ancestors. Indicine introgression into American cattle occurred in the Americas, and not Europe. We argue that cattle migration, movement and trading followed by admixture have been important forces in shaping modern bovine genomic variation. PMID:24675901

Protein malnutrition blunts the increment of taurine transporter expression by a high-fat diet and impairs taurine reestablishment of insulin secretion.

PubMed

Branco, Renato Chaves Souto; Camargo, Rafael Ludemann; Batista, Thiago Martins; Vettorazzi, Jean Franciesco; Borck, Patrícia Cristine; Dos Santos-Silva, Junia Carolina Rebelo; Boschero, Antonio Carlos; Zoppi, Cláudio Cesar; Carneiro, Everardo Magalhães

2017-09-01

Taurine (Tau) restores β-cell function in obesity; however, its action is lost in malnourished obese rodents. Here, we investigated the mechanisms involved in the lack of effects of Tau in this model. C57BL/6 mice were fed a control diet (CD) (14% protein) or a protein-restricted diet (RD) (6% protein) for 6 wk. Afterward, mice received a high-fat diet (HFD) for 8 wk [CD + HFD (CH) and RD + HFD (RH)] with or without 5% Tau supplementation after weaning on their drinking water [CH + Tau (CHT) and RH + Tau (RHT)]. The HFD increased insulin secretion through mitochondrial metabolism in CH and RH. Tau prevented all those alterations in CHT only. The expression of the taurine transporter (Tau-T), as well as Tau content in pancreatic islets, was increased in CH but had no effect on RH. Protein malnutrition programs β cells and impairs Tau-induced restoration of mitochondrial metabolism and biogenesis. This may be associated with modulation of the expression of Tau-T in pancreatic islets, which may be responsible for the absence of effect of Tau in protein-malnourished obese mice.-Branco, R. C. S., Camargo, R. L., Batista, T. M., Vettorazzi, J. F., Borck, P. C., dos Santos-Silva, J. C. R., Boschero, A. C., Zoppi, C. C., Carneiro, E. M. Protein malnutrition blunts the increment of taurine transporter expression by a high-fat diet and impairs taurine reestablishment of insulin secretion. © FASEB.

Additional effects of taurine on the benefits of BCAA intake for the delayed-onset muscle soreness and muscle damage induced by high-intensity eccentric exercise.

PubMed

Ra, Song-Gyu; Miyazaki, Teruo; Ishikura, Keisuke; Nagayama, Hisashi; Suzuki, Takafumi; Maeda, Seiji; Ito, Masaharu; Matsuzaki, Yasushi; Ohmori, Hajime

2013-01-01

Taurine (TAU) has a lot of the biological, physiological, and pharmocological functions including anti-inflammatory and anti-oxidative stress. Although previous studies have appreciated the effectiveness of branched-chain amino acids (BCAA) on the delayed-onset muscle soreness (DOMS), consistent finding has not still convinced. The aim of this study was to examine the additional effect of TAU with BCAA on the DOMS and muscle damages after eccentric exercise. Thirty-six untrained male volunteers were equally divided into four groups, and ingested a combination with 2.0 g TAU (or placebo) and 3.2 g BCAA (or placebo), thrice a day, 2 weeks prior to and 4 days after elbow flexion eccentric exercise. Following the period after eccentric exercise, the physiological and blood biochemical markers for DOMS and muscle damage showed improvement in the combination of TAU and BCAA supplementation rather than in the single or placebo supplementations. In conclusion, additional supplement of TAU with BCAA would be a useful way to attenuate DOMS and muscle damages induced by high-intensity exercise.

CO2 induced pHi changes in the brain of polar fish: a TauCEST application.

PubMed

Wermter, Felizitas C; Maus, Bastian; Pörtner, Hans-O; Dreher, Wolfgang; Bock, Christian

2018-06-22

Chemical exchange saturation transfer (CEST) from taurine to water (TauCEST) can be used for in vivo mapping of taurine concentrations as well as for measurements of relative changes in intracellular pH (pH i ) at temperatures below 37°C. Therefore, TauCEST offers the opportunity to investigate acid-base regulation and neurological disturbances of ectothermic animals living at low temperatures, and in particular to study the impact of ocean acidification (OA) on neurophysiological changes of fish. Here, we report the first in vivo application of TauCEST imaging. Thus, the study aimed to investigate the TauCEST effect in a broad range of temperatures (1-37°C) and pH (5.5-8.0), motivated by the high taurine concentration measured in the brains of polar fish. The in vitro data show that the TauCEST effect is especially detectable in the low temperature range and strictly monotonic for the relevant pH range (6.8-7.5). To investigate the specificity of TauCEST imaging for the brain of polar cod (Boreogadus saida) at 1.5°C simulations were carried out, indicating a taurine contribution of about 65% to the in vivo expected CEST effect, if experimental parameters are optimized. B. saida was acutely exposed to three different CO 2 concentrations in the sea water (control normocapnia; comparatively moderate hypercapnia OA m  = 3300 μatm; high hypercapnia OA h  = 4900 μatm). TauCEST imaging of the brain showed a significant increase in the TauCEST effect under the different CO 2 concentrations of about 1.5-3% in comparison with control measurements, indicative of changes in pH i or metabolite concentration. Consecutive recordings of 1 H MR spectra gave no support for a concentration induced change of the in vivo observed TauCEST effect. Thus, the in vivo application of TauCEST offers the possibility of mapping relative changes in pH i in the brain of polar cod during exposure to CO 2 . © 2018 John Wiley & Sons, Ltd.

Bilirubin Binding to PPARα Inhibits Lipid Accumulation

PubMed Central

Stec, David E.; John, Kezia; Trabbic, Christopher J.; Luniwal, Amarjit; Hankins, Michael W.; Baum, Justin

2016-01-01

Numerous clinical and population studies have demonstrated that increased serum bilirubin levels protect against cardiovascular and metabolic diseases such as obesity and diabetes. Bilirubin is a potent antioxidant, and the beneficial actions of moderate increases in plasma bilirubin have been thought to be due to the antioxidant effects of this bile pigment. In the present study, we found that bilirubin has a new function as a ligand for PPARα. We show that bilirubin can bind directly to PPARα and increase transcriptional activity. When we compared biliverdin, the precursor to bilirubin, on PPARα transcriptional activation to known PPARα ligands, WY 14,643 and fenofibrate, it showed that fenofibrate and biliverdin have similar activation properties. Treatment of 3T3-L1 adipocytes with biliverdin suppressed lipid accumulation and upregulated PPARα target genes. We treated wild-type and PPARα KO mice on a high fat diet with fenofibrate or bilirubin for seven days and found that both signal through PPARα dependent mechanisms. Furthermore, the effect of bilirubin on lowering glucose and reducing body fat percentage was blunted in PPARα KO mice. These data demonstrate a new function for bilirubin as an agonist of PPARα, which mediates the protection from adiposity afforded by moderate increases in bilirubin. PMID:27071062

Antenatal taurine reduces cerebral cell apoptosis in fetal rats with intrauterine growth restriction.

PubMed

Liu, Jing; Wang, Xiaofeng; Liu, Ying; Yang, Na; Xu, Jing; Ren, Xiaotun

2013-08-15

From pregnancy to parturition, Sprague-Dawley rats were daily administered a low protein diet to establish a model of intrauterine growth restriction. From the 12(th) day of pregnancy, 300 mg/kg rine was daily added to food until spontaneous delivery occurred. Brain tissues from normal neonatal rats at 6 hours after delivery, neonatal rats with intrauterine growth restriction, and neonatal rats with intrauterine growth restriction undergoing taurine supplement were obtained for further experiments. The terminal deoxyribonucleotidyl transferase (TdT)-mediated biotin-16-dUTP nick-end labeling assay revealed that the number of apoptotic cells in the brain tissue of neonatal rats with intrauterine growth restriction significantly increased. Taurine supplement in pregnant rats reduced cell apoptosis in brain tissue from neonatal rats with intrauterine growth restriction. nohistochemical staining revealed that taurine supplement increased glial cell line-derived neurotrophic factor expression and decreased caspase-3 expression in the cerebral cortex of intrauterine growth-restricted fetal rats. These results indicate that taurine supplement reduces cell apoptosis through the glial cell line-derived neurotrophic factor-caspase-3 signaling pathway, resulting in a protective effect on the intrauterine growth-restricted fetal rat brain.

Antenatal taurine reduces cerebral cell apoptosis in fetal rats with intrauterine growth restriction

PubMed Central

Liu, Jing; Wang, Xiaofeng; Liu, Ying; Yang, Na; Xu, Jing; Ren, Xiaotun

2013-01-01

From pregnancy to parturition, Sprague-Dawley rats were daily administered a low protein diet to establish a model of intrauterine growth restriction. From the 12th day of pregnancy, 300 mg/kg rine was daily added to food until spontaneous delivery occurred. Brain tissues from normal neonatal rats at 6 hours after delivery, neonatal rats with intrauterine growth restriction, and neonatal rats with intrauterine growth restriction undergoing taurine supplement were obtained for further experiments. The terminal deoxyribonucleotidyl transferase (TdT)-mediated biotin-16-dUTP nick-end labeling assay revealed that the number of apoptotic cells in the brain tissue of neonatal rats with intrauterine growth restriction significantly increased. Taurine supplement in pregnant rats reduced cell apoptosis in brain tissue from neonatal rats with intrauterine growth restriction. nohistochemical staining revealed that taurine supplement increased glial cell line-derived neurotrophic factor expression and decreased caspase-3 expression in the cerebral cortex of intrauterine growth-restricted fetal rats. These results indicate that taurine supplement reduces cell apoptosis through the glial cell line-derived neurotrophic factor-caspase-3 signaling pathway, resulting in a protective effect on the intrauterine growth-restricted fetal rat brain. PMID:25206528

[The influence of C-taurine antioxidant complex on biochemical blood parameters in the process of treatment of patients with diabetes mellitus of type II with nonproliferative diabetic retinopathy].

PubMed

Lekishvili, S E

2014-02-01

The purpose of this investigation is to study the effect of C- taurine complex of antioxidants on blood biochemical parameters in the process of treatment of patients with diabetes mellitus of type II with NPDR. 68 patients (136 eyes) were enrolled in the study. The monitoring of the patient lasted for 3 months. The character of changes of the basic visual functions has been examined. The patients were divided into 2 groups (main and control). Treatment of patients with main group conducted antioxidant complex Taurine + Vitamin C for 42 days. namely. Thus, we have revealed antioxidant activity of the combination of taurine and vitamin C with positive effect on the indexes of carbohydrate, lipid metabolism and hepatoprotective characteristics in patients with diabetes mellitus type II with NPDR. Taking into consideration the peculiarities of correlation relationships between functional, clinical and biochemical parameters and the results of experimental studies on animal it is acceptable to use Taurine complex + Vitamin C as part of conservative treatment of patients with diabetes mellitus type II with NPDR.

Relationship among serum taurine, serum adipokines, and body composition during 8-week human body weight control program.

PubMed

You, Jeong Soon; Park, Ji Yeon; Zhao, Xu; Jeong, Jin Seok; Choi, Mi Ja; Chang, Kyung Ja

2013-01-01

Human adipose tissue is not only a storage organ but also an active endocrine organ to release adipokines. This study was conducted to investigate the relationship among serum taurine and adipokine levels, and body composition during 8-week human body weight control program in obese female college students. The program consisted of diet therapy, exercise, and behavior modification. After the program, body weight, body fat mass, percent body fat, and body mass index (BMI) were significantly decreased. Serum triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) levels were significantly decreased. Also serum adiponectin level was significantly increased and serum leptin level was significantly decreased. There were no differences in serum taurine and homocysteine levels. The change of serum adiponectin level was positively correlated with change of body fat mass and percent body fat. These results may suggest that body fat loss by human body weight control program is associated with an increase in serum adiponectin in obese female college students. Therefore, further study such as taurine intervention study is needed to know more exact correlation between dietary taurine intake and serum adipokines or body composition.

The retention and recovery of amino acids from pork longissimus muscle following cooking to either 60°C or 75°C.

PubMed

Wilkinson, B H P; Lee, E; Purchas, R W; Morel, P C H

2014-01-01

Samples of pork longissimus muscle (n=16) cooked to either 60°C or 75°C in a water bath for 90 min were assessed for amino acid composition. Recovery of protein in the cooked meat plus the cooking juice was >93% and was slightly higher at 60°C (P=0.031), but retention in the meat was only 89% and 82% for the lower and higher temperatures (P<0.0001). Individual amino acids varied in recovery and retention with retention being particularly low for taurine and histidine. The balance of indispensable amino acids was less than ideal, with leucine and valine being the limiting amino acids by about 30% for both raw and cooked pork. Cooking had no detrimental effect on amino acid balance. Some examples of small effects of genotype and sex on amino acid composition of pork were shown. © 2013.

A Comparison of Phenotypic Traits Related to Trypanotolerance in Five West African Cattle Breeds Highlights the Value of Shorthorn Taurine Breeds

PubMed Central

Berthier, David; Peylhard, Moana; Dayo, Guiguigbaza-Kossigan; Flori, Laurence; Sylla, Souleymane; Bolly, Seydou; Sakande, Hassane; Chantal, Isabelle; Thevenon, Sophie

2015-01-01

Background Animal African Trypanosomosis particularly affects cattle and dramatically impairs livestock development in sub-Saharan Africa. African Zebu (AFZ) or European taurine breeds usually die of the disease in the absence of treatment, whereas West African taurine breeds (AFT), considered trypanotolerant, are able to control the pathogenic effects of trypanosomosis. Up to now, only one AFT breed, the longhorn N’Dama (NDA), has been largely studied and is considered as the reference trypanotolerant breed. Shorthorn taurine trypanotolerance has never been properly assessed and compared to NDA and AFZ breeds. Methodology/Principal Findings This study compared the trypanotolerant/susceptible phenotype of five West African local breeds that differ in their demographic history. Thirty-six individuals belonging to the longhorn taurine NDA breed, two shorthorn taurine Lagune (LAG) and Baoulé (BAO) breeds, the Zebu Fulani (ZFU) and the Borgou (BOR), an admixed breed between AFT and AFZ, were infected by Trypanosoma congolense IL1180. All the cattle were genetically characterized using dense SNP markers, and parameters linked to parasitaemia, anaemia and leukocytes were analysed using synthetic variables and mixed models. We showed that LAG, followed by NDA and BAO, displayed the best control of anaemia. ZFU showed the greatest anaemia and the BOR breed had an intermediate value, as expected from its admixed origin. Large differences in leukocyte counts were also observed, with higher leukocytosis for AFT. Nevertheless, no differences in parasitaemia were found, except a tendency to take longer to display detectable parasites in ZFU. Conclusions We demonstrated that LAG and BAO are as trypanotolerant as NDA. This study highlights the value of shorthorn taurine breeds, which display strong local adaptation to trypanosomosis. Thanks to further analyses based on comparisons of the genome or transcriptome of the breeds, these results open up the way for better knowledge of host-pathogen interactions and, furthermore, for identifying key biological pathways. PMID:25954819

A comparison of phenotypic traits related to trypanotolerance in five west african cattle breeds highlights the value of shorthorn taurine breeds.

PubMed

Berthier, David; Peylhard, Moana; Dayo, Guiguigbaza-Kossigan; Flori, Laurence; Sylla, Souleymane; Bolly, Seydou; Sakande, Hassane; Chantal, Isabelle; Thevenon, Sophie

2015-01-01

Animal African Trypanosomosis particularly affects cattle and dramatically impairs livestock development in sub-Saharan Africa. African Zebu (AFZ) or European taurine breeds usually die of the disease in the absence of treatment, whereas West African taurine breeds (AFT), considered trypanotolerant, are able to control the pathogenic effects of trypanosomosis. Up to now, only one AFT breed, the longhorn N'Dama (NDA), has been largely studied and is considered as the reference trypanotolerant breed. Shorthorn taurine trypanotolerance has never been properly assessed and compared to NDA and AFZ breeds. This study compared the trypanotolerant/susceptible phenotype of five West African local breeds that differ in their demographic history. Thirty-six individuals belonging to the longhorn taurine NDA breed, two shorthorn taurine Lagune (LAG) and Baoulé (BAO) breeds, the Zebu Fulani (ZFU) and the Borgou (BOR), an admixed breed between AFT and AFZ, were infected by Trypanosoma congolense IL1180. All the cattle were genetically characterized using dense SNP markers, and parameters linked to parasitaemia, anaemia and leukocytes were analysed using synthetic variables and mixed models. We showed that LAG, followed by NDA and BAO, displayed the best control of anaemia. ZFU showed the greatest anaemia and the BOR breed had an intermediate value, as expected from its admixed origin. Large differences in leukocyte counts were also observed, with higher leukocytosis for AFT. Nevertheless, no differences in parasitaemia were found, except a tendency to take longer to display detectable parasites in ZFU. We demonstrated that LAG and BAO are as trypanotolerant as NDA. This study highlights the value of shorthorn taurine breeds, which display strong local adaptation to trypanosomosis. Thanks to further analyses based on comparisons of the genome or transcriptome of the breeds, these results open up the way for better knowledge of host-pathogen interactions and, furthermore, for identifying key biological pathways.

Development of capillary electrophoresis methods for quantitative determination of taurine in vehicle system and biological media.

PubMed

da Silva, Dayse L P; Rüttinger, Hans H; Mrestani, Yahia; Baum, Walter F; Neubert, Reinhard H H

2006-06-01

CE methods have been developed for the determination of taurine in pharmaceutical formulation (microemulsion) and in biological media such as sweat. The CE system with end-column pulsed amperometric detection has been found to be an interesting method in comparison with UV and fluorescence detection for its simplicity and rapidity. A gold-disk electrode of 100 mm diameter was used as the working electrode. The effects of a field decoupler at the end of the capillary, separation voltage, injection and pressure times were investigated. A detection limit of 4 x 10(-5) mol/L was reached using integrated pulsed amperometric detection, a method successfully applied to taurine analysis of the biological samples such as sweat. For taurine analysis of oil-in-water microemulsion, fluorescence detector was the favored method, the detection limit of which was 4 x 10(-11) mol/L.

Effects of taurine on markers of muscle damage, inflammatory response and physical performance in triathletes.

PubMed

Martinez Galan, Bryan S; Giolo de Carvalho, Flavia; Carvalho Santos, Priscila; Bucken Gobbi, Ronaldo; Kalva-Filho, Carlos; Papoti, Marcelo; Sanchez Silva, Adelino; Freitas, Ellen C

2017-07-25

The practice of prolonged exercise with high intensity, as seen in triathlon training, can cause physiological imbalances that might result in muscle fatigue, muscle damage and changes in systemic inflammatory response, thus reduce the athletes physical performance, therefore, both adequate total caloric and macronutrient intake also the use of a specific ergogenic aid, as taurine supplementation would be an alternative to prevent inflammation and muscle damage. In order to verify the effects of 8 weeks of taurine and chocolate milk supplementation, markers of muscle damage, inflammation, and aerobic capacity were quantified in triathletes. A double-blind, crossover, randomized study was conducted with 9 male long distance triathletes, aged 25-35 years. Supplementation of 3 g of taurine (TAU) or placebo (PLA) associated with 400 ml low fat chocolate milk was performed during an 8-week period. In order to verify the effects of the supplementation protocol markers of muscle damage as lactate dehydrogenase (LDH) and creatine kinase (CK), and inflammatory markers tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were quantified, also triathletes performance was evaluated by exhaust test on a treadmill. It was observed a significant increase in taurine and CK plasma levels after TAU supplementation (p=0.02 and p=0.01, respectively). However, LDH concentrations did not differ significantly after the supplementations performed, and there were no changes in physical performance parameters; anaerobic threshold, perceived exertion, heart rate, and the concentrations of IL-6 and TNF-α. Taurine supplementation did not provide benefits on performance and muscle damage in triathletes.

Effect of extender and amino acid supplementation on sperm quality of cooled-preserved Andalusian donkey (Equus asinus) spermatozoa.

PubMed

Dorado, J; Acha, D; Ortiz, I; Gálvez, M J; Carrasco, J J; Gómez-Arrones, V; Calero-Carretero, R; Hidalgo, M

2014-04-01

The main aim of this study was to evaluate the efficacy of two commercially available liquid stallion semen extenders for the preservation of Andalusian donkey semen at 5°C for up to 72h, and to evaluate the effect of amino acid addition on sperm quality of cooled donkey semen. In addition, this study investigated the effect of seasons on semen characteristics of Andalusian jackasses. Throughout a year, 50 ejaculates were collected from ten adult donkeys and a complete semen evaluation was performed immediately after collection. In Experiment 1, semen samples (n=32) were pooled, divided into two aliquots, and cooled in either Gent(®) A or INRA 96(®). In Experiment 2, pooled semen samples (n=9) were cooled in Gent A(®) supplemented with 0 (as control), 20, 40, or 60mM for each glutamine, proline, or taurine. Fresh semen and chilled samples were assessed for sperm motility, morphology, acrosome integrity, and plasma membrane integrity. Sperm motility variables were greater (P<0.05) in Gent(®) A than in INRA 96(®). The presence of glutamine, proline, or taurine in Gent(®) A improved (P<0.001) the motility of Andalusian donkey spermatozoa. Differences (P<0.05) in some sperm variables were observed among seasons. In conclusion, Gent(®) A maintained sperm motility characteristics after 72h of cold storage to a greater extent than INRA 96(®). Moreover, motility was greater when Gent(®) A supplemented at different concentrations of amino acids than Gent(®) A with no supplementation. An effect of seasons on the semen quality of the Andalusian donkey was demonstrated. Copyright © 2014 Elsevier B.V. All rights reserved.

Radiation protection following nuclear power accidents: a survey of putative mechanisms involved in the radioprotective actions of taurine during and after radiation exposure

PubMed Central

Christophersen, Olav Albert

2012-01-01

There are several animal experiments showing that high doses of ionizing radiation lead to strongly enhanced leakage of taurine from damaged cells into the extracellular fluid, followed by enhanced urinary excretion. This radiation-induced taurine depletion can itself have various harmful effects (as will also be the case when taurine depletion is due to other causes, such as alcohol abuse or cancer therapy with cytotoxic drugs), but taurine supplementation has been shown to have radioprotective effects apparently going beyond what might be expected just as a consequence of correcting the harmful consequences of taurine deficiency per se. The mechanisms accounting for the radioprotective effects of taurine are, however, very incompletely understood. In this article an attempt is made to survey various mechanisms that potentially might be involved as parts of the explanation for the overall beneficial effect of high levels of taurine that has been found in experiments with animals or isolated cells exposed to high doses of ionizing radiation. It is proposed that taurine may have radioprotective effects by a combination of several mechanisms: (1) during the exposure to ionizing radiation by functioning as an antioxidant, but perhaps more because it counteracts the prooxidant catalytic effect of iron rather than functioning as an important scavenger of harmful molecules itself, (2) after the ionizing radiation exposure by helping to reduce the intensity of the post-traumatic inflammatory response, and thus reducing the extent of tissue damage that develops because of severe inflammation rather than as a direct effect of the ionizing radiation per se, (3) by functioning as a growth factor helping to enhance the growth rate of leukocytes and leukocyte progenitor cells and perhaps also of other rapidly proliferating cell types, such as enterocyte progenitor cells, which may be important for immunological recovery and perhaps also for rapid repair of various damaged tissues, especially in the intestines, and (4) by functioning as an antifibrogenic agent. A detailed discussion is given of possible mechanisms involved both in the antioxidant effects of taurine, in its anti-inflammatory effects and in its role as a growth factor for leukocytes and nerve cells, which might be closely related to its role as an osmolyte important for cellular volume regulation because of the close connection between cell volume regulation and the regulation of protein synthesis as well as cellular protein degradation. While taurine supplementation alone would be expected to exert a therapeutic effect far better than negligible in patients that have been exposed to high doses of ionizing radiation, it may on theoretical grounds be expected that much better results may be obtained by using taurine as part of a multifactorial treatment strategy, where it may interact synergistically with several other nutrients, hormones or other drugs for optimizing antioxidant protection and minimizing harmful posttraumatic inflammatory reactions, while using other nutrients to optimize DNA and tissue repair processes, and using a combination of good diet, immunostimulatory hormones and perhaps other nontoxic immunostimulants (such as beta-glucans) for optimizing the recovery of antiviral and antibacterial immune functions. Similar multifactorial treatment strategies may presumably be helpful in several other disease situations (including severe infectious diseases and severe asthma) as well as for treatment of acute intoxications or acute injuries (both mechanical ones and severe burns) where severely enhanced oxidative and/or nitrative stress and/or too much secretion of vasodilatory neuropeptides from C-fibres are important parts of the pathogenetic mechanisms that may lead to the death of the patient. Some case histories (with discussion of some of those mechanisms that may have been responsible for the observed therapeutic outcome) are given for illustration of the likely validity of these concepts and their relevance both for treatment of severe infections and non-infectious inflammatory diseases such as asthma and rheumatoid arthritis. PMID:23990836

Proximate Composition, Amino Acid, Mineral, and Heavy Metal Content of Dried Laver

PubMed Central

Hwang, Eun-Sun; Ki, Kyung-Nam; Chung, Ha-Yull

2013-01-01

Laver, a red algae belonging to the genus Porphyra, is one of the most widely consumed edible seaweeds. The most popular commercial dried laver species, P. tenera and P. haitanensis, were collected from Korea and China, respectively, and evaluated for proximate composition, amino acids, minerals, trace heavy metals, and color. The moisture and ash contents of P. tenera and P. haitanensis ranged from 3.66~6.74% and 8.78~9.07%, respectively; crude lipid and protein contents were 1.96~2.25% and 32.16~36.88%, respectively. Dried lavers were found to be a good source of amino acids, such as asparagine, isoleucine, leucine, and taurine, and γ-aminobutyric acid. K, Ca, Mg, Na, P, I, Fe, and Se minerals were selected for analysis. A clear regional variation existed in the amino acid, mineral, and trace metal contents of lavers. Regular consumption of lavers may have heath benefits because they are relatively low in fat and high in protein, and contain functional amino acids and minerals. PMID:24471123

Proximate composition, amino Acid, mineral, and heavy metal content of dried laver.

PubMed

Hwang, Eun-Sun; Ki, Kyung-Nam; Chung, Ha-Yull

2013-06-01

Laver, a red algae belonging to the genus Porphyra, is one of the most widely consumed edible seaweeds. The most popular commercial dried laver species, P. tenera and P. haitanensis, were collected from Korea and China, respectively, and evaluated for proximate composition, amino acids, minerals, trace heavy metals, and color. The moisture and ash contents of P. tenera and P. haitanensis ranged from 3.66~6.74% and 8.78~9.07%, respectively; crude lipid and protein contents were 1.96~2.25% and 32.16~36.88%, respectively. Dried lavers were found to be a good source of amino acids, such as asparagine, isoleucine, leucine, and taurine, and γ-aminobutyric acid. K, Ca, Mg, Na, P, I, Fe, and Se minerals were selected for analysis. A clear regional variation existed in the amino acid, mineral, and trace metal contents of lavers. Regular consumption of lavers may have heath benefits because they are relatively low in fat and high in protein, and contain functional amino acids and minerals.

Chemosensory responses by the heterotrophic marine dinoflagellateCrypthecodinium cohnii.

PubMed

Hauser, D C; Levandowsky, M; Hutner, S H; Chunosoff, L; Hollwitz, J S

1974-12-01

Chemosensory responses by the colorles inshore marine dinoflagellateCrypthecodinium cohnii were observed in quadrant-divided Petri plates containing an agar layer + liquid overlay. A suspension of organisms in salt solution was poured onto this and allowed to stand 3 hr. A differential tendency of the cells to become firmly attached or embedded in the substratum was observed when various substances were incorporated in the gel. A positive response (tendency to attach) occurred with: α-L-fucose, dimethyl-β-propiothetin, betaine, sucrose, glycine, L-alanine, hemin, and fructose; negative response: formalin, glutathione, acid hydrolyzed agar, protamine SO4, L-glutamic acid, lactose, glutamine, taurine, L-aspartic acid, putrescine 2 HCl, choline citrate, choline bitartrate, K citrate, and choline HCl. γ-Aminobutyric acid was negative or positive dependeng on concentration. Dead or immotile cells did not become attached. The following compounds elicited no response: α-D-fucose, dimethyl acetothetin chloride, cyclic AMP, and glucose.

Methylmercury-induced inhibition of regulatory volume decrease in astrocytes: characterization of osmoregulator efflux and its reversal by amiloride.

PubMed

Aschner, M; Vitarella, D; Allen, J W; Conklin, D R; Cowan, K S

1998-11-16

Swelling of neonatal rat primary astrocyte cultures by hypotonic media leads to regulatory volume decrease (RVD) and the resumption of resting cell volume. RVD is associated with activation of conductive K+ and Cl- channels, allowing for the escape of KCl, as well as the release of osmoregulators, such as taurine and myoinositol. As we have previously shown [D. Vitarella, H.K. Kimelberg, M. Aschner, Inhibition of RVD in swollen rat primary astrocyte cultures by methylmercury (MeHg) is due to increase amiloride-sensitive Na+ uptake, Brain Res. 732 (1996) 169-178.], MeHg, when added to hypotonic buffer inhibits RVD, primarily due to increased cellular permeability to Na+ via the Na+/H+ antiporter. The present study was, therefore, undertaken to assess the ability of cation-anion cotransport blockers to reverse the inhibitory effect of MeHg on RVD in swollen astrocytes, and to further characterize MeHg-induced changes in astrocytic osmoregulatory release processes. The studies demonstrate the following: (1) MeHg-induced inhibition of RVD is partially inhibited by the Na+/H+ antiporter blocker, amiloride, but not SITS (4-acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic acid), DIDS (4,4'-diisothiocyano-2,2'-stilbenedisulfonic acid), furosemide or bumetanide; (2) exposure of swollen astrocytes to MeHg is associated with specific effects on osmoregulatory release, leading to significant inhibition of taurine release and a significant increase in potassium and myoinositol release compared with release in hypotonic conditions. Copyright 1998 Elsevier Science B.V.

Developmental changes in expression of GABAA receptor-channels in rat intrinsic cardiac ganglion neurones

PubMed Central

Fischer, Harald; Harper, Alexander A; Anderson, Colin R; Adams, David J

2005-01-01

The effects of γ-aminobutyric acid (GABA) on the electrophysiological properties of intracardiac neurones were investigated in the intracardiac ganglion plexus in situ and in dissociated neurones from neonatal, juvenile and adult rat hearts. Focal application of GABA evoked a depolarizing, excitatory response in both intact and dissociated intracardiac ganglion neurones. Under voltage clamp, both GABA and muscimol elicited inward currents at −60 mV in a concentration-dependent manner. The fast, desensitizing currents were mimicked by the GABAA receptor agonists muscimol and taurine, and inhibited by the GABAA receptor antagonists, bicuculline and picrotoxin. The GABAA0 antagonist (1,2,5,6-tetrahydropyridin-4-yl)methyl phosphonic acid (TPMPA), had no effect on GABA-induced currents, suggesting that GABAA receptor-channels mediate the response. The GABA-evoked current amplitude recorded from dissociated neurones was age dependent whereby the peak current density measured at −100 mV was ∼ 20 times higher for intracardiac neurones obtained from neonatal rats (P2–5) compared with adult rats (P45–49). The decrease in GABA sensitivity occurred during the first two postnatal weeks and coincides with maturation of the sympathetic innervation of the rat heart. Immunohistochemical staining using antibodies against GABA demonstrate the presence of GABA in the intracardiac ganglion plexus of the neonatal rat heart. Taken together, these results suggest that GABA and taurine may act as modulators of neurotransmission and cardiac function in the developing mammalian intrinsic cardiac nervous system. PMID:15731187

The metabolic response in fish to mildly elevated water temperature relates to species-dependent muscular concentrations of imidazole compounds and free amino acids.

PubMed

Geda, Fikremariam; Declercq, Annelies M; Remø, Sofie C; Waagbø, Rune; Lourenço, Marta; Janssens, Geert P J

2017-04-01

Fish species show distinct differences in their muscular concentrations of imidazoles and free amino acids (FAA). This study was conducted to investigate whether metabolic response to mildly elevated water temperature (MEWT) relates to species-dependent muscular concentrations of imidazoles and FAA. Thirteen carp and 17 Nile tilapia, housed one per aquarium, were randomly assigned to either acclimation (25°C) or MEWT (30°C) for 14 days. Main muscular concentrations were histidine (HIS; P<0.001) in carp versus N-α-acetylhistidine (NAH; P<0.001) and taurine (TAU; P=0.001) in tilapia. Although the sum of imidazole (HIS+NAH) and TAU in muscle remained constant over species and temperatures (P>0.05), (NAH+HIS)/TAU ratio was markedly higher in carp versus tilapia, and decreased with MEWT only in carp (P<0.05). Many of the muscular FAA concentrations were higher in carp than in tilapia (P<0.05). Plasma acylcarnitine profile suggested a higher use of AA and fatty acids in carp metabolism (P<0.05). On the contrary, the concentration of 3-hydroxyisovalerylcarnitine, a sink of leucine catabolism, (P=0.009) pointed to avoidance of leucine use in tilapia metabolism. Despite a further increase of plasma longer-chain acylcarnitines in tilapia at MEWT (P=0.009), their corresponding beta-oxidation products (3-hydroxy-longer-chain acylcarnitines) remained constant. Together with higher plasma non-esterified fatty acids (NEFA) in carp (P=0.001), the latter shows that carp, being a fatter fish, more readily mobilises fat than tilapia at MEWT, which coincides with more intensive muscular mobilization of imidazoles. This study demonstrates that fish species differ in their metabolic response to MEWT, which is associated with species-dependent changes in muscle imidazole to taurine ratio. Copyright © 2017 Elsevier Ltd. All rights reserved.

Taurine alleviates malathion induced lipid peroxidation, oxidative stress, and proinflammatory cytokine gene expressions in rats.

PubMed

Ince, Sinan; Arslan-Acaroz, Damla; Demirel, Hasan Huseyin; Varol, Nuray; Ozyurek, Hatice Arzu; Zemheri, Fahriye; Kucukkurt, Ismail

2017-12-01

The present study was considered to evaluate the protective effect of taurine on malathion-induced toxicity in rats. Totally, 48 male rats were divided into 6 equal groups: 0.5ml physiological salt solution was given orally to control rats. 0.5ml corn oil was given orally to rats in corn oil group. Malathion at dose of 27mg/kg (1/50 of LD 50 ) was dissolved in 0.5ml corn oil and given to orally rats in malathion group. The other groups; malathion (27mg/kg) and taurine (dissolved in 0.5ml physiological salt solution) at dose of 50, 100, and 200mg/kg were given orally to rats for 30days, respectively. Malathion treatment decreased acetylcholinesterase levels in serum (30%) and liver (25%) compared to the control group. Malathion resulted in a significant increase in malondialdehyde levels whereas decreased glutathione levels, superoxide dismutase, and catalase activities in rats. Also, IF-γ, IL1-β, TNF-α, and NFĸB mRNA expression levels were found to be increased 5, 1.7, 2.3, and 2.5 fold in malathion treated rats compared to control, respectively. However, treatment of taurine, in a dose-dependent manner, resulted in a reversal of malathion-induced lipid peroxidation, antioxidant enzyme activities, and mRNA expression levels of proinflammatory cytokines. Moreover, taurine demonstrated preventive action against malathion-induced histopathological changes in rat tissues. In conclusion, taurine exhibited a protective effect in rats against malathion-induced lipid peroxidation, besides it ameliorated antioxidant status, decreased mRNA expression levels of proinflammatory cytokine and repaired rat tissues. Copyright © 2017. Published by Elsevier Masson SAS.

Peroxisome proliferator-activated receptor-α agonists protect cortical neurons from inflammatory mediators and improve peroxisomal function.

PubMed

Gray, Elizabeth; Ginty, Mark; Kemp, Kevin; Scolding, Neil; Wilkins, Alastair

2011-04-01

Inflammation is known to cause significant neuronal damage and axonal injury in many neurological disorders. Among the range of inflammatory mediators, nitric oxide is a potent neurotoxic agent. Recent evidence has suggested that cellular peroxisomes may be important in protecting neurons from inflammatory damage. To assess the influence of peroxisomal activation on nitric oxide-mediated neurotoxicity, we investigated the effects of the peroxisomal proliferator-activated receptor (PPAR)-α agonist fenofibrate on cortical neurons exposed to a nitric oxide donor or co-cultured with activated microglia. Fenofibrate protected neurons and axons against both nitric oxide donor-induced and microglia-derived nitric oxide-induced toxicity. Moreover, cortical neurons treated with this compound showed a significant increase in gene expression of ABCD3 (the gene encoding for peroxisomal membrane protein-70), with a concomitant increase in protein levels of PPAR-α and catalase, which was associated with a functional increase in the activity of this enzyme. Collectively, these observations provide evidence that modulation of PPAR-α activity and peroxisomal function by fenofibrate attenuates nitric oxide-mediated neuronal and axonal damage, suggesting a new therapeutic approach to protect against neurodegenerative changes associated with neuroinflammation. © 2011 The Authors. European Journal of Neuroscience © 2011 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

Influence of the amino acid moiety on deconjugation of bile acid amidates by cholylglycine hydrolase or human fecal cultures.

PubMed

Huijghebaert, S M; Hofmann, A F

1986-07-01

The influence of the chemical structure of the amino acid (or amino acid analogue) moiety of a number of synthetic cholyl amidates on deconjugation by cholylglycine hydrolase from Clostridium perfringens was studied in vitro at pH 5.4. Conjugates with alkyl homologues of glycine were hydrolyzed more slowly as the number of methylene units increased (cholylglycine greater than cholyl-beta-alanine greater than cholyl-gamma-aminobutyrate). In contrast, for conjugates with the alkyl homologues of taurine, cholylaminopropane sulfonate was hydrolyzed slightly faster than cholyltaurine, whereas cholylaminomethane sulfonate was hydrolyzed much more slowly. When glycine was replaced by other neutral alpha-amino acids, rates of hydrolysis decreased with increasing steric hindrance near the amide bond (cholyl-L-alpha-alanine much much greater than cholyl-L-leucine much greater than cholyl-L-valine greater than cholyl-L-tyrosine much greater than cholyl-D-valine). Conjugation with acidic or basic amino acids also greatly reduced the rates of hydrolysis, as cholyl-L-aspartate, cholyl-L-cysteate, cholyl-L-lysine, and cholyl-L-histidine were all hydrolyzed at a rate less than one-tenth that of cholylglycine. Methyl esterification of the carboxylic group of the amino acid moiety reduced the hydrolysis, but such substrates (cholylglycine methyl ester and cholyl-beta-alanine methyl ester) were completely hydrolyzed after overnight incubation with excess of enzyme. In contrast, cholyl-cholamine was not hydrolyzed at all, suggesting that a negative charge at the end of the side chain is required for optimal hydrolysis. Despite the lack of specificity for the amino acid moiety, a bile salt moiety was required, as the cholylglycine hydrolase did not display general carboxypeptidase activity for other non-bile acid substrates containing a terminal amide bond: hippuryl-L-phenylalanine and hippuryl-L-arginine, as well as oleyltaurine and oleylglycine, were not hydrolyzed. Fecal bacterial cultures from healthy volunteers also hydrolyzed cholyl-L-valine and cholyl-D-valine more slowly than cholylglycine, suggesting that cholylglycine hydrolase from Clostridium perfringens has a substrate specificity similar to that of the deconjugating enzymes of the fecal flora. The results indicate that modification of the position of the amide bond, introduction of steric hindrance near the amide bond, or loss of a negative charge on the terminal group of the amino acid moiety of the bile acid conjugate greatly reduces the rate of bacterial deconjugation in vitro when compared to that of the naturally occurring glycine and taurine conjugates.

Effects of standard ethanolic extract from Erythrina velutina in acute cerebral ischemia in mice.

PubMed

Rodrigues, Francisca Taciana Sousa; de Sousa, Caren Nádia Soares; Ximenes, Naiara Coelho; Almeida, Anália Barbosa; Cabral, Lucas Moraes; Patrocínio, Cláudio Felipe Vasconcelos; Silva, Aline Holanda; Leal, Luzia Kalyne Almeida Moreira; Honório Júnior, José Eduardo Ribeiro; Macedo, Danielle; Vasconcelos, Silvânia Maria Mendes

2017-12-01

The objective of this study was to verify a possible neuroprotective effect of the ethanolic extract of Erythrina velutina (EEEV). Male Swiss mice were submitted to transient cerebral ischemia by occlusion of both carotid arteries for 30 min and treated for 5 days with EEEV (200 or 400 mg/kg) or Memantine (MEM) 10 mg/kg, with initiation of treatment 2 or 24 h after Ischemia. On the 6th day after the induction of ischemia, the animals were submitted to evaluation of locomotor activity and memory and then sacrificed. The brains were dissected for the removal of the prefrontal cortex (PFC), hippocampus (HC) and striatum (ST) for determination of amino acid concentrations. In the step down and Y-maze tests, ischemia caused damage to the animals and treatment with EEEV or MEM reversed this effect. The animals submitted to ischemia also showed memory deficit in the object recognition test, an effect that was reverted by EEEV400 and MEM10. Amino acid dosage showed an increase in excitatory amino acid concentrations in the PFC of the ischemic animals and this effect was reversed by the treatment with EEEV400/24H. Regarding the inhibitory amino acids, ischemia caused an increase of taurine in the PFC while treatment with MEM10/24H or EEEV400/24H reversed this effect. In HC, an increase in excitatory amino acids was also observed in ischemiated animals having treatment with EEEV200/2H or EEEV400/24H reversed this effect. Similar effect was also observed in the same area in relation to the inhibitory amino acids with treatment with MEM10/24H or EEEV400/24H. In the ST, ischemia was also able to cause an increase in excitatory amino acids that was reversed more efficiently by the treatments with MEM10/24H and EEEV200. Also in this area, an increase of taurine and GABA was observed and only the treatment with EEEV200/2H showed a reversion of this effect. In view of these findings, EEEV presents a neuroprotective effect possibly due to its action on amino acid concentrations, and is therefore a potential therapeutic tool in reducing the damage caused by ischemia. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Genetic diversity, population structure, and correlations between locally adapted zebu and taurine breeds in Brazil using SNP markers.

PubMed

Campos, Bárbara Machado; do Carmo, Adriana Santana; do Egito, Andrea Alves; da Mariante, Arthur Silva; do Albuquerque, Maria Socorro Muaés; de Gouveia, João José Simoni; Malhado, Carlos Henrique Mendes; Verardo, Lucas Lima; da Silva, Marcos Vinícius Gualberto Barbosa; Carneiro, Paulo Luiz Souza

2017-12-01

Genetic diversity is one of the most important issues in studies on conservation of cattle breeds and endangered species. The objective of this study was to estimate the levels of genetic differentiation between locally adapted taurine (Bos taurus taurus) and zebu (Bos taurus indicus) breeds in Brazil, which were genotyped for more than 777,000 SNPs. The fixation index (F ST ), principal component analysis (PCA), and Bayesian clustering were estimated. The F ST highlighted genetic differentiation between taurine and zebu breeds. The taurine lines, Caracu and Caracu Caldeano, had significant genetic differentiation (F ST close to 5%) despite their recent selection for different uses (meat and milk). This genetic variability can be used for conservation of locally adapted animals, as well as for breeding programs on zebu breeds. Introgression of zebu in locally adapted breeds was identified, especially in Curraleiro Pé-Duro breed. The Gyr breed, however, had low breed purity at genomic level due to its very heterogeneous mixing pattern.

Montmorillonite-lipid hybrid carriers for ionizable and neutral poorly water-soluble drugs: Formulation, characterization and in vitro lipolysis studies.

PubMed

Dening, Tahnee J; Rao, Shasha; Thomas, Nicky; Prestidge, Clive A

2017-06-30

Lipid-based formulations (LBFs) are a popular strategy for enhancing the gastrointestinal solubilization and absorption of poorly water-soluble drugs. In light of this, montmorillonite-lipid hybrid (MLH) particles, composed of medium-chain triglycerides, lecithin and montmorillonite clay platelets, have been developed as a novel solid-state LBF. Owing to the unique charge properties of montmorillonite, whereby the clay platelet surfaces carry a permanent negative charge and the platelet edges carry a pH-dependent charge, three model poorly water-soluble drugs with different charge properties; blonanserin (weak base, pKa 7.7), ibuprofen (weak acid, pKa 4.5) and fenofibrate (neutral), were formulated as MLH particles and their performance during biorelevant in vitro lipolysis at pH 7.5 was investigated. For blonanserin, drug solubilization during in vitro lipolysis was significantly reduced 3.4-fold and 3.2-fold for MLH particles in comparison to a control lipid solution and silica-lipid hybrid (SLH) particles, respectively. It was hypothesized that strong electrostatic interactions between the anionic montmorillonite platelet surfaces and cationic blonanserin molecules were responsible for the inferior performance of MLH particles. In contrast, no significant influence on drug solubilization was observed for ibuprofen- and fenofibrate-loaded MLH particles. The results of the current study indicate that whilst MLH particles are a promising novel formulation strategy for poorly water-soluble drugs, drug ionization tendency and the potential for drug-clay interactions must be taken into consideration to ensure an appropriate performance. Copyright © 2017 Elsevier B.V. All rights reserved.

Serum preadipocyte factor-1 concentrations in females with obesity and type 2 diabetes mellitus: the influence of very low calorie diet, acute hyperinsulinemia, and fenofibrate treatment.

PubMed

Kavalkova, P; Touskova, V; Roubicek, T; Trachta, P; Urbanova, M; Drapalova, J; Haluzikova, D; Mraz, M; Novak, D; Matoulek, M; Lacinova, Z; Haluzik, M

2013-10-01

Appropriate differentiation capacity of adipose tissue significantly affects its ability to store lipids and to protect nonadipose tissues against lipid spillover and development of insulin resistance. Preadipocyte factor-1 (Pref-1) is an important negative regulator of preadipocyte differentiation. The aim of our study was to explore the changes in circulating Pref-1 concentrations in female subjects with obesity (OB) (n=19), females with obesity and type 2 diabetes mellitus (T2DM) (n=22), and sex- and age-matched healthy control subjects (C) (n=22), and to study its modulation by very low calorie diet (VLCD), acute hyperinsulinemia during isoglycemic-hyperinsulinemic clamp, and 3 months' treatment with PPAR-α agonist fenofibrate. At baseline, serum Pref-1 concentrations were significantly higher in patients with T2DM compared to control group, while only nonsignificant trend towards higher levels was observed in OB group. 3 weeks of VLCD decreased Pref-1 levels in both OB and T2DM group, whereas 3 months of fenofibrate treatment had no significant effect. Hyperinsulinemia during the clamp significantly suppressed Pref-1 levels in both C and T2DM subjects and this suppression was unaffected by fenofibrate treatment. In a combined population of all groups, circulating Pref-1 levels correlated positively with insulin, leptin and glucose levels and HOMA (homeostasis model assessment) index. We conclude that elevated Pref-1 concentrations in T2DM subjects may contribute to impaired adipose tissue differentiation capacity associated with insulin resistance in obese patients with T2DM. The decrease of Pref-1 levels after VLCD may be involved in the improvement of metabolic status and the amelioration of insulin resistance in T2DM patients. © Georg Thieme Verlag KG Stuttgart · New York.

Effect of peroxisome proliferator-activated receptor alpha activators on tumor necrosis factor expression in mice during endotoxemia.

PubMed

Hill, M R; Clarke, S; Rodgers, K; Thornhill, B; Peters, J M; Gonzalez, F J; Gimble, J M

1999-07-01

Inflammatory mediators orchestrate the host immune and metabolic response to acute bacterial infections and mediate the events leading to septic shock. Tumor necrosis factor (TNF) has long been identified as one of the proximal mediators of endotoxin action. Recent studies have implicated peroxisome proliferator-activated receptor alpha (PPARalpha) as a potential target to modulate regulation of the immune response. Since PPARalpha activators, which are hypolipidemic drugs, are being prescribed for a significant population of older patients, it is important to determine the impact of these drugs on the host response to acute inflammation. Therefore, we examined the role of PPARalpha activators on the regulation of TNF expression in a mouse model of endotoxemia. CD-1 mice treated with dietary fenofibrate or Wy-14,643 had fivefold-higher lipopolysaccharide (LPS)-induced TNF plasma levels than LPS-treated control-fed animals. Higher LPS-induced TNF levels in drug-fed animals were reflected physiologically in significantly lower glucose levels in plasma and a significantly lower 50% lethal dose than those in LPS-treated control-fed animals. Utilizing PPARalpha wild-type (WT) and knockout (KO) mice, we showed that the effect of fenofibrate on LPS-induced TNF expression was indeed mediated by PPARalpha. PPARalpha WT mice fed fenofibrate also had a fivefold increase in LPS-induced TNF levels in plasma compared to control-fed animals. However, LPS-induced TNF levels were significantly decreased and glucose levels in plasma were significantly increased in PPARalpha KO mice fed fenofibrate compared to those in control-fed animals. Data from peritoneal macrophage studies indicate that Wy-14,643 modestly decreased TNF expression in vitro. Similarly, overexpression of PPARalpha in 293T cells decreased activity of a human TNF promoter-luciferase construct. The results from these studies suggest that any anti-inflammatory activity of PPARalpha in vivo can be masked by other systemic effects of PPARalpha activators.

Free amino acids in fibromyalgia syndrome: relationship with clinical picture.

PubMed

Ruggiero, Valeria; Mura, Massimiliano; Cacace, Enrico; Era, Benedetta; Peri, Marcella; Sanna, Giuseppina; Fais, Antonella

2017-04-01

The objectives of our study were to evaluate free amino acid (FAA) concentrations in the serum of patients affected by fibromyalgia syndrome (FMS) and to determine the relationships between FAA levels and FMS clinical parameters. Thus, serum amino acid concentrations were quantified (HPLC analysis) in 23 females with fibromyalgia (according to the American College of Rheumatology classification criteria) and 20 healthy females. The results showed significantly higher serum concentrations of aspartate, cysteine, glutamate, glycine, isoleucine, leucine, methionine, ornithine, phenylalanine, sarcosine, serine, taurine, tyrosine and valine in FMS patients vs. healthy controls. Patients with higher Fibromyalgia Impact Questionnaire (FIQ) scores showed increased levels of alanine, glutamine, isoleucine, leucine, phenylalanine, proline and valine. In conclusion, our results indicate an imbalance in some FAAs in FMS patients. Increased Glu is particularly interesting, as it could explain the deficit in monoaminergic transmission involved in pain.

Protective Role of Taurine against Arsenic-Induced Mitochondria-Dependent Hepatic Apoptosis via the Inhibition of PKCδ-JNK Pathway

PubMed Central

Das, Joydeep; Ghosh, Jyotirmoy; Manna, Prasenjit; Sil, Parames C.

2010-01-01

Background Oxidative stress-mediated hepatotoxic effect of arsenic (As) is mainly due to the depletion of glutathione (GSH) in liver. Taurine, on the other hand, enhances intracellular production of GSH. Little is known about the mechanism of the beneficial role of taurine in As-induced hepatic pathophysiology. Therefore, in the present study we investigated its beneficial role in As-induced hepatic cell death via mitochondria-mediated pathway. Methodology/Principal Findings Rats were exposed to NaAsO2 (2 mg/kg body weight for 6 months) and the hepatic tissue was used for oxidative stress measurements. In addition, the pathophysiologic effect of NaAsO2 (10 µM) on hepatocytes was evaluated by determining cell viability, mitochondrial membrane potential and ROS generation. As caused mitochondrial injury by increased oxidative stress and reciprocal regulation of Bcl-2, Bcl-xL/Bad, Bax, Bim in association with increased level of Apaf-1, activation of caspase 9/3, cleavage of PARP protein and ultimately led to apoptotic cell death. In addition, As markedly increased JNK and p38 phosphorylation with minimal disturbance of ERK. Pre-exposure of hepatocytes to a JNK inhibitor SP600125 prevented As-induced caspase-3 activation, ROS production and loss in cell viability. Pre-exposure of hepatocytes to a p38 inhibitor SB2035, on the other hand, had practically no effect on these events. Besides, As activated PKCδ and pre-treatment of hepatocytes with its inhibitor, rottlerin, suppressed the activation of JNK indicating that PKCδ is involved in As-induced JNK activation and mitochondrial dependent apoptosis. Oral administration of taurine (50 mg/kg body weight for 2 weeks) both pre and post to NaAsO2 exposure or incubation of the hepatocytes with taurine (25 mM) were found to be effective in counteracting As-induced oxidative stress and apoptosis. Conclusions/Significance Results indicate that taurine treatment improved As-induced hepatic damages by inhibiting PKCδ-JNK signalling pathways. Therefore taurine supplementation could provide a new approach for the reduction of hepatic complication due to arsenic poisoning. PMID:20830294

Mechanisms of diarrhoea in myotonic dystrophy.

PubMed

Rönnblom, A; Andersson, S; Danielsson, A

1998-07-01

Gastrointestinal (GI) symptoms are common in myotonic dystrophy (MD). Diarrhoea is one of the more disabling of these GI complaints. The mechanisms behind diarrhoea in MD have not previously been investigated systematically. To elucidate the mechanisms behind diarrhoea in MD. Twenty patients with MD and suffering from diarrhoea were investigated in order to detect malabsorption (blood tests and faecal fat excretion) and bile acid malabsorption ([75Se]selenahomocholic acid-taurine (SeHCAT) retention) and to study intestinal morphology (duodenal and rectal biopsies). Two patients had deficiency of folic acid and four showed reduced levels of pancreatic isoamylase, but none of them had steatorrhoea. Two out of eight patients had abnormal bile acid breath tests with normal SeHCAT, indicating small bowel bacterial overgrowth and 12 displayed reduced SeHCAT retention. Duodenal biopsies were normal in eight patients and five out of nine rectal biopsies displayed slight inflammation. A possible mechanism of diarrhoea in MD could be identified in most of the patients. Bile acid malabsorption seems to be a frequent cause and can be treated successfully.

Rapid and reliable quantitation of amino acids and myo-inositol in mouse brain by high performance liquid chromatography and tandem mass spectrometry.

PubMed

Bathena, Sai P; Huang, Jiangeng; Epstein, Adrian A; Gendelman, Howard E; Boska, Michael D; Alnouti, Yazen

2012-04-15

Amino acids and myo-inositol have long been proposed as putative biomarkers for neurodegenerative diseases. Accurate measures and stability have precluded their selective use. To this end, a sensitive liquid chromatography tandem mass spectrometry (LC-MS/MS) method based on multiple reaction monitoring was developed to simultaneously quantify glutamine, glutamate, γ-aminobutyric acid (GABA), aspartic acid, N-acetyl aspartic acid, taurine, choline, creatine, phosphocholine and myo-inositol in mouse brain by methanol extractions. Chromatography was performed using a hydrophilic interaction chromatography silica column within in a total run time of 15 min. The validated method is selective, sensitive, accurate, and precise. The method has a limit of quantification ranging from 2.5 to 20 ng/ml for a range of analytes and a dynamic range from 2.5-20 to 500-4000 ng/ml. This LC-MS/MS method was validated for biomarker discovery in models of human neurological disorders. Copyright © 2012 Elsevier B.V. All rights reserved.

Potential of nor-Ursodeoxycholic Acid in Cholestatic and Metabolic Disorders.

PubMed

Trauner, Michael; Halilbasic, Emina; Claudel, Thierry; Steinacher, Daniel; Fuchs, Claudia; Moustafa, Tarek; Pollheimer, Marion; Krones, Elisabeth; Kienbacher, Christian; Traussnigg, Stefan; Kazemi-Shirazi, Lili; Munda, Petra; Hofer, Harald; Fickert, Peter; Paumgartner, Gustav

2015-01-01

24-nor-ursodeoxycholic acid (norUDCA) is a side-chain shortened derivate of ursodeoxycholic acid (UDCA). Since norUDCA is only ineffectively conjugated with glycine or taurine, it has specific physicochemical and therapeutic properties distinct from UDCA. Nonamidated norUDCA undergoes cholehepatic shunting enabling 'ductular targeting' and inducing a bicarbonate-rich hypercholeresis, with cholangioprotective effects. At the same time it has direct anti-inflammatory, antilipotoxic, anti fibrotic, and antiproliferative properties targeting various liver cell populations. norUDCA appears to be one of the most promising novel treatment approaches targeting the liver and the bile duct system at multifactorial and multicellular levels. This review article is a summary of a lecture given at the XXIII International Bile Acid Meeting (Falk Symposium 194) on 'Bile Acids as Signal Integrators and Metabolic Modulators' held in Freiburg, October 8-9, 2014, and summarizes the recent progress with norUDCA as a novel therapeutic approach in cholestatic and metabolic (liver) disorders. 2015 S. Karger AG, Basel.

The role of organic osmolytes in the response of cultured astrocytes to hyperosmolarity.

PubMed

Hijab, Samina; Havalad, Suresh; Snyder, Ann K

2011-09-01

Idiogenic osmoles are volume-regulatory organic solutes that accumulate within a cell in response to hyperosmolar conditions such as those found in diabetic ketoacidosis or hypernatremic dehydration in infants. Intracellular metabolites known to play this role include certain amino acids and taurine, polyols, and trimethylamines. In this study, in vitro astrocyte cultures prepared from the cerebral cortices of 1-day-old Sprague-Dawley rats were exposed to graded conditions of hypernatremia (325-375 mOsm/kg), a range that can be observed in vivo, for 24, 48, and 72 hours. Cell survival and generation of idiogenic osmoles were determined. Next, we assessed the ability of selected exogenous osmoles to protect the cultured cells from the effects of hypernatremia. Significant cell loss occurred after 48 to 72 hours of exposure and was proportional to the degree of hyperosmolarity. Addition of myoinositol (1 mM) to the cultures reduced cell loss resulting from hypernatremia by approximately 50%. In agreement with previous studies, intracellular levels of myoinositol and taurine correlated with the degree of in vitro hypernatremic exposure and play a significant role in increasing survival of astrocytes subjected to hypertonic insult. (C) 2011 Lippincott Williams & Wilkins, Inc.

Chemical Chaperones Reduce ER Stress and Restore Glucose Homeostasis in a Mouse Model of Type 2 Diabetes

NASA Astrophysics Data System (ADS)

Özcan, Umut; Yilmaz, Erkan; Özcan, Lale; Furuhashi, Masato; Vaillancourt, Eric; Smith, Ross O.; Görgün, Cem Z.; Hotamisligil, Gökhan S.

2006-08-01

Endoplasmic reticulum (ER) stress is a key link between obesity, insulin resistance, and type 2 diabetes. Here, we provide evidence that this mechanistic link can be exploited for therapeutic purposes with orally active chemical chaperones. 4-Phenyl butyric acid and taurine-conjugated ursodeoxycholic acid alleviated ER stress in cells and whole animals. Treatment of obese and diabetic mice with these compounds resulted in normalization of hyperglycemia, restoration of systemic insulin sensitivity, resolution of fatty liver disease, and enhancement of insulin action in liver, muscle, and adipose tissues. Our results demonstrate that chemical chaperones enhance the adaptive capacity of the ER and act as potent antidiabetic modalities with potential application in the treatment of type 2 diabetes.

Regulatory role for phosphatidylcholine transfer protein/StarD2 in the metabolic response to peroxisome proliferator activated receptor alpha (PPARalpha).

PubMed

Kang, Hye Won; Kanno, Keishi; Scapa, Erez F; Cohen, David E

2010-04-01

Phosphatidylcholine transfer protein (PC-TP, a.k.a. StarD2) is abundantly expressed in liver and is regulated by PPARalpha. When fed the synthetic PPARalpha ligand fenofibrate, Pctp(-/-) mice exhibited altered lipid and glucose metabolism. Microarray profiling of livers from fenofibrate fed wild type and Pctp(-/-) mice revealed differential expression of a broad array of metabolic genes, as well as their regulatory transcription factors. PC-TP expression in cell culture controlled the activities of both PPARalpha and HNF4alpha, suggesting that the mechanism by which it modulates hepatic metabolism is at least in part via activation of transcription factors that govern nutrient homeostasis. 2009 Elsevier B.V. All rights reserved.

Dietary taurine intake, nutrients intake, dietary habits and life stress by depression in Korean female college students: a case-control study.

PubMed

Park, Ji-Yeon; You, Jeong-Soon; Chang, Kyung-Ja

2010-08-24

The purpose of this study was to investigate the dietary taurine intake, nutrients intake, dietary habits and life stress by depression in Korean female college students. In this study, research data were collected in March 2009 and 65 patients with depression and 65 controls without depression participated. The CES-D (Center for Epidemiologic Studies Depression) scale was used for depression measure and controls were matched for age. A 3-day recall method was used for dietary assessment (2 weekdays and 1 weekend day). Average height, weight and body mass index (BMI) were 161.3+/-0.5 cm, 55.3+/-1.0 kg and 21.2+/-0.4 kg/m2 for depression patients and those of control group were 161.4+/-0.7 cm, 53.1+/-0.8 kg and 20.3+/-0.2 kg/m2, respectively. Average dietary taurine intakes of depression patients and control group were 89.1 and 88.0 mg/day, respectively. There was no significant difference in dietary taurine intake between depression patients and control group. The average intakes of vitamin A (p<0.05), beta-carotene (p<0.01), vitamin C (p<0.05), folic acid (p<0.05) and fiber (p<0.05) of depression patients were significantly lower compared to control group. The average total dietary habit score of depression patients (47.2) was significantly lower than that of control group (51.3) (p<0.01). The average dietary habit scores of "eating meals at regular times" (p<0.05), "eating adequate amount of meals" (p<0.05), "having meals with diverse foods" (p<0.05), "avoiding eating spicy foods" (p<0.01) and "eating protein foods such as meat, fish, eggs, beans more than 2 times a day" (p<0.05) were significantly lower in depression patients compare to control group. The average scores of total life stress (p<0.001) and all stress categories of depression patients were significantly higher than those of control group except faculty problem score. These results show that depression patients have poor dietary habits and unbalanced nutrition status. Also depression patients have higher life stress score.Therefore, continuous nutrition education and counselling for good dietary habits and balanced nutrition status are needed to prevent depression in Korean college students.

[Blood oxygen transport, prooxidant -- antioxidant status, and vasoactive characteristics of vascular endothelium in rats treated with endotoxin and taurine].

PubMed

Milosh, T S; Maksimovich, N E

2014-01-01

Experiments on a group of 74 pregnant rats upon intramuscular introduction of E. coli lipopolysaccharides during pregnancy revealed the correction effect of taurine on the blood oxygen transport function, prooxidant - antioxidant status, and vasoactive characteristics of vascular endothelium.

Amino and fatty acid dynamics of octopus (Octopus vulgaris) early life stages under ocean warming.

PubMed

Lopes, Vanessa M; Faleiro, Filipa; Baptista, Miguel; Pimentel, Marta S; Paula, José R; Couto, Ana; Bandarra, Narcisa; Anacleto, Patrícia; Marques, António; Rosa, Rui

2016-01-01

The oceans are becoming warmer, and the higher temperatures are expected to have a major impact on marine life at different levels of biological organization, especially at the most vulnerable early life stages. Thus, we hypothesize that the future warmer scenarios (here +3 °C) will affect the biochemical composition (amino acid - AA, and fatty acid-FA) of octopod (Octopus vulgaris) embryos and recently-hatched pelagic paralarvae. The main essential amino acids found in octopus embryos were arginine, leucine and lysine; while aspartic and glutamic acids, and taurine were the main non-essential amino acids. Palmitic, eicosapentaenoic and docosahexaenoic acids were the main FAs found in octopus tissues. Relevant ontogenetic changes were observed, namely a steep decrease in the content of many AAs, and a selective retention of FAs, thus evidencing the protein-based metabolism of these cephalopods. Temperature per si did not elicit significant changes in the overall FA composition, but was responsible for a significant decrease in the content of several AAs, indicating increased embryonic consumption. Copyright © 2015 Elsevier Ltd. All rights reserved.

Recent advances in the understanding of bile acid malabsorption.

PubMed

Pattni, Sanjeev; Walters, Julian R F

2009-01-01

Bile acid malabsorption (BAM) is a syndrome of chronic watery diarrhoea with excess faecal bile acids. Disruption of the enterohepatic circulation of bile acids following surgical resection is a common cause of BAM. The condition is easily diagnosed by the selenium homocholic acid taurine (SeHCAT) test and responds to bile acid sequestrants. Idiopathic BAM (IBAM, primary bile acid diarrhoea) is the condition where no definitive cause for low SeHCAT retention can be identified. Review of PubMed and major journals. Evidence is accumulating that BAM is more prevalent than first thought. Management of chronic diarrhoea involves excluding secondary causes. Treatment of the condition is with bile acid binders. SeHCAT testing is not widely performed, limiting awareness of how common this condition can be. The underlying mechanism for IBAM has been unclear. Increasing awareness of the condition is important. Alternative mechanisms of IBAM have been suggested which involve an increased bile acid pool size and reduced negative feedback regulation of bile acid synthesis by FGF19. New sequestrants are available. Further research into the precise mechanism of IBAM is needed. Improvements in the recognition of the condition and optimization of treatment are required.

Signatures of selection for environmental adaptation and zebu × taurine hybrid fitness in East African shorthorn zebu

USDA-ARS?s Scientific Manuscript database

The East African Shorthorn Zebu (EASZ) cattle are ancient hybrid between Asian zebu × African taurine cattle preferred by local farmers due to their adaptability to the African environment. The genetic controls of these adaptabilities are not clearly understood yet. Here, we genotyped 92 EASZ sample...

Modulatory Effect of Taurine on 7,12-Dimethylbenz(a)Anthracene-Induced Alterations in Detoxification Enzyme System, Membrane Bound Enzymes, Glycoprotein Profile and Proliferative Cell Nuclear Antigen in Rat Breast Tissue.

PubMed

Vanitha, Manickam Kalappan; Baskaran, Kuppusamy; Periyasamy, Kuppusamy; Selvaraj, Sundaramoorthy; Ilakkia, Aruldoss; Saravanan, Dhiravidamani; Venkateswari, Ramachandran; Revathi Mani, Balasundaram; Anandakumar, Pandi; Sakthisekaran, Dhanapal

2016-08-01

The modulatory effect of taurine on 7,12-dimethylbenz(a)anthracene (DMBA)-induced breast cancer in rats was studied. DMBA (25 mg/kg body weight) was administered to induce breast cancer in rats. Protein carbonyl levels, activities of membrane bound enzymes (Na(+) /K(+) ATPase, Ca(2+) ATPase, and Mg(2+) ATPase), phase I drug metabolizing enzymes (cytochrome P450, cytochrome b5, NADPH cytochrome c reductase), phase II drug metabolizing enzymes (glutathione-S-transferase and UDP-glucuronyl transferase), glycoprotein levels, and proliferative cell nuclear antigen (PCNA) were studied. DMBA-induced breast tumor bearing rats showed abnormal alterations in the levels of protein carbonyls, activities of membrane bound enzymes, drug metabolizing enzymes, glycoprotein levels, and PCNA protein expression levels. Taurine treatment (100 mg/kg body weight) appreciably counteracted all the above changes induced by DMBA. Histological examination of breast tissue further supported our biochemical findings. The results of the present study clearly demonstrated the chemotherapeutic effect of taurine in DMBA-induced breast cancer. © 2016 Wiley Periodicals, Inc.

Age- and region-specific imbalances of basal amino acids and monoamine metabolism in limbic regions of female Fmr1 knock-out mice.

PubMed

Gruss, Michael; Braun, Katharina

2004-07-01

The Fragile X syndrome, a common form of mental retardation in humans, originates from the loss of expression of the Fragile X mental retardation gene leading to the absence of the encoded Fragile X mental retardation protein 1 (FMRP). A broad pattern of morphological and behavioral abnormalities is well described for affected humans as well as Fmr1 knock-out mice, a transgenic animal model for the human Fragile X syndrome. In the present study, we examined neurochemical differences between female Fmr1 knock-out and wildtype mice with particular focus on neurotransmission. Significant age- and region-specific differences of basal tissue neurotransmitter and metabolite levels measured by high performance liquid chromatography were found. Those differences were more numerous in juvenile animals (postnatal day (PND) 28-31) compared to adults (postnatal day 209-221). In juvenile female knock-out mice, especially aspartate and taurine were increased in cortical regions, striatum, cerebellum, and brainstem. Furthermore, compared to the wildtype animals, the juvenile knock-out mice displayed an increased level of neuronal inhibition in the hippocampus and brainstem reflected by decreased ratios of (aspartate + glutamate)/(taurine + GABA), as well as an increased dopamine (DA) turnover in cortical regions, striatum, and hippocampus. These results provide the first evidence that the lack of FMRP expression in female Fmr1 knock-out mice is accompanied by age-dependent, region-specific alterations in brain amino acids, and monoamine turnover, which might be related to the reported synaptical and behavioural alterations in these animals.

Rapamycin ameliorates brain metabolites alterations after transient focal ischemia in rats.

PubMed

Chauhan, Anjali; Sharma, Uma; Jagannathan, Naranamangalam R; Gupta, Yogendra Kumar

2015-06-15

Rapamycin has been shown to protect against middle cerebral artery occlusion (MCAo) induced ischemic injury. In this study, the neuroprotective effect of rapamycin on the metabolic changes induced by MCAo was evaluated using nuclear magnetic resonance (NMR) spectroscopy of brain tissues. MCAo in rats was induced by insertion of nylon filament. One hour after ischemia, rapamycin (250 µg/kg, i.p.) in dimethyl sulfoxide was administered. Reperfusion was done 2h after ischemia. Twenty-four hours after ischemia phospholipase A2 (PLA2) levels and metabolic changes were assessed. Perchloric acid extraction was performed on the brain of all animals (n=7; sham, vehicle; DMSO and rapamycin 250 µg/kg) and the various brain metabolites were assessed by NMR spectroscopy. In all 44 metabolites were assigned in the proton NMR spectrum of rat brain tissues. In the vehicle group, we observed increased lactate levels and decreased levels of glutamate/glutamine, choline containing compounds, creatine/phosphocreatine (Cr/PCr), taurine, myo-inositol, γ-amino butryic acid (GABA), N-aspartyl aspartate (NAA), purine and pyrimidine metabolites. In rapamycin treated rats, there was increase in the levels of choline containing compounds, NAA, myo-inositol, glutamate/glutamine, GABA, Cr/PCr and taurine as compared to those of vehicle control (P<0.05). Rapamycin treatment reduced PLA2 levels as compared to vehicle group (P<0.05). Our findings indicated that rapamycin reduced the increased PLA2 levels and altered brain metabolites after MCAo. These protective effects might be attributed to its effect on cell membrane metabolism; glutamate induced toxicity and calcium homeostasis in stroke. Copyright © 2015 Elsevier B.V. All rights reserved.

On the mechanism for PPAR agonists to enhance ABCA1 gene expression

PubMed Central

Ogata, Masaki; Tsujita, Maki; Hossain, Mohammad Anwar; Akita, Nobukatsu; Gonzalez, Frank J.; Staels, Bart; Suzuki, Shogo; Fukutomi, Tatsuya; Kimura, Genjiro; Yokoyama, Shinji

2009-01-01

Expression of ATP binding cassette transporter A1 (ABCA1), a major regulator of high density lipoprotein (HDL) biogenesis, is known to be up-regulated by the transcription factor liver X receptor (LXR) α, and expression is further enhanced by activation of the peroxisome proliferator activated receptors (PPARs). We investigated this complex regulatory network using specific PPAR agonists: four fibrates (fenofibrate, bezafibrate, gemfibrozil and LY518674), a PPAR δ agonist (GW501516) and a PPAR γ agonist (pioglitazone). All of these compounds increased the expression of LXRs, PPARs and ABCA1 mRNAs, and associated apoA-I-mediated lipid release in THP-1 macrophage, WI38 fibroblast and mouse fibroblast. When mouse fibroblasts lacking expression of PPAR α were examined, the effects of fenofibrate and LY518674 were markedly diminished while induction by other ligands were retained. The PPAR α promoter was activated by all of these compounds in an LXR α-dependent manner, and partially in a PPAR α-dependent manner, in mouse fibroblast. The LXR responsive element (LXRE)-luciferase activity was enhanced by all the compounds in an LXR α-dependent manner in mouse fibroblast. This activation was exclusively PPAR α-dependent by fenofibrate and LY518674, but nonexclusively by the others. We conclude that PPARs and LXRs are involved in the regulation of ABCA1 expression and HDL biogenesis in a cooperative signal transduction pathway. PMID:19201410

Evaluation of the light scattering and the turbidity microtiter plate-based methods for the detection of the excipient-mediated drug precipitation inhibition.

PubMed

Petruševska, Marija; Urleb, Uroš; Peternel, Luka

2013-11-01

The excipient-mediated precipitation inhibition is classically determined by the quantification of the dissolved compound in the solution. In this study, two alternative approaches were evaluated, one is the light scattering (nephelometer) and other is the turbidity (plate reader) microtiter plate-based methods which are based on the quantification of the compound precipitate. Following the optimization of the nephelometer settings (beam focus, laser gain) and the experimental conditions, the screening of 23 excipients on the precipitation inhibition of poorly soluble fenofibrate and dipyridamole was performed. The light scattering method resulted in excellent correlation (r>0.91) between the calculated precipitation inhibitor parameters (PIPs) and the precipitation inhibition index (PI(classical)) obtained by the classical approach for fenofibrate and dipyridamole. Among the evaluated PIPs AUC100 (nephelometer) resulted in only four false positives and lack of false negatives. In the case of the turbidity-based method a good correlation of the PI(classical) was obtained for the PIP maximal optical density (OD(max), r=0.91), however, only for fenofibrate. In the case of the OD(max) (plate reader) five false positives and two false negatives were identified. In conclusion, the light scattering-based method outperformed the turbidity-based one and could be reliably used for identification of novel precipitation inhibitors. Copyright © 2013 Elsevier B.V. All rights reserved.

Impact of fibrates on circulating cystatin C levels: a systematic review and meta-analysis of clinical trials.

PubMed

Sahebkar, Amirhossein; Simental-Mendía, Luis E; Pirro, Matteo; Montecucco, Fabrizio; Carbone, Federico; Banach, Maciej; Barreto, George E; Butler, Alexandra E

2018-06-29

To assess the effect of fibrates on circulating cystatin C levels. Clinical studies evaluating the effect of a fibrate on circulating cystatin C levels were searched in PubMed-Medline, SCOPUS, Web of Science and Google Scholar databases. A random-effect model and generic inverse variance method were used for quantitative data synthesis, sensitivity analysis conducted using the leave-one-out method, and weighted random-effects meta-regression performed to evaluate potential confounders on cystatin C levels. This meta-analysis of data from 9 published studies (16 treatment arms) involved a total of 2195 subjects. In a single-arm analysis of clinical trials (without control group; 8 studies comprising 14 treatment arms), fibrate therapy increased circulating cystatin C concentrations (WMD: 0.07 mg/dL, 95% CI: 0.04, 0.10, p <0.001; I 2 = 82.66%). When the analysis was restricted to randomized controlled trials (4 studies comprising 6 treatment arms), again elevation of circulating cystatin C levels was observed (WMD: 0.06 mg/L, 95% CI: 0.03, 0.09, p <0.001; I 2 = 42.98%). Elevated cystatin C levels were only seen with fenofibrate, not other fibrates. The results suggest that fenofibrate treatment adversely affects cystatin C levels and might partially explain the limited efficacy of fenofibrate in reducing cardiovascular events.

Fermented goats' milk produced with selected multiple starters as a potentially functional food.

PubMed

Minervini, Fabio; Bilancia, Maria Teresa; Siragusa, Sonya; Gobbetti, Marco; Caponio, Francesco

2009-09-01

A screening among five lactic acid bacteria, used alone or in combination, led to select a mixed starter (Streptococcus thermophilus CR12, Lactobacillus casei LC01, Lactobacillus helveticus PR4, Lactobacillus plantarum 1288) capable to produce a fermented goats' milk containing gamma-aminobutyric acid (GABA) and angiotensin-I converting enzyme (ACE)-inhibitory peptides. The fermented milk was characterized by cell counts of lactic acid bacteria not lower than 7.0 log cfu g(-1), even after 45 days of storage at 4 degrees C. Fermentation of goats' milk resulted in the production of ca. 28 mg kg(-1) of GABA. Furthermore the fermented goats' milk had an in vitro ACE-inhibitory activity of ca. 73%. Prolonged cold storage did not significantly affect both the concentration of GABA and the ACE-inhibitory activity. Moreover, the taurine content did not significantly vary during both fermentation and the entire storage period.

Proximate composition, antihypertensive and antioxidative properties of the semimembranosus muscle from pork and beef after cooking and in vitro digestion.

PubMed

Jensen, Ida-Johanne; Dort, Junio; Eilertsen, Karl-Erik

2014-02-01

The aims of this study were to evaluate and compare proximate composition, antihypertensive activity and antioxidative capacity of the semimembranosus muscle from pork and beef and to study how these characteristics were affected by household preparation and subsequent digestion. The proximate composition was similar between pork and beef. Both pork and beef contained protein with the essential amino acids. Cooking in a heated pan did not affect the retention of lipid or sum of amino acids, but reduced the amount of the free amino acid taurine. The antihypertensive effect did not differ significantly between pork and beef, whereas the antioxidative capacity did. Cooking affected the antioxidative capacity negatively. The results from this study show that pork and beef are equally good sources of protein and bioactive properties, and whereas the nutritional composition is not affected, bioactive properties may be reduced after household preparations. © 2013.

Effects of acute ammonia toxicity on oxidative stress, immune response and apoptosis of juvenile yellow catfish Pelteobagrus fulvidraco and the mitigation of exogenous taurine.

PubMed

Zhang, Muzi; Li, Ming; Wang, Rixin; Qian, Yunxia

2018-08-01

Ammonia can easily form in intensive culture systems due to ammonification of uneaten food and animal excretion, which usually brings detrimental health effects to fish. However, little information is available on the mechanisms of the detrimental effects of ammonia stress and mitigate means in fish. In this study, the four experimental groups were carried out to test the response of yellow catfish to ammonia toxicity and their mitigation through taurine: group 1 was injected with NaCl, group 2 was injected with ammonium acetate, group 3 was injected with ammonium acetate and taurine, and group 4 was injected taurine. The results showed that ammonia poisoning could induce ammonia, glutamine, glutamate and malondialdehyde accumulation, and subsequently lead to blood deterioration (red blood cell, hemoglobin and serum biochemical index reduced), oxidative stress (superoxide dismutase and catalase activities declined) and immunosuppression (lysozyme, 50% hemolytic complement, total immunoglobulin, phagocytic index and respiratory burst reduced), but the exogenous taurine could mitigate the adverse effect of ammonia poisoning. In addition, ammonia poisoning could induce up-regulation of antioxidant enzymes (Cu/Zn-SOD, CAT, GPx and GR), inflammatory cytokines (TNF, IL-1 and IL-8) and apoptosis (p53, Bax, caspase 3 and caspase 9) genes transcription, suggesting that cell apoptotic and inflammation may relate to oxidative stress. This result will be helpful to understand the mechanism of aquatic toxicology induced by ammonia in fish. Copyright © 2018 Elsevier Ltd. All rights reserved.

Acute administration of high doses of taurine does not substantially improve high-intensity running performance and the effect on maximal accumulated oxygen deficit is unclear.

PubMed

Milioni, Fabio; Malta, Elvis de Souza; Rocha, Leandro George Spinola do Amaral; Mesquita, Camila Angélica Asahi; de Freitas, Ellen Cristini; Zagatto, Alessandro Moura

2016-05-01

The aim of the present study was to investigate the effects of acute administration of taurine overload on time to exhaustion (TTE) of high-intensity running performance and alternative maximal accumulated oxygen deficit (MAODALT). The study design was a randomized, placebo-controlled, crossover design. Seventeen healthy male volunteers (age: 25 ± 6 years; maximal oxygen uptake: 50.5 ± 7.6 mL·kg(-1)·min(-1)) performed an incremental treadmill-running test until voluntary exhaustion to determine maximal oxygen uptake and exercise intensity at maximal oxygen uptake. Subsequently, participants completed randomly 2 bouts of supramaximal treadmill-running at 110% exercise intensity at maximal oxygen uptake until exhaustion (placebo (6 g dextrose) or taurine (6 g) supplementation), separated by 1 week. MAODALT was determined using a single supramaximal effort by summating the contribution of the phosphagen and glycolytic pathways. When comparing the results of the supramaximal trials (i.e., placebo and taurine conditions) no differences were observed for high-intensity running TTE (237.70 ± 66.00 and 277.30 ± 40.64 s; p = 0.44) and MAODALT (55.77 ± 8.22 and 55.06 ± 7.89 mL·kg(-1); p = 0.61), which seem to indicate trivial and unclear differences using the magnitude-based inferences approach, respectively. In conclusion, acute 6 g taurine supplementation before exercise did not substantially improve high-intensity running performance and showed an unclear effect on MAODALT.

Fenofibrate

MedlinePlus

... reduce the amounts of fatty substances such as cholesterol and triglycerides in the blood and to increase ... heart disease) in the blood. Build-up of cholesterol and fats along the walls of the arteries ( ...

Use of antioxidants reduce lipid peroxidation and improve quality of crossbred ram sperm during its cryopreservation.

PubMed

Banday, Mohamad Naiem; Lone, Farooz Ahmad; Rasool, Fabiha; Rashid, Muzamil; Shikari, Arif

2017-02-01

Ram sperm are subjected to extreme oxidative stress during their preservation at -196 °C resulting in reduced quality at post thaw. Therefore, the main objective of this study was to evaluate the effect of antioxidants taurine, quercetin and reduced glutathione on the post thaw quality of crossbred ram sperm. A total of twenty four ejaculates from six crossbred rams were collected and extended with tris-based extender with no antioxidant (Control), with taurine (40 mM), quercetin (5 μg/ml) and reduced glutathione (5 mM). The post thaw sperm quality was determined by percent sperm motility, live sperm count, intact acrosome and hypo-osmotic swelling test (HOST) reacted spermatozoa and lipid peroxidation was measured in terms of malondialdehyde (MDA) level both in seminal plasma and sperm cell. At post thaw, percent sperm motility and live sperm count were significantly (p < 0.05) higher for taurine than control and reduced glutathione but did not differ significantly (p > 0.05) from quercetin. The percent HOST reacted spermatozoa were significantly higher for taurine than control, quercetin and reduced glutathione. Seminal plasma MDA level was significantly (p < 0.05) lower for taurine than control and non-significantly lower than quercetin and reduced glutathione. However, spermatic MDA level did not differ significantly (p > 0.05) among the control and antioxidants. In conclusion, taurine at 40 mM reduced lipid peroxidation and improved post thaw sperm quality of cryopreserved crossbred ram semen. Further, transportation time of semen samples in an ice chest at 4-5 °C may be included as a part of equilibration period, when collection shed and frozen semen unit are located at a distance. Copyright © 2016 Elsevier Inc. All rights reserved.

Energy drinks and their component modulate attention, memory, and antioxidant defences in rats.

PubMed

Valle, M T Costa; Couto-Pereira, N S; Lampert, C; Arcego, D M; Toniazzo, A P; Limberger, R P; Dallegrave, E; Dalmaz, C; Arbo, M D; Leal, M B

2017-08-12

This study aimed to evaluate the effects of the subchronic consumption of energy drinks and their constituents (caffeine and taurine) in male Wistar rats using behavioural and oxidative measures. Energy drinks (ED 5, 7.5, and 10 mL/kg) or their constituents, caffeine (3.2 mg/kg) and taurine (40 mg/kg), either separately or in combination, were administered orally to animals for 28 days. Attention was measured though the ox-maze apparatus and the object recognition memory test. Following behavioural analyses, markers of oxidative stress, including SOD, CAT, GPx, thiol content, and free radicals, were measured in the prefrontal cortex, hippocampus, and striatum. The latency time to find the first reward was lower in animals that received caffeine, taurine, or a combination of both (P = 0.003; ANOVA/Bonferroni). In addition, these animals took less time to complete the ox-maze task (P = 0.0001; ANOVA/Bonferroni), and had better short-term memory (P < 0.01, Kruskal-Wallis). The ED 10 group showed improvement in the attention task, but did not differ on other measures. In addition, there was an imbalance in enzymatic markers of oxidative stress in the prefrontal cortex, the hippocampus, and the striatum. In the group that received both caffeine and taurine, there was a significant increase in the production of free radicals in the prefrontal cortex and in the hippocampus (P < 0.0001; ANOVA/Bonferroni). Exposure to a combination of caffeine and taurine improved memory and attention, and led to an imbalance in the antioxidant defence system. These results differed from those of the group that was exposed to the energy drink. This might be related to other components contained in the energy drink, such as vitamins and minerals, which may have altered the ability of caffeine and taurine to modulate memory and attention.

Exercise and taurine in inflammation, cognition, and peripheral markers of blood-brain barrier integrity in older women.

PubMed

Chupel, Matheus Uba; Minuzzi, Luciele Guerra; Furtado, Guilherme; Santos, Mário Leonardo; Hogervorst, Eef; Filaire, Edith; Teixeira, Ana Maria

2018-07-01

Immunosenescence contribute to increase the blood-brain barrier (BBB) permeability, leading cognitive impairment and neurodegeneration. Thus, we investigated the anti-inflammatory effect of exercise and taurine supplementation on peripheral markers of BBB, inflammation, and cognition of elderly women. Forty-eight elderly women (age, 83.58 ± 6.9 years) participated in the study, and were allocated into combined exercise training (CET: n = 13), taurine supplementation (TAU: n = 12), exercise training associated with taurine (CET+TAU: n = 11), or control (CG: n = 12) groups. Exercise was applied twice a week (multi-modal exercise). Taurine ingestion was 1.5 g., once a day. Participants were evaluated before and after 14-weeks of intervention. Plasma levels of interleukin (IL)-1β, IL-1ra, IL-6, IL-10, IL-17, tumor necrosis factor alpha (TNF-α), and serum concentration of S100β and neuron specific enolase (NSE) were determined. The mini mental state examination (MMSE) was also applied. Concentrations of S100β were maintained in all intervention groups, while a subtle increase in the CG was found. NSE levels increased only in TAU group (p < 0.05). CET reduced TNF-α, IL-6, and IL-1β/IL-1ra, IL-6/IL10, and TNF-α/IL-10 ratios (p < 0.05). TAU decreased the IL-1β/IL-1ra ratio (p < 0.05). MMSE score increased only in the CET+TAU group (p < 0.05). Multiple regression analysis showed that there was a trend for changes in IL-1β and the Charlson Comorbidity Index to be independently associated with changes in S100β. Exercise and taurine decreased inflammation, and maintained the BBB integrity in elderly women. Exercise emerged as an important tool to improve brain health even when started at advanced ages.

Taurine: a novel tumor marker for enhanced detection of breast cancer among female patients.

PubMed

El Agouza, I M; Eissa, S S; El Houseini, M M; El-Nashar, Dalia E; Abd El Hameed, O M

2011-09-01

The antioxidant Taurine found to display antineoplastic effect through down regulation of angiogenesis and enhancement of tumor cell apoptosis. It has been found that progressive inhibition of apoptosis and induction of angiogenesis may contribute to tumor initiation, growth and metastasis in the pathogenesis of breast cancer. To correlate taurine level with the levels of some bioomolecules operating in both angiogenesis (VEGF, CD31) and apoptosis (TNF-α and Caspas-3) which could help for breast cancer pronostication and to evaluate a possible role of serum taurine level as an early marker for breast cancer in Egyptian patients. Four groups of a total 85 female candidates were studied in this work. The first group consists of 50 female patients at National Cancer Institute (NCI), Cairo University were diagnosed and undergoing surgery for breast carcinoma. In the second group 10 having benign breast lesions, were included. The third group consists of five cases, with positive family history. Twenty healthy females were also recruited as control. A preoperative blood sample were taken from each patient to measure serum level of VEGF; Taurine; CA15.3 and TNF- α. Sample of fresh tumor and their corresponding safety margins were obtained from the first and second groups, for determination of caspase-3; histopathological examination and immunohistochemical assay of VEGF and CD31. No significant differences in the serum level of CA15.3 between the breast cancer patients, the high risk and the control group. TNF-α (apoptotic biomolecule) level showed a significant difference only between breast cancer group and control group. The VEGF (angiogenic biomarker) showed a highly significant difference between breast cancer patients, the high risk and the control group. Regarding the antioxidant taurine (antiangiogenic biomolecule) serum level in breast cancer group exhibited a value strongly lower than the high risk and control group. Also the correlative ratio between the angiogenic/apoptotic biomarker (VEGF/TNF-α) showed a highly significant difference between the main previous three groups. Same observation were also noticed in the correlation between angiogenic/antiangiogenic (VEGF/taurine) ratio in the same groups. Moreover the enzymatic activities of Casp-3 in the tissue homogenate were statistically higher in adjacent normal tissues than in malignant tissues. The result of immunohistochemical investigation showed a significant increase in the density of intracellular VEGF and microvessel density expressed as CD31 in cancer cases compared to normal adjacent tissue. It is suggested that assessment of taurine level in sera of patients with high risk for breast cancer are of great value in the early diagnosis of malignant changes in the breast.

Telbivudine

MedlinePlus

... is in a class of medications called nucleoside analogues. It works by decreasing the amount of hepatitis ... IMPORTANT WARNING section and any of the following: chloroquine (Aralen);erythromycin (E.E.S., E-Mycin, Erythrocin); fenofibrate ( ...

[Fibrates therapy: Rational use fenofibrate 2016. Executive summary].

PubMed

Brea, Angel; Millán, Jesús; Ascaso, Juan F; Blasco, Mariano; Díaz, Angel; González-Santos, Pedro; Hernández-Mijares, Antonio; Mantilla, Teresa; Pedro-Botet, Juan C; Pintó, Xavier

To control lipid factors risk, beyond proper management of LDL cholesterol according to individual risk, detection and treatment of atherogenic dyslipidemia and abnormal levels of triglycerides or HDL cholesterol it should be considered for address a global cardiovascular protection, both in primary and secondary prevention. In this sense, these recommendations collect data on efficacy and safety about the combination statin with fibrates, often necessary for total control of dyslipidemia, particularly in patients with metabolic disorders such as diabetes mellitus, metabolic syndrome or visceral obesity. Reference to control and monitoring of treatment is also done, as well as benefits of fenofibrate not linked directly to their lipid-lowering effect. Copyright © 2016 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

[Consensus for pharmacologic treatment of atherogenic dyslipidemia with statin-fenofibrate combined therapy].

PubMed

2016-01-01

LDLc levels are associated with increase of cardiovascular risk, and statins are currently used for their control. Nevertheless, a despite of LDLc levels at goal, a residual risk is persistent, commonly associated with persistent lipids modifications (high triglycerides and low HDLc). So, it is necessary to evaluate triglycerides and HDL to assessment cardiovascular risk. Clinical data are consistent with efficacy and safety of combination therapy with statin and other lipid lowering drugs, for instance fenofibrate. Patients with hipertriglyceridemia and low HDLc are the group with most potential improve. In that patients with atherogenic dyslipidemia, the target for therapeutic objectives related with non-HDL-cholesterol is a priority, because non-HDL-cholesterol is considered as a more accuracy measure to assessment cardiovascular risk. Copyright © 2015. Published by Elsevier España.

[The significance of fenofibrate in the therapy of atherogenic dyslipoproteinaemia].

PubMed

Kucera, M; Oravec, S; Ocadlík, I

2010-08-01

There are accepted the lipid levels goals in all world, which are needed to achievement in primary and secondary prevention. Despite efficacy of current standards of care (including achievement of LDL-C, blood pressure and blood sugar goals), patients with atherogenic dyslipidemia (DLP) (high TG levels, low HDL-C, high apolipoprotein B and small dense LDL-particles), which is common in patients with diabetes melitus (DM), metabolic syndrome or cardiovascular diseases (KVD), remain exposed to a high residual risk of major cardiovascular events and microvascular complications. Statin therapy does not adequately address vascular risk asociated with elevated triglycerides (TG) and low HDL-C levels. As ACCORD lipid trial last time shows, the addition of lipid-modifying activity of fenofibrate to statin therapy benefited only certain subgroups of patients at increased cardiometabolic risk.

Application of chemometrics to assess the influence of ultrasound frequency, Lactobacillus sakei culture and drying on beef jerky manufacture: Impact on amino acid profile, organic acids, texture and colour.

PubMed

Shikha Ojha, K; Granato, Daniel; Rajuria, Gaurav; Barba, Francisco J; Kerry, Joseph P; Tiwari, Brijesh K

2018-01-15

The effects of ultrasound (US) frequency, addition of Lactobacillus sakei culture and drying time on key nutritional (protein, amino acids, and organic acids) and physicochemical properties (texture and colour) of cultured and uncultured beef jerky were evaluated. Cultured and uncultured jerky samples were subjected to US frequencies of 25kHz, 33kHz and 45kHz for 30min prior to marination and drying. Principal component analysis demonstrated a significant effect of beef jerky processing conditions on physicochemical properties. Taurine content of jerky samples was found to increase with an increase in ultrasonic frequencies for cultured samples. No significant changes in colour values were observed for ultrasound pre-treated and control samples. Interactive effects of culture treatment, drying and ultrasonic frequency were observed. This study demonstrates that the nutritional profile of beef jerky can be improved through the incorporation of L. sakei. Copyright © 2017 Elsevier Ltd. All rights reserved.

High-fat diet affects gut nutrients transporters in hypo and hyperthyroid mice by PPAR-a independent mechanism.

PubMed

Losacco, Mariana Cerqueira; de Almeida, Carolina Fernanda Theodora; Hijo, Andressa Harumi Torelli; Bargi-Souza, Paula; Gama, Patricia; Nunes, Maria Tereza; Goulart-Silva, Francemilson

2018-06-01

High fat diet consumes and thyroid hormones (THs) disorders may affect nutrients metabolism, but their impact on the absorptive epithelium, the first place of nutrients access, remains unknown. Our aim was to evaluate the intestinal morphology and nutrients transporters content in mice fed standard (LFD) or high fat (HFD) diets in hypo or hyperthyroidism-induced condition. C57BL/6 male mice fed LFD or HFD diets for 12 weeks, followed by saline, PTU (antithyroid drug) or T3 treatment up to 30 days. The mice were euthanized and proximal intestine was removed to study GLUT2, GLUT5, PEPT1, FAT-CD36, FATP4, NPC1L1 and NHE3 distribution by Western blotting. Since PPAR-a is activated by fatty acids, which is abundant in the HFD, we also evaluated whether PPAR-a affects nutrients transporters. Thus, mice were treated with fenofibrate, a PPAR-a agonist. HFD decreased GLUT2, PEPT1, FAT-CD6 and NPC1L1, but increased NHE3, while GLUT5 and FATP4 remained unaltered. THs did not alter distribution of nutrients transporters neither in LFD nor in HFD groups, but they increased villi length and depth crypt in LFD and HFD, respectively. Fenofibrate did not affect content of nutrients transporters, excluding PPAR-a involvement on the HFD-induced changes. We assume that chronic HFD consumption reduced most of the nutrients transporters content in the small intestine of mice, which might limit the entrance of nutrients and gain weight. Since NHE3 promotes sodium absorption, and it was increased in HFD group, this finding could contribute to explain the hypertension observed in obesity. Copyright © 2018 Elsevier Inc. All rights reserved.

Effects of peroxisome proliferator activated receptors (PPAR)-γ and -α agonists on cochlear protection from oxidative stress

PubMed Central

Wright, Matthew B.; Kucharava, Krystsina; Huerzeler, Nathan; Levano, Soledad; Brand, Yves; Leitmeyer, Katharina; Glutz, Andrea; Bausch, Alexander; Bodmer, Daniel

2017-01-01

Various insults cause ototoxicity in mammals by increasing oxidative stress leading to apoptosis of auditory hair cells (HCs). The thiazolidinediones (TZDs; e.g., pioglitazone) and fibrate (e.g., fenofibrate) drugs are used for the treatment of diabetes and dyslipidemia. These agents target the peroxisome proliferator-activated receptors, PPARγ and PPARα, which are transcription factors that influence glucose and lipid metabolism, inflammation, and organ protection. In this study, we explored the effects of pioglitazone and other PPAR agonists to prevent gentamicin-induced oxidative stress and apoptosis in mouse organ of Corti (OC) explants. Western blots showed high levels of PPARγ and PPARα proteins in mouse OC lysates. Immunofluorescence assays indicated that PPARγ and PPARα proteins are present in auditory HCs and other cell types in the mouse cochlea. Gentamicin treatment induced production of reactive oxygen species (ROS), lipid peroxidation, caspase activation, PARP-1 cleavage, and HC apoptosis in cultured OCs. Pioglitazone mediated its anti-apoptotic effects by opposing the increase in ROS induced by gentamicin, which inhibited the subsequent formation of 4-hydroxy-2-nonenal (4-HNE) and activation of pro-apoptotic mediators. Pioglitazone mediated its effects by upregulating genes that control ROS production and detoxification pathways leading to restoration of the reduced:oxidized glutathione ratio. Structurally diverse PPAR agonists were protective of HCs. Pioglitazone (PPARγ-specific), tesaglitazar (PPARγ/α-specific), and fenofibric acid (PPARα-specific) all provided >90% protection from gentamicin toxicity by regulation of overlapping subsets of genes controlling ROS detoxification. This study revealed that PPARs play important roles in the cochlea, and that PPAR-targeting drugs possess therapeutic potential as treatment for hearing loss. PMID:29182629

Achievement of lipid targets with the combination of rosuvastatin and fenofibric Acid in patients with type 2 diabetes mellitus.

PubMed

Rosenson, Robert S; Carlson, Dawn M; Kelly, Maureen T; Setze, Carolyn M; Hirshberg, Boaz; Stolzenbach, James C; Williams, Laura A

2011-02-01

The objective of this study was to assess the proportion of patients with type 2 diabetes mellitus (T2DM) attaining individual and combined targets of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), non-HDL-C, and apolipoprotein B (ApoB) after treatment with rosuvastatin (R) + fenofibric acid (FA) compared with corresponding-dose R monotherapy. This post hoc analysis evaluated data from the T2DM subset of patients with mixed dyslipidemia (LDL-C ≥130 mg/dL, HDL-C <40/50 mg/dL in men/women, and TG ≥150 mg/dL) from 2 randomized studies. Patients included in the analysis (N = 456) were treated with R (5, 10, or 20 mg), FA 135 mg, or R (5, 10, or 20 mg) + FA 135 mg for 12 weeks. Attainment of LDL-C <100 mg/dL, HDL-C >40/50 mg/dL in men/women, TG <150 mg/dL, non-HDL-C <130 mg/dL, ApoB <90 mg/dL, and the combined targets of these parameters was assessed. Treatment with R + FA resulted in a significantly higher proportion of patients achieving optimal levels of HDL-C (46.8% vs. 20.8%, P = 0.009 for R 10 mg + FA), TG (60.0% vs. 34.0%, P = 0.02 for R 10 mg + FA; 54.0% vs. 26.4%, P = 0.005 for R 20 mg + FA), non-HDL-C (55.1% vs. 36.4%, P = 0.04 for R 5 mg + FA), ApoB (58.0% vs. 36.4%, P = 0.02 for R 5 mg + FA); and the combined targets of LDL-C, HDL-C, and TG (28.3% vs. 8.3%, P = 0.02 for R 10 mg + FA) and all 5 parameters (26.1% vs. 8.3%, P = 0.03 for R 10 mg + FA) than corresponding-dose R monotherapies. A significantly greater proportion of T2DM patients achieved individual and combined lipid targets when treated with the combination of R + FA than corresponding-dose R monotherapies.

[Improvement and prediction of intestinal drug absorption].

PubMed

Miyake, Masateru

2013-01-01

The suppository preparation, which can improve the absorption of poorly absorbable drugs safer than commercially available suppositories, was developed by utilizing sodium laurate and taurine. Additionally, the novel oral absorption-improving system was also established by utilizing polyamines and bile acids. Furthermore, to evaluate the efficacy of these new formulations and estimate the absorbability of new drug candidates in humans, the in vitro prediction system utilizing an isolated human intestinal tissues was developed and successfully predicted the fraction of dose absorbed for several model drugs. These findings would contribute to the development of new dosage forms and new drugs for oral administration.

Altered peripheral amino acid profile indicate a systemic impact of active celiac disease and a possible role of amino acids in disease pathogenesis.

PubMed

Torinsson Naluai, Åsa; Saadat Vafa, Ladan; Gudjonsdottir, Audur H; Arnell, Henrik; Browaldh, Lars; Nilsson, Staffan; Agardh, Daniel

2018-01-01

We have previously performed a Genome Wide Association and linkage study that indicated a new disease triggering mechanism involving amino acid metabolism and nutrient sensing signaling pathways. The aim of this study was to investigate if plasma amino acid levels differed among children with celiac disease compared with disease controls. Fasting plasma samples from 141 children with celiac disease and 129 non-celiac disease controls, were analyzed for amino acid levels by liquid chromatography-tandem mass spectrometry (LC/MS). A general linear model using age and experimental effects as covariates was used to compare amino acid levels between children with a diagnosis of celiac disease and controls. Seven out of twenty-three analyzed amino acids were elevated in children with celiac disease compared with controls (tryptophan, taurine, glutamic acid, proline, ornithine, alanine and methionine). The significance of the individual amino acids do not survive multiple correction, however, multivariate analyses of the amino acid profile showed significantly altered amino acid levels in children with celiac disease overall and after correction for age, sex and experimental effects (p = 8.4 × 10-8). These findings support the idea that amino acids could influence systemic inflammation and play a possible role in disease pathogenesis.

Factors affecting the formation of eutectic solid dispersions and their dissolution behavior.

PubMed

Vippagunta, Sudha R; Wang, Zeren; Hornung, Stefanie; Krill, Steven L

2007-02-01

The objective of this work was to obtain a fundamental understanding of the factors, specifically the properties of poorly water-soluble drugs and water-soluble carriers, which influence predominantly, the formation of eutectic or monotectic crystalline solid dispersion and their dissolution behavior. A theoretical model was applied on five poorly water-soluble drugs (fenofibrate, flurbiprofen, griseofulvin, naproxen, and ibuprofen) having diverse physicochemical properties and water-soluble carrier (polyethylene glycol (PEG) 8000) for the evaluation of these factors. Of these, two drugs, fenofibrate and flurbiprofen, and PEG of different molecular weights (3350, 8000, and 20000), were chosen as model drugs and carriers for further investigation. Experimental phase diagrams were constructed and dissolution testing was performed to assess the performance of the systems. The theoretical model predicted the formation of eutectic or monotectic solid dispersions of fenofibrate, griseofulvin, ibuprofen, and naproxen with PEG, holding the contribution of specific intermolecular interactions between compound and carrier to zero. In the case of the flurbiprofen-PEG eutectic system, intermolecular interactions between drug and polymer needed to be taken into consideration to predict the experimental phase diagram. The results of the current work suggest that the thermodynamic function of melting point and heat of fusion (as a measure of crystal energy of drug) plays a significant role in the formation of a eutectic system. Lipophilicity of the compound (as represented by cLog P) was also demonstrated to have an effect. Specific interactions between drug and carrier play a significant role in influencing the eutectic composition. Molar volume of the drug did not seem to have an impact on eutectic formation. The polymer molecular weight appeared to have an impact on the eutectic composition for flurbiprofen, which exhibits specific interactions with PEG, whereas no such impact of polymer molecular weight on eutectic composition was observed for fenofibrate, which does not exhibit specific interactions with PEG. The impact of polymer molecular weight on dissolution of systems where specific drug-polymer interactions are exhibited was also observed. The current work provides valuable insight into factors affecting formation and dissolution of eutectic systems, which can facilitate the rational selection of suitable water-soluble carriers. Copyright (c) 2006 Wiley-Liss, Inc.

Cellular model for induction of drip loss in meat.

PubMed

Lambert, I H; Nielsen, J H; Andersen, H J; Ørtenblad, N

2001-10-01

Drip loss from porcine muscle (M. longissimus dorsi) contained high concentrations of K(+) ( approximately 135 mM) and organic osmolytes, for example, taurine ( approximately 15 mM), as well as significant amounts of protein ( approximately 125 mg.mL(-1)). Thus, the drip reflects release of intramuscular components. To simulate events taking place at the time of slaughter and leading to release of osmolytes and subsequent formation of drip loss, C2C12 myotubes were exposed to anoxia and reduction in pH (from 7.4 to 6.0). Anoxia and acidification increased the cellular Ca(2+) concentration ([Ca(2+)](i)) at a rate of 22-32 nM.min(-)(1). The anoxia-induced increase in [Ca(2+)](i) was mainly due to influx via sarcolemmal Na(+) channels. As mammalian cells swell and release lysophospholipids during anoxia, C2C12 cells and primary porcine muscle cells were exposed to either hypotonic shock or lysophosphatidylcholine (LPC) and the release of taurine was followed. The swelling-induced taurine efflux was blocked in the presence of the anion channel blocker (DIDS), the 5-lipooxygenase inhibitors (ETH 615-139 and NDGA) but unaffected by the presence of vitamin E. In contrast, the LPC-induced taurine release was unaffected by DIDS but abolished by antioxidants (butylated hydroxytoluene and vitamin E). Thus, stress-induced taurine release from muscles may precede by two different mechanisms, one being 5-lipooxygenase dependent and the other involving generation of reactive oxygen species. A model for the cellular events, preceding formation of drip in meat, is presented.

Thrombin increases hyposmotic taurine efflux and accelerates ICI-swell and RVD in 3T3 fibroblasts by a src-dependent EGFR transactivation.

PubMed

Vázquez-Juárez, E; Ramos-Mandujano, G; Lezama, R A; Cruz-Rangel, S; Islas, L D; Pasantes-Morales, H

2008-02-01

The present study in Swiss3T3 fibroblasts examines the effect of thrombin on hyposmolarity-induced osmolyte fluxes and RVD, and the contribution of the src/EGFR pathway. Thrombin (5 U/ml) added to a 30% hyposmotic medium markedly increased hyposmotic 3H-taurine efflux (285%), accelerated the volume-sensitive Cl- current (ICI-swell) and increased RVD rate. These effects were reduced (50-65%) by preventing the thrombin-induced intracellular Ca2+ [Ca2+]i rise with EGTA-AM, or with the phospholipase C (PLC) blocker U73122. Ca2+calmodulin (CaM) and calmodulin kinase II (CaMKII) also participate in this Ca2+-dependent pathway. Thrombin plus hyposmolarity increased src and EGFR phosphorylation, whose blockade by PP2 and AG1478, decreased by 30-50%, respectively, the thrombin effects on hyposmotic taurine efflux, ICI-swell and RVD. Ca2+- and src/EGFR-mediated pathways operate independently as shown by (1) the persistence of src and EGFR activation when [Ca2+]i rise is prevented and (2) the additive effect on taurine efflux, ICI-swell or RVD by simultaneous inhibition of the two pathways, which essentially suppressed these events. PLC-Ca2+- and src/EGFR-signaling pathways operate in the hyposmotic condition and because thrombin per se failed to increase taurine efflux and ICI-swell under isosmotic condition it seems that it is merely amplifying these previously activated mechanisms. The study shows that thrombin potentiates hyposmolarity-induced osmolyte fluxes and RVD by increasing src/EGFR-dependent signaling, in addition to the Ca2+-dependent pathway.

Effects of Organic and Inorganic Nitrogen on the Growth and Production of Domoic Acid by Pseudo-nitzschia multiseries and P. australis (Bacillariophyceae) in Culture.

PubMed

Martin-Jézéquel, Véronique; Calu, Guillaume; Candela, Leo; Amzil, Zouher; Jauffrais, Thierry; Séchet, Véronique; Weigel, Pierre

2015-11-26

Over the last century, human activities have altered the global nitrogen cycle, and anthropogenic inputs of both inorganic and organic nitrogen species have increased around the world, causing significant changes to the functioning of aquatic ecosystems. The increasing frequency of Pseudo-nitzschia spp. in estuarine and coastal waters reinforces the need to understand better the environmental control of its growth and domoic acid (DA) production. Here, we document Pseudo-nitzschia spp. growth and toxicity on a large set of inorganic and organic nitrogen (nitrate, ammonium, urea, glutamate, glutamine, arginine and taurine). Our study focused on two species isolated from European coastal waters: P. multiseries CCL70 and P. australis PNC1. The nitrogen sources induced broad differences between the two species with respect to growth rate, biomass and cellular DA, but no specific variation could be attributed to any of the inorganic or organic nitrogen substrates. Enrichment with ammonium resulted in an enhanced growth rate and cell yield, whereas glutamate did not support the growth of P. multiseries. Arginine, glutamine and taurine enabled good growth of P. australis, but without toxin production. The highest DA content was produced when P. multiseries grew with urea and P. australis grew with glutamate. For both species, growth rate was not correlated with DA content but more toxin was produced when the nitrogen source could not sustain a high biomass. A significant negative correlation was found between cell biomass and DA content in P. australis. This study shows that Pseudo-nitzschia can readily utilize organic nitrogen in the form of amino acids, and confirms that both inorganic and organic nitrogen affect growth and DA production. Our results contribute to our understanding of the ecophysiology of Pseudo-nitzschia spp. and may help to predict toxic events in the natural environment.

Distinct signatures of host–microbial meta-metabolome and gut microbiome in two C57BL/6 strains under high-fat diet

PubMed Central

Walker, Alesia; Pfitzner, Barbara; Neschen, Susanne; Kahle, Melanie; Harir, Mourad; Lucio, Marianna; Moritz, Franco; Tziotis, Dimitrios; Witting, Michael; Rothballer, Michael; Engel, Marion; Schmid, Michael; Endesfelder, David; Klingenspor, Martin; Rattei, Thomas; Castell, Wolfgang zu; de Angelis, Martin Hrabé; Hartmann, Anton; Schmitt-Kopplin, Philippe

2014-01-01

A combinatory approach using metabolomics and gut microbiome analysis techniques was performed to unravel the nature and specificity of metabolic profiles related to gut ecology in obesity. This study focused on gut and liver metabolomics of two different mouse strains, the C57BL/6J (C57J) and the C57BL/6N (C57N) fed with high-fat diet (HFD) for 3 weeks, causing diet-induced obesity in C57N, but not in C57J mice. Furthermore, a 16S-ribosomal RNA comparative sequence analysis using 454 pyrosequencing detected significant differences between the microbiome of the two strains on phylum level for Firmicutes, Deferribacteres and Proteobacteria that propose an essential role of the microbiome in obesity susceptibility. Gut microbial and liver metabolomics were followed by a combinatory approach using Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) and ultra performance liquid chromatography time of tlight MS/MS with subsequent multivariate statistical analysis, revealing distinctive host and microbial metabolome patterns between the C57J and the C57N strain. Many taurine-conjugated bile acids (TBAs) were significantly elevated in the cecum and decreased in liver samples from the C57J phenotype likely displaying different energy utilization behavior by the bacterial community and the host. Furthermore, several metabolite groups could specifically be associated with the C57N phenotype involving fatty acids, eicosanoids and urobilinoids. The mass differences based metabolite network approach enabled to extend the range of known metabolites to important bile acids (BAs) and novel taurine conjugates specific for both strains. In summary, our study showed clear alterations of the metabolome in the gastrointestinal tract and liver within a HFD-induced obesity mouse model in relation to the host–microbial nutritional adaptation. PMID:24906017

Effects of Organic and Inorganic Nitrogen on the Growth and Production of Domoic Acid by Pseudo-nitzschia multiseries and P. australis (Bacillariophyceae) in Culture

PubMed Central

Martin-Jézéquel, Véronique; Calu, Guillaume; Candela, Leo; Amzil, Zouher; Jauffrais, Thierry; Séchet, Véronique; Weigel, Pierre

2015-01-01

Over the last century, human activities have altered the global nitrogen cycle, and anthropogenic inputs of both inorganic and organic nitrogen species have increased around the world, causing significant changes to the functioning of aquatic ecosystems. The increasing frequency of Pseudo-nitzschia spp. in estuarine and coastal waters reinforces the need to understand better the environmental control of its growth and domoic acid (DA) production. Here, we document Pseudo-nitzschia spp. growth and toxicity on a large set of inorganic and organic nitrogen (nitrate, ammonium, urea, glutamate, glutamine, arginine and taurine). Our study focused on two species isolated from European coastal waters: P. multiseries CCL70 and P. australis PNC1. The nitrogen sources induced broad differences between the two species with respect to growth rate, biomass and cellular DA, but no specific variation could be attributed to any of the inorganic or organic nitrogen substrates. Enrichment with ammonium resulted in an enhanced growth rate and cell yield, whereas glutamate did not support the growth of P. multiseries. Arginine, glutamine and taurine enabled good growth of P. australis, but without toxin production. The highest DA content was produced when P. multiseries grew with urea and P. australis grew with glutamate. For both species, growth rate was not correlated with DA content but more toxin was produced when the nitrogen source could not sustain a high biomass. A significant negative correlation was found between cell biomass and DA content in P. australis. This study shows that Pseudo-nitzschia can readily utilize organic nitrogen in the form of amino acids, and confirms that both inorganic and organic nitrogen affect growth and DA production. Our results contribute to our understanding of the ecophysiology of Pseudo-nitzschia spp. and may help to predict toxic events in the natural environment. PMID:26703627

Metabolites associated with adaptation of microorganisms to an acidophilic, metal-rich environment identified by stable-isotope-enabled metabolomics.

PubMed

Mosier, Annika C; Justice, Nicholas B; Bowen, Benjamin P; Baran, Richard; Thomas, Brian C; Northen, Trent R; Banfield, Jillian F

2013-03-12

Microorganisms grow under a remarkable range of extreme conditions. Environmental transcriptomic and proteomic studies have highlighted metabolic pathways active in extremophilic communities. However, metabolites directly linked to their physiology are less well defined because metabolomics methods lag behind other omics technologies due to a wide range of experimental complexities often associated with the environmental matrix. We identified key metabolites associated with acidophilic and metal-tolerant microorganisms using stable isotope labeling coupled with untargeted, high-resolution mass spectrometry. We observed >3,500 metabolic features in biofilms growing in pH ~0.9 acid mine drainage solutions containing millimolar concentrations of iron, sulfate, zinc, copper, and arsenic. Stable isotope labeling improved chemical formula prediction by >50% for larger metabolites (>250 atomic mass units), many of which were unrepresented in metabolic databases and may represent novel compounds. Taurine and hydroxyectoine were identified and likely provide protection from osmotic stress in the biofilms. Community genomic, transcriptomic, and proteomic data implicate fungi in taurine metabolism. Leptospirillum group II bacteria decrease production of ectoine and hydroxyectoine as biofilms mature, suggesting that biofilm structure provides some resistance to high metal and proton concentrations. The combination of taurine, ectoine, and hydroxyectoine may also constitute a sulfur, nitrogen, and carbon currency in the communities. Microbial communities are central to many critical global processes and yet remain enigmatic largely due to their complex and distributed metabolic interactions. Metabolomics has the possibility of providing mechanistic insights into the function and ecology of microbial communities. However, our limited knowledge of microbial metabolites, the difficulty of identifying metabolites from complex samples, and the inability to link metabolites directly to community members have proven to be major limitations in developing advances in systems interactions. Here, we show that combining stable-isotope-enabled metabolomics with genomics, transcriptomics, and proteomics can illuminate the ecology of microorganisms at the community scale.

Extrasynaptic localization of glycine receptors in the rat supraoptic nucleus: further evidence for their involvement in glia-to-neuron communication.

PubMed

Deleuze, C; Alonso, G; Lefevre, I A; Duvoid-Guillou, A; Hussy, N

2005-01-01

Neurons of the rat supraoptic nucleus (SON) express glycine receptors (GlyRs), which are implicated in the osmoregulation of neuronal activity. The endogenous agonist of the receptors has been postulated to be taurine, shown to be released from astrocytes. We here provide additional pieces of evidence supporting the absence of functional glycinergic synapses in the SON. First, we show that blockade of GlyRs with strychnine has no effect on either the amplitude or frequency of miniature inhibitory postsynaptic currents recorded in SON neurons, whereas they were all suppressed by the GABA(A) antagonist gabazine. Then, double immunostaining of sections with presynaptic markers and either GlyR or GABA(A) receptor (GABA(A)R) antibodies indicates that, in contrast with GABA(A)Rs, most GlyR membrane clusters are not localized facing presynaptic terminals, indicative of their extrasynaptic localization. Moreover, we found a striking anatomical association between SON GlyR clusters and glial fibrillary acidic protein (GFAP)-positive astroglial processes, which contain high levels of taurine. This type of correlation is specific to GlyRs, since GABA(A)R clusters show no association with GFAP-positive structures. These results substantiate and strengthen the concept of extrasynaptic GlyRs mediating a paracrine communication between astrocytes and neurons in the SON.

Effects of aniracetam on extracellular levels of transmitter amino acids in the hippocampus of the conscious gerbils: an intracranial microdialysis study.

PubMed

Yu, Siming; Cai, Jingxia

2003-03-27

The effects of aniracetam on extracellular amino acid levels in the hippocampus of conscious gerbils, with or without transient cerebral ischemia/reperfusion, were measured by microdialysis and reverse phase-high performance liquid chromatography. Increased extracellular levels of aspartate and glutamate that were observed in the hippocampus of conscious gerbils during transient global forebrain ischemia were reversed by aniracetam. In contrast, the level of extracellular gamma-aminobutyric acid was increased, while taurine was maintained at a higher level than other amino acids by administration of aniracetam (100 mg/kg, p.o.) 60 min before ischemia. Further, in contrast to ischemic animals, administration of aniracetam (100 mg/kg, p.o.) enhanced the release of glutamate and aspartate in the normal gerbil hippocampus. The results suggest that these effects might be due to a partial calcium agonist activity of aniracetam, and that the effects of aniracetam on amino acid levels might be a mechanism of protection against delayed neuronal death in the ischemic hippocampus, thereby improving memory dysfunction induced by ischemia/reperfusion.

Therapeutic Mechanisms of Bile Acids and Nor-Ursodeoxycholic Acid in Non-Alcoholic Fatty Liver Disease.

PubMed

Steinacher, Daniel; Claudel, Thierry; Trauner, Michael

2017-01-01

Non-alcoholic fatty liver disease is one of the most rapidly rising clinical problems in the 21st century. So far no effective drug treatment has been established to cure this disease. Bile acids (BAs) have a variety of signaling properties, which can be used therapeutically for modulating hepatic metabolism and inflammation. A side-chain shorted derivative of ursodeoxycholic acid (UDCA) is 24 nor-ursodeoxycholic acid (NorUDCA) and it represents a new class of drugs for treatment of liver diseases. NorUDCA has unique biochemical and therapeutic properties, since it is relatively resistant to conjugation with glycine or taurine compared to UDCA. NorUDCA undergoes cholehepatic shunting, resulting in ductular targeting, bicarbonate-rich hypercholeresis, and cholangiocyte protection. Furthermore, it showed anti-fibrotic, anti-inflammatory, and anti-lipotoxic properties in several animal models. As such, NorUDCA is a promising new approach in the treatment of cholestatic and metabolic liver diseases. This review is a summary of current BA-based therapeutic approaches in the treatment of the fatty liver disease. © 2017 S. Karger AG, Basel.

Managing bile acid diarrhoea

PubMed Central

Walters, Julian R. F.; Pattni, Sanjeev S.

2010-01-01

Bowel symptoms including diarrhoea can be produced when excess bile acids (BA) are present in the colon. This condition, known as bile acid or bile salt malabsorption, has been under recognized, as the best diagnostic method, the 75Se-homocholic acid taurine (SeHCAT) test, is not available in many countries and is not fully utilized in others. Reduced SeHCAT retention establishes that this is a complication of many other gastrointestinal diseases. Repeated studies show SeHCAT tests are abnormal in about 30% of patients otherwise diagnosed as diarrhoea-predominant irritable bowel syndrome or functional diarrhoea, with an estimated population prevalence of around 1%. Recent work suggests that the condition previously called idiopathic bile acid malabsorption (BAM) is not in fact due to a defect in absorption, but results from an overproduction of BA because of defective feedback inhibition of hepatic bile acid synthesis, a function of the ileal hormone fibroblast growth factor 19 (FGF19). The approach to treatment currently depends on binding excess BA, to reduce their secretory actions, using colestyramine, colestipol and, most recently, colesevelam. Colesevelam has a number of potential advantages that merit further investigation in trials directed at patients with bile acid diarrhoea. PMID:21180614

Managing bile acid diarrhoea.

PubMed

Walters, Julian R F; Pattni, Sanjeev S

2010-11-01

Bowel symptoms including diarrhoea can be produced when excess bile acids (BA) are present in the colon. This condition, known as bile acid or bile salt malabsorption, has been under recognized, as the best diagnostic method, the (75)Se-homocholic acid taurine (SeHCAT) test, is not available in many countries and is not fully utilized in others. Reduced SeHCAT retention establishes that this is a complication of many other gastrointestinal diseases. Repeated studies show SeHCAT tests are abnormal in about 30% of patients otherwise diagnosed as diarrhoea-predominant irritable bowel syndrome or functional diarrhoea, with an estimated population prevalence of around 1%. Recent work suggests that the condition previously called idiopathic bile acid malabsorption (BAM) is not in fact due to a defect in absorption, but results from an overproduction of BA because of defective feedback inhibition of hepatic bile acid synthesis, a function of the ileal hormone fibroblast growth factor 19 (FGF19). The approach to treatment currently depends on binding excess BA, to reduce their secretory actions, using colestyramine, colestipol and, most recently, colesevelam. Colesevelam has a number of potential advantages that merit further investigation in trials directed at patients with bile acid diarrhoea.

Changes in brain amino acid content induced by hyposmolar stress and energy deprivation.

PubMed

Haugstad, T S; Valø, E T; Langmoen, I A

1995-12-01

The changes in endogenous amino acids in brain extracellular and intracellular compartments evoked by hyposmotic stress and energy deprivation were compared. Tissue content and release of ten amino acids were measured simultaneously in rat hippocampal slices by means of high performance liquid chromatography. Hyposmotic stress induced a large release of taurine (25568 pmol mg-1 protein), and a smaller release of glutamate, accompanied by an inverse change in tissue content. Adding mannitol to correct osmolarity, blocked these changes. Energy deprivation caused an increase in the release of all amino acids except glutamine. The release was particularly large for glutamate and GABA (31141 and 13282 pmol mg-1, respectively). The intracellular concentrations were generally reduced, but the total amount of the released amino acids increased In contrast to the effect seen during hyposmolar stress, mannitol enhanced the changes due to energy deprivation. The results show that hyposmolar stress and energy deprivation cause different content and release profiles, suggesting that the mechanisms involved in the two situations are either different or modulated in different ways. The intracellular amino acid depletion seen during energy deprivation shows that increased outward transport is probably a primary event, and increased amino acid formation likely secondary to this release.

Bile acids: regulation of apoptosis by ursodeoxycholic acid

PubMed Central

Amaral, Joana D.; Viana, Ricardo J. S.; Ramalho, Rita M.; Steer, Clifford J.; Rodrigues, Cecília M. P.

2009-01-01

Bile acids are a group of molecular species of acidic steroids with peculiar physical-chemical and biological characteristics. At high concentrations they become toxic to mammalian cells, and their presence is pertinent in the pathogenesis of several liver diseases and colon cancer. Bile acid cytoxicity has been related to membrane damage, but also to nondetergent effects, such as oxidative stress and apoptosis. Strikingly, hydrophilic ursodeoxycholic acid (UDCA), and its taurine-conjugated form (TUDCA), show profound cytoprotective properties. Indeed, these molecules have been described as potent inhibitors of classic pathways of apoptosis, although their precise mode of action remains to be clarified. UDCA, originally used for cholesterol gallstone dissolution, is currently considered the first choice therapy for several forms of cholestatic syndromes. However, the beneficial effects of both UDCA and TUDCA have been tested in other experimental pathological conditions with deregulated levels of apoptosis, including neurological disorders, such as Alzheimer's, Parkinson's, and Huntington's diseases. Here, we review the role of bile acids in modulating the apoptosis process, emphasizing the anti-apoptotic effects of UDCA and TUDCA, as well as their potential use as novel and alternate therapeutic agents for the treatment of apoptosis-related diseases. PMID:19417220

Bile acids: regulation of apoptosis by ursodeoxycholic acid.

PubMed

Amaral, Joana D; Viana, Ricardo J S; Ramalho, Rita M; Steer, Clifford J; Rodrigues, Cecília M P

2009-09-01

Bile acids are a group of molecular species of acidic steroids with peculiar physical-chemical and biological characteristics. At high concentrations they become toxic to mammalian cells, and their presence is pertinent in the pathogenesis of several liver diseases and colon cancer. Bile acid cytoxicity has been related to membrane damage, but also to nondetergent effects, such as oxidative stress and apoptosis. Strikingly, hydrophilic ursodeoxycholic acid (UDCA), and its taurine-conjugated form (TUDCA), show profound cytoprotective properties. Indeed, these molecules have been described as potent inhibitors of classic pathways of apoptosis, although their precise mode of action remains to be clarified. UDCA, originally used for cholesterol gallstone dissolution, is currently considered the first choice therapy for several forms of cholestatic syndromes. However, the beneficial effects of both UDCA and TUDCA have been tested in other experimental pathological conditions with deregulated levels of apoptosis, including neurological disorders, such as Alzheimer's, Parkinson's, and Huntington's diseases. Here, we review the role of bile acids in modulating the apoptosis process, emphasizing the anti-apoptotic effects of UDCA and TUDCA, as well as their potential use as novel and alternate therapeutic agents for the treatment of apoptosis-related diseases.

DISSEMINATING EVIDENCE FROM A LANDMARK TRIAL: CROSS-SECTIONAL ANALYSIS OF DESCRIPTIONS AND INTERPRETATIONS OF THE ACCORD-LIPID TRIAL IN THE NEWS AND BIOMEDICAL LITERATURE

PubMed Central

Downing, Nicholas S.; Cheng, Theresa; Krumholz, Harlan M.; Shah, Nilay D.; Ross, Joseph S.

2014-01-01

The lipid component of the Action to Control Cardiovascular Risk in Diabetes trial (ACCORD-Lipid) was a landmark, publicly-funded trial demonstrating that fenofibrate, when added to statin therapy, was not associated with improved cardiovascular outcomes among patients with diabetes. We performed a cross-sectional study of all articles describing results of ACCORD-Lipid in the news and biomedical literature in the 15 months following its publication. For articles published in biomedical journals, we determined whether there was an association between authors’ conflict of interests (COI) and trial interpretation. We identified 67 news and 141 biomedical journal articles discussing ACCORD-Lipid. Approximately 30% of news and biomedical journal articles described fenofibrate as ineffective, whereas nearly 20% concluded it was effective. Among articles making a recommendation, approximately 50% of news and 67% of biomedical journal articles supported continued fibrate use. Authors with COI were more likely to describe fenofibrate as effective (27.1% vs. 8.9%; relative risk [RR]=3.03, 95% confidence interval [CI], 1.22–7.50; P=0.008) and to support continued fibrate use (77.4% vs. 45.8%; RR=1.69, 95% CI, 1.07–2.67; P=0.006). ACCORD-Lipid was described inconsistently in news and biomedical journal articles, possibly creating uncertainty among patients and physicians, and COI were associated with more favorable trial interpretation. PMID:24796406

Crustacean zooplankton release copious amounts of dissolved organic matter as taurine in the ocean.

PubMed

Clifford, Elisabeth L; Hansell, Dennis A; Varela, Marta M; Nieto-Cid, Mar; Herndl, Gerhard J; Sintes, Eva

2017-11-01

Taurine (Tau), an amino acid-like compound, is present in almost all marine metazoans including crustacean zooplankton. It plays an important physiological role in these organisms and is released into the ambient water throughout their life cycle. However, limited information is available on the release rates by marine organisms, the concentrations and turnover of Tau in the ocean. We determined dissolved free Tau concentrations throughout the water column and its release by abundant crustacean mesozooplankton at two open ocean sites (Gulf of Alaska and North Atlantic). At both locations, the concentrations of dissolved free Tau were in the low nM range (up to 15.7 nM) in epipelagic waters, declining sharply in the mesopelagic to about 0.2 nM and remaining fairly stable throughout the bathypelagic waters. Pacific amphipod-copepod assemblages exhibited lower dissolved free Tau release rates per unit biomass (0.8 ± 0.4 μmol g -1 C-biomass h -1 ) than Atlantic copepods (ranging between 1.3 ± 0.4 μmol g -1 C-biomass h -1 and 9.5 ± 2.1 μmol g -1 C-biomass h -1 ), in agreement with the well-documented inverse relationship between biomass-normalized excretion rates and body size. Our results indicate that crustacean zooplankton might contribute significantly to the dissolved organic matter flux in marine ecosystems via dissolved free Tau release. Based on the release rates and assuming steady state dissolved free Tau concentrations, turnover times of dissolved free Tau range from 0.05 d to 2.3 d in the upper water column and are therefore similar to those of dissolved free amino acids. This rapid turnover indicates that dissolved free Tau is efficiently consumed in oceanic waters, most likely by heterotrophic bacteria.

[Effect of dizocilpine maleate and taurine on the circuitry of glutamate and glutamine in rat striatum exposed by manganese].

PubMed

Jia, Ke; Xu, Zhaofa; Xu, Bin

2008-01-01

To observe the effect of MK-801 and taurine on the activities of GS and PAG and the glutamatic neuron content in the rat striatum exposed by manganese. 40 Wistar rats were random divided into four groups. The first group was the control group which was subcutaneously injected at the content of 0.9% NaCl. The second group was MnCl2 group which was subcutaneously injected at the content of 0.9% NaCl. The third and fourth groups were pretreatment groups which were subcutaneously injected of 0.3 micromol/kg MK-801 and 1 mmol/kg taurine. After 2h, the first group was peritoneally injected at the content of 0.9% NaCl, the 2nd-4th group were peritoneally injected at the dose of 200 micromol/kg MnCl2. All administration was given at the dose of 5 ml/kg for 25d, the pretreatment groups were given for every other day. At the 24h after the administration of MnCl2, the 4 rats brain tissue in every groups were removed after the rats were perfused from the left ventricles to with 4% ploymerisatum. The glutamatic neuron content were determined by immunohistochemical method (SABC). The activities of GS and PAG in the residual rat striatum were determined. In comparison with control group, the percentage of positive area and integral optical densities of glutamate immunocreative cell increased significantly in MnCl2 group (P < 0.01), the activity of GS decreased significantly in MnCl2 group, the activity of PAG increased significantly in MnCl2 group. In comparison with MnCl2 group, the percentage of positive area and integral optical density of glutamate immunocreative cell decreased significantly in MK-801 and taurine pretreatment group, the activity of GS increased significantly in MK-801 and taurine pretreatment group , the activity of PAG decreased significantly in MK-801 pretreatment group. MK-801 and taurine have a certain protective effect on "the circuitry of glutamate and glutamine" disrupted with Mn.

Taurine supplementation improves economy of movement in the cycle test independently of the detrimental effects of ethanol.

PubMed

Paulucio, Dailson; Costa, Bruno M; Santos, Caleb G M; Nogueira, Fernando; Koch, Alexander; Machado, Marco; Velasques, Bruna; Ribeiro, Pedro; Pompeu, Fernando Ams

2017-12-01

Taurine (TA) ingestion has been touted as blunting the deleterious effects of ethanol (ET) ingestion on motor performance. This study investigated the effects of ingestion of 0.6 mL·kg -1 of ET, 6 grams of TA, and ethanol in combination with taurine (ET+TA) on economy of movement (EM) and heart rate (HR). Nine volunteers, five female (22 ± 3 years) and four male (26 ± 5 years), participated in a study that used a counterbalanced experimental design. EM and HR were measured for 6 min while the subjects were pedalling at a fixed load 10% below the anaerobic threshold. The blood alcohol concentration (BAC) was similar between ET and ET+TA treatments at 30 min after ingestion and after exercise (12.3 mmol·L -1 vs. 13.7 mmol·L -1 , and 9.7 mmol • L -1 vs 10.9 mmol·L -1 , respectively). EM was significantly different among treatments, with lower mL·W -1 following ingestion of TA (-7.1%, p<0.001) than placebo and ET+TA (-2.45%, p=0.001) compared to ET. HR (bpm) was significantly (p<0.05) higher for ET (137 ± 14 bpm) than the other three treatments (placebo = 129 ± 14 bpm; TA = 127 ± 11 bpm; TA+ET = 133 ± 12 and ET = 137 ± 14 bpm). Taurine improved EM when compared to placebo or ET, and reduced HR when compared to ET. The combination of ET+TA also enhanced EM compared to placebo, and reduced HR in comparison to ET alone. Therefore, these findings indicate that taurine improves EM and counteracts ethanol-induced increases in HR during submaximal exercise.

Normal or increased bile acid uptake in isolated mucosa from patients with bile acid malabsorption.

PubMed

Bajor, Antal; Kilander, Anders; Fae, Anita; Gälman, Cecilia; Jonsson, Olof; Ohman, Lena; Rudling, Mats; Sjövall, Henrik; Stotzer, Per-Ove; Ung, Kjell-Arne

2006-04-01

Bile acid malabsorption as reflected by an abnormal Se-labelled homocholic acid-taurine (SeHCAT) test is associated with diarrhoea, but the mechanisms and cause-and-effect relations are unclear. Primarily, to determine whether there is a reduced active bile acid uptake in the terminal ileum in patients with bile acid malabsorption. Secondarily, to study the linkage between bile acid malabsorption and hepatic bile acid synthesis. Ileal biopsies were taken from patients with diarrhoea and from controls with normal bowel habits. Maximal active bile acid uptake was assessed in ileal biopsies using a previously validated technique based on uptake of C-labelled taurocholate. To monitor the hepatic synthesis, 7alpha-hydroxy-4-cholesten-3-one, a bile acid precursor, was assayed in blood. The SeHCAT-retention test was used to diagnose bile acid malabsorption. The taurocholate uptake in specimens from diarrhoea patients was higher compared with the controls [median, 7.7 (n=53) vs 6.1 micromol/g per min (n=17)] (P<0.01) but no difference was seen between those with bile acid malabsorption (n=18) versus diarrhoea with a normal SeHCAT test (n=23). The SeHCAT values and 7alpha-hydroxy-4-cholesten-3-one were inversely correlated. The data do not support bile acid malabsorption being due to a reduced active bile acid uptake capacity in the terminal ileum.

Prebiotic syntheses of vitamin coenzymes: I. Cysteamine and 2-mercaptoethanesulfonic acid (coenzyme M)

NASA Technical Reports Server (NTRS)

Miller, S. L.; Schlesinger, G.

1993-01-01

The reaction of NH3 and SO3(2-) with ethylene sulfide is shown to be a prebiotic synthesis of cysteamine and 2-mercaptoethanesulfonic acid (coenzyme M). A similar reaction with ethylene imine would give cysteamine and taurine. Ethylene oxide would react with NH3 and N(CH3)3 to give the phospholipid components ethanolamine and choline. The prebiotic sources of ethylene sulfide, ethylene imine and ethylene oxide are discussed. Cysteamine itself is not a suitable thioester for metabolic processes because of acyl transfer to the amino group, but this can be prevented by using an amide of cysteamine. The use of cysteamine in coenzyme A may have been due to its prebiotic abundance. The facile prebiotic synthesis of both cysteamine and coenzyme M suggests that they were involved in very early metabolic pathways.

Atom Tunneling in the Hydroxylation Process of Taurine/α-Ketoglutarate Dioxygenase Identified by Quantum Mechanics/Molecular Mechanics Simulations.

PubMed

Álvarez-Barcia, Sonia; Kästner, Johannes

2017-06-01

Taurine/α-ketoglutarate dioxygenase is one of the most studied α-ketoglutarate-dependent dioxygenases (αKGDs), involved in several biotechnological applications. We investigated the key step in the catalytic cycle of the αKGDs, the hydrogen transfer process, by a quantum mechanics/molecular mechanics approach (B3LYP/CHARMM22). Analysis of the charge and spin densities during the reaction demonstrates that a concerted mechanism takes place, where the H atom transfer happens simultaneously with the electron transfer from taurine to the Fe═O cofactor. We found the quantum tunneling of the hydrogen atom to increase the rate constant by a factor of 40 at 5 °C. As a consequence, a quite high kinetic isotope effect close to 60 is obtained, which is consistent with the experimental value.

Bile acid patterns in commercially available oxgall powders used for the evaluation of the bile tolerance ability of potential probiotics

PubMed Central

Hu, Peng-Li; Yuan, Ya-Hong; Yue, Tian-Li

2018-01-01

This study aimed to analyze the bile acid patterns in commercially available oxgall powders used for evaluation of the bile tolerance ability of probiotic bacteria. Qxgall powders purchased from Sigma-Aldrich, Oxoid and BD Difco were dissolved in distilled water, and analyzed. Conjugated bile acids were profiled by ion-pair high-performance liquid chromatography (HPLC), free bile acids were detected as their p-bromophenacyl ester derivatives using reversed-phase HPLC after extraction with acetic ether, and total bile acids were analyzed by enzymatic-colorimetric assay. The results showed that 9 individual bile acids (i.e., taurocholic acid, glycocholic acid, taurodeoxycholic acid, glycodeoxycholic acid, taurochenodeoxycholic acid, glycochenodeoxycholic acid, cholic acid, chenodeoxycholic acid, deoxycholic acid) were present in each of the oxgall powders tested. The content of total bile acid among the three oxgall powders was similar; however, the relative contents of the individual bile acids among these oxgall powders were significantly different (P < 0.001). The oxgall powder from Sigma-Aldrich was closer to human bile in the ratios of glycine-conjugated bile acids to taurine-conjugated bile acids, dihydroxy bile acids to trihydroxy bile acids, and free bile acids to conjugated bile acids than the other powders were. It was concluded that the oxgall powder from Sigma-Aldrich should be used instead of those from Oxoid and BD Difco to evaluate the bile tolerance ability of probiotic bacteria as human bile model. PMID:29494656

Maternal supplementation with rumen-protected methionine increases prepartal plasma methionine concentration and alters hepatic mRNA abundance of 1-carbon, methionine, and transsulfuration pathways in neonatal Holstein calves.

PubMed

Jacometo, C B; Zhou, Z; Luchini, D; Corrêa, M N; Loor, J J

2017-04-01

An important mechanism of nutritional "programming" induced by supplementation with methyl donors during pregnancy is the alteration of mRNA abundance in the offspring. We investigated the effects of rumen-protected Met (RPM) on abundance of 17 genes in the 1-carbon, Met, and transsulfuration pathways in calf liver from cows fed the same basal diet without (control, CON) or with RPM at 0.08% of diet dry matter/d (MET) from -21 through +30 d around calving. Biopsies (n = 8 calves per diet) were harvested on d 4, 14, 28, and 50 of age. Cows fed RPM had greater plasma concentration of Met (17.8 vs. 28.2 μM) at -10 d from calving. However, no difference was present in colostrum yield and free AA concentrations. Greater abundance on d 4 and 14 of betaine-homocysteine S-methyltransferase 2 (BHMT2), adenosylhomocysteinase (AHCY; also known as SAHH), and cystathionine-β-synthase (CBS) in MET calves indicated alterations in Met, choline, and homocysteine metabolism. Those data agree with the greater abundance of methionine adenosyltransferase 1A (MAT1A) in MET calves. Along with CBS, the greater abundance of glutamate-cysteine ligase (GCLC) and glutathione reductase (GSR) on d 4 in MET calves indicated a short-term postnatal alteration in the use of homocysteine for taurine and glutathione synthesis (both are potent intracellular antioxidants). The striking 7-fold upregulation at d 50 versus 4 of cysteine sulfinic acid decarboxylase (CSAD), catalyzing the last step of taurine synthesis, in MET and CON calves underscores an important role of taurine during postnatal calf growth. The unique role of taurine in the young calf is further supported by the upregulation of CBS, GCLC, and GSR at d 50 versus 14 and 28 in MET and CON. Although betaine-homocysteine S-methyltransferase (BHMT) activity did not differ in MET and CON, it increased ∼50% at d 14 and 28 versus 4. A significant positive correlation (r = 0.79) was present between BHMT abundance and BHMT activity regardless of treatment. The gradual upregulation over time of BHMT2 and SAHH coupled with the gradual upregulation of MAT1A and the DNA (cytosine-5-)-methyltransferases (DNMT1, DNMT3A, DNMT3B) in MET and CON calves was indicative of adaptations potentially driven by differences in intake of milk replacer and starter feed as calves grew. In that context, the ∼2.5-fold increase in abundance of DNMT3B at d 50 versus 4 in MET and CON indicate that DNA methylation might be an important component of the physiologic adaptations of calf liver. The data indicate that calves from MET-supplemented cows underwent alterations in Met, choline, and homocysteine metabolism partly to synthesize taurine and glutathione, which would be advantageous for controlling metabolic-related stress. Whether the effects in MET calves were directly related to increased Met supply in utero remains to be determined. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Taurine protects against As2O3-induced autophagy in pancreas of rat offsprings through Nrf2/Trx pathway.

PubMed

Bai, Jie; Yao, Xiaofeng; Jiang, Liping; Qiu, Tianming; Liu, Shuang; Qi, Baoxu; Zheng, Yue; Kong, Yuan; Yang, Guang; Chen, Min; Liu, Xiaofang; Sun, Xiance

2016-04-01

Arsenic was increasingly to blame as a risk factor for type 2 diabetes mellitus. In our previous study, we had found iAs stimulated autophagic flux and caused autophagic cell death through ROS pathway in INS-1 cells. Since NF-E2-related factor 2 (Nrf2) and the thioredoxin (Trx) system was a crucial line of defense against ROS, we investigated whether Nrf2/Trx pathway contributed to As2O3-stimulated autophagy and the role of taurine in this study. After treatment with 2 mg/kg BW-8 mg/kg BW As2O3 for 57 d, the expression of Nrf2 protein was decreased significantly in offsprings' pancreas. The expression of Trx gene was decreased significantly in pancreas subsequently. Finally, the generation of reactive oxygen species stimulated autophagy in arsenic-treated pancreas. Taurine could reverse arsenic-inhibited Nrf2 and Trx and inhibit autophagy. In short, inhibition of Nrf2/Trx pathway might play an important role in the pathogenesis of arsenic-related diabetes. Taurine could serve as nutrition supplementation against arsenic-related diabetes in high arsenic exposure area. Copyright © 2016 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

Food Overconsumption in Healthy Adults Triggers Early and Sustained Increases in Serum Branched-Chain Amino Acids and Changes in Cysteine Linked to Fat Gain.

PubMed

Elshorbagy, Amany K; Samocha-Bonet, Dorit; Jernerén, Fredrik; Turner, Cheryl; Refsum, Helga; Heilbronn, Leonie K

2018-06-13

Plasma concentrations of branched-chain amino acids (BCAAs) and the sulfur-containing amino acid cysteine are associated with obesity and insulin resistance. BCAAs predict future diabetes. We investigated amino acid changes during food overconsumption. Forty healthy men and women with a body mass index (mean ± SEM) of 25.6 ± 0.6 were overfed by 1250 kcal/d for 28 d, increasing consumption of all macronutrients. Insulin sensitivity and body composition were assessed at baseline (day 0) and day 28. Fasting serum amino acids were measured at days 0, 3, and 28. Linear mixed-effects models evaluated the effect of time in the total group and separately in those with low and high body fat gain (below compared with at or above median fat gain, 1.95 kg). At days 0 and 28, insulin-induced suppression of serum amino acids during a hyperinsulinemic-euglycemic clamp test and, in a subset (n = 20), adipose tissue mRNA expression of selected amino acid metabolizing enzymes were assessed. Weight increased by 2.8 kg. High fat gainers gained 2.6 kg fat mass compared with 1.1 kg in low fat gainers. Valine and isoleucine increased at day 3 (+17% and +22%, respectively; P ≤ 0.002) and remained elevated at day 28, despite a decline in valine (P = 0.019) from day 3 values. Methionine, cystathionine, and taurine were unaffected. Serum total cysteine (tCys) transiently increased at day 3 (+11%; P = 0.022) only in high fat gainers (P-interaction = 0.043), in whom the cysteine catabolic enzyme cysteine dioxygenase (CDO1) was induced (+26%; P = 0.025) in adipose tissue (P-interaction = 0.045). Overconsumption did not alter adipose tissue mRNA expression of the BCAA-metabolizing enzymes branched-chain keto acid dehydrogenase E1α polypeptide (BCKDHA) or branched-chain amino transferase 1 (BCAT1). In the total population at day 0, insulin infusion decreased all serum amino acids (-11% to -47%; P < 0.01), except for homocysteine and tCys, which were unchanged, and glutathione, which was increased by 54%. At day 28, insulin increased tCys (+8%), and the insulin-induced suppression of taurine and phenylalanine observed at day 0, but not that of BCAAs, was significantly impaired. These findings highlight the role of nutrient oversupply in increasing fasting BCAA concentrations in healthy adults. The link between cysteine availability, CDO1 expression, and fat gain deserves investigation. This trial was registered at www.clinicaltrials.gov as NCT00562393.

TAUROURSODEOXYCHOLIC ACID PREVENTS HEARING LOSS AND HAIR CELL DEATH IN Cdh23erl/erl MICE

PubMed Central

HU, J.; XU, M.; YUAN, J.; LI, B.; Entenman, S.; YU, H.; ZHENG, Q.Y.

2016-01-01

Sensorineural hearing loss has long been the subject of experimental and clinical research for many years. The recently identified novel mutation of the Cdh23 gene, Cdh23erl/erl, was proven to be a mouse model of human autosomal recessive nonsyndromic deafness (DFNB12). Tauroursodeoxycholic acid (TUDCA), a taurine-conjugated bile acid, has been used in experimental research and clinical applications related to liver disease, diabetes, neurodegenerative diseases, and other diseases associated with apoptosis. Because hair cell apoptosis was implied to be the cellular mechanism leading to hearing loss in Cdh23erl/erl mice (erl mice), this study investigated TUDCA’s otoprotective effects in erl mice: preventing hearing impairment and protecting against hair cell death. Our results showed that systemic treatment with TUDCA significantly alleviated hearing loss and suppressed hair cell death in erl mice. Additionally, TUDCA inhibited apoptotic genes and caspase-3 activation in erl mouse cochleae. The data suggest that TUDCA could be a potential therapeutic agent for human DFNB12. PMID:26748055

Management of bile acid malabsorption using low-fat dietary interventions: a useful strategy applicable to some patients with diarrhoea-predominant irritable bowel syndrome?

PubMed

Watson, Lorraine; Lalji, Amyn; Bodla, Shankar; Muls, Ann; Andreyev, H Jervoise N; Shaw, Clare

2015-12-01

This study evaluates the efficacy of low-fat dietary interventions in the management of gastrointestinal (GI) symptoms due to bile acid malabsorption. In total, 40 patients with GI symptoms and a 7-day (75)selenium homocholic acid taurine (SeHCAT) scan result of <20%, were prospectively recruited and then advised regarding a low-fat dietary intervention. Before and after dietary intervention, patients rated their GI symptoms using a 10-point numerical scale, and recorded their intake in 7-day dietary diaries. After dietary intervention, the median scores for all GI symptoms decreased, with a significant reduction for urgency, bloating, lack of control, bowel frequency (p ≥: 0.01). Mean dietary fat intake reduced to 42 g fat after intervention (p ≥: 0.01). Low-fat dietary interventions in patients with a SeHCAT scan result of <20% leads to clinically important improvement in GI symptoms and should be widely used. © Royal College of Physicians 2015. All rights reserved.

[The 75-seleno-homocholic acid-taurine test (SeHCAT). A useful method for detecting the idiopathic malabsorption of bile salts in chronic functional diarrhea].

PubMed

D'Arienzo, A; Maurelli, L; Di Siervi, P; Panarese, A; Giannattasio, F; Scuotto, A; Squame, G; Mazzacca, G

1989-07-15

The 75-SeHCAT test has been used for identifying, within a group of patients with chronic functional diarrhea, a subgroup of cases with ileal bile acid malabsorption. Thirty-four subjects were studied: 10 healthy subjects and 24 patients with chronic functional diarrhea. Findings are expressed as percentage of basal abdominal radioactivity after 7 days. Normal values in our control subjects were: over 25% on day 4 and over 10% on day 7. Pathological results were found in 9 of 24 patients (37.5%) on day 4 and of 24 patients (41.7%) on day 7. A significant correlation was found between the percentages of retention on days 4 and 7 (p less than 0.001). In SeHCAT-positive patients cholestyramine administration led to clinical improvement. According to our experience, the SeHCAT test is a useful tool for the evaluation of bile acid malabsorption in the differential diagnosis of chronic functional diarrhea.

Animal Proteins as Important Contributors to a Healthy Human Diet.

PubMed

Elmadfa, Ibrahim; Meyer, Alexa L

2017-02-08

Adequate protein intake is critical for health and development. Generally, protein of animal origin is of higher quality for humans owing to its amino acid pattern and good digestibility. When administered in mixtures it can enhance the quality of plant proteins, but its availability is often low in low-income communities, especially in young children, the elderly, and pregnant and lactating women, who have increased requirements and in whom high-quality protein also stimulates (bone) growth and maintenance. Although high protein intake was associated with increased type 2 diabetes mellitus risk, milk and seafood are good sources of branched chain amino acids and taurine, which act beneficially on glucose metabolism and blood pressure. However, high consumption of protein-rich animal food is also associated with adverse health effects and higher risk for noncommunicable diseases, partly related to other components of these foods, like saturated fatty acids and potential carcinogens in processed meat but also the atherogenic methionine metabolite homocysteine. In moderation, however, animal proteins are especially important for health maintenance in vulnerable persons.

Nonstatin therapies for management of dyslipidemia: a review.

PubMed

Sando, Karen R; Knight, Michelle

2015-10-01

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the United States. Recently published cholesterol treatment guidelines emphasize the use of statins as the preferred treatment strategy for both primary and secondary prevention of CVD. However, the optimal treatment strategy for patients who cannot tolerate statin therapy or those who need additional lipid-lowering therapy is unclear in light of recent evidence that demonstrates a lack of improved cardiovascular outcomes with combination therapy. The purpose of this review is to summarize and interpret evidence that evaluates nonstatin drug classes in reducing cardiovascular outcomes, to provide recommendations for use of nonstatin therapies in clinical practice, and to review emerging nonstatin therapies for management of dyslipidemia. Relevant articles were identified through searches of PubMed, International Pharmaceutical Abstracts, and the Cochrane Database of Systematic Reviews by using the terms niacin, omega-3 fatty acids (FAs), clofibrate, fibrate, fenofibrate, fenofibric acid, gemfibrozil, cholestyramine, colestipol, colesevelam, ezetimibe, proprotein convertase subtilisin/kexin 9 (PCSK9), cholesteryl ester transfer protein (CETP), and cardiovascular outcomes. Only English language, human clinical trials, meta-analyses, and systematic reviews were included. Additional references were identified from citations of published articles. Niacin may reduce cardiovascular events as monotherapy; however, recent trials in combination with statins have failed to show a benefit. Trials with omega-3 FAs have failed to demonstrate significant reductions in cardiovascular outcomes. Fibrates may improve cardiovascular outcomes as monotherapy; however, trials in combination with statins have failed to show a benefit, except in those with elevated triglycerides (>200 mg/dL) or low HDL-C (<40 mg/dL). There is a lack of data that evaluates bile acid sequestrant in combination with statin therapy on reducing cardiovascular events. Ezetimibe-statin combination therapy can reduce cardiovascular outcomes in those with chronic kidney disease and following vascular surgery or acute coronary syndrome. Long-term effects of emerging nonstatin therapies (CETP and PCSK9 inhibitors) are currently being evaluated in ongoing Phase III trials. Nonstatin therapies have a limited role in reducing cardiovascular events in those maintained on guideline-directed statin therapy. In certain clinical situations, such as patients who are unable to tolerate statin therapy or recommended intensities of statin therapy, those with persistent severe elevations in triglycerides, or patients with high cardiovascular risk, some nonstatin therapies may be useful in reducing cardiovascular events. Future research is needed to evaluate the role of nonstatin therapies in those who are unable to tolerate guideline-directed statin doses. Copyright © 2015 Elsevier HS Journals, Inc. All rights reserved.

Controlled crystallization of the lipophilic drug fenofibrate during freeze-drying: elucidation of the mechanism by in-line Raman spectroscopy.

PubMed

de Waard, Hans; De Beer, Thomas; Hinrichs, Wouter L J; Vervaet, Chris; Remon, Jean-Paul; Frijlink, Henderik W

2010-12-01

We developed a novel process, "controlled crystallization during freeze-drying" to produce drug nanocrystals of poorly water-soluble drugs. This process involves freeze-drying at a relatively high temperature of a drug and a matrix material from a mixture of tertiary butyl alcohol and water, resulting in drug nanocrystals incorporated in a matrix. The aim of this study was to elucidate the mechanisms that determine the size of the drug crystals. Fenofibrate was used as a model lipophilic drug. To monitor the crystallization during freeze-drying, a Raman probe was placed just above the sample in the freeze-dryer. These in-line Raman spectroscopy measurements clearly revealed when the different components crystallized during freeze-drying. The solvents crystallized only during the freezing step, while the solutes only crystallized after the temperature was increased, but before drying started. Although the solutes crystallized only after the freezing step, both the freezing rate and the shelf temperature were critical parameters that determined the final crystal size. At a higher freezing rate, smaller interstitial spaces containing the freeze-concentrated fraction were formed, resulting in smaller drug crystals (based on dissolution data). On the other hand, when the solutes crystallized at a lower shelf temperature, the degree of supersaturation is higher, resulting in a higher nucleation rate and consequently more and therefore smaller crystals. In conclusion, for the model drug fenofibrate, a high freezing rate and a relatively low crystallization temperature resulted in the smallest crystals and therefore the highest dissolution rate.

[UV-induced DNA damage and protective effects of antioxidants on DNA damage in human lens epithelial cells studied with comet assay].

PubMed

Wu, Zhi-hong; Wang, Mian-rong; Yan, Qi-chang; Pu, Wei; Zhang, Jin-song

2006-11-01

To investigate the mechanism of UV-induced DNA damage and repair and the protective effects of antioxidants on DNA damage in human lens epithelial cells. Human lens epithelial cells were irradiated at UV-doses 0.0 (control group), 2.5, 5.0, 7.5, 10.0 mJ/cm(2) (treated group 1 - 4). The amounts of DNA single strand breaks (SSB) were measured with the alkaline comet assay (CA). The spontaneous repair of DNA SSB after exposure to UV at 10.0 mJ/cm(2) was also determined in human lens epithelial cells. Human lens epithelial cells were treated with different concentration of VitaminC (VitC), taurine, superoxide dismutase (SOD) and epigallocatechin gallate (EGCG) before and after ultraviolet radiation, the effects of antioxidants on DNA damage was examined with alkaline comet assay. The amount of DNA SSB in control group and treated groups 1 - 4 showed increased tendency, was dose-dependent to the dose of UV irradiation, the differences of DNA SSB in 5 group were significantly (P < 0.01). UV-induced DNA SSB at 10.0 mJ/cm(2) in human lens epithelial cells, the half repair time was 60 minutes. Human lens epithelial cells were treated with different concentrations of taurine, SOD and EGCG before ultraviolet radiation. The differences of DNA damage in control and various antioxidant treated groups was statistically significant (F = 6.591, 13.542, 4.626 in cells treated with taurine, SOD and EGCG, respectively, P < 0.01), the difference of VitC effect on DNA in control and treated group were not significantly (F = 1.451, P > 0.05). Human lens epithelial cells were treated with different concentration of VitC, taurine, SOD and EGCG after ultraviolet radiation. The differences of DNA damage between the control and treated group were statistically significant (F = 6.571, 4.810, 6.824, 9.182 in cells treated with VitC, taurine, SOD and EGCG, respectively, P < 0.01). The differences of protective effects on DNA damage in these four different kinds of antioxidants added before UV irradiation were statistically significant (P < 0.01). The differences of protective effects on DNA damage in these four different kinds of antioxidant added after UV irradiation were not significantly (P > 0.05). UV irradiation has a dose-dependent effect on the DNA SSB of lens epithelial cells. Exogenesis VitC, taurine, SOD, EGCG possess protective effective to UV-induced DNA damage. SOD is one of the most powerful antioxidants if added before the UV irradiation and followed by EGCG, taurine and VitC orderly. Four kinds of antioxidants show no apparently differences added after UV-irradiation. SOD and EGCG both are powerful antioxidants.

Taurine: A Potential Ergogenic Aid for Preventing Muscle Damage and Protein Catabolism and Decreasing Oxidative Stress Produced by Endurance Exercise

PubMed Central

De Carvalho, Flávia G.; Galan, Bryan S. M.; Santos, Priscila C.; Pritchett, Kelly; Pfrimer, Karina; Ferriolli, Eduardo; Papoti, Marcelo; Marchini, Júlio S.; de Freitas, Ellen C.

2017-01-01

The aim of this study was to evaluate the effects of taurine and chocolate milk supplementation on oxidative stress and protein metabolism markers, and aerobic parameters in triathletes. Methods: A double-blind, crossover study was conducted with 10 male triathletes, aged 30.9 ± 1.3 year, height 1.79 ± 0.01 m and body weight 77.45 ± 2.4 kg. Three grams of taurine and 400 ml of chocolate milk (TAUchoc), or a placebo (chocolate milk) (CHOC) was ingested post exercise for 8 weeks. Oxidative stress marker levels, and 24 h urinary nitrogen, creatinine, and urea excretion were measured before and after 8 weeks of training and supplementation with TAUchoc or CHOC. A maximal incremental running test on a treadmill was performed in order to evaluate aerobic parameters: Vmax, heart rate (HR) and rate of perceived exertion (RPE). Results: TAUchoc treatment during the 8 weeks resulted in increased taurine plasma levels (PRE 201.32 ± 29.03 μmol/L and POST 234.36 ± 35.51 μmol/L, p = 0.01), decreased malondialdehyde levels (19.4%, p = 0.03) and urinary nitrogen excretion (−33%, p = 0.03), and promoted positive nitrogen balance (p = 0.01). There were no changes in reduced glutathione (TAUchoc PRE 0.72 ± 0.08 mmol/L and POST 0.83 ± 0.08 mmol/L; CHOC PRE 0.69 ± 0.08 mmol/L and POST 0.81 ± 0.06 mmol/L), vitamin E plasma levels (TAUchoc PRE 33.99 ± 2.52 μmol/L and 35.95 ± 2.80 μmol/L and CHOC PRE 31.48 ± 2.12 μmol/L and POST 33.77 ± 3.64 μmol/L), or aerobic parameters, which were obtained in the last phase of the maximal incremental running test (Vmax TAUchoc PRE 13 ± 1.4 km/h and POST 13.22 ± 1.34 km/h; CHOC PRE 13.11 ± 2.34 km/h and POST 13.11 ± 2.72 km/h), the heart rate values were TAUchoc PRE 181.89 ± 24.18 bpm and POST 168.89 ± 46.56 bpm; CHOC PRE 181.56 ± 2.14 bpm and POST 179.78 ± 3.4 bpm, and the RPE were TAUchoc PRE 8.33 ± 2.4 AU and POST 9.1 ± 2.1 AU; CHOC PRE 8.11 ± 4.94 AU and POST 8.78 ± 2.78 AU). Conclusion: Taurine supplementation did not improve aerobic parameters, but was effective in increasing taurine plasma levels and decreasing oxidative stress markers, which suggests that taurine may prevent oxidative stress in triathletes. PMID:28979213

Evaluation of phenolic compounds and lipid-lowering effect of Morus nigra leaves extract.

PubMed

Zeni, Ana Lúcia B; Moreira, Tatianne D; Dalmagro, Ana Paula; Camargo, Anderson; Bini, Larissa A; Simionatto, Edésio L; Scharf, Dilamara R

2017-01-01

Morus nigra L. (Moraceae) is a tree known as black mulberry and the leaves are used in folk medicine in the treatment of diabetes, high cholesterol and menopause symptoms. The aim of this study was to evaluate the M. nigra leaves phytochemical profile in different extractions and the hypolipidemic effect of the infusion comparing to the fenofibrate. Morus nigra infusion (MN) showed higher amounts of phenolics and flavonoids (83.85 mg/g and 79.96 µg/g, respectively), as well as antioxidant activity (83.85%) than decoction or hydromethanolic extracts. Although, decoction showed the best result for ascorbic acid (4.35 mg/100 g) than hydromethanolic or infusion (2.51 or 2.13 mg/100 g, respectively). The phenolic acids gallic, chlorogenic and caffeic and the flavonoids quercetin, rutin and catechin were found in the M. nigra extracts. Hyperlipidemic rats treated with 100, 200 or 400 mg/kg of MN decreased serum cholesterol, triglycerides and normalized lipoproteins. Furthermore, MN inhibited lipid peroxidation in liver, kidney and brain of hyperlipidemic rats. This study provides evidence that M. nigra leaves extracts are rich in polyphenols, mainly chlorogenic acid, which normalized hyperlipidemic disturbance. The results suggest a potential therapeutic effect of the M. nigra leaves infusion on dislipidemic condition and related oxidative stress.

Taurine activates strychnine-sensitive glycine receptors in neurons of the rat inferior colliculus.

PubMed

Xu, Han; Zhou, Ke-Qing; Huang, Yi-Na; Chen, Lin; Xu, Tian-Le

2004-09-24

Taurine (Tau) is one of the most abundant free amino acids in the mammalian central nervous system. Whether the neurotransmission of the central auditory system is regulated or modulated by Tau is not clear. In the present study, we investigated the electrophysiological and pharmacological properties of Tau-activated currents in acutely dissociated neurons of the rat inferior colliculus (IC) using whole cell patch clamp recordings. At a holding potential of -60 mV and under a condition of chloride equilibrium potential near 0 mV, Tau activated an inward current and its half-maximal activation concentration was equal to 0.37 mM. The measured reversal potential of Tau-activated currents was close to theoretical chloride equilibrium potential. The currents evoked by Tau at both low (1 mM) and high (10 mM) concentrations were almost completely inhibited by strychnine, a glycine receptor antagonist. The Tau-activated current, however, was not affected by bicuculline, a GABA(A) receptor antagonist. Tau at increased concentrations progressively reduced the current response to subsequent glycine application. At saturated concentrations, Tau-activated current and glycine-activated current were mutually cross-desensitized by each other. These findings indicate that Tau activates glycine receptors in neurons of the rat IC and thus may have a functional role in regulating or modulating the neurotransmission of the central auditory system in mammals.

Effects of a block in cysteine catabolism on energy balance and fat metabolism in mice

PubMed Central

Niewiadomski, Julie; Zhou, James Q.; Roman, Heather B.; Liu, Xiaojing; Hirschberger, Lawrence L.; Locasale, Jason W.; Stipanuk, Martha H.

2016-01-01

To gain further insights into the effect of elevated cysteine levels on energy metabolism and the possible mechanisms by which cysteine may have these effects, we conducted studies in cysteine dioxygenase (Cdo1)–null mice. Cysteine dioxygenase (CDO) catalyzes the first step of the major pathway for cysteine catabolism. When CDO is absent, tissue and plasma cysteine levels are elevated, resulting in enhanced flux of cysteine through desulfhydration reactions. When Cdo1-null mice were fed a high-fat diet, they gained more weight than their wild-type controls, regardless of whether the diet was supplemented with taurine. Cdo1-null mice had markedly lower leptin levels, higher feed intakes, and markedly higher abundance of hepatic stearoyl-CoA desaturase 1 (SCD1) compared to wild-type control mice, and these differences were not affected by the fat or taurine content of the diet. Thus, reported associations of elevated cysteine levels with greater weight gain and with elevated hepatic Scd1 expression holds in the Cdo1-null mouse model. Hepatic accumulation of acylcarnitines suggested impaired mitochondrial β-oxidation of fatty acids in Cdo1-null mice. The strong associations of elevated cysteine levels with excess H2S production and impairments in energy metabolism suggest that H2S signaling could be involved. PMID:26995761

Effects of a block in cysteine catabolism on energy balance and fat metabolism in mice.

PubMed

Niewiadomski, Julie; Zhou, James Q; Roman, Heather B; Liu, Xiaojing; Hirschberger, Lawrence L; Locasale, Jason W; Stipanuk, Martha H

2016-01-01

To gain further insights into the effects of elevated cysteine levels on energy metabolism and the possible mechanisms underlying these effects, we conducted studies in cysteine dioxygenase (Cdo1)-null mice. Cysteine dioxygenase (CDO) catalyzes the first step of the major pathway for cysteine catabolism. When CDO is absent, tissue and plasma cysteine levels are elevated, resulting in enhanced flux of cysteine through desulfhydration reactions. When Cdo1-null mice were fed a high-fat diet, they gained more weight than their wild-type controls, regardless of whether the diet was supplemented with taurine. Cdo1-null mice had markedly lower leptin levels, higher feed intakes, and markedly higher abundance of hepatic stearoyl-CoA desaturase 1 (SCD1) compared to wild-type control mice, and these differences were not affected by the fat or taurine content of the diet. Thus, reported associations of elevated cysteine levels with greater weight gain and with elevated hepatic Scd1 expression are also seen in the Cdo1-null mouse model. Hepatic accumulation of acylcarnitines suggests impaired mitochondrial β-oxidation of fatty acids in Cdo1-null mice. The strong associations of elevated cysteine levels with excess H2 S production and impairments in energy metabolism suggest that H2 S signaling could be involved. © 2016 New York Academy of Sciences.

Synergistic protective effect of N-acetylcysteine and taurine against cisplatin-induced nephrotoxicity in rats.

PubMed

Abdel-Wahab, Wessam M; Moussa, Farouzia I; Saad, Najwa A

2017-01-01

Cisplatin (cis-diaminedichloroplatinum II; CDDP) is an effective anticancer drug, but it has limitations because of its nephrotoxicity. This study investigates the protective effect of N -acetylcysteine (NAC) and taurine (TAU), both individually and in combination, against CDDP nephrotoxicity in rats. For this purpose, 48 male rats were assigned into eight groups (n=6) as follows: 1) control group, 2) NAC group, 3) TAU group, 4) NAC-TAU group, 5) CDDP group, 6) CDDP-NAC group, 7) CDDP-TAU group, and 8) CDDP-NAC-TAU group. Cisplatin was administered as a single intraperitoneal injection at a concentration of 6 mg/kg. Three days after CDDP administration, NAC (50 mg/kg) and/or TAU (50 mg/kg) were administered three times weekly for four consecutive weeks. Kidney function markers in serum, urinary glucose and protein, as well as oxidant and antioxidant parameters in renal tissue were assessed. Administration of CDDP significantly elevated urinary glucose and protein, as well as serum creatinine, urea, and uric acid. Moreover, CDDP enhanced lipid peroxidation and suppressed the major enzymatic antioxidants in the kidney tissue. Treatment with NAC or TAU protected against the alterations in the serum, urine, and renal tissue when used individually along with CDDP. Furthermore, a combined therapy of both was more effective in ameliorating CDDP-induced nephrotoxicity, which points out to their synergistic effect.

An integrated metabonomic and proteomic study on Kidney-Yin Deficiency Syndrome patients with diabetes mellitus in China.

PubMed

Jiang, Ning; Liu, Hong-fang; Li, Si-di; Zhou, Wen-xia; Zhang, Yong-xiang; Zhang, Qi; Yan, Xian-zhong

2015-06-01

To investigate specific changes in metabolites and proteins of Kidney-Yin Deficiency Syndrome (KYDS) patients with diabetes mellitus (DM) in China. KYDS (n=29) and non-KYDS (n=23) patients with DM were recruited for this study. The KYDS was diagnosed by two senior TCM clinicians separately. The metabonomic and proteomic profiles of the patients were assessed using a metabonomic strategy based on NMR with multivariate analysis and a proteomic strategy based on MALDI-TOF-MS, respectively. Eighteen upregulated peptides and thirty downregulated peptides were observed in the plasma of the KYDS patients. Comparing the proteomic profiles of the KYDS and non-KYDS groups, however, no significantly differentially expressed peptides were found. At the same time, major metabolic alterations were found to distinguish the two groups, including eight significantly changed metabolites (creatinine, citrate, TMAO, phenylalanine, tyrosine, alanine, glycine and taurine). The levels of creatinine, citrate, TMAO, phenylalanine and tyrosine were decreased, whereas the levels of alanine, glycine and taurine were increased in the KYDS patients. These biochemical changes were found to be associated with alterations in amino acid metabolism, energy metabolism and gut microflora. The identification of distinct expression profiles of metabolites and signaling pathways in KYDS patients with DM suggests that there are indeed molecular signatures underlying the principles of 'Syndrome Differentiation' in traditional Chinese medicine.

Effects of propofol, midazolam and thiopental sodium on outcome and amino acids accumulation in focal cerebral ischemia-reperfusion in rats.

PubMed

Chen, Lianhua; Gong, Qinyan; Xiao, Changsi

2003-02-01

To investigate the effects of propofol, midazolam and thiopental sodium on outcomes and amino acid accumulation in focal cerebral ischemia-reperfusion in rats. Male Sprague Dawley (SD) rats were scheduled to undergo 3-hour middle cerebral artery occlusion by intraluminal suture and 24-hour reperfusion. Neurologic outcomes were scored on a 0-5 grading scale. Infarct volume was shown with triphenyltetrazolium chloride staining and measured by an image analysis system. Concentrations of various amino acids (aspartate, glutamate, glycine, taurine, and gama-aminobutyric acid) were measured after 3 hours of reperfusion using high performance liquid chromatography. Propofol, midazolam and thiopental sodium were given intraperitoneally at the beginning of reperfusion. Both propofol and midazolam attenuated neurological deficits and reduced infarct and edema volumes. Propofol showed better neurological protection than midazolam while thiopental sodium did not exhibit any protective effect. Both propofol and midazolam decreased excitatory amino acids accumulation, while propofol increased gama-aminobutyric acid accumulation in ischemic areas in reperfusion. Propofol and midazolam, but not thiopental sodium, may provide protective effects against reperfusion induced injury in rats subjected to focal cerebral ischemia. This neurological protection may be due to the acceleration of excitatory amino acids elimination in reperfusion.

Amino acid composition in parenteral nutrition: what is the evidence?

PubMed Central

Yarandi, Shadi S.; Zhao, Vivian M.; Hebbar, Gautam; Ziegler, Thomas R.

2011-01-01

Purpose of review Complete parenteral nutrition solutions contain mixed amino acid products providing all nine essential amino acids and a varying composition of nonessential amino acids. Relatively little rigorous comparative efficacy research on altered parenteral nutrition amino acid composition has been published in recent years. Recent findings Limited data from randomized, double-blind, adequately powered clinical trials to define optimal doses of total or individual amino acids in parenteral nutrition are available. An exception is the growing number of studies on the efficacy of glutamine supplementation of parenteral nutrition or given as a single parenteral agent. Parenteral glutamine appears to confer benefit in selected patients; however, additional data to define optimal glutamine dosing and the patient subgroups who may most benefit from this amino acid are needed. Although some promising studies have been published, little data are available in the current era of nutrition support on the clinical efficacy of altered doses of arginine, branched chain amino acids, cysteine, or taurine supplementation of parenteral nutrition. Summary Despite routine use of parenteral nutrition, surprisingly little clinical efficacy data are available to guide total or specific amino acid dosing in adult and pediatric patients requiring this therapy. This warrants increased attention by the research community and funding agencies to better define optimal amino acid administration strategies in patient subgroups requiring parenteral nutrition. PMID:21076291

Genetic Diversity of Seven Cattle Breeds Inferred Using Copy Number Variations

PubMed Central

Pierce, Magretha D.; Dzama, Kennedy; Muchadeyi, Farai C.

2018-01-01

Copy number variations (CNVs) comprise deletions, duplications, and insertions found within the genome larger than 50 bp in size. CNVs are thought to be primary role-players in breed formation and adaptation. South Africa boasts a diverse ecology with harsh environmental conditions and a broad spectrum of parasites and diseases that pose challenges to livestock production. This has led to the development of composite cattle breeds which combine the hardiness of Sanga breeds and the production potential of the Taurine breeds. The prevalence of CNVs within these respective breeds of cattle and the prevalence of CNV regions (CNVRs) in their diversity, adaptation and production is however not understood. This study therefore aimed to ascertain the prevalence, diversity, and correlations of CNVRs within cattle breeds used in South Africa. Illumina Bovine SNP50 data and PennCNV were utilized to identify CNVRs within the genome of 287 animals from seven cattle breeds representing Sanga, Taurine, Composite, and cross breeds. Three hundred and fifty six CNVRs of between 36 kb to 4.1 Mb in size were identified. The null hypothesis that one CNVR loci is independent of another was tested using the GENEPOP software. One hunded and two and seven of the CNVRs in the Taurine and Sanga/Composite cattle breeds demonstrated a significant (p ≤ 0.05) association. PANTHER overrepresentation analyses of correlated CNVRs demonstrated significant enrichment of a number of biological processes, molecular functions, cellular components, and protein classes. CNVR genetic variation between and within breed group was measured using phiPT which allows intra-individual variation to be suppressed and hence proved suitable for measuring binary CNVR presence/absence data. Estimate PhiPT within and between breed variance was 2.722 and 0.518 respectively. Pairwise population PhiPT values corresponded with breed type, with Taurine Holstein and Angus breeds demonstrating no between breed CNVR variation. Phylogenetic trees were drawn. CNVRs primarily clustered animals of the same breed type together. This study successfully identified, characterized, and analyzed 356 CNVRs within seven cattle breeds. CNVR correlations were evident, with many more correlations being present among the exotic Taurine breeds. CNVR genetic diversity of Sanga, Taurine and Composite breeds was ascertained with breed types exposed to similar selection pressures demonstrating analogous incidences of CNVRs. PMID:29868114

Association between bile acid turnover and osteoporosis in postmenopausal women.

PubMed

Hanly, Ruth; Ryan, Nicola; Snelling, Hayley; Walker-Bone, Karen; Dizdarevic, Sabina; Peters, A Michael

2013-06-01

The intestinal absorption of vitamin D is linked to bile acid absorption. This link may be abnormal in patients with osteoporosis. The aim of this study was to investigate a possible relation between osteoporosis and bile acid turnover, measured as whole-body Se-75-HCAT retention (WBR), in postmenopausal women. Whole-body counts were recorded using an uncollimated gamma camera 3 h and 7 days after oral administration of Se-75-homocholic acid taurine (Se-75-HCAT) in 16 women aged 58-85 years with dual-photon X-ray absorptiometry (DEXA)-proven osteoporosis. WBR was expressed as physical decay-corrected counts at 7 days as a percentage of the counts at 3 h. Seven patients had unexplained diarrhoea. Six patients (five with diarrhoea) had WBR less than 19%. There was a significant difference in DEXA t-score between women with and without diarrhoea (P<0.02). There was a significant negative correlation (R s=-0.58; P<0.02) between WBR and alcohol consumption rated on a three-point scale: <1, 2-7 and >7 U/week. Our results indicate an association between osteoporosis and diarrhoea that may be the result of abnormal bile acid turnover. The role of alcohol requires further investigation.

1 H NMR-based water-soluble lower molecule characterization and fatty acid composition of boiled Wuding chicken during processing.

PubMed

Xiao, Zhichao; Luo, Yuting; Wang, Guiying; Ge, Changrong; Zhou, Guanghong; Zhang, Wangang; Liao, Guozhou

2018-06-13

Boiled Wuding chicken was produced using whole chicken by washing, boiling 1 h with salt, deep frying and boiling 2 h. The effect of process on the WLOM (water-soluble lower molecule) profiles of products was characterized using proton nuclear magnetic resonance spectroscopy ( 1 H-NMR) and fatty acid composition of products was analyzed using gas chromatography-mass spectrometry (GC-MS). The metabonome was dominated by 49 WLOM and 22 fatty acid compounds were detected. PC1 and PC2 explained a total of 93.4% and 3% of variance, respectively. Compared with control group, the total WLOM and fatty acid content of the chicken breast were significantly decreased in other three processing stages (P<0.05). Comprehensive multivariate data analysis showed significant differences about precursor substance between the different processing including creatine, lactate, creatinine, glucose, taurine, anserine and acetate (P<0.05). These results contribute to a more accurate understanding of precursor substance changes of flavor in chicken meat during processing. Boiled treated chicken had significant effects on fatty acid and WLOM compounds. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.