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Sample records for carnosine

  1. [Conformers of carnosine].

    Science.gov (United States)

    Kliuev, S A

    2006-01-01

    The geometric and energetic parameters of most stable conformations of carnosine were calculated by the semiempirical guantum-chemical method PM3. The carnosine-water-zinc (II) clusters were simulated. PMID:16909845

  2. Carnosine, carnosinase and kidney diseases

    OpenAIRE

    Katarzyna Kiliś-Pstrusińska

    2012-01-01

     Carnosine (beta-alanyl-L-histidine) is an endogenously synthesized dipeptide which is present in different human tissues, including the kidney. Carnosine is hydrolyzed by the enzyme carnosinase. There are two carnosinase homologues: serum secreted carnosinase and non-specific cytosolic dipeptidase, encoded by the genes CNDP1 and CNDP2 respectively and located on chromosome 18q22.3. Carnosine functions as a radical oxygen species scavenger and as a natural angiotensin converting enzyme inhibi...

  3. Carnosine, carnosinase and kidney diseases

    Directory of Open Access Journals (Sweden)

    Katarzyna Kiliś-Pstrusińska

    2012-04-01

    Full Text Available  Carnosine (beta-alanyl-L-histidine is an endogenously synthesized dipeptide which is present in different human tissues, including the kidney. Carnosine is hydrolyzed by the enzyme carnosinase. There are two carnosinase homologues: serum secreted carnosinase and non-specific cytosolic dipeptidase, encoded by the genes CNDP1 and CNDP2 respectively and located on chromosome 18q22.3. Carnosine functions as a radical oxygen species scavenger and as a natural angiotensin converting enzyme inhibitor. Carnosine inhibits advanced glycation end product formation and reduces the synthesis of matrix proteins such as fibronectin and collagen type VI of podocytes and mesangial cells. In experimental studies it was shown that carnosine reduces the level of proinflammatory and profibrotic cytokines. It is suggested that carnosine is a naturally occurring anti-aging substance in human organisms with a beneficial effect on the cardiovascular system.This paper reports the results of studies concerning carnosine’s role in kidney diseases, particularly in ischemia/reperfusion induced acute renal failure, diabetic nephropathy, gentamicin-induced nephrotoxicity and also in blood pressure regulation. The correlations between serum carnosine and serum carnosinase activity and polymorphism in the CNDP1 gene are analyzed. The role of CNDP1 gene polymorphism in the development of diabetic nephropathy and non-diabetic chronic kidney disease is discussed. Carnosine is engaged in different metabolic pathways. It has nephroprotective features. Further studies of carnosine metabolism and its biological properties, particularly those concerning the human organism, are required.

  4. Intrinsic carnosine metabolism in the human kidney

    OpenAIRE

    Peters, Verena; Klessens, Celine Q. F.; Baelde, Hans J.; Singler, Benjamin; Veraar, Kimberley A. M.; Zutinic, Ana; Drozak, Jakub; Zschocke, Johannes; Schmitt, Claus P.; Heer, Emile

    2015-01-01

    Histidine-containing dipeptides like carnosine and anserine have protective functions in both health and disease. Animal studies suggest that carnosine can be metabolized within the kidney. The goal of this study was to obtain evidence of carnosine metabolism in the human kidney and to provide insight with regards to diabetic nephropathy. Expression, distribution, and localization of carnosinase-1 (CNDP1), carnosine synthase (CARNS), and taurine transporters (TauT) were measured in human kidn...

  5. Expression profiles of carnosine synthesis–related genes in mice after ingestion of carnosine or ß-alanine

    OpenAIRE

    Miyaji Takayuki; Sato Mikako; Maemura Hirohiko; Takahata Yoshihisa; Morimatsu Fumiki

    2012-01-01

    Abstract Background Carnosine is a dipeptide that improves exercise performance. The carnosine synthesis mechanism through carnosine and ß-alanine ingestion remains unclear. Therefore, we investigated the tissue distribution of carnosine synthase, ATP-grasp domain-containing protein-1 (ATPGD1) mRNA, and ATPGD1 and carnosine specific dipeptidase (CN1) gene expression profiles in mice that were given carnosine or ß-alanine orally. Methods ddY mice (7-week-old) were randomly divided into three g...

  6. Expression profiles of carnosine synthesis–related genes in mice after ingestion of carnosine or ß-alanine

    OpenAIRE

    Miyaji, Takayuki; Sato, Mikako; Maemura, Hirohiko; Takahata, Yoshihisa; Morimatsu, Fumiki

    2012-01-01

    Background Carnosine is a dipeptide that improves exercise performance. The carnosine synthesis mechanism through carnosine and ß-alanine ingestion remains unclear. Therefore, we investigated the tissue distribution of carnosine synthase, ATP-grasp domain-containing protein-1 (ATPGD1) mRNA, and ATPGD1 and carnosine specific dipeptidase (CN1) gene expression profiles in mice that were given carnosine or ß-alanine orally. Methods ddY mice (7-week-old) were randomly divided into three groups (n ...

  7. Differential Neuroprotective Effects of Carnosine, Anserine, and N-Acetyl Carnosine against Permanent Focal Ischemia

    OpenAIRE

    Min, Jiangyong; Senut, Marie-Claude; Rajanikant, Krishnamurthy; Greenberg, Eric; Bandagi, Ram; Zemke, Daniel; Mousa, Ahmad; Kassab, Mounzer; Farooq, Muhammad U.; Gupta, Rishi; Majid, Arshad

    2008-01-01

    Carnosine (β-alanyl-L-histidine) has been shown to exhibit neuroprotection in rodent models of cerebral ischemia. In the present study, we further characterized the effects of carnosine treatment in a mouse model of permanent focal cerebral ischemia and compared them with its related peptides anserine and N-acetylated carnosine. We also evaluated the efficacy of bestatin, a carnosinase inhibitor, in ameliorating ischemic brain damage. Permanent focal cerebral ischemia was induced by occlusion...

  8. New derivative of carnosine for nanoparticle assemblies.

    Science.gov (United States)

    Bellia, Francesco; Oliveri, Valentina; Rizzarelli, Enrico; Vecchio, Graziella

    2013-01-01

    Carnosine (β-alanyl-l-histidine) is an endogenous dipeptide, extensively studied owing to its multifunctional activity exhibited in tissues of several animal species. This natural compound may act as a physiological buffer, ion-chelating agent (especially for copper(II) and zinc(II)), antioxidant and antiglycating agent. The main limit for the therapeutical uses of carnosine is the rapid hydrolysis mostly in human plasma by carnosinase. The chemical derivatization of carnosine is a promising strategy to improve the bioavailability of the dipeptide and facilitating the site-specific transport to different tissues. On this basis, a new carnosine derivative with biotin was synthesized and structurally characterized by NMR and MS measurements, with aim of exploiting the avidin-biotin technology that offers a universal system for selective delivery of any biotinylated agent. The stability of the new carnosine derivative towards the hydrolytic action of serum carnosinase as well as the copper(II) binding ability of the carnosine-biotin conjugate were also assessed. The binding affinity of the new molecular entity to avidin and streptavidin, investigated by a spectrophotometric assay, was exploited to functionalize avidin- and streptavidin-gold nanoparticles with the carnosine-biotin conjugate. PMID:24158014

  9. Transport characteristics of L-carnosine and the anticancer derivative 4-toluenesulfonylureido-carnosine in a human epithelial cell line

    DEFF Research Database (Denmark)

    Nielsen, Carsten Uhd; Supuran, Claudiu T; Scozzafava, Andrea;

    2002-01-01

    The aim of the present study was to evaluate whether the transepithelial transport of the anticancer compound 4-toluenesulfonylureido-carnosine (Ts-carnosine) and the dipeptide moiety L-carnosine was due to a hPepT1 carrier-mediated flux.......The aim of the present study was to evaluate whether the transepithelial transport of the anticancer compound 4-toluenesulfonylureido-carnosine (Ts-carnosine) and the dipeptide moiety L-carnosine was due to a hPepT1 carrier-mediated flux....

  10. On the enigma of carnosine?s anti-ageing actions

    OpenAIRE

    Hipkiss, Alan R

    2009-01-01

    On the enigma of carnosine?s anti-ageing actions correspondance: Corresponding author. (Hipkiss, Alan R.) (Hipkiss, Alan R.) School of Clinical and Experimental Medicine--> , College of Medical and Dental Sciences--> , The University of Birmingham--> , Edgbaston--> , Birmingham--> , B15 2TT--> , U.K--> - UNITED KINGDOM (Hipkiss, Alan R.) UNITED KINGDOM ...

  11. Carnosine facilitates nitric oxide production in endothelial f-2 cells.

    Science.gov (United States)

    Takahashi, Satoru; Nakashima, Yukiko; Toda, Ken-Ichi

    2009-11-01

    We examined the effect of carnosine (beta-alanyl-histidine) on nitric oxide (NO) production and endothelial NO synthase (eNOS) activation in endothelial F-2 cells. Carnosine enhanced NO production in a dose-dependent manner, and the stimulatory effect of carnosine was observed at concentrations exceeding 5 mM. The carnosine-stimulated NO production was inhibited by N(G)-nitro-L-arginine methyl ester, but not by N(G)-nitro-D-arginine methyl ester. In contrast, beta-alanine, histidine (carnosine components) and anserine (N-methyl carnosine) failed to increase NO production. Carnosine had no effect on NO production for the initial 5 min, but thereafter resulted in a gradual increase in NO production up to 15 min. Carnosine did not induce phosphorylation of eNOS at Ser1177. The carnosine-induced increase in NO production was observed even when extracellular Ca2+ was depleted by ethylene glycol bis(2-aminoethyl ether)-N,N,N'-N'-tetraacetic acid however, the effect was abolished upon depletion of intracellular Ca2+ by BAPTA. After F-2 cells were incubated with carnosine for 4 min, intracellular Ca2+ concentration gradually increased. The carnosine-induced increase in intracellular Ca2+ concentration occurred even in the absence of extracellular Ca2+. These results indicate that carnosine facilitates NO production in endothelial F-2 cells. It is also suggested that eNOS is activated by Ca2+, which might be released from intracellular Ca2+ stores in response to carnosine. PMID:19881293

  12. Physiological role of carnosine in contracting muscle.

    Science.gov (United States)

    Begum, Gulshanara; Cunliffe, Adam; Leveritt, Michael

    2005-10-01

    High-intensity exercise leads to reductions in muscle substrates (ATP, PCr6, and glycogen) and a subsequent accumulation of metabolites (ADP, P, H(+), and Mg(+)) with a possible increase in free radical production. These factors independently and collectively have deleterious effects on muscle, with significant repercussions on high-intensity performance or training sessions. The effect of carnosine on overcoming muscle fatigue appears to be related to its ability to buffer the increased H(+) concentration following high-intensity work. Carnosine, however, has other roles such as an antioxidant, a metal chelator, a Ca(2+) and enzyme regulator, an inhibitor of protein glycosylation and protein-protein cross-linking. To date7comma; only 1 study has investigated the effects of carnosine supplementation (not in pure form) on exercise performance in human subjects and found no improvement in repetitive high-intensity work. Much data has come from in vitro work on animal skeletal muscle fibers or other components of muscle contractile mechanisms. Thus further research needs to be carried out on humans to provide additional understanding on the effects of carnosine in vivo. PMID:16327029

  13. Free radical scavenging and radioprotective effects of carnosine and anserine

    Energy Technology Data Exchange (ETDEWEB)

    Fu Haiying [Nuclear Professional School, School of Engineering, University of Tokyo, 2-22 Shirakata shirane, Tokaimura, Nakagun, Ibaraki 319-1188 (Japan); Katsumura, Yosuke [Nuclear Professional School, School of Engineering, University of Tokyo, 2-22 Shirakata shirane, Tokaimura, Nakagun, Ibaraki 319-1188 (Japan); Advanced Science Research Center, Japan Atomic Energy Agency, 2-4 Shirakata shirane, Tokaimura, Nakagun, Ibaraki 319-1195 (Japan); Department of Nuclear Engineering and Management, School of Engineering, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-8656 (Japan)], E-mail: katsu@n.t.u-tokyo.ac.jp; Lin Mingzhang [Advanced Science Research Center, Japan Atomic Energy Agency, 2-4 Shirakata shirane, Tokaimura, Nakagun, Ibaraki 319-1195 (Japan); Muroya, Yusa; Hata, Kuniki [Nuclear Professional School, School of Engineering, University of Tokyo, 2-22 Shirakata shirane, Tokaimura, Nakagun, Ibaraki 319-1188 (Japan); Fujii, Kentaro; Yokoya, Akinari; Hatano, Yoshihiko [Advanced Science Research Center, Japan Atomic Energy Agency, 2-4 Shirakata shirane, Tokaimura, Nakagun, Ibaraki 319-1195 (Japan)

    2009-12-15

    Two histidine-containing natural dipeptides, carnosine and anserine ({beta}-alanyl-1-methyl-L-histidine), have been examined for their antioxidant and radioprotective abilities. Pulse radiolysis studies indicated the antioxidative properties of carnosine and anserine aqueous solutions at different pH. The rate constants for the reaction OH radical with carnosine at neutral pH were determined to be 5.3x10{sup 9} M{sup -1} s{sup -1} at 300 nm, and 4.1x10{sup 9} M{sup -1} s{sup -1} at 400 nm, respectively. Carnosine and anserine also protected plasmid pUC18 DNA from X-ray radiation-induced strand breaks as evidenced from the studies by agarose gel electrophoresis. Carnosine showed higher protective efficiency under the experimental conditions. Our data demonstrated that carnosine and anserine may play an important role in the maintenance of the antioxidant system.

  14. Free radical scavenging and radioprotective effects of carnosine and anserine

    Science.gov (United States)

    Fu, Haiying; Katsumura, Yosuke; Lin, Mingzhang; Muroya, Yusa; Hata, Kuniki; Fujii, Kentaro; Yokoya, Akinari; Hatano, Yoshihiko

    2009-12-01

    Two histidine-containing natural dipeptides, carnosine and anserine (β-alanyl-1-methyl- L-histidine), have been examined for their antioxidant and radioprotective abilities. Pulse radiolysis studies indicated the antioxidative properties of carnosine and anserine aqueous solutions at different pH. The rate constants for the reaction OH radical with carnosine at neutral pH were determined to be 5.3×10 9 M -1 s -1 at 300 nm, and 4.1×10 9 M -1 s -1 at 400 nm, respectively. Carnosine and anserine also protected plasmid pUC18 DNA from X-ray radiation-induced strand breaks as evidenced from the studies by agarose gel electrophoresis. Carnosine showed higher protective efficiency under the experimental conditions. Our data demonstrated that carnosine and anserine may play an important role in the maintenance of the antioxidant system.

  15. Muscle Carnosine Is Associated with Cardiometabolic Risk Factors in Humans

    OpenAIRE

    De Courten, Barbora; Kurdiova, Timea; de Courten, Maximilian PJ; Belan, Vitazoslav; Everaert, Inge; Vician, Marek; Teede, Helena; Gasperikova, Daniela; Aldini, Giancarlo; Derave, Wim; Ukropec, Jozef; Ukropcova, Barbara

    2015-01-01

    BACKGROUND: Carnosine is a naturally present dipeptide abundant in skeletal muscle and an over-the counter food additive. Animal data suggest a role of carnosine supplementation in the prevention and treatment of obesity, insulin resistance, type 2 diabetes and cardiovascular disease but only limited human data exists. METHODS AND RESULTS: Samples of vastus lateralis muscle were obtained by needle biopsy. We measured muscle carnosine levels (high-performance liquid chromatography), % body ...

  16. Important role of muscle carnosine in rowing performance

    OpenAIRE

    Baguet, A.; Bourgois, J; Vanhee, L.; Achten, E; Derave, W.

    2010-01-01

    The role of the presence of carnosine (ß-alanyl-l-histidine) in millimolar concentrations in human skeletal muscle is poorly understood. Chronic oral ß-alanine supplementation is shown to elevate muscle carnosine content and improve anaerobic exercise performance during some laboratory tests, mainly in the untrained. It remains to be determined whether carnosine loading can improve single competition-like events in elite athletes. The aims of the present study were to investigate if performan...

  17. Use of Carnosine for Oxidative Stress Reduction in Different Pathologies

    Directory of Open Access Journals (Sweden)

    V. D. Prokopieva

    2016-01-01

    Full Text Available The main properties and biological effects of the antioxidant carnosine, the natural dipeptide β-alanyl-L-histidine, are considered. Data on the effective use of carnosine in different pathologies are presented. Special attention is paid to issues of use of carnosine in neurologic and mental diseases, in alcoholism as well as in physiological states accompanied by activation of free-radical processes and formation of oxidative stress.

  18. Use of Carnosine for Oxidative Stress Reduction in Different Pathologies.

    Science.gov (United States)

    Prokopieva, V D; Yarygina, E G; Bokhan, N A; Ivanova, S A

    2016-01-01

    The main properties and biological effects of the antioxidant carnosine, the natural dipeptide β-alanyl-L-histidine, are considered. Data on the effective use of carnosine in different pathologies are presented. Special attention is paid to issues of use of carnosine in neurologic and mental diseases, in alcoholism as well as in physiological states accompanied by activation of free-radical processes and formation of oxidative stress. PMID:26904160

  19. Muscle carnosine is associated with cardiometabolic risk factors in Humans

    OpenAIRE

    Barbora de Courten; Timea Kurdiova; de Courten, Maximilian P.J.; Vitazoslav Belan; Inge Everaert; Marek Vician; Helena Teede; Daniela Gasperikova; Giancarlo Aldini; Wim Derave; Jozef Ukropec; Barbara Ukropcova

    2015-01-01

    BACKGROUND: Carnosine is a naturally present dipeptide abundant in skeletal muscle and an over-the counter food additive. Animal data suggest a role of carnosine supplementation in the prevention and treatment of obesity, insulin resistance, type 2 diabetes and cardiovascular disease but only limited human data exists. METHODS AND RESULTS: Samples of vastus lateralis muscle were obtained by needle biopsy. We measured muscle carnosine levels (high-performance liquid chromatography), % body ...

  20. Use of Carnosine for Oxidative Stress Reduction in Different Pathologies

    OpenAIRE

    Prokopieva, V. D.; Yarygina, E. G.; Bokhan, N. A.; Ivanova, S. A.

    2016-01-01

    The main properties and biological effects of the antioxidant carnosine, the natural dipeptide β-alanyl-L-histidine, are considered. Data on the effective use of carnosine in different pathologies are presented. Special attention is paid to issues of use of carnosine in neurologic and mental diseases, in alcoholism as well as in physiological states accompanied by activation of free-radical processes and formation of oxidative stress.

  1. Carnosine induced formation of silver nanochains: A radiolytic study

    Science.gov (United States)

    Malkar, Vishwabharati V.; Mukherjee, Tulsi; Kapoor, Sudhir

    2015-02-01

    Interaction of carnosine with silver clusters and its nanoparticles is studied at pH 8.2 and 9.2. Using time resolved kinetic measurements we show that carnosine interacts with the charged silver clusters. Using ionizing radiation silver particles are also produced in aqueous solution. In the presence of carnosine distinct differences in the surface plasmon absorption band of Ag nanoparticles is observed with change in pH. The results suggest that silver nanochains get formed through dipole-dipole interaction due to weak interaction with carnosine. UV-Vis spectrophotometry and transmission electron microscopy are used to characterize the nanoparticles.

  2. Could carnosine or related structures suppress Alzheimer's disease?

    Science.gov (United States)

    Hipkiss, Alan R

    2007-05-01

    Reactive oxygen species, reactive nitrogen species, copper and zinc ions, glycating agents and reactive aldehydes, protein cross-linking and proteolytic dysfunction may all contribute to Alzheimer's disease (AD). Carnosine (beta-alanyl-L-histidine) is a naturally-occurring, pluripotent, homeostatic agent. The olfactory lobe is normally enriched in carnosine and zinc. Loss of olfactory function and oxidative damage to olfactory tissue are early symptoms of AD. Amyloid peptide aggregates in AD brain are enriched in zinc ions. Carnosine can chelate zinc ions. Protein oxidation and glycation are integral components of the AD pathophysiology. Carnosine can suppress amyloid-beta peptide toxicity, inhibit production of oxygen free-radicals, scavenge hydroxyl radicals and reactive aldehydes, and suppresses protein glycation. Glycated protein accumulates in the cerebrospinal fluid (CSF) of AD patients. Homocarnosine levels in human CSF dramatically decline with age. CSF composition and turnover is controlled by the choroid plexus which possesses a specific transporter for carnosine and homocarnosine. Carnosine reacts with protein carbonyls and suppress the reactivity of glycated proteins. Carbonic anhydrase (CA) activity is diminished in AD patient brains. Administration of CA activators improves learning in animals. Carnosine is a CA activator. Protein cross-links (gamma-glutamyl-epsilon-amino) are present in neurofibrillary tangles in AD brain. gamma-Glutamyl-carnosine has been isolated from biological tissue. Carnosine stimulates vimentin expression in cultured human fibroblasts. The protease oxidised-protein-hydrolase is co-expressed with vimentin. Carnosine stimulates proteolysis in cultured myocytes and senescent cultured fibroblasts. These observations suggest that carnosine and related structures should be explored for therapeutic potential towards AD and other neurodegenerative disorders. PMID:17522447

  3. Endogenous L-Carnosine Level in Diabetes Rat Cardiac Muscle

    Science.gov (United States)

    Liu, Yali; Su, Dan; Zhang, Ling; Wei, Shaofeng; Liu, Kuangyi; Peng, Mi; Li, Hanyun; Song, Yonggui

    2016-01-01

    A novel method for quantitation of cardiac muscle carnosine levels using HPLC-UV is described. In this simple and reliable method, carnosine from the rat cardiac muscle and the internal standard, thymopentin, were extracted by protein precipitation with acetonitrile. The method was linear up to 60.96 μg·mL−1 for L-carnosine. The calibration curve was linear in concentration ranges from 0.5 to 60.96 μg·mL−1. The relative standard deviations obtained for intra- and interday precision were lower than 12% and the recoveries were higher than 90% for both carnosine and internal standard. We successfully applied this method to the analysis of endogenous carnosine in cardiac muscle of the diabetes rats and healthy control rats. The concentration of carnosine was significantly lower in the diabetes rats group, compared to that in the healthy control rats. These results support the usefulness of this method as a means of quantitating carnosine and illustrate the important role of L-carnosine in cardiac muscle.

  4. Endogenous L-Carnosine Level in Diabetes Rat Cardiac Muscle.

    Science.gov (United States)

    Liu, Yali; Su, Dan; Zhang, Ling; Wei, Shaofeng; Liu, Kuangyi; Peng, Mi; Li, Hanyun; Song, Yonggui

    2016-01-01

    A novel method for quantitation of cardiac muscle carnosine levels using HPLC-UV is described. In this simple and reliable method, carnosine from the rat cardiac muscle and the internal standard, thymopentin, were extracted by protein precipitation with acetonitrile. The method was linear up to 60.96 μg·mL(-1) for L-carnosine. The calibration curve was linear in concentration ranges from 0.5 to 60.96 μg·mL(-1). The relative standard deviations obtained for intra- and interday precision were lower than 12% and the recoveries were higher than 90% for both carnosine and internal standard. We successfully applied this method to the analysis of endogenous carnosine in cardiac muscle of the diabetes rats and healthy control rats. The concentration of carnosine was significantly lower in the diabetes rats group, compared to that in the healthy control rats. These results support the usefulness of this method as a means of quantitating carnosine and illustrate the important role of L-carnosine in cardiac muscle. PMID:27190533

  5. Endogenous L-Carnosine Level in Diabetes Rat Cardiac Muscle

    Directory of Open Access Journals (Sweden)

    Yali Liu

    2016-01-01

    Full Text Available A novel method for quantitation of cardiac muscle carnosine levels using HPLC-UV is described. In this simple and reliable method, carnosine from the rat cardiac muscle and the internal standard, thymopentin, were extracted by protein precipitation with acetonitrile. The method was linear up to 60.96 μg·mL−1 for L-carnosine. The calibration curve was linear in concentration ranges from 0.5 to 60.96 μg·mL−1. The relative standard deviations obtained for intra- and interday precision were lower than 12% and the recoveries were higher than 90% for both carnosine and internal standard. We successfully applied this method to the analysis of endogenous carnosine in cardiac muscle of the diabetes rats and healthy control rats. The concentration of carnosine was significantly lower in the diabetes rats group, compared to that in the healthy control rats. These results support the usefulness of this method as a means of quantitating carnosine and illustrate the important role of L-carnosine in cardiac muscle.

  6. Effect of carnosine on erythrocyte deformability in diabetic rats.

    Science.gov (United States)

    Yapislar, Hande; Aydogan, Sami

    2012-12-01

    It is known that oxidative stress plays an important role in the chronic complications of diabetes. Lipid peroxidation is one of the consequences of oxidative stress. Erythrocyte deformability abilities are reduced as a result of lipid peroxidation. Conversely, a decrease nitric oxide (NO) production seems to be responsible in endothelial dysfunction which occurs in diabetic vascular complications. Carnosine is a molecule with anti-oxidant properties. The aim of this study was to investigate erythrocyte deformability indices and the effects of carnosine on erythrocyte deformability in diabetes and to determine a possible relationship between carnosine and nitric oxide. Male Wistar albino rats were used in the study. Injections were administered to seven groups consisting of eight rats each. The groups were: Control, Carnosine, L-NAME (NG-nitro-L-arginine methyl ester), Diabetic, STZ (Streptozotocin) +Carnosine, STZ+L-NAME and STZ+Carnosine+L-NAME. In addition, glucose, insulin, MDA (Malondialdehyde) and NO levels were measured and erythrocyte deformability indices were calculated in all groups. Erythrocyte deformability indices and NO levels were decreased and MDA levels were found to be increased in diabetic group. It was also found that carnosine can significantly reverse erythrocyte deformability, reduce lipid peroxidation and increase NO levels in diabetes. It can be concluded that carnosine can recover from microvascular circulation problems by increasing erythrocyte deformability, can protect cells and tissues against lipid peroxidation and can be used as a multi-functional anti-oxidant in the treatment of diabetes mellitus to prevent the complications of diabetes. PMID:22946660

  7. Expression profiles of carnosine synthesis–related genes in mice after ingestion of carnosine or ß-alanine

    Directory of Open Access Journals (Sweden)

    Miyaji Takayuki

    2012-04-01

    Full Text Available Abstract Background Carnosine is a dipeptide that improves exercise performance. The carnosine synthesis mechanism through carnosine and ß-alanine ingestion remains unclear. Therefore, we investigated the tissue distribution of carnosine synthase, ATP-grasp domain-containing protein-1 (ATPGD1 mRNA, and ATPGD1 and carnosine specific dipeptidase (CN1 gene expression profiles in mice that were given carnosine or ß-alanine orally. Methods ddY mice (7-week-old were randomly divided into three groups (n = 6 to 8 animals per group and were orally given 2 g/kg body weight of carnosine, ß-alanine, or water. After 15, 30, 60, 120, 180, or 360 min of treatment, the tissues (brain, blood, liver, kidneys, olfactory bulbs, hindleg muscles were collected. The obtained tissues measured the expression of ATPGD1 and CN1 genes using quantitative PCR methods. Results The ATPGD1 gene was expressed in muscle and to a lesser extent in brain. The expression of ATPGD1 in the vastus lateralis muscle increased significantly at 180 min (P = 0.023 after carnosine ingestion and 60 (P = 0.023 and 180 min (P = 0.025 after ß-alanine ingestion. Moreover, the carnosine group showed a significantly increased renal expression of the CN1 gene 60 min after ingestion (P = 0.0015. Conclusions The ATPGD1 gene showed high expression levels in brain and muscle. The ß-alanine or carnosine administration significantly increased ATPGD1 and CN1 expression in mice.

  8. Carnosine and its possible roles in nutrition and health.

    Science.gov (United States)

    Hipkiss, Alan R

    2009-01-01

    The dipeptide carnosine has been observed to exert antiaging activity at cellular and whole animal levels. This review discusses the possible mechanisms by which carnosine may exert antiaging action and considers whether the dipeptide could be beneficial to humans. Carnosine's possible biological activities include scavenger of reactive oxygen species (ROS) and reactive nitrogen species (RNS), chelator of zinc and copper ions, and antiglycating and anticross-linking activities. Carnosine's ability to react with deleterious aldehydes such as malondialdehyde, methylglyoxal, hydroxynonenal, and acetaldehyde may also contribute to its protective functions. Physiologically carnosine may help to suppress some secondary complications of diabetes, and the deleterious consequences of ischemic-reperfusion injury, most likely due to antioxidation and carbonyl-scavenging functions. Other, and much more speculative, possible functions of carnosine considered include transglutaminase inhibition, stimulation of proteolysis mediated via effects on proteasome activity or induction of protease and stress-protein gene expression, upregulation of corticosteroid synthesis, stimulation of protein repair, and effects on ADP-ribose metabolism associated with sirtuin and poly-ADP-ribose polymerase (PARP) activities. Evidence for carnosine's possible protective action against secondary diabetic complications, neurodegeneration, cancer, and other age-related pathologies is briefly discussed. PMID:19595386

  9. Experimental and Theoretical Study of Carnosine in THz Range

    Science.gov (United States)

    Yan, Hai-Tao; Wang, Wei-Ning

    2005-12-01

    The characteristic fingerprints of carnosine from 0.2 to 2.6 THz are first measured by terahertz time-domain spectroscopy at room temperature. For the pure carnosine, the refractive index varies between 1.79 and 1.85 with the average value 1.84, while for the carnosine-polyethylene mixture, four absorption peaks centred at 1.37, 1.56, 1.85 and 2.49 THz are detected. A comparison of the theoretical predictions using the density functional theory with the experimental results shows satisfactory agreement except somewhat blue shift.

  10. Endogenous L-Carnosine Level in Diabetes Rat Cardiac Muscle

    OpenAIRE

    Yali Liu; Dan Su; Ling Zhang; Shaofeng Wei; Kuangyi Liu; Mi Peng; Hanyun Li; Yonggui Song

    2016-01-01

    A novel method for quantitation of cardiac muscle carnosine levels using HPLC-UV is described. In this simple and reliable method, carnosine from the rat cardiac muscle and the internal standard, thymopentin, were extracted by protein precipitation with acetonitrile. The method was linear up to 60.96 μg·mL−1 for L-carnosine. The calibration curve was linear in concentration ranges from 0.5 to 60.96 μg·mL−1. The relative standard deviations obtained for intra- and interday precision were lower...

  11. Possible Benefit of Dietary Carnosine towards Depressive Disorders.

    Science.gov (United States)

    Hipkiss, Alan R

    2015-09-01

    Many stress-related and depressive disorders have been shown to be associated with one or more of the following; shortened telomeres, raised cortisol levels and increased susceptibility to age-related dysfunction. It is suggested here that insufficient availability of the neurological peptide, carnosine, may provide a biochemical link between stress- and depression-associated phenomena: there is evidence that carnosine can enhance cortisol metabolism, suppress telomere shortening and exert anti-aging activity in model systems. Dietary supplementation with carnosine has been shown to suppress stress in animals, and improve behaviour, cognition and well-being in human subjects. It is therefore proposed that the therapeutic potential of carnosine dietary supplementation towards stress-related and depressive disorders should be examined. PMID:26425385

  12. Oral Carnosine Supplementation Prevents Vascular Damage in Experimental Diabetic Retinopathy

    NARCIS (Netherlands)

    Pfister, Frederick; Riedl, Eva; Wang, Qian; vom Hagen, Franziska; Deinzer, Martina; Harmsen, Martin Conrad; Molema, Grietje; Yard, Benito; Feng, Yuxi; Hammes, Hans-Peter

    2011-01-01

    Backgrounds/Aims: Pericyte loss, vasoregression and neuroglial activation are characteristic changes in incipient diabetic retinopathy. In this study, the effect of the antioxidant and antiglycating dipeptide carnosine was studied on the development of experimental diabetic retinopathy. Materials/Me

  13. Exercise training and beta-alanine-induced muscle carnosine loading.

    OpenAIRE

    Tine eBex; Weiliang eChung; Audrey eBaguet; Eric eAchten; Wim eDerave

    2015-01-01

    Purpose. Beta-alanine (BA) supplementation has been shown to augment muscle carnosine concentration, thereby promoting high-intensity exercise performance. Trained muscles of athletes have a higher increase in carnosine concentration after BA supplementation compared to untrained muscles, but it remains to be determined whether this is due to an accumulation of acute exercise effects or to chronic adaptations from prior training. The aim of the present study was to investigate whether high-vo...

  14. Possible Benefit of Dietary Carnosine towards Depressive Disorders

    OpenAIRE

    Hipkiss, Alan R

    2015-01-01

    Many stress-related and depressive disorders have been shown to be associated with one or more of the following; shortened telomeres, raised cortisol levels and increased susceptibility to age-related dysfunction. It is suggested here that insufficient availability of the neurological peptide, carnosine, may provide a biochemical link between stress- and depression-associated phenomena: there is evidence that carnosine can enhance cortisol metabolism, suppress telomere shortening and exert an...

  15. Exercise Training and Beta-Alanine-Induced Muscle Carnosine Loading

    OpenAIRE

    Bex, Tine; Chung, Weiliang; Baguet, Audrey; Achten, Eric; Derave, Wim

    2015-01-01

    Purpose Beta-alanine (BA) supplementation has been shown to augment muscle carnosine concentration, thereby promoting high-intensity (HI) exercise performance. Trained muscles of athletes have a higher increase in carnosine concentration after BA supplementation compared to untrained muscles, but it remains to be determined whether this is due to an accumulation of acute exercise effects or to chronic adaptations from prior training. The aim of the present study was to investigate whether ...

  16. Ergogenic Effects of β-Alanine and Carnosine: Proposed Future Research to Quantify Their Efficacy

    OpenAIRE

    John Caruso; Jessica Charles; Kayla Unruh; Rachel Giebel; Lexis Learmonth; William Potter

    2012-01-01

    β-alanine is an amino acid that, when combined with histidine, forms the dipeptide carnosine within skeletal muscle. Carnosine and β-alanine each have multiple purposes within the human body; this review focuses on their roles as ergogenic aids to exercise performance and suggests how to best quantify the former’s merits as a buffer. Carnosine normally makes a small contribution to a cell’s total buffer capacity; yet β-alanine supplementation raises intracellular carnosine concentrations that...

  17. Structural Elucidation of a Carnosine-Acrolein Adduct and its Quantification in Human Urine Samples.

    Science.gov (United States)

    Bispo, Vanderson S; de Arruda Campos, Ivan P; Di Mascio, Paolo; Medeiros, Marisa H G

    2016-01-01

    Aldehydes accumulate in inflammation, during myocardial infarction and have been associated with pain symptoms. One pathway of aldehyde detoxification is the conjugation with carnosine. A 3-methylpyridinium carnosine adduct from the reaction of carnosine and acrolein was characterized using extensive spectroscopic measurements. The adduct with urinary concentrations of 1.82 ± 0.68 nmol/mg of creatinine is one of the most abundant acrolein metabolites in urine and opens promising therapeutic strategies for carnosine. PMID:26783107

  18. Muscle carnosine metabolism and β-alanine supplementation in relation to exercise and training

    OpenAIRE

    Derave, Wim; Everaert, Inge; Beeckman, Sam; Baguet, Audrey

    2010-01-01

    Carnosine is a dipeptide with a high concentration in mammalian skeletal muscle. It is synthesized by carnosine synthase from the amino acids L-histidine and beta-alanine, of which the latter is the rate-limiting precursor, and degraded by carnosinase. Recent studies have shown that the chronic oral ingestion of beta-alanine can substantially elevate (up to 80%) the carnosine content of human skeletal muscle. Interestingly, muscle carnosine loading leads to improved performance in high-intens...

  19. Muscle Carnosine Is Associated with Cardiometabolic Risk Factors in Humans.

    Directory of Open Access Journals (Sweden)

    Barbora de Courten

    Full Text Available Carnosine is a naturally present dipeptide abundant in skeletal muscle and an over-the counter food additive. Animal data suggest a role of carnosine supplementation in the prevention and treatment of obesity, insulin resistance, type 2 diabetes and cardiovascular disease but only limited human data exists.Samples of vastus lateralis muscle were obtained by needle biopsy. We measured muscle carnosine levels (high-performance liquid chromatography, % body fat (bioimpedance, abdominal subcutaneous and visceral adiposity (magnetic resonance imaging, insulin sensitivity (euglycaemic hyperinsulinemic clamp, resting energy expenditure (REE, indirect calorimetry, free-living ambulatory physical activity (accelerometers and lipid profile in 36 sedentary non-vegetarian middle aged men (45±7 years with varying degrees of adiposity and glucose tolerance. Muscle carnosine content was positively related to % body fat (r = 0.35, p = 0.04 and subcutaneous (r = 0.38, p = 0.02 but not visceral fat (r = 0.17, p = 0.33. Muscle carnosine content was inversely associated with insulin sensitivity (r = -0.44, p = 0.008, REE (r = -0.58, p<0.001 and HDL-cholesterol levels (r = -0.34, p = 0.048. Insulin sensitivity and physical activity were the best predictors of muscle carnosine content after adjustment for adiposity.Our data shows that higher carnosine content in human skeletal muscle is positively associated with insulin resistance and fasting metabolic preference for glucose. Moreover, it is negatively associated with HDL-cholesterol and basal energy expenditure. Intervention studies targeting insulin resistance, metabolic and cardiovascular disease risk factors are necessary to evaluate its putative role in the prevention and management of type 2 diabetes and cardiovascular disease.

  20. Exercise training and beta-alanine-induced muscle carnosine loading.

    Directory of Open Access Journals (Sweden)

    Tine eBex

    2015-05-01

    Full Text Available Purpose. Beta-alanine (BA supplementation has been shown to augment muscle carnosine concentration, thereby promoting high-intensity exercise performance. Trained muscles of athletes have a higher increase in carnosine concentration after BA supplementation compared to untrained muscles, but it remains to be determined whether this is due to an accumulation of acute exercise effects or to chronic adaptations from prior training. The aim of the present study was to investigate whether high-volume (HV and/or high-intensity (HI exercise can improve BA-induced carnosine loading in untrained subjects.Methods. All participants (n=28 were supplemented with 6.4 g/day of BA for 23 days. The subjects were allocated to a control group, HV or HI training group. During the BA supplementation period, the training groups performed 9 exercise sessions consisting of either 75–90 min continuous cycling at 35–45% Wmax (HV or 3 to 5 repeats of 30s cycling at 165% Wmax with 4 min recovery (HI. Carnosine content was measured in soleus and gastrocnemius medialis by proton magnetic resonance spectroscopy.Results. There was no difference in absolute increase in carnosine content between the groups in soleus and gastrocnemius muscle. For the average muscle carnosine content, a higher absolute increase was found in HV (+ 2.95 mM; P = 0.046 and HI (+ 3.26 mM; P = 0.028 group compared to the control group (+ 1.91 mM. However, there was no additional difference between the HV and HI training group.Conclusions. HV and HI exercise training showed no significant difference on BA-induced muscle carnosine loading in soleus and gastrocnemius muscle. It can be suggested that there can be a small cumulative effect of exercise on BA supplementation efficiency, although differences did not reach significance on individual muscle level.

  1. Carnosine treatment for gulf war illness: a randomized controlled trial.

    Science.gov (United States)

    Baraniuk, James Nicholas; El-Amin, Suliman; Corey, Rebecca; Rayhan, Rakib; Timbol, Christian

    2013-05-01

    About 25% of 1990-1991 Persian Gulf War veterans experience disabling fatigue, widespread pain, and cognitive dysfunction termed Gulf War illness (GWI) or Chronic Multisymptom Illness (CMI). A leading theory proposes that wartime exposures initiated prolonged production of reactive oxygen species (ROS) and central nervous system injury. The endogenous antioxidant L-carnosine (B-alanyl-L-histidine) is a potential treatment since it is a free radical scavenger in nervous tissue. To determine if nutritional supplementation with L-carnosine would significantly improve pain, cognition and fatigue in GWI, a randomized double blind placebo controlled 12 week dose escalation study involving 25 GWI subjects was employed. L-carnosine was given as 500, 1000, and 1500 mg increasing at 4 week intervals. Outcomes included subjective fatigue, pain and psychosocial questionnaires, and instantaneous fatigue and activity levels recorded by ActiWatch Score devices. Cognitive function was evaluated by WAIS-R digit symbol substitution test. Carnosine had 2 potentially beneficial effects: WAIS-R scores increased significantly, and there was a decrease in diarrhea associated with irritable bowel syndrome. No other significant incremental changes were found. Therefore, 12 weeks of carnosine (1500 mg) may have beneficial cognitive effects in GWI. Fatigue, pain, hyperalgesia, activity and other outcomes were resistant to treatment. PMID:23618477

  2. Carnosine has antinociceptive properties in the inflammation-induced nociceptive response in mice.

    Science.gov (United States)

    Ohsawa, Masahiro; Mutoh, Junpei; Asato, Megumi; Yamamoto, Shohei; Ono, Hideki; Hisa, Hiroaki; Kamei, Junzo

    2012-05-01

    Carnosine is a biologically active dipeptide that is found in fish and chicken muscle. Recent studies have revealed that carnosine has neuroprotective activity in zinc-induced neural cell apoptosis and ischemic stroke. In the present study, we examined the expression of carnosine in the spinal cord, and the antinociceptive potency of carnosine in a mouse model of inflammation-induced nociceptive pain. Immunohistochemical studies with antiserum against carnosine showed an abundance of carnosine-immunoreactivity in the dorsal horn of the mouse spinal cord. Double-immunostaining techniques revealed that carnosine was expressed in the neurons and astrocytes in the spinal cord. Oral administration of carnosine attenuated the number of writhing behaviors induced by the intraperitoneal administration of 0.6% acetic acid. Treatment with carnosine also attenuated the second phase, but not the first phase, of the nociceptive response to formalin. Moreover, intrathecal, but not intraplanter, administration of carnosine attenuated the second phase of the nociceptive response to formalin. Our immunohistochemical and behavioral data suggest that carnosine has antinociceptive effects toward inflammatory pain, which may be mediated by the attenuation of nociceptive sensitization in the spinal cord. PMID:22366199

  3. Effects of carnosine on the evoked potentials in hippocampal CA1 region

    Institute of Scientific and Technical Information of China (English)

    Zhou-yan FENG; Xiao-jing ZHENG; Jing WANG

    2009-01-01

    Objective: To directly examine the effects of carnosine on neuronal excitation and inhibition in rat hippocampus in vivo. Methods: Artificial cerebrospinal fluid with carnosine was directly administrated over the exposed rat hippocampus. The changes of neuron activity in the CA1 region of hippocampus were evaluated by orthodromically- and antidromically-evoked potentials, as well as paired-pulse stimulation paradigm. Results: In both orthodromic and antidromic response potentials, carnosine transformed population spikes (PSs) with single spike into epileptiform multiple spikes. In addition, similar to the effect of γ-aminobutyric acidA (GABAA) antagonist picrotoxin, carnosine decreased paired-pulse stimulating depression significantly.However, no significant change was observed in the spontaneous field potentials during the application of carnosine. Conclusion:The results indicate a disinhibition-induced excitation effect of carnosine on the CA1 pyramidal neurons. It provides important information against the application of carnosine as a potential anticonvulsant in clinical treatment.

  4. Protection of neuronal cells against reactive oxygen species by carnosine and related compounds.

    Science.gov (United States)

    Boldyrev, Alexander; Bulygina, Elena; Leinsoo, Toomas; Petrushanko, Irina; Tsubone, Shiori; Abe, Hiroki

    2004-01-01

    Carnosine and related compounds were compared in terms of their abilities to decrease the levels of reactive oxygen species (ROS) in suspensions of isolated neurons activated by N-methyl-D-aspartic acid (NMDA) using both stationary fluorescence measurements and flow cytometry. Carnosine was found to suppress the fluorescent signal induced by ROS production and decreased the proportion of highly fluorescent neurons, while histidine showed opposite effects. N-Acetylated derivatives of both carnosine and histidine demonstrated weak (statistically indistinguishable) suppressive effects on the ROS signal. N-Methylated derivatives of carnosine suppressed intracellular ROS generation to the same extent as carnosine. This rank of effectiveness is distinct from that previously obtained for the anti-radical ability of CRCs (anserine>carnosine>ophidine). These differences suggest that the similar ability of carnosine and its N-methylated derivatives to protect neuronal cells against the excitotoxic effect of NMDA is not solely related to the antioxidant properties of these compounds. PMID:14698913

  5. Distribution of carnosine-like peptides in the nervous system of developing and adult zebrafish (Danio rerio) and embryonic effects of chronic carnosine exposure

    OpenAIRE

    Senut, Marie-Claude; Azher, Seema; Margolis, Frank L.; Patel, Kamakshi; Mousa, Ahmad; Majid, Arshad

    2009-01-01

    Carnosine-like peptides (carnosine-LP) are a family of histidine derivatives that are present in the nervous system of various species and that exhibit antioxidant, anti-matrix-metalloproteinase, anti-excitotoxic, and free-radical scavenging properties. They are also neuroprotective in animal models of cerebral ischemia. Although the function of carnosine-LP is largely unknown, the hypothesis has been advanced that they play a role in the developing nervous system. Since the zebrafish is an e...

  6. CONTENT OF NUTRIENTS AND NUTRICINES - CARNOSINE IN DARK CHICKEN MEAT

    Directory of Open Access Journals (Sweden)

    Gordana Kralik

    2010-06-01

    Full Text Available The aim of this study was to determine content of nutrients and carnosine concentration in thighs (dark meat of chickens of the Ross 308 provenance with respect to chicken gender. Amount of carnosine is determined by the HPLC device. Thigh muscle tissue of female and male chickens contains 339.28±68.17 μg/g and 319.29±65.47 μg/g of carnosine (P>0.05, respectively. Live end weights of chickens are also shown, with average male chickens weights of 2377 g and female chickens 2104 g (P0.05 are also shown. The obtained research results are explained in the context of other relevant studies on a similar topic.

  7. A carnosine intervention study in overweight human volunteers: bioavailability and reactive carbonyl species sequestering effect

    Science.gov (United States)

    Regazzoni, Luca; de Courten, Barbora; Garzon, Davide; Altomare, Alessandra; Marinello, Cristina; Jakubova, Michaela; Vallova, Silvia; Krumpolec, Patrik; Carini, Marina; Ukropec, Jozef; Ukropcova, Barbara; Aldini, Giancarlo

    2016-06-01

    Carnosine is a natural dipeptide able to react with reactive carbonyl species, which have been recently associated with the onset and progression of several human diseases. Herein, we report an intervention study in overweight individuals. Carnosine (2 g/day) was orally administered for twelve weeks in order to evaluate its bioavailability and metabolic fate. Two carnosine adducts were detected in the urine samples of all subjects. Such adducts are generated from a reaction with acrolein, which is one of the most toxic and reactive compounds among reactive carbonyl species. However, neither carnosine nor adducts have been detected in plasma. Urinary excretion of adducts and carnosine showed a positive correlation although a high variability of individual response to carnosine supplementation was observed. Interestingly, treated subjects showed a significant decrease in the percentage of excreted adducts in reduced form, accompanied by a significant increase of the urinary excretion of both carnosine and carnosine-acrolein adducts. Altogether, data suggest that acrolein is entrapped in vivo by carnosine although the response to its supplementation is possibly influenced by individual diversities in terms of carnosine dietary intake, metabolism and basal production of reactive carbonyl species.

  8. Carnosine Content in Skeletal Muscle Is Dependent on Vitamin B6 Status in Rats

    OpenAIRE

    Suidasari, Sofya; Stautemas, Jan; Uragami, Shinji; Yanaka, Noriyuki; Derave, Wim; Kato, Norihisa

    2016-01-01

    Carnosine, a histidine-containing dipeptide, is well known to be associated with skeletal muscle performance. However, there is limited information on the effect of dietary micronutrients on muscle carnosine level. Pyridoxal 5′-phosphate (PLP), the active form of vitamin B6, is involved in amino acid metabolisms in the body as a cofactor. We hypothesized that enzymes involved in β-alanine biosynthesis, the rate-limiting precursor of carnosine, may also be PLP dependent. Thus, we examined the ...

  9. CARNOSINE CONTENT AND MUSCLE OXIDATIVE STABILITY OF MALE AND FEMALE BROILER CHICKENS

    OpenAIRE

    Gordana Kralik; Helga Medić; Nives Marušić; Zlata Kralik; Manuela Grčević

    2011-01-01

    Carnosine is a dipeptide with antioxidative effects in broiler muscles. Its anti-ageing effect has also been determined recently, which is especially important for human health and vitality preservation. The research investigated concentration of carnosine in breast and thigh muscles of Cobb 500 broilers. It was carried out on 20 male and female broilers that were conventionally fattened for 42 days. Carnosine concentrations and TBARS values were measured on fresh breast and thigh muscles ...

  10. Neuroprotective Effect of Carnosine on Primary Culture of Rat Cerebellar Cells under Oxidative Stress.

    Science.gov (United States)

    Lopachev, A V; Lopacheva, O M; Abaimov, D A; Koroleva, O V; Vladychenskaya, E A; Erukhimovich, A A; Fedorova, T N

    2016-05-01

    Dipeptide carnosine (β-alanyl-L-histidine) is a natural antioxidant, but its protective effect under oxidative stress induced by neurotoxins is studied insufficiently. In this work, we show the neuroprotective effect of carnosine in primary cultures of rat cerebellar cells under oxidative stress induced by 1 mM 2,2'-azobis(2-amidinopropane)dihydrochloride (AAPH), which directly generates free radicals both in the medium and in the cells, and 20 nM rotenone, which increases the amount of intracellular reactive oxygen species (ROS). In both models, adding 2 mM carnosine to the incubation medium decreased cell death calculated using fluorescence microscopy and enhanced cell viability estimated by the MTT assay. The antioxidant effect of carnosine inside cultured cells was demonstrated using the fluorescence probe dichlorofluorescein. Carnosine reduced by half the increase in the number of ROS in neurons induced by 20 nM rotenone. Using iron-induced chemiluminescence, we showed that preincubation of primary neuronal cultures with 2 mM carnosine prevents the decrease in endogenous antioxidant potential of cells induced by 1 mM AAPH and 20 nM rotenone. Using liquid chromatography-mass spectrometry, we showed that a 10-min incubation of neuronal cultures with 2 mM carnosine leads to a 14.5-fold increase in carnosine content in cell lysates. Thus, carnosine is able to penetrate neurons and exerts an antioxidant effect. Western blot analysis revealed the presence of the peptide transporter PEPT2 in rat cerebellar cells, which suggests the possibility of carnosine transport into the cells. At the same time, Western blot analysis showed no carnosine-induced changes in the level of apoptosis regulating proteins of the Bcl-2 family and in the phosphorylation of MAP kinases, which suggests that carnosine could have minimal or no side effects on proliferation and apoptosis control systems in normal cells. PMID:27297901

  11. The Neuroprotective Effects of Carnosine in Early Stage of Focal Ischemia Rodent Model

    OpenAIRE

    Park, Hui-Seung; Han, Kyung-Hoon; Shin, Jeoung-A; Park, Joo-Hyun; Song, Kwan-Young; Kim, Doh-Hee

    2014-01-01

    Objective This study was conducted to elucidate neuroprotective effect of carnosine in early stage of stroke. Methods Early stage of rodent stroke model and neuroblastoma chemical hypoxia model was established by middle cerebral artery occlusion and antimycin A. Neuroprotective effect of carnosine was investigated with 100, 250, and 500 mg of carnosine treatment. And antioxidant expression was analyzed by enzyme linked immunosorbent assay (ELISA) and western blot in brain and blood. Results I...

  12. Molecular Identification of Carnosine Synthase as ATP-grasp Domain-containing Protein 1 (ATPGD1)*

    OpenAIRE

    Drozak, Jakub; Veiga-da-Cunha, Maria; Vertommen, Didier; Stroobant, Vincent; Van Schaftingen, Emile

    2010-01-01

    Carnosine (β-alanyl-l-histidine) and homocarnosine (γ-aminobutyryl-l-histidine) are abundant dipeptides in skeletal muscle and brain of most vertebrates and some invertebrates. The formation of both compounds is catalyzed by carnosine synthase, which is thought to convert ATP to AMP and inorganic pyrophosphate, and whose molecular identity is unknown. In the present work, we have purified carnosine synthase from chicken pectoral muscle about 1500-fold until only two major polypeptides of 100 ...

  13. Impairment of Electron Transfer Chain Induced by Acute Carnosine Administration in Skeletal Muscle of Young Rats

    OpenAIRE

    José Roberto Macarini; Soliany Grassi Maravai; José Henrique Cararo; Nádia Webber Dimer; Cinara Ludvig Gonçalves; Luiza Wilges Kist; Mauricio Reis Bogo; Patrícia Fernanda Schuck; Emilio Luiz Streck; Gustavo Costa Ferreira

    2014-01-01

    Serum carnosinase deficiency is an inherited disorder that leads to an accumulation of carnosine in the brain tissue, cerebrospinal fluid, skeletal muscle, and other tissues of affected patients. Considering that high levels of carnosine are associated with neurological dysfunction and that the pathophysiological mechanisms involved in serum carnosinase deficiency remain poorly understood, we investigated the in vivo effects of carnosine on bioenergetics parameters, namely, respiratory chain ...

  14. A carnosine intervention study in overweight human volunteers: bioavailability and reactive carbonyl species sequestering effect

    OpenAIRE

    Luca Regazzoni; Barbora de Courten; Davide Garzon; Alessandra Altomare; Cristina Marinello; Michaela Jakubova; Silvia Vallova; Patrik Krumpolec; Marina Carini; Jozef Ukropec; Barbara Ukropcova; Giancarlo Aldini

    2016-01-01

    Carnosine is a natural dipeptide able to react with reactive carbonyl species, which have been recently associated with the onset and progression of several human diseases. Herein, we report an intervention study in overweight individuals. Carnosine (2 g/day) was orally administered for twelve weeks in order to evaluate its bioavailability and metabolic fate. Two carnosine adducts were detected in the urine samples of all subjects. Such adducts are generated from a reaction with acrolein, whi...

  15. Effects of carnosine on the evoked potentials in hippocampal CA1 region*

    OpenAIRE

    Feng, Zhou-yan; Zheng, Xiao-jing; Wang, Jing

    2009-01-01

    Objective: To directly examine the effects of carnosine on neuronal excitation and inhibition in rat hippocampus in vivo. Methods: Artificial cerebrospinal fluid with carnosine was directly administrated over the exposed rat hippocampus. The changes of neuron activity in the CA1 region of hippocampus were evaluated by orthodromically- and antidromically-evoked potentials, as well as paired-pulse stimulation paradigm. Results: In both orthodromic and antidromic response potentials, carnosine t...

  16. Structural Elucidation of a Carnosine-Acrolein Adduct and its Quantification in Human Urine Samples

    OpenAIRE

    Vanderson S. Bispo; Ivan P. de Arruda Campos; Paolo Di Mascio; Medeiros, Marisa H. G.

    2016-01-01

    Aldehydes accumulate in inflammation, during myocardial infarction and have been associated with pain symptoms. One pathway of aldehyde detoxification is the conjugation with carnosine. A 3-methylpyridinium carnosine adduct from the reaction of carnosine and acrolein was characterized using extensive spectroscopic measurements. The adduct with urinary concentrations of 1.82 ± 0.68 nmol/mg of creatinine is one of the most abundant acrolein metabolites in urine and opens promising therapeutic s...

  17. Studies on adsorption of carnosine on silver nanoparticles by SERS

    Science.gov (United States)

    Thomas, S.; Biswas, N.; Malkar, V. V.; Mukherjee, T.; Kapoor, S.

    2010-05-01

    The surface-enhanced Raman scattering (SERS) studies of L-carnosine was carried out in aqueous silver sol at pH ˜ 9 and compared with the normal Raman spectrum of the molecule. The experimentally observed Raman bands were assigned based on the results of DFT calculations. Significant changes in the relative intensity are seen in the SERS spectrum when compared to the normal Raman spectrum. The studies suggest that the interaction of carnosine is primarily through the carboxylate group with the imidazole ring in an upright position with respect to the silver surface and the alanine moiety assuming a parallel orientation with the surface where NH 2 group is close to the silver surface.

  18. Carnosine Treatment for Gulf War Illness: A Randomized Controlled Trial

    OpenAIRE

    Baraniuk, James Nicholas; El-Amin, Suliman; Corey, Rebecca; Rayhan, Rakib; Timbol, Christian

    2013-01-01

    About 25% of 1990-1991 Persian Gulf War veterans experience disabling fatigue, widespread pain, and cognitive dysfunction termed Gulf War illness (GWI) or Chronic Multisymptom Illness (CMI). A leading theory proposes that wartime exposures initiated prolonged production of reactive oxygen species (ROS) and central nervous system injury. The endogenous antioxidant L-carnosine (β-alanyl-L-histidine) is a potential treatment since it is a free radical scavenger in nervous tissue. To determine if...

  19. Carnosine metabolism in diabetes is altered by reactive metabolites.

    Science.gov (United States)

    Peters, Verena; Lanthaler, Barbara; Amberger, Albert; Fleming, Thomas; Forsberg, Elisabete; Hecker, Markus; Wagner, Andreas H; Yue, Wyatt W; Hoffmann, Georg F; Nawroth, Peter; Zschocke, Johannes; Schmitt, Claus P

    2015-11-01

    Carnosinase 1 (CN1) contributes to diabetic nephropathy by cleaving histidine-dipeptides which scavenge reactive oxygen and carbonyl species and increase nitric oxide (NO) production. In diabetic mice renal CN1 activity is increased, the regulatory mechanisms are unknown. We therefore analysed the in vitro and in vivo regulation of CN1 activity using recombinant and human CN1, and the db/db mouse model of diabetes. Glucose, leptin and insulin did not modify recombinant and human CN1 activity in vitro, glucose did not alter renal CN1 activity of WT or db/db mice ex vivo. Reactive metabolite methylglyoxal and Fenton reagent carbonylated recombinant CN1 and doubled CN1 efficiency. NO S-nitrosylated CN1 and decreased CN1 efficiency for carnosine by 70 % (p carnosine and anserine. Renal carbonyl stress was strongly increased and NO production halved, CN1 highly carbonylated and less S-nitrosylated compared to WT mice. GSH and NO2/3 concentrations were reduced and inversely related with carnosine degradation rate (r = -0.82/-0.85). Thus, reactive metabolites of diabetes upregulate CN1 activity by post-translational modifications, and thus decrease the availability of reactive metabolite-scavenging histidine dipeptides in the kidney in a positive feedback loop. Interference with this vicious circle may represent a new therapeutic target for mitigation of DN. PMID:26081982

  20. Would carnosine or a carnivorous diet help suppress aging and associated pathologies?

    Science.gov (United States)

    Hipkiss, Alan R

    2006-05-01

    Carnosine (beta-alanyl-L-histidine) is found exclusively in animal tissues. Carnosine has the potential to suppress many of the biochemical changes (e.g., protein oxidation, glycation, AGE formation, and cross-linking) that accompany aging and associated pathologies. Glycation, generation of advanced glycosylation end-products (AGEs), and formation of protein carbonyl groups play important roles in aging, diabetes, its secondary complications, and neurodegenerative conditions. Due to carnosine's antiglycating activity, reactivity toward deleterious carbonyls, zinc- and copper-chelating activity and low toxicity, carnosine and related structures could be effective against age-related protein carbonyl stress. It is suggested that carnivorous diets could be beneficial because of their carnosine content, as the dipeptide has been shown to suppress some diabetic complications in mice. It is also suggested that carnosine's therapeutic potential should be explored with respect to neurodegeneration. Olfactory tissue is normally enriched in carnosine, but olfactory dysfunction is frequently associated with neurodegeneration. Olfactory administration of carnosine could provide a direct route to compromised tissue, avoiding serum carnosinases. PMID:16804013

  1. Carnosine Prevents Apoptosis of Glomerular Cells and Podocyte Loss in STZ Diabetic Rats

    NARCIS (Netherlands)

    Riedl, Eva; Pfister, Frederick; Braunagel, Margarita; Brinkkoetter, Paul; Sternik, Paula; Deinzer, Martina; Bakker, Stephan J. L.; Henning, Rob H.; van den Born, Jacob; Kraemer, Bernhard K.; Navis, Gerjan; Hammes, Hans-Peter; Yard, Benito; Koeppel, Hannes

    2011-01-01

    Background/Aims: We identified carnosinase-1 (CN-1) as risk-factor for diabetic nephropathy (DN). Carnosine, the substrate for CN-1, supposedly is a protective factor regarding diabetic complications. In this study, we hypothesized that carnosine administration to diabetic rats might protect the kid

  2. Inhibitory effect of carnosine on interleukin-8 production in intestinal epithelial cells through translational regulation.

    Science.gov (United States)

    Son, Dong Ok; Satsu, Hideo; Kiso, Yoshinobu; Totsuka, Mamoru; Shimizu, Makoto

    2008-05-01

    The enhanced intestinal production of pro-inflammatory cytokines leads to inflammation and carcinogenesis, and therefore its down-regulation by nutrients could represent a promising therapeutic approach. We found for the first time that the secretion of interleukin-8 (IL-8) in intestinal epithelial cells stimulated by hydrogen peroxide or TNF-alpha was suppressed in the presence of carnosine (beta-Ala-His), a dietary dipeptide. Interestingly, carnosine had no influence on the stimulus-induced IL-8 mRNA expression, although the intracellular production and secretion of IL-8 were significantly inhibited by carnosine. The inhibitory effect of carnosine on the IL-8 secretion differed from that of other histidine-containing dipeptides like Gly-His, Ala-His, and anserine (beta-Ala-1-methyl-His), which inhibited both the hydrogen peroxide-induced secretion and mRNA expression of IL-8. These observations indicate that carnosine inhibited IL-8 secretion along a unique pathway, in which IL-8 production was suppressed at a post-transcriptional level, for instance, translation. The hypothesis that carnosine inhibited the translation of IL-8 mRNA is supported by the finding that the phosphorylation of eIF4E, an initiation factor, in stimulated Caco-2 cells was inhibited by carnosine. These results suggest that carnosine is a novel type of anti-inflammatory agent that down-regulates the inflammatory response in intestinal epithelial cells by a unique mechanism. PMID:18397832

  3. Carnosine Content in Skeletal Muscle Is Dependent on Vitamin B6 Status in Rats.

    Science.gov (United States)

    Suidasari, Sofya; Stautemas, Jan; Uragami, Shinji; Yanaka, Noriyuki; Derave, Wim; Kato, Norihisa

    2015-01-01

    Carnosine, a histidine-containing dipeptide, is well known to be associated with skeletal muscle performance. However, there is limited information on the effect of dietary micronutrients on muscle carnosine level. Pyridoxal 5'-phosphate (PLP), the active form of vitamin B6, is involved in amino acid metabolisms in the body as a cofactor. We hypothesized that enzymes involved in β-alanine biosynthesis, the rate-limiting precursor of carnosine, may also be PLP dependent. Thus, we examined the effects of dietary vitamin B6 on the muscle carnosine content of rats. Male and female rats were fed a diet containing 1, 7, or 35 mg pyridoxine (PN) HCl/kg for 6 weeks. Carnosine in skeletal muscles was quantified by ultra-performance liquid chromatography coupled with tandem mass spectrometry. In the gastrocnemius muscle of male rats, carnosine concentration was significantly higher in the 7 and 35 mg groups (+70 and +61%, respectively) than in the 1 mg PN HCl/kg group, whereas that in the soleus muscle of male rats was significantly higher only in the 7 mg group (+43%) than in the 1 mg PN HCl/kg group (P carnosine concentration was significantly higher in the 7 and 35 mg groups (+32 to +226%) than in the 1 mg PN HCl/kg group (P carnosine content was found in soleus muscle of women of the lower plasma PLP tertile, but this was not observed in gastrocnemius muscle or in men. We conclude that adequate dietary vitamin B6 is essential for maintaining carnosine in skeletal muscles of rats. Significantly lower soleus carnosine content among women close to PLP deficiency suggests that a similar phenomenon exists in the humans. PMID:26835452

  4. Preventive effect of L-carnosine on changes in the thermal nociceptive threshold in streptozotocin-induced diabetic mice.

    Science.gov (United States)

    Kamei, Junzo; Ohsawa, Masahiro; Miyata, Shigeo; Tanaka, Shun-ichi

    2008-12-14

    Sensory abnormality is one of the serious complications in diabetes. Since the effective therapeutic regimen to ameliorate the diabetic sensory abnormality is very few, the present study was then designed to investigate the effect of zinc L-carnosine on the changes of nociceptive threshold in diabetic mice. Zinc L-carnosine (75-300 mg/kg, p.o.) was administered once daily from 1 day after streptozotocin treatment. Diabetic mice showed shorter tail-flick latency at 1-4 weeks after streptozotocin treatment and longer tail-flick latency at 6-9 weeks after its treatment. The shortened tail-flick latency in early stage of diabetic mice was ameliorated by treatment with zinc L-carnosine. Moreover, zinc L-carnosine also slowed the onset of hypoalgesia in diabetic mice. Tail-flick latency in non-diabetic mice was not affected by the zinc L-carnosine treatment, indicating that zinc L-carnosine did not affect normal nociceptive transmission. Moreover, L-carnosine, but not zinc sulfate, ameliorated the abnormal sensory perception in diabetic mice. Interestingly, the ameliorative effect of zinc l-carnosine on the abnormal sensory perception in diabetic mice is much stronger than that of L-carnosine. These results provide the evidence of the ameliorative potential of zinc L-carnosine on the progressive diabetic neuropathy. Moreover, L-carnosine combined with zinc shows more potent amelioration of abnormal sensory perception in diabetic mice than by itself. PMID:18930724

  5. Protective role of carnosine in mice with cadmium-induced acute hepatotoxicity.

    Science.gov (United States)

    Fouad, Amr A; Qureshi, Habib A; Yacoubi, Mohamed T; Al-Melhim, Walid N

    2009-11-01

    The hepatoprotective effect of carnosine was investigated against cadmium-induced acute liver injury in mice. Hepatotoxicity was induced by a single i.p. injection of cadmium chloride (6.5mg/kg). Carnosine treatment (10mg/kg/day, i.p.) was applied for three consecutive days, starting one day before cadmium administration. Carnosine significantly decreased the cadmium-induced elevations in serum aminotransferases. Carnosine suppressed lipid peroxidation and restored the deficits in the antioxidant defense mechanisms (reduced glutathione level, and catalase and superoxide dismutase activities) in liver tissue resulted from cadmium administration. Also, the reductions in hepatic nitric oxide and zinc ion levels, and the increases in hepatic cadmium ion concentration, and myeloperoxidase and caspase-3 activities following cadmium exposure were significantly attenuated by carnosine treatment. In addition, carnosine markedly ameliorated cadmium-induced liver tissue damage as evidenced by light and electron microscopic examinations. It was concluded that carnosine can be considered a potential candidate to protect the liver against the deleterious effect of acute cadmium intoxication. PMID:19748544

  6. Quantification of Carnosine-Aldehyde Adducts in Human Urine.

    Science.gov (United States)

    da Silva Bispo, Vanderson; Di Mascio, Paolo; Medeiros, Marisa

    2014-10-01

    Lipid peroxidation generates several reactive carbonyl species, including 4-hydroxy-2-nonenal (HNE), acrolein (ACR), 4-hydroxy-2-hexenal (HHE) and malondialdehyde. One major pathwayof aldehydes detoxification is through conjugation with glutathione catalyzed by glutathione-S-transferases or, alternatively, by conjugation with endogenous histidine containing dipeptides, such as carnosine (CAR). In this study, on-line reverse-phase high-performance liquid chromatography (HPLC) separation with tandem mass spectrometry detection was utilized for the accurate quantification of CAR- ACR, CAR-HHE and CAR-HNE adducts in human urinary samples from non-smokers young adults. Standard adducts were prepared and isolated by HPLC. The results showed the presence of a new product from the reaction of CAR with ACR. This new adduct was completely characterized by HPLC/MS-MSn, 1H RMN, COSY and HSQC. The new HPLC/MS/MS methodology employing stable isotope-labeled internal standards (CAR-HHEd5 and CAR-HNEd11) was developed for adducts quantification. This methodology permits quantification of 10pmol CAR-HHE and 1pmol of CAR-ACR and CAR-HNE. Accurate determinations in human urine sample were performed and showed 4.65±1.71 to CAR-ACR, 5.13±1.76 to CAR-HHE and 5.99±3.19nmol/mg creatinine to CAR-HNE. Our results indicate that carnosine pathways can be an important detoxification route of a, ß -unsaturated aldehydes. Moreover, carnosine adducts may be useful as redox stress indicator. PMID:26461323

  7. Mass Spectrometric and Computational Investigation of the Protonated Carnosine-Carboplatin Complex Fragmentation.

    Science.gov (United States)

    Ritacco, Ida; Sicilia, Emilia; Shoeib, Tamer; Korany, Mohamed; Russo, Nino

    2015-08-17

    Platinum(II)-based anticancer drugs are square-planar d(8) complexes that, activated by hydrolysis, cause cancer cell death by binding to nuclear DNA and distorting its structure. For that reason, interactions of platinum anticancer drugs with DNA have been extensively investigated, aiming at disentangling the mechanism of action and toxicity. Less attention, however, has been devoted to the formation of adducts between platinum drugs with biological ligands other than DNA. These adducts can cause the loss and deactivation of the drug before it arrives at the ultimate target and are also thought to contribute to the drug's toxicity. Here are reported the outcomes of electrospray ionization mass spectrometry experiments and density functional theory (DFT) computations carried out to investigate the fragmentation pathways of the protonated carnosine-carboplatin complex, [Carnosine + CarbPt + H](+). DFT calculations at the B3LYP/LANL2DZ level employed to probe fragmentation mechanisms account for all experimental data. Because of the relative rigidity of the structure of the most stable 1A conformer, stabilized by three strong hydrogen bonds, the first step of all of the examined fragmentation pathways is the interconversion of the 1A conformer into the less stable structure 1B. Formation of the [Carnosine + H](+) fragment from the precursor ion, [Carnosine + CarbPt + H](+), is calculated to be the lowest-energy process. At slightly higher energies, the loss of two amino groups is observed to produce the [Carnosine + (CarbPt - NH3) + H](+) and [Carnosine + (CarbPt - 2NH3) + H](+) ions. At significantly higher energies, the loss of CO2 occurs, yielding the final [Carnosine + (CarbPt - NH3) - CO2 + H](+) and [Carnosine + (CarbPt - 2NH3) - CO2 + H](+) products. Formation of the [CarbPt + H](+) fragment from [Carnosine + CarbPt + H](+), even if not hampered by a high activation barrier, is calculated to be very unfavorable from a thermodynamic point of view. PMID:26238420

  8. Therapeutic efficacy of natural dipeptide carnosine against human cervical carcinoma cells.

    Science.gov (United States)

    Pandurangan, Muthuraman; Enkhtaivan, Gansukh; Kim, Doo Hwan

    2016-09-01

    Natural substances have been attracted several researchers in the recent years, because of its potential antioxidant, anti-inflammatory and anti-cancer properties. We have investigated the effect of carnosine on cell viability, apoptosis, DNA damage, reactive oxygen species (ROS) and caspase 3 enzyme expression in human cervical carcinoma and Madin-Darby Kidney Cells (MDCK) cells. Carnosine inhibited cancer cell growth up to 23%. ROS level was increased up to 30 and 31% in MDCK and HeLa cells respectively. Tunnel assay showed 42 and 14% of positive apoptotic cells in cancer and normal cells respectively. The alteration in mitochondrial and nuclear morphology was determined. The extended lace-like network of normal mitochondria found in control cells. Carnosine treatment significantly altered the mitochondrial morphology of normal cervical carcinoma cell. Mitochondria were condensed clump structures in carnosine treated cancer cells. Carnosine reduced the number of colonies of cervical carcinoma cells. Caspase 3 expression was corresponded to the appearance of immunofluorescence in the cytoplasm. Caspase 3 expression was gradually increased in cervical carcinoma cells. In Silico, docking study was performed to recognize the binding activity of carnosine against a subunit of the caspase 3, and carnosine was able to bind to the drug binding pocket of caspase 3. The glide energy is -5.2 kcal/mol, suggesting the high binding affinity of carnosine to caspase 3. Taking all these data together, the natural dipeptide L-carnosine could be a suitable antiproliferative agent in cervical carcinoma cells. Copyright © 2016 John Wiley & Sons, Ltd. PMID:27000946

  9. Effect of carnosine on the immunosuppressive effect of histamine

    International Nuclear Information System (INIS)

    This paper studies the ability of carnosine (beta-imidazole-lactate) to affect histamine-induced immunosuppression of proliferative activity of various lymphocyte subpopulations and the realization of this effect through surface histamine receptors of the cells. The experiments were carried out on mice; lymphocytes were incubated with tritium-labeled thymidine for 4 h, after which their radioactivity was determined on a scintillation counter. The results show that histamine has an inhibitory action on antigen-induced proliferation of T suppressor lymphocytes through H-2 histamine receptors, for this effect was considerably inhibited by the H-2 histamine blockers metiamide, but not by the H-1 histamine blocker mepyramine

  10. Effect of carnosine on the immunosuppressive effect of histamine

    Energy Technology Data Exchange (ETDEWEB)

    Sharpan, Yu. V.

    1985-04-01

    This paper studies the ability of carnosine (beta-imidazole-lactate) to affect histamine-induced immunosuppression of proliferative activity of various lymphocyte subpopulations and the realization of this effect through surface histamine receptors of the cells. The experiments were carried out on mice; lymphocytes were incubated with tritium-labeled thymidine for 4 h, after which their radioactivity was determined on a scintillation counter. The results show that histamine has an inhibitory action on antigen-induced proliferation of T suppressor lymphocytes through H-2 histamine receptors, for this effect was considerably inhibited by the H-2 histamine blockers metiamide, but not by the H-1 histamine blocker mepyramine.

  11. Carnosine content in skeletal muscle is dependent on vitamin B6 status in rats

    OpenAIRE

    Sofya eSuidasari; Jan eStautemas; Shinji eUragami; Noriyuki eYanaka; Wim eDerave; Norihisa eKato

    2016-01-01

    Carnosine, a histidine-containing dipeptide, is well known to be associated with skeletal muscle performance. However, there is limited information on the effect of dietary micronutrients on muscle carnosine level. Pyridoxal 5′-phosphate (PLP), the active form of vitamin B6, is involved in amino acid metabolisms in the body as a co-factor. We hypothesized that enzymes involved in β-alanine biosynthesis, the rate-limiting precursor of carnosine, may also be PLP-dependent. Thus, we examined the...

  12. Amide proton transfer of carnosine in aqueous solution studied in vitro by WEX and CEST experiments.

    OpenAIRE

    Bodet, O.; Goerke, S; Behl, N.; Roeloffs, V.; Zaiss, M.; Bachert, P.

    2015-01-01

    Amide protons of peptide bonds induce an important chemical exchange saturation transfer (CEST) contrast in vivo. As a simple in vitro model for a peptide amide proton CEST effect, we suggest herein the dipeptide carnosine. We show that the metabolite carnosine creates a CEST effect and we study the properties of the exchange of the amide proton (-NH) of the carnosine peptide bond (NHCPB) in model solutions for a pH range from 6 to 8.3 and a temperature range from T = 5 degrees C to 43 degree...

  13. Carnosine inhibits KRAS-mediated HCT116 proliferation by affecting ATP and ROS production.

    Science.gov (United States)

    Iovine, Barbara; Iannella, Maria Luigia; Nocella, Francesca; Pricolo, Maria Rosaria; Bevilacqua, Maria Assunta

    2012-02-28

    Carnosine is a natural dipeptide that has generated particular interest for its antioxidant, anti-aging and especially for its antiproliferative properties. In this study, we demonstrate that carnosine inhibits the proliferation of human HCT116 colon cancer cells. In this cell line, the activating KRAS mutation induces mitochondrial ROS, the signaling molecules for cell proliferation. We observed that 50-100 mM carnosine decreases ATP and ROS concentration and induces cell cycle arrest in G1 phase. In HCT116 cells these effects are related to decreased ERK1/2 phosphorylation and increased p21waf1 protein. Our findings support the concept that carnosine could inhibit HCT116 cell growth via its antioxidant activity and its ability to affect glycolysis. PMID:22137144

  14. Systematic review and stratified meta-analysis of the efficacy of carnosine in animal models of ischemic stroke

    OpenAIRE

    Davis, C.K.; Laud, P J; Bahor, Z.; Rajanikant, G.K.; Majid, A

    2016-01-01

    Carnosine is a naturally occurring pleotropic dipeptide which influences multiple deleterious mechanisms that are activated during stroke. Numerous published studies have reported that carnosine has robust efficacy in ischemic stroke models. To further evaluate these data, we have conducted a systematic review and meta-analysis of published studies. We included publications describing in vivo models of ischemic stroke where the neuroprotective efficacy of carnosine was being evalu...

  15. Carnosine Inhibits the Proliferation of Human Gastric Cancer SGC-7901 Cells through Both of the Mitochondrial Respiration and Glycolysis Pathways

    OpenAIRE

    Yao Shen; Jianbo Yang; Juan Li; Xiaojie Shi; Li Ouyang; Yueyang Tian; Jianxin Lu

    2014-01-01

    Carnosine, a naturally occurring dipeptide, has been recently demonstrated to possess anti-tumor activity. However, its underlying mechanism is unclear. In this study, we investigated the effect and mechanism of carnosine on the cell viability and proliferation of the cultured human gastric cancer SGC-7901 cells. Carnosine treatment did not induce cell apoptosis or necrosis, but reduced the proliferative capacity of SGC-7901 cells. Seahorse analysis showed SGC-7901 cells cultured with pyruvat...

  16. Carnosine retards tumor growth in vivo in an NIH3T3-HER2/neu mouse model

    OpenAIRE

    Meixensberger Jürgen; Gebhardt Rolf; Hengstler Jan; Hermes Matthias; Geiger Kathrin D; Fuchs Beate; Zemitzsch Nadine; Renner Christof; Gaunitz Frank

    2010-01-01

    Abstract Background It was previously demonstrated that the dipeptide carnosine inhibits growth of cultured cells isolated from patients with malignant glioma. In the present work we investigated whether carnosine also affects tumor growth in vivo and may therefore be considered for human cancer therapy. Results A mouse model was used to investigate whether tumor growth in vivo can be inhibited by carnosine. Therefore, NIH3T3 fibroblasts, conditionally expressing the human epidermal growth fa...

  17. Carnosine: can understanding its actions on energy metabolism and protein homeostasis inform its therapeutic potential?

    OpenAIRE

    Hipkiss, Alan R; Cartwright, Stephanie P.; Bromley, Clare; Gross, Stephane R.; Bill, Roslyn M.

    2013-01-01

    The dipeptide carnosine (β-alanyl-L-histidine) has contrasting but beneficial effects on cellular activity. It delays cellular senescence and rejuvenates cultured senescent mammalian cells. However, it also inhibits the growth of cultured tumour cells. Based on studies in several organisms, we speculate that carnosine exerts these apparently opposing actions by affecting energy metabolism and/or protein homeostasis (proteostasis). Specific effects on energy metabolism include the dipeptide’s ...

  18. Quantification of carnosine- related peptides by microchip electrophoresis with chemiluminescence detection

    OpenAIRE

    Zhao, Shulin; Huang, Yong; Shi, Ming; Huang, Junming; Liu, Yi-Ming

    2009-01-01

    A microchip electrophoresis (MCE) method with chemiluminescence (CL) detection was developed for the determination of carnosine-related peptides including carnosine, homocarnosine and anserine in biological samples. A simple integrated MCE-CL system was built to perform the assays. The highly sensitive CL detection was achieved by means of the CL reaction between hydrogen peroxide and N-(4-aminobutyl)- N-ethylisoluminol-tagged peptides in the presence of adenine as a CL enhancer and Co2+ as a...

  19. The effects of carnosine in an experimental rat model of septic shock

    OpenAIRE

    Sahin, Sabiha; Oter, Serdar; Burukoglu, Dilek; Sutken, Emine

    2013-01-01

    Background To examine the effect of carnosine on liver function and histological findings in experimental septic shock model, 24 Sprague-Dawley rats were used. Material/Methods Rats were divided into control, septic shock, and carnosine-treated septic shock groups. Femoral vein and artery catheterization were performed on all rats. Rats in the control group underwent laparotomy and catheterization; in the test groups, cecal ligation-perforation and bladder cannulation were added. Rats in the ...

  20. L-carnosine alters some hemorheologic and lipid peroxidation parameters in nephrectomized rats

    OpenAIRE

    Yapislar, Hande; Taskin, Eylem

    2014-01-01

    Background Chronic kidney disease (CKD) is a major health problem worldwide. Oxidative stress is one of the mediators of this disease. Systemic complications of oxidative stress are involved in the pathogenesis of hypertension, endothelial dysfunction, shortened erythrocyte lifespan, deformability, and nitric oxide (NO) dysfunction. L-carnosine is known as an antioxidant. In this study, our aim was to investigate the effect of carnosine on hemorheologic and cardiovascular parameters in CKD-in...

  1. Inhibition of the growth of transformed and neoplastic cells by the dipeptide carnosine.

    OpenAIRE

    Holliday, R; McFarland, G. A.

    1996-01-01

    Human diploid fibroblasts growth normally in medium containing physiological concentrations of the naturally occurring dipeptide carnosine (beta-alanyl-L-histidine). These concentrations are cytotoxic to transformed and neoplastic cells lines in modified Eagle medium (MEM), whereas these cells grow vigorously in Dulbecco's modified Eagle medium (DMEM) containing carnosine. This difference is due to the presence of 1 mM sodium pyruvate in DMEM. Seven human cell lines and two rodent cell lines ...

  2. Antioxidant effect of carnosine pretreatment on cisplatin-induced renal oxidative stress in rats

    OpenAIRE

    S. Noori; Mahboob, Tabassum

    2010-01-01

    Cisplatin mediated nephrotoxicity is remarkably documented by reactive oxygen species. Carnosine is a naturally occurring dipeptide and has a scavenging property. The aim of present study was to assess the lipid peroxidation and antioxidant enzymes in association with oxidative stress in cisplatin -treated and 10 subsequent doses of carnosine-pretreated rats. 24 male Albino Wistar rats, were randomly divided into four groups (n=6). Group I remains untreated; Group II received Cisplatin (3 mg ...

  3. Antioxidant activity of carnosine, homocarnosine, and anserine present in muscle and brain.

    OpenAIRE

    Kohen, R; Yamamoto, Y.; Cundy, K C; Ames, B N

    1988-01-01

    Carnosine, homocarnosine, and anserine are present in high concentrations in the muscle and brain of many animals and humans. However, their exact function is not clear. The antioxidant activity of these compounds has been examined by testing their peroxyl radical-trapping ability at physiological concentrations. Carnosine, homocarnosine, anserine, and other histidine derivatives all showed antioxidant activity. All of these compounds showing peroxyl radical-trapping activity were also electr...

  4. Protective effect of carnosine after chronic cerebral hypoperfusion possibly through suppressing astrocyte activation

    OpenAIRE

    Ma, Jing; Chen, Jihui; Bo, Shuhong; Lu, Xiaotong; Zhang, Jian

    2015-01-01

    Aim: Subcortical ischemic vascular dementia (SIVD) induced by chronic hypoperfusion is a common cause of vascular dementia. The aim of this study was to determine whether the protective effect of carnosine on white matter lesion after chronic cerebral hypoperfusion through suppressing astrocyte activation. Methods: Adult male mice (C57BL/6 strain) were subjected to permanent occlusion of the right unilateral common carotid arteries (rUCCAO) and treated with carnosine or histidine. Open field ...

  5. Inhibition of oxidative stress in brain during rat adjuvant arthritis by carnosine, trolox and novel trolox-carnosine.

    Science.gov (United States)

    Poništ, S; Slovák, L; Kuncírová, V; Fedorova, T; Logvinenko, A; Muzychuk, O; Mihalová, D; Bauerová, K

    2015-01-01

    Carnosine (CARN) is an anti-glycating agent able to quench superoxide, and to neutralize 4-hydroxynonenal. Trolox-carnosine (CARN-T) was synthesized because of its resistance against degradation and to improve CARN antioxidant capacity. We evaluated the impact of trolox (TRO), CARN and its derivative CARN-T on oxidative stress (OS) in brain during rat adjuvant arthritis (AA). The experiments were done on healthy, control arthritic and arthritic animals with administration of CARN 150 mg/kg b.w., TRO 41 mg/kg b.w. and CARN-T 75 mg/kg b.w. in a daily dose during 28 days. Antioxidants did not affect the body weight on day 14, but on day 28 TRO enhanced the weight reduction. On day 14 and 28 CARN-T and TRO reduced arthritic score. IL-1beta, MCP-1 and MMP-9 were measured in plasma on day 14. MCP-1 was decreased by CARN-T and TRO. All antioxidants reduced IL-1beta and MMP-9 levels. Malondialdehyde, 4-hydroxynonenal and protein carbonyls were increased in brain. CARN, CARN-T and TRO prevented higher lipid and protein oxidation in brain. CARN and CARN-T caused no weight reduction like TRO that has an advantage in inflammatory arthritis. Moreover the antioxidants administered had a similar therapeutic effects on arthritic score, markers of inflammation in plasma and OS in brain. PMID:26681078

  6. Efficacy of Carnosine in Modulating Radiation-Induced Oxidative Damage and Neurotransmitter Alterations in Rat Brain

    International Nuclear Information System (INIS)

    The present study was designed to investigate the role of carnosine (β-alanyl-L-histidine) in alleviating oxidative damage and alteration of neurotransmitters in the brain of rats exposed to gamma radiation. Male albino rats were whole body exposed to a single dose of γ- rays (5 Gy). Carnosine (50 mg/Kg/day) was administered via gavages as follows: a) during 28 successive days, b) during 14 successive days before whole body gamma irradiation and administered distilled water for 14 days after irradiation, c) during 14 successive days before whole body gamma irradiation and during 14 days after irradiation with carnosine. The animals were sacrificed at 1, 7 and 14 days post irradiation. (3 hours after the last dose of carnosine). The results revealed that exposure to γ- rays, (5 Gy(, resulted in significant increases of the levels of thiobarbituric acid reactive substances (TBARS), protein carbonyls (CO), and advanced oxidation protein products (AOPP), associated with significant decreases of superoxide dismutase (SOD) and catalase (CAT) activities, and glutathione (GSH) content which indicate oxidative stress. Gamma rays also, induced significant decrease of the serotonin (5-HT), dopamine (DA), norepinephrine (NE) and epinephrine (EPI) contents as well as significant increase of 5-hydroxy-indole-acetic-acid (5-HIAA) level and monoamine oxidase (MAO) activity which indicated alterations in the metabolism of monoamines. Carnosine has significantly attenuated oxidative stress, and monoamine alterations in the cerebral hemispheres of irradiated rats. Carnosine might preserve the integrity of brain functions.

  7. Impairment of electron transfer chain induced by acute carnosine administration in skeletal muscle of young rats.

    Science.gov (United States)

    Macarini, José Roberto; Maravai, Soliany Grassi; Cararo, José Henrique; Dimer, Nádia Webber; Gonçalves, Cinara Ludvig; Kist, Luiza Wilges; Bogo, Mauricio Reis; Schuck, Patrícia Fernanda; Streck, Emilio Luiz; Ferreira, Gustavo Costa

    2014-01-01

    Serum carnosinase deficiency is an inherited disorder that leads to an accumulation of carnosine in the brain tissue, cerebrospinal fluid, skeletal muscle, and other tissues of affected patients. Considering that high levels of carnosine are associated with neurological dysfunction and that the pathophysiological mechanisms involved in serum carnosinase deficiency remain poorly understood, we investigated the in vivo effects of carnosine on bioenergetics parameters, namely, respiratory chain complexes (I-III, II, and II-III), malate dehydrogenase, succinate dehydrogenase, and creatine kinase activities and the expression of mitochondrial-specific transcription factors (NRF-1, PGC-1α , and TFAM) in skeletal muscle of young Wistar rats. We observed a significant decrease of complexes I-III and II activities in animals receiving carnosine acutely, as compared to control group. However, no significant alterations in respiratory chain complexes, citric acid cycle enzymes, and creatine kinase activities were found between rats receiving carnosine chronically and control group animals. As compared to control group, mRNA levels of NRF-1, PGC-1α , and TFAM were unchanged. The present findings indicate that electron transfer through the respiratory chain is impaired in skeletal muscle of rats receiving carnosine acutely. In case these findings are confirmed by further studies and ATP depletion is also observed, impairment of bioenergetics could be considered a putative mechanism responsible for the muscle damage observed in serum carnosinase-deficient patients. PMID:24877122

  8. Impairment of Electron Transfer Chain Induced by Acute Carnosine Administration in Skeletal Muscle of Young Rats

    Directory of Open Access Journals (Sweden)

    José Roberto Macarini

    2014-01-01

    Full Text Available Serum carnosinase deficiency is an inherited disorder that leads to an accumulation of carnosine in the brain tissue, cerebrospinal fluid, skeletal muscle, and other tissues of affected patients. Considering that high levels of carnosine are associated with neurological dysfunction and that the pathophysiological mechanisms involved in serum carnosinase deficiency remain poorly understood, we investigated the in vivo effects of carnosine on bioenergetics parameters, namely, respiratory chain complexes (I–III, II, and II-III, malate dehydrogenase, succinate dehydrogenase, and creatine kinase activities and the expression of mitochondrial-specific transcription factors (NRF-1, PGC-1α, and TFAM in skeletal muscle of young Wistar rats. We observed a significant decrease of complexes I–III and II activities in animals receiving carnosine acutely, as compared to control group. However, no significant alterations in respiratory chain complexes, citric acid cycle enzymes, and creatine kinase activities were found between rats receiving carnosine chronically and control group animals. As compared to control group, mRNA levels of NRF-1, PGC-1α, and TFAM were unchanged. The present findings indicate that electron transfer through the respiratory chain is impaired in skeletal muscle of rats receiving carnosine acutely. In case these findings are confirmed by further studies and ATP depletion is also observed, impairment of bioenergetics could be considered a putative mechanism responsible for the muscle damage observed in serum carnosinase-deficient patients.

  9. CARNOSINE CONTENT AND MUSCLE OXIDATIVE STABILITY OF MALE AND FEMALE BROILER CHICKENS

    Directory of Open Access Journals (Sweden)

    Gordana Kralik

    2011-12-01

    Full Text Available Carnosine is a dipeptide with antioxidative effects in broiler muscles. Its anti-ageing effect has also been determined recently, which is especially important for human health and vitality preservation. The research investigated concentration of carnosine in breast and thigh muscles of Cobb 500 broilers. It was carried out on 20 male and female broilers that were conventionally fattened for 42 days. Carnosine concentrations and TBARS values were measured on fresh breast and thigh muscles with respect to broiler sex. Content of carnosine was slightly higher in female broiler breast muscles than in male’s (1079.85 : 1012.66 μg/g tissue; P>0.05. Female broiler thigh muscle tissue also contained higher carnosine values than male’s (464.69 : 404.97 μg/g tissue; P>0.05. The research proved that carnosine was more deposited in breast muscle tissue than in thigh muscle tissue, regardless of broiler sex. Lipid peroxidation products measured as TBARS values (mg MDA/kg tissue did not statistically differ according to broiler sex or muscle type (P>0.05. Further research needs to be directed towards control of peroxidation products during meat storage.

  10. Antioxidative and anti-inflammatory protection from carnosine in the striatum of MPTP-treated mice.

    Science.gov (United States)

    Tsai, Shih-Jei; Kuo, Wei-Wen; Liu, Wen-Hu; Yin, Mei-Chin

    2010-11-10

    Mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were used to examine the neuroprotective effects of carnosine. Carnosine at 0.5, 1, and 2 g/L was directly added to the drinking water for 4 weeks. MPTP treatment significantly depleted striatal glutathione content, reduced the activity of glutathione peroxidase (GPX), superoxide dismutase (SOD), and catalase, increased malondialdehyde and reactive oxygen species levels, and elevated interleukin-6, nitrite, and tumor necrosis factor-α production as well as enhanced inducible nitric oxide synthase (iNOS) activity in the striatum (P carnosine significantly attenuated MPTP-induced glutathione loss, retained the activity of GPX and SOD, diminished oxidative stress, and lowered inflammatory cytokines and nitrite levels as well as suppressed iNOS activity (P Carnosine preintake significantly elevated GPX mRNA expression and declined iNOS mRNA expression (P carnosine also significantly improved MPTP-induced dopamine depletion and maintained 3,4-dihydroxyphenylacetic acid and homovanillic acid levels (P carnosine could provide antioxidative and anti-inflammatory protection for the striatum against the development of Parkinson's disease. PMID:20925384

  11. Radiochemical synthesis and preliminary in vivo evaluation of new radioactive platinum complexes with carnosine

    Energy Technology Data Exchange (ETDEWEB)

    Maurin, MichaL [Department of Radiopharmaceuticals, National Medicines Institute, 30/34 CheLmska Street, 00-725 Warsaw (Poland)], E-mail: mmaurin@il.waw.pl; Garnuszek, Piotr [Department of Radiopharmaceuticals, National Medicines Institute, 30/34 CheLmska Street, 00-725 Warsaw (Poland)

    2010-02-15

    Application of cross-linking agents such as SATA and 2-iminothiolane (2-IT) for radiochemical synthesis of new radioactive Pt(II) and Pt(IV) complexes with carnosine was investigated. The mixed-ligand Pt(II)([{sup 125}I]Hist)(Carnosine) complex has been synthesized in a multi-step reaction. First, carnosine was modified by the attachment of SATA. After chromatographic purification, the conjugate was unprotected to form a reactive sulfhydryl functional group, and then the modified carnosine was substituted to PtCl{sub 2}[{sup 125}I]Hist complex. The Pt(II)(IT-[{sup 125}I]Carnosine) and Pt(IV)(IT-[{sup 131}I]Carnosine) complexes were synthesized in a three-step reaction. First, carnosine was labeled with iodine radionuclide ({sup 125}I or {sup 131}I), followed by conjugation with 2-IT. The modified IT-[*I]Carnosine was complexed with tetrachloroplatinate or hexachloroplatinate. Comparative biodistribution studies were performed in normal Wistar rats and in Lewis rats with implanted (s.c.) rat pancreatic tumor cells (AR42J). The HPLC analysis showed a relatively fast formation of the new mixed-ligand Pt([{sup 125}I]Hist)(Carnosine) complex (yield ca. 50% after 20 h). Reaction of K{sub 2}PtCl{sub 4} with [{sup 125}I]Carnosine modified by 2-IT proceeded rapidly and with a high yield (>95% after 2 h). The synthesis of the Pt(IV)IT-[*I]Carnosine complex was the slower reaction in comparison to the analogous synthesis of the Pt(II) complex (yield ca. 70% after 12 h), thus a purification step was necessary. The biodistribution study proved the in vivo stability of the newly synthesized complexes (a low accumulation in thyroid gland and in GIT) and showed that the conjugation of the modified carnosine changes significantly biodistribution scheme of the Pt complexes comparing to the reference Pt(II)[*I]Hist and Pt(IV)([*I]Hist){sub 2} complexes. The mixed-ligand complex was rapidly excreted in urine and revealed the highest accumulation in kidneys (>5%ID/g). A very high

  12. Carnosine content in skeletal muscle is dependent on vitamin B6 status in rats

    Directory of Open Access Journals (Sweden)

    Sofya eSuidasari

    2016-01-01

    Full Text Available Carnosine, a histidine-containing dipeptide, is well known to be associated with skeletal muscle performance. However, there is limited information on the effect of dietary micronutrients on muscle carnosine level. Pyridoxal 5′-phosphate (PLP, the active form of vitamin B6, is involved in amino acid metabolisms in the body as a co-factor. We hypothesized that enzymes involved in β-alanine biosynthesis, the rate-limiting precursor of carnosine, may also be PLP-dependent. Thus, we examined the effects of dietary vitamin B6 on the muscle carnosine content of rats. Male and female rats were fed a diet containing 1, 7, or 35 mg pyridoxine HCl/kg for 6 weeks. Carnosine in skeletal muscles was quantified by ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS. In the gastrocnemius muscle of male rats, carnosine concentration was significantly higher in the 7 and 35 mg groups (+70% and +61%, respectively than in the 1 mg pyridoxine HCl/kg group, whereas that in the soleus muscle of male rats was significantly higher only in the 7 mg group (+43% than in the 1 mg pyridoxine HCl/kg group (P<0.05. In both muscles of female rats, carnosine concentration was significantly higher in the 7 and 35 mg groups (+32% ~ +226% than in the 1 mg pyridoxine HCl/kg group (P<0.05. We also found that compared to the 1 mg group, β-alanine concentrations in the 7 and 35 mg groups were markedly elevated in gastrocnemius muscles of male (+153% and +148%, respectively, P<0.05 and female (+381% and +437%, respectively, P<0.05 rats. Noteworthy, the concentrations of ornithine in the 7 and 35 mg groups were decreased in gastrocnemius muscles of male rats (−46% and −54%, respectively, P<0.05, which strongly inversely correlated with β-alanine concentration (r=−0.84, P<0.01. In humans, 19% lower muscle carnosine content was found in soleus muscle of women of the lower plasma PLP tertile, but this was not observed in gastrocnemius muscle

  13. Phytosome-hyaluronic acid systems for ocular delivery of L-carnosine.

    Science.gov (United States)

    Abdelkader, Hamdy; Longman, Michael R; Alany, Raid G; Pierscionek, Barbara

    2016-01-01

    This study reports on L-carnosine phytosomes as an alternative for the prodrug N-acetyl-L-carnosine as a novel delivery system to the lens. L-carnosine was loaded into lipid-based phytosomes and hyaluronic acid (HA)-dispersed phytosomes. L-carnosine-phospholipid complexes (PC) of different molar ratios, 1:1 and 1:2, were prepared by the solvent evaporation method. These complexes were characterized with thermal and spectral analyses. PC were dispersed in either phosphate buffered saline pH 7.4 or HA (0.1% w/v) in phosphate buffered saline to form phytosomes PC1:1, PC1:2, and PC1:2 HA, respectively. These phytosomal formulations were studied for size, zeta potential, morphology, contact angle, spreading coefficient, viscosity, ex vivo transcorneal permeation, and cytotoxicity using primary human corneal cells. L-carnosine-phospholipid formed a complex at a 1:2 molar ratio and phytosomes were in the size range of 380-450 nm, polydispersity index of 0.12-0.2. The viscosity of PC1:2 HA increased by 2.4 to 5-fold compared with HA solution and PC 1:2, respectively; significantly lower surface tension, contact angle, and greater spreading ability for phytosomes were also recorded. Ex vivo transcorneal permeation parameters showed significantly controlled corneal permeation of L-carnosine with the novel carrier systems without any significant impact on primary human corneal cell viability. Ex vivo porcine lenses incubated in high sugar media without and with L-carnosine showed concentration-dependent marked inhibition of lens brunescence indicative of the potential for delaying changes that underlie cataractogenesis that may be linked to diabetic processes. PMID:27366062

  14. L-carnosine affects the growth of Saccharomyces cerevisiae in a metabolism-dependent manner.

    Directory of Open Access Journals (Sweden)

    Stephanie P Cartwright

    Full Text Available The dipeptide L-carnosine (β-alanyl-L-histidine has been described as enigmatic: it inhibits growth of cancer cells but delays senescence in cultured human fibroblasts and extends the lifespan of male fruit flies. In an attempt to understand these observations, the effects of L-carnosine on the model eukaryote, Saccharomyces cerevisiae, were examined on account of its unique metabolic properties; S. cerevisiae can respire aerobically, but like some tumor cells, it can also exhibit a metabolism in which aerobic respiration is down regulated. L-Carnosine exhibited both inhibitory and stimulatory effects on yeast cells, dependent upon the carbon source in the growth medium. When yeast cells were not reliant on oxidative phosphorylation for energy generation (e.g. when grown on a fermentable carbon source such as 2% glucose, 10-30 mM L-carnosine slowed growth rates in a dose-dependent manner and increased cell death by up to 17%. In contrast, in media containing a non-fermentable carbon source in which yeast are dependent on aerobic respiration (e.g. 2% glycerol, L-carnosine did not provoke cell death. This latter observation was confirmed in the respiratory yeast, Pichia pastoris. Moreover, when deletion strains in the yeast nutrient-sensing pathway were treated with L-carnosine, the cells showed resistance to its inhibitory effects. These findings suggest that L-carnosine affects cells in a metabolism-dependent manner and provide a rationale for its effects on different cell types.

  15. Protective activity of carnosine and anserine against zinc-induced neurotoxicity: a possible treatment for vascular dementia.

    Science.gov (United States)

    Mizuno, Dai; Konoha-Mizuno, Keiko; Mori, Miwako; Sadakane, Yutaka; Koyama, Hironari; Ohkawara, Susumu; Kawahara, Masahiro

    2015-08-01

    Carnosine (β-alanyl-L-histidine) is a small dipeptide with numerous beneficial effects, including the maintenance of the acid-base balance, antioxidant properties, chelating agent, anti-crosslinking, and anti-glycation activities. High levels of carnosine and its analogue anserine (1-methyl carnosine) are found in skeletal muscle and the brain. Zinc (Zn)-induced neurotoxicity plays a crucial role in the pathogenesis of vascular dementia (VD), and carnosine inhibits Zn-induced neuronal death. Here, the protective activity of carnosine against Zn-induced neurotoxicity and its molecular mechanisms such as cellular Zn influx and Zn-induced gene expression were investigated using immortalised hypothalamic neurons (GT1-7 cells). Carnosine and anserine protected against Zn-induced neurotoxicity not by preventing increases in intracellular Zn(2+) but by participating in the regulation of the endoplasmic reticulum (ER) stress pathway and the activity-regulated cytoskeletal protein (Arc). Accordingly, carnosine and anserine protected against neurotoxicity induced by ER-stress inducers thapsigargin and tunicamycin. Hence, carnosine and anserine are expected to have future therapeutic potential for VD and other neurodegenerative diseases. PMID:25846004

  16. Synthesis and characterization of L-carnosine coated iron oxide nanoparticles

    International Nuclear Information System (INIS)

    Research highlights: → L-Carnosine coated iron oxide nanoparticles (CCIO NPs) have been prepared via co-precipitation of Fe3O4 (magnetite) in the presence of L-carnosine. → FTIR analysis showed that the binding of carnosine onto the surface of iron oxide is through unidentate linkage of carboxyl group. → Magnetization measurements revealed that L-carnosine iron oxide composite has immeasurable coercivity and remanence with absence of hysteritic behavior, which implies superparamagnetic behaviour at room temperature. → The synthesized amino acid-coated magnetic nanoparticles might be applied to cell separation, diagnosis and targeted drug delivery for cancer therapy. - Abstract: L-Carnosine coated iron oxide nanoparticles (CCIO NPs) have been prepared via co-precipitation of iron oxide in the presence of L-carnosine. Crystalline phase was identified as magnetite with an average crystallite size of 8 nm as estimated from X-ray line profile fitting. Particle size estimated from TEM by log-normal fitting was ∼11 nm. FTIR analysis showed that the binding of carnosine onto the surface of iron oxide is through unidentate linkage of carboxyl group. CCIO NPs showed superparamagnetic charactersitic at room temperature. The magnetic core size of superparamagnetic CCIO NPs was found slightly smaller than the size obtained from TEM, due to the presence of magnetically dead layer. Magnetization measurements revealed that L-carnosine iron oxide composite has immeasurable coercivity and remanence with absence of hysteritic behavior, which implies superparamagnetic behavior at room temperature. The low value of saturation magnetization compared to the bulk magnetite has been explained by spin canting. LDH activity tests showed slight cytotoxicity of high dose of CCIO NPs. The ac conductivity of CCIO NPs was found to be greater than that of carnosine and the effective conduction mechanism was found as correlated barrier hopping (CBH). dc activation energy of the product at

  17. Synthesis and characterization of L-carnosine coated iron oxide nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Durmus, Z. [Department of Chemistry, Fatih University, B. Cekmece, 34500 Istanbul (Turkey); Kavas, H. [Department of Physics, Fatih University, B. Cekmece, 34500 Istanbul (Turkey); Baykal, A., E-mail: hbaykal@fatih.edu.tr [Department of Chemistry, Fatih University, B. Cekmece, 34500 Istanbul (Turkey); Sozeri, H. [TUBITAK-UME, National Metrology Institute, PO Box 54, 41470 Gebze-Kocaeli (Turkey); Alpsoy, L. [Department of Biology, Fatih University, B. Cekmece, 34500 Istanbul (Turkey); Celik, S.U. [Department of Chemistry, Fatih University, B. Cekmece, 34500 Istanbul (Turkey); Toprak, M.S. [Department of Functional Materials, Royal Institute of Technology, SE16440 Kista-Stockholm (Sweden)

    2011-02-03

    Research highlights: > L-Carnosine coated iron oxide nanoparticles (CCIO NPs) have been prepared via co-precipitation of Fe{sub 3}O{sub 4} (magnetite) in the presence of L-carnosine. > FTIR analysis showed that the binding of carnosine onto the surface of iron oxide is through unidentate linkage of carboxyl group. > Magnetization measurements revealed that L-carnosine iron oxide composite has immeasurable coercivity and remanence with absence of hysteritic behavior, which implies superparamagnetic behaviour at room temperature. > The synthesized amino acid-coated magnetic nanoparticles might be applied to cell separation, diagnosis and targeted drug delivery for cancer therapy. - Abstract: L-Carnosine coated iron oxide nanoparticles (CCIO NPs) have been prepared via co-precipitation of iron oxide in the presence of L-carnosine. Crystalline phase was identified as magnetite with an average crystallite size of 8 nm as estimated from X-ray line profile fitting. Particle size estimated from TEM by log-normal fitting was {approx}11 nm. FTIR analysis showed that the binding of carnosine onto the surface of iron oxide is through unidentate linkage of carboxyl group. CCIO NPs showed superparamagnetic charactersitic at room temperature. The magnetic core size of superparamagnetic CCIO NPs was found slightly smaller than the size obtained from TEM, due to the presence of magnetically dead layer. Magnetization measurements revealed that L-carnosine iron oxide composite has immeasurable coercivity and remanence with absence of hysteritic behavior, which implies superparamagnetic behavior at room temperature. The low value of saturation magnetization compared to the bulk magnetite has been explained by spin canting. LDH activity tests showed slight cytotoxicity of high dose of CCIO NPs. The ac conductivity of CCIO NPs was found to be greater than that of carnosine and the effective conduction mechanism was found as correlated barrier hopping (CBH). dc activation energy of the

  18. [Increased manganese superoxide dismutase and cyclin B1 expression in carnosine-induced inhibition of glioblastoma cell proliferation].

    Science.gov (United States)

    Rybakova, Yu S; Kalen, A L; Eckers, J C; Fedorova, T N; Goswami, P C; Sarsour, E H

    2015-01-01

    Carnosine is an endogenous dipeptide with antiproliferative properties. Here we show that carnosine selectively inhibits proliferation of human glioblastoma cells (U-118-MG) compared to breast (MB231) and oral (Cal27 and FaDu) cancer cells. Carnosine-induced inhibition of U-118-MG proliferation is associated with a significant: decrease in cellular reactive oxygen species levels, increase in manganese superoxide dismutase (MnSOD) and increase in cyclin B1 expression resulting in G2-block. We conclude that the antiproliferative property of carnosine is due to its ability to enhance MnSOD and cyclin B1 expression. These results will be of significance to the potential application of carnosine in brain cancer therapy. PMID:26350743

  19. Absolute quantification of carnosine in human calf muscle by proton magnetic resonance spectroscopy

    International Nuclear Information System (INIS)

    Carnosine has been shown to be present in the skeletal muscle and in the brain of a variety of animals and humans. Despite the various physiological functions assigned to this metabolite, its exact role remains unclear. It has been suggested that carnosine plays a role in buffering in the intracellular physiological pHi range in skeletal muscle as a result of accepting hydrogen ions released in the development of fatigue during intensive exercise. It is thus postulated that the concentration of carnosine is an indicator for the extent of the buffering capacity. However, the determination of the concentration of this metabolite has only been performed by means of muscle biopsy, which is an invasive procedure. In this paper, we utilized proton magnetic resonance spectroscopy (1H MRS) in order to perform absolute quantification of carnosine in vivo non-invasively. The method was verified by phantom experiments and in vivo measurements in the calf muscles of athletes and untrained volunteers. The measured mean concentrations in the soleus and the gastrocnemius muscles were found to be 2.81 ± 0.57/4.8 ± 1.59 mM (mean ± SD) for athletes and 2.58 ± 0.65/3.3 ± 0.32 mM for untrained volunteers, respectively. These values are in agreement with previously reported biopsy-based results. Our results suggest that 1H MRS can provide an alternative method for non-invasively determining carnosine concentration in human calf muscle in vivo

  20. Absolute quantification of carnosine in human calf muscle by proton magnetic resonance spectroscopy

    Science.gov (United States)

    Özdemir, Mahir S.; Reyngoudt, Harmen; DeDeene, Yves; Sazak, Hakan S.; Fieremans, Els; Delputte, Steven; D'Asseler, Yves; Derave, Wim; Lemahieu, Ignace; Achten, Eric

    2007-12-01

    Carnosine has been shown to be present in the skeletal muscle and in the brain of a variety of animals and humans. Despite the various physiological functions assigned to this metabolite, its exact role remains unclear. It has been suggested that carnosine plays a role in buffering in the intracellular physiological pHi range in skeletal muscle as a result of accepting hydrogen ions released in the development of fatigue during intensive exercise. It is thus postulated that the concentration of carnosine is an indicator for the extent of the buffering capacity. However, the determination of the concentration of this metabolite has only been performed by means of muscle biopsy, which is an invasive procedure. In this paper, we utilized proton magnetic resonance spectroscopy (1H MRS) in order to perform absolute quantification of carnosine in vivo non-invasively. The method was verified by phantom experiments and in vivo measurements in the calf muscles of athletes and untrained volunteers. The measured mean concentrations in the soleus and the gastrocnemius muscles were found to be 2.81 ± 0.57/4.8 ± 1.59 mM (mean ± SD) for athletes and 2.58 ± 0.65/3.3 ± 0.32 mM for untrained volunteers, respectively. These values are in agreement with previously reported biopsy-based results. Our results suggest that 1H MRS can provide an alternative method for non-invasively determining carnosine concentration in human calf muscle in vivo.

  1. Absolute quantification of carnosine in human calf muscle by proton magnetic resonance spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Oezdemir, Mahir S [Department of Electronics and Information Systems, MEDISIP, Ghent University-IBBT-IBiTech, De Pintelaan 185 block B, B-9000 Ghent (Belgium); Reyngoudt, Harmen [Department of Radiology, Ghent University Hospital, De Pintelaan 185, Ghent (Belgium); Deene, Yves de [Department of Radiotherapy, Ghent University Hospital, De Pintelaan 185, Ghent (Belgium); Sazak, Hakan S [Department of Statistics, Ege University, 35100 Bornova, Izmir (Turkey); Fieremans, Els [Department of Electronics and Information Systems, MEDISIP, Ghent University-IBBT-IBiTech, De Pintelaan 185 block B, B-9000 Ghent (Belgium); Delputte, Steven [Department of Electronics and Information Systems, MEDISIP, Ghent University-IBBT-IBiTech, De Pintelaan 185 block B, B-9000 Ghent (Belgium); D' Asseler, Yves [Department of Electronics and Information Systems, MEDISIP, Ghent University-IBBT-IBiTech, De Pintelaan 185 block B, B-9000 Ghent (Belgium); Derave, Wim [Department of Movement and Sports Science, Ghent University, Watersportlaan 2, Ghent (Belgium); Lemahieu, Ignace [Department of Electronics and Information Systems, MEDISIP, Ghent University-IBBT-IBiTech, De Pintelaan 185 block B, B-9000 Ghent (Belgium); Achten, Eric [Department of Radiology, Ghent University Hospital, De Pintelaan 185, Ghent (Belgium)

    2007-12-07

    Carnosine has been shown to be present in the skeletal muscle and in the brain of a variety of animals and humans. Despite the various physiological functions assigned to this metabolite, its exact role remains unclear. It has been suggested that carnosine plays a role in buffering in the intracellular physiological pH{sub i} range in skeletal muscle as a result of accepting hydrogen ions released in the development of fatigue during intensive exercise. It is thus postulated that the concentration of carnosine is an indicator for the extent of the buffering capacity. However, the determination of the concentration of this metabolite has only been performed by means of muscle biopsy, which is an invasive procedure. In this paper, we utilized proton magnetic resonance spectroscopy ({sup 1}H MRS) in order to perform absolute quantification of carnosine in vivo non-invasively. The method was verified by phantom experiments and in vivo measurements in the calf muscles of athletes and untrained volunteers. The measured mean concentrations in the soleus and the gastrocnemius muscles were found to be 2.81 {+-} 0.57/4.8 {+-} 1.59 mM (mean {+-} SD) for athletes and 2.58 {+-} 0.65/3.3 {+-} 0.32 mM for untrained volunteers, respectively. These values are in agreement with previously reported biopsy-based results. Our results suggest that {sup 1}H MRS can provide an alternative method for non-invasively determining carnosine concentration in human calf muscle in vivo.

  2. Carnosine's effect on amyloid fibril formation and induced cytotoxicity of lysozyme.

    Directory of Open Access Journals (Sweden)

    Josephine W Wu

    Full Text Available Carnosine, a common dipeptide in mammals, has previously been shown to dissemble alpha-crystallin amyloid fibrils. To date, the dipeptide's anti-fibrillogensis effect has not been thoroughly characterized in other proteins. For a more complete understanding of carnosine's mechanism of action in amyloid fibril inhibition, we have investigated the effect of the dipeptide on lysozyme fibril formation and induced cytotoxicity in human neuroblastoma SH-SY5Y cells. Our study demonstrates a positive correlation between the concentration and inhibitory effect of carnosine against lysozyme fibril formation. Molecular docking results show carnosine's mechanism of fibrillogenesis inhibition may be initiated by binding with the aggregation-prone region of the protein. The dipeptide attenuates the amyloid fibril-induced cytotoxicity of human neuronal cells by reducing both apoptotic and necrotic cell deaths. Our study provides solid support for carnosine's amyloid fibril inhibitory property and its effect against fibril-induced cytotoxicity in SH-SY5Y cells. The additional insights gained herein may pave way to the discovery of other small molecules that may exert similar effects against amyloid fibril formation and its associated neurodegenerative diseases.

  3. Theoretical and experimental investigation of carnosine and its oxygenated adducts. The reaction with the nickel ion

    Science.gov (United States)

    Pavlos, Dimitrios; Petropouleas, Panayiotis; Hatzipanayioti, Despina

    2015-11-01

    DFT theoretical calculations at B3LYP/TZVP or LANL2DZ level of theory, for neutral, zwitterions, protonated and anionic carnosine, were performed. Energies, the structural and spectroscopic parameters were calculated in the gas phase and aqueous medium. Additional H-bonds stabilize the ionized forms of carnosine, creating "nests" into which metal ions or bio-molecules may be sheltered. Based on Fukui functions, the reactivity of the abovementioned forms of carnosine, with 1O2, may lead to oxygenated species. The theoretical spectroscopic parameters have been correlated to our experimental results. The effect of H2O2 and the electrochemistry of aqueous carnosine solutions were examined. Theoretical models containing Ni(II), carnosine and water were constructed. In the isolated mauve solid, formulated [Ni(carn)2(H2O)5], the COOsbnd , Nπ and/or NH2 were bonded. When H2O2 was added, the imidazole NMR signals disappeared. A redox couple clearly indicates one electron process, the electron coming from either the oxidation of imidazole ring or the nickel(II)/Ni(III) couple.

  4. Effects of carnosine on cyclophosphamide-induced hematopoietic suppression in mice.

    Science.gov (United States)

    Xu, Meng; He, Rong-Rong; Zhai, Yu-Jia; Abe, Keiichi; Kurihara, Hiroshi

    2014-01-01

    Cyclophosphamide is one of the most widely used chemotherapeutic agents in treating cancers. Chemotherapy drug-induced oxidative stress produces side effects. The severity of myelosuppression increases with a high dose of cyclophosphamide. Chicken soup or chicken essence, a traditional Chinese aliment, is a popular health supplement for patients with cancers or other diseases in Asia. As a major functional component of chicken meat extract, carnosine (beta-alanyl-L-histidine), a dipeptide of the amino acids beta-alanine and histidine, has been shown to have strong antioxidant activities. In the present study, we investigated the effects of carnosine on hematopoietic suppression in mice treated with cyclophosphamide. As expected, we found that cyclophosphamide administration (with a single dose of 150 mg/kg) induced a rapid (within 24 hours) and severe hematopoietic suppression in mice. We further showed that carnosine administration (100 mg/kg/day or 200 mg/kg/day for continuous seven days) could substantially improve suppressed hematopoietic functions and accelerate the recovery of leukocyte counts, bone marrow spontaneous proliferation, colony stimulating activity (CSA) in serum, and production of endogenous cytokines such as interleukin-3 (IL-3) and stem cell factor (SCF). These results indicate that carnosine has the potential to promote the recovery from hematopoietic suppression induced by cyclophosphamide. Our data suggest that carnosine holds a potential in clinical application to minimize the side effects induced by chemotherapeutic agents such as cyclophosphamide and thus will substantially improve the overall anti-tumor effects of the standard chemotherapies. PMID:24467540

  5. Carnosine retards tumor growth in vivo in an NIH3T3-HER2/neu mouse model

    Directory of Open Access Journals (Sweden)

    Meixensberger Jürgen

    2010-01-01

    Full Text Available Abstract Background It was previously demonstrated that the dipeptide carnosine inhibits growth of cultured cells isolated from patients with malignant glioma. In the present work we investigated whether carnosine also affects tumor growth in vivo and may therefore be considered for human cancer therapy. Results A mouse model was used to investigate whether tumor growth in vivo can be inhibited by carnosine. Therefore, NIH3T3 fibroblasts, conditionally expressing the human epidermal growth factor receptor 2 (HER2/neu, were implanted into the dorsal skin of nude mice, and tumor growth in treated animals was compared to control mice. In two independent experiments nude mice that received tumor cells received a daily intra peritoneal injection of 500 μl of 1 M carnosine solution. Measurable tumors were detected 12 days after injection. Aggressive tumor growth in control animals, that received a daily intra peritoneal injection of NaCl solution started at day 16 whereas aggressive growth in mice treated with carnosine was delayed, starting around day 19. A significant effect of carnosine on tumor growth was observed up to day 24. Although carnosine was not able to completely prevent tumor growth, a microscopic examination of tumors revealed that those from carnosine treated animals had a significant lower number of mitosis (p Conclusion As a naturally occurring substance with a high potential to inhibit growth of malignant cells in vivo, carnosine should be considered as a potential anti-cancer drug. Further experiments should be performed in order to understand how carnosine acts at the molecular level.

  6. Inhibition of 6-hydroxydopamine-induced endoplasmic reticulum stress by l-carnosine in SH-SY5Y cells.

    Science.gov (United States)

    Oh, Yun-Mi; Jang, Eun-Hee; Ko, Jeong-Hyeon; Kang, Ju-Hee; Park, Chang-Shin; Han, Seung Baik; Kim, Jun Sig; Kim, Kyung Hwan; Pie, Jae-Eun; Shin, Dong Wun

    2009-07-31

    Conditions that cause endoplasmic reticulum malfunction (ER stress) play a key role in the development of various human diseases including neurodegenerative diseases. Carnosine is an endogenous peptide, present in excitable tissues such as brain and skeletal muscle. Although there are reports suggesting that carnosine has a biological role independent of its antioxidant activity, there have been no reports of the effects of carnosine on the ER stress response. We investigated the effects of carnosine on 6-hydroxydopamine (6-OHDA)-induced cell death and ER stress in SH-SY5Y cells. After assessing control cell viability in serum-free conditions for 24h (100% viability), we found that 50 microM 6-OHDA reduced cell viability to 76.4% of control values, whereas addition of 10mM carnosine significantly reduced cell death to 96.1% viability in a dose-dependent manner. Consistent with its cytoprotective action, carnosine markedly inhibited subsequent ER stress responses, including phosphorylation of eukaryotic initiation factor 2alpha (eIF2alpha) and c-jun, expression of glucose regulatory protein 78 and C/EBP homologous protein, and mRNA splicing of X-box protein 1. The measurement of reactive oxygen species (ROS) generation by 6-OHDA showed that addition of 10mM carnosine slightly but obviously inhibits the 6-OHDA-induced ROS production. In conclusion, our results show that carnosine almost completely inhibits 6-OHDA-induced ER stress responses and cytotoxicity, and that slight antioxidant activity of carnosine against 6-OHDA is observed. Further in vivo studies are needed to investigate clinical uses for carnosine. PMID:19394406

  7. Carnosine decreases IGFBP1 production in db/db mice through suppression of HIF-1.

    Science.gov (United States)

    Forsberg, Elisabete A; Botusan, Ileana R; Wang, Jing; Peters, Verena; Ansurudeen, Ishrath; Brismar, Kerstin; Catrina, Sergiu Bogdan

    2015-06-01

    IGF binding protein 1 (IGFBP1) is a member of the binding proteins for the IGF with an important role in glucose homeostasis. Circulating IGFBP1 is derived essentially from the liver where it is mainly regulated negatively by insulin. Carnosine, a natural antioxidant, has been shown to improve metabolic control in different animal models of diabetes but its mechanisms of action are still not completely unraveled. We therefore investigate the effect of carnosine treatment on the IGFBP1 regulation in db/db mice. Db/db mice and heterozygous non-diabetic mice received for 4 weeks regular water or water supplemented with carnosine. Igfbp1 mRNA expression in the liver was evaluated using qPCR and the protein levels in plasma by western blot. Plasma IGF1 and insulin were analyzed using immunoassays. HepG2 cells were used to study the in vitro effect of carnosine on IGFBP1. The modulation of hypoxia inducible factor-1 alpha (HIF-1α) which is the central mediator of hypoxia-induction of IGFBP1 was analyzed using: WB, reporter gene assay and qPCR. Carnosine decreased the circulating IGFBP1 levels and the liver expression Igfbp1, through a complex mechanism acting both directly by suppressing the HIF-1α-mediated IGFBP1 induction and indirectly through increasing circulating insulin level followed by a decrease in the blood glucose levels and increased the plasma levels or IGF1. Reduction of IGFBP1 in diabetes through insulin-dependent and insulin-independent pathways is a novel mechanism by which carnosine contributes to the improvement of the metabolic control in diabetes. PMID:25869614

  8. Analytical and physicochemical characterisation of the senile cataract drug dipeptide [Beta]-alanyl-L-histidine (carnosine)

    OpenAIRE

    Abdelkader, Hamdy; Swinden, Julian; Pierscionek, Barbara K; Alany, Raid G

    2015-01-01

    This study presents a simple but sensitive HPLC chromatographic method with a stability-indicating assay for determination and physicochemical characterisation of L-carnosine, a promising senile cataract prophylactic agent. Chromatographic analysis was conducted using a reverse phase (RP)-HPLC system and an isocratic mobile phase of 98% v/v trifluoroacetic acid (0.1% v/v) and 2% v/v acetonitrile with detection at 220nm. L-carnosine was subjected to stress conditions to force its degradation u...

  9. Phytosome-hyaluronic acid systems for ocular delivery of L-carnosine

    Directory of Open Access Journals (Sweden)

    Abdelkader H

    2016-06-01

    Full Text Available Hamdy Abdelkader,1,2 Michael R Longman,1 Raid G Alany,1,3 Barbara Pierscionek4 1Drug Discovery, Delivery and Patient Care (DDDPC Theme, School of Life Sciences, Pharmacy and Chemistry, Kingston University London, Kingston Upon Thames, London, UK; 2Department of Pharmaceutics, Faculty of Pharmacy, Minia University, Mina, Egypt; 3School of Pharmacy, The University of Auckland, Auckland, New Zealand; 4Vision Cognition and Neuroscience Theme, Faculty of Science, Engineering and Computing, Kingston University London, Kingston Upon Thames, London, UK Abstract: This study reports on L-carnosine phytosomes as an alternative for the prodrug N-acetyl-L-carnosine as a novel delivery system to the lens. L-carnosine was loaded into lipid-based phytosomes and hyaluronic acid (HA-dispersed phytosomes. L-carnosine-phospholipid complexes (PC of different molar ratios, 1:1 and 1:2, were prepared by the solvent evaporation method. These complexes were characterized with thermal and spectral analyses. PC were dispersed in either phosphate buffered saline pH 7.4 or HA (0.1% w/v in phosphate buffered saline to form phytosomes PC1:1, PC1:2, and PC1:2 HA, respectively. These phytosomal formulations were studied for size, zeta potential, morphology, contact angle, spreading coefficient, viscosity, ex vivo transcorneal permeation, and cytotoxicity using primary human corneal cells. L-carnosine-phospholipid formed a complex at a 1:2 molar ratio and phytosomes were in the size range of 380–450 nm, polydispersity index of 0.12–0.2. The viscosity of PC1:2 HA increased by 2.4 to 5-fold compared with HA solution and PC 1:2, respectively; significantly lower surface tension, contact angle, and greater spreading ability for phytosomes were also recorded. Ex vivo transcorneal permeation parameters showed significantly controlled corneal permeation of L-carnosine with the novel carrier systems without any significant impact on primary human corneal cell viability. Ex vivo

  10. β-Alanine ingestion increases muscle carnosine content and combat specific performance in soldiers

    OpenAIRE

    Hoffman, Jay R; Landau, Geva; Stout, Jeffrey R.; Hoffman, Mattan W.; Shavit, Nurit; Rosen, Philip; Moran, Daniel S.; Fukuda, David H.; Shelef, Ilan; Carmom, Erez; Ostfeld, Ishay

    2014-01-01

    The purpose of this study was to examine the effect of β-alanine (BA) ingestion on tissue carnosine levels and the impact such changes would have on combat specific activity. Eighteen soldiers (19.9 ± 0.8 year) from an elite combat unit were randomly assigned to either a BA or placebo (PL) group. Before and following a 30-day supplementation period carnosine content of the gastrocnemius muscle and brain was determined by proton magnetic resonance spectroscopy. During each testing session, par...

  11. PEPT2-mediated transport of 5-aminolevulinic acid and carnosine in astrocytes

    OpenAIRE

    Xiang, Jianming; Hu, Yongjun; Smith, David E.; Keep, Richard F

    2006-01-01

    5-Aminolevulinic acid (ALA) and carnosine have important physiological and pathophysiological roles in the CNS. Both are substrates for the proton-coupled oligopeptide transporter PEPT2. The purpose of the current study was to determine the importance of PEPT2 in the uptake of ALA and carnosine in rat and mouse (PEPT2+/+ and PEPT2−/−) cultured neonatal astrocytes. Although neonatal astrocytes are known to express PEPT2, its quantitative importance in the transport of these compounds is not kn...

  12. Vibrational study on the cobalt binding mode of Carnosine

    Science.gov (United States)

    Torreggiani, Armida; Taddei, Paola; Tinti, Anna; Fini, Giancarlo

    2002-10-01

    The Co(II)- L-Carnosine (Carnos) system was investigated at different pH and metal/ligand molar ratios by Raman and IR spectroscopy. Raman spectra present some marker bands yielding information on the ability of the Co(II)/Carnos system to bind molecular oxygen and to identify the metal co-ordination site of the imidazole ring (N π or N τ atom) of Carnos. The existence of different oxygenated species is greatly affected by pH and the structure of the predominant complexes depends on the available nitrogen atoms. Under basic conditions, binuclear complexes binding molecular oxygen are the predominant species and two forms (monobridged and dibridged) were identified by the Raman νO-O band (750-850 cm -1). Decreasing pH to 7, the species present in the system are less able to bind oxygen. Hydrogen peroxide and a Co(III) chelate not binding O 2, were formed with a significant conversion of peroxo into superoxo complexes. A slight excess of Carnos does not enhance metal chelation. In slightly acidic conditions, the formation of H 2O 2 and superoxo species is more enhanced than at pH 7 and another Co(III) chelate is probably formed.

  13. Ligand binding studies in the mouse olfactory bulb: identification and characterisation of a L-[3H]carnosine binding site

    International Nuclear Information System (INIS)

    Binding sites for the dipeptide L-carnosine (β-alanyl-t-histidine) have been detected in membranes prepared from mouse olfactory bulbs. The binding of L-[3H]- carnosine was saturable, reversible and stereospecific and had a Ksub(d) of about 770 nM. The stereospecific binding of L-carnosine represented about 30% of the totoal binding at pH 6.8, and decreased markedly with increasing pH. Binding was stimulated by calcium, unaffected by zinc, magnesium or manganese and inhibted by sodium and potassium. Carnosine binding was sensitive to trypsin and phospholipases A and C, but not to neuraminidase. Nystatin and filipin, which interact with membrane lipids, also interfered with binding. Some peptide analogues of carnosine were potent inhibitors of binding, but a variety of drugs serving as potent inhibitors in other binding systems had no effect on carnosine binding. Carnosine binding to mouse olfactory bulb membranes was 15-fold higher than that seen in membranes prepared from cerebral hemispheres, 5-fold higher than in cerebellum membranes and 3-fold higher than in membranes from spinal medulla and the olfactory tubercle-lateral olfactory tract area. (Auth.)

  14. Carnosine inhibits the proliferation of human gastric cancer SGC-7901 cells through both of the mitochondrial respiration and glycolysis pathways.

    Directory of Open Access Journals (Sweden)

    Yao Shen

    Full Text Available Carnosine, a naturally occurring dipeptide, has been recently demonstrated to possess anti-tumor activity. However, its underlying mechanism is unclear. In this study, we investigated the effect and mechanism of carnosine on the cell viability and proliferation of the cultured human gastric cancer SGC-7901 cells. Carnosine treatment did not induce cell apoptosis or necrosis, but reduced the proliferative capacity of SGC-7901 cells. Seahorse analysis showed SGC-7901 cells cultured with pyruvate have active mitochondria, and depend on mitochondrial oxidative phosphorylation more than glycolysis pathway for generation of ATP. Carnosine markedly decreased the absolute value of mitochondrial ATP-linked respiration, and reduced the maximal oxygen consumption and spare respiratory capacity, which may reduce mitochondrial function correlated with proliferative potential. Simultaneously, carnosine also reduced the extracellular acidification rate and glycolysis of SGC-7901 cells. Our results suggested that carnosine is a potential regulator of energy metabolism of SGC-7901 cells both in the anaerobic and aerobic pathways, and provided a clue for preclinical and clinical evaluation of carnosine for gastric cancer therapy.

  15. Physiological and therapeutic effects of carnosine on cardiometabolic risk and disease.

    Science.gov (United States)

    Baye, Estifanos; Ukropcova, Barbara; Ukropec, Jozef; Hipkiss, Alan; Aldini, Giancarlo; de Courten, Barbora

    2016-05-01

    Obesity, type 2 diabetes (T2DM) and cardiovascular disease (CVD) are the most common preventable causes of morbidity and mortality worldwide. They represent major public health threat to our society. Increasing prevalence of obesity and T2DM contributes to escalating morbidity and mortality from CVD and stroke. Carnosine (β-alanyl-L-histidine) is a dipeptide with anti-inflammatory, antioxidant, anti-glycation, anti-ischaemic and chelating roles and is available as an over-the-counter food supplement. Animal evidence suggests that carnosine may offer many promising therapeutic benefits for multiple chronic diseases due to these properties. Carnosine, traditionally used in exercise physiology to increase exercise performance, has potential preventative and therapeutic benefits in obesity, insulin resistance, T2DM and diabetic microvascular and macrovascular complications (CVD and stroke) as well as number of neurological and mental health conditions. However, relatively little evidence is available in humans. Thus, future studies should focus on well-designed clinical trials to confirm or refute a potential role of carnosine in the prevention and treatment of chronic diseases in humans, in addition to advancing knowledge from the basic science and animal studies. PMID:26984320

  16. Carnosine reverses the aging-induced down regulation of brain regional serotonergic system.

    Science.gov (United States)

    Banerjee, Soumyabrata; Ghosh, Tushar K; Poddar, Mrinal K

    2015-12-01

    The purpose of the present investigation was to study the role of carnosine, an endogenous dipeptide biomolecule, on brain regional (cerebral cortex, hippocampus, hypothalamus and pons-medulla) serotonergic system during aging. Results showed an aging-induced brain region specific significant (a) increase in Trp (except cerebral cortex) and their 5-HIAA steady state level with an increase in their 5-HIAA accumulation and declination, (b) decrease in their both 5-HT steady state level and 5-HT accumulation (except cerebral cortex). A significant decrease in brain regional 5-HT/Trp ratio (except cerebral cortex) and increase in 5-HIAA/5-HT ratio were also observed during aging. Carnosine at lower dosages (0.5-1.0μg/Kg/day, i.t. for 21 consecutive days) didn't produce any significant response in any of the brain regions, but higher dosages (2.0-2.5μg/Kg/day, i.t. for 21 consecutive days) showed a significant response on those aging-induced brain regional serotonergic parameters. The treatment with carnosine (2.0μg/Kg/day, i.t. for 21 consecutive days), attenuated these brain regional aging-induced serotonergic parameters and restored towards their basal levels that observed in 4 months young control rats. These results suggest that carnosine attenuates and restores the aging-induced brain regional down regulation of serotonergic system towards that observed in young rats' brain regions. PMID:26364584

  17. The carnosine content of vastus lateralis is elevated in resistance-trained bodybuilders.

    Science.gov (United States)

    Tallon, Mark J; Harris, Roger C; Boobis, Les H; Fallowfield, Joanne L; Wise, John A

    2005-11-01

    Resistance training is associated with periods of acute intracellular hypoxia with increased H(+) production and low intramuscular pH. The aim of this study was to investigate the possible adaptive response in muscle carnosine (beta-alanyl-L-histidine) in bodybuilders. Extracts of biopsies of m. vastus lateralis of 6 national-level competitive bodybuilders and 6 age-matched untrained but moderately active healthy subjects were analyzed by high-performance liquid chromatography. Significant differences were shown in carnosine (p carnosine in bodybuilders was twice that in controls. The carnosine contents measured are the highest recorded in human muscle and represent a 20% contribution to muscle buffering capacity. Taurine was 38% lower in bodybuilders, though the difference was not significant. Possible causes for the changes observed are prolonged repetitive exposure to low muscle pH, change of diet or dietary supplement use, or the use of anabolic steroids. The increase in buffering capacity could influence the ability to carry out intense muscular activity. PMID:16287364

  18. Simple enzymatic procedure for L-carnosine synthesis: whole-cell biocatalysis and efficient biocatalyst recycling.

    Science.gov (United States)

    Heyland, Jan; Antweiler, Nicolai; Lutz, Jochen; Heck, Tobias; Geueke, Birgit; Kohler, Hans-Peter E; Blank, Lars M; Schmid, Andreas

    2010-01-01

    β-Peptides and their derivates are usually stable to proteolysis and have an increased half-life compared with α-peptides. Recently, β-aminopeptidases were described as a new enzyme class that enabled the enzymatic degradation and formation of β-peptides. As an alternative to the existing chemical synthesis routes, the aim of the present work was to develop a whole-cell biocatalyst for the synthesis and production of β-peptides using this enzymatic activity. For the optimization of the reaction system we chose the commercially relevant β,α-dipeptide L-carnosine (β-alanine-L-histidine) as model product. We were able to show that different recombinant yeast and bacteria strains, which overexpress a β-peptidase, could be used directly as whole-cell biocatalysts for the synthesis of L-carnosine. By optimizing relevant reaction conditions for the best-performing recombinant Escherichia coli strain, such as pH and substrate concentrations, we obtained high l-carnosine yields of up to 71%. Long-time as well as biocatalyst recycling experiments indicated a high stability of the developed biocatalyst for at least five repeated batches. Application of the recombinant E. coli in a fed-batch process enabled the accumulation of l-carnosine to a concentration of 3.7 g l(-1). PMID:21255308

  19. Possible Protective Role of Carnosine against gamma-Radiation-Induced Cardiac Dysfunction in Mice

    International Nuclear Information System (INIS)

    Oxidative Stress with subsequent production of reactive oxygen species (ROS) has been postulated as one of the mechanisms of cardiac toxicity. Carnosine (β-alanyl-L-histidine) a biological antioxidant, is a relatively non-toxic dipeptide which possesses many functions (antiglycator, scavenger of ions of zinc and copper, toxic aldehydes and protein carbonyls) that are likely to suppress oxidative stress. The aim of the present work is to investigate the possible protective effects of carnosine on gamma-radiation-induced cardiac damage in mice. Carnosine was supplemented daily to mice (50 mg/ Kg body wt), by gavage, 10 days before whole body gamma-irradiation at a dose of 5 Gy (applied as a shot dose). The results obtained showed that whole body gamma-irradiation of mice produced biochemical alteration in levels of serum glucose and lipid profile fractions. Furthermore, some markers of cardiac injury enzymes as serum lactate dehydrogenase (LDH), creatin phosphokinase (CPK) and aspartate transaminase (AST) activities showed significant increases associated with alteration in the antioxidant status of cardiac tissues. Significant increases of lipid peroxidation end product malonaldehyde (MDA) and protein carbonyl levels, xanthine oxidase (XO) activity along with reduction in the activity of cardiac antioxidant enzymes; glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT) were observed. Carnosine-treatment prior irradiation has attenuated the cardiotoxic effects of radiation obvious by reduction in the levels of MDA and protein carbonyl and XO activity, rescued the depletion of endogenous antioxidant enzymes and diminished the increases of cardiac injury markers. It could be postulated that carnosine as a multi-functional dietary supplement could exert a modulator role in the radiation-induced cardiac damage and serum biochemical changes through its antioxidant properties

  20. Ergogenic Effects of β-Alanine and Carnosine: Proposed Future Research to Quantify Their Efficacy

    Directory of Open Access Journals (Sweden)

    John Caruso

    2012-06-01

    Full Text Available β-alanine is an amino acid that, when combined with histidine, forms the dipeptide carnosine within skeletal muscle. Carnosine and β-alanine each have multiple purposes within the human body; this review focuses on their roles as ergogenic aids to exercise performance and suggests how to best quantify the former’s merits as a buffer. Carnosine normally makes a small contribution to a cell’s total buffer capacity; yet β-alanine supplementation raises intracellular carnosine concentrations that in turn improve a muscle’s ability to buffer protons. Numerous studies assessed the impact of oral β-alanine intake on muscle carnosine levels and exercise performance. β-alanine may best act as an ergogenic aid when metabolic acidosis is the primary factor for compromised exercise performance. Blood lactate kinetics, whereby the concentration of the metabolite is measured as it enters and leaves the vasculature over time, affords the best opportunity to assess the merits of β-alanine supplementation’s ergogenic effect. Optimal β-alanine dosages have not been determined for persons of different ages, genders and nutritional/health conditions. Doses as high as 6.4 g day−1, for ten weeks have been administered to healthy subjects. Paraesthesia is to date the only side effect from oral β-alanine ingestion. The severity and duration of paraesthesia episodes are dose-dependent. It may be unwise for persons with a history of paraesthesia to ingest β-alanine. As for any supplement, caution should be exercised with β-alanine supplementation.

  1. Aging-induced changes in brain regional serotonin receptor binding: Effect of Carnosine.

    Science.gov (United States)

    Banerjee, S; Poddar, M K

    2016-04-01

    Monoamine neurotransmitter, serotonin (5-HT) has its own specific receptors in both pre- and post-synapse. In the present study the role of carnosine on aging-induced changes of [(3)H]-5-HT receptor binding in different brain regions in a rat model was studied. The results showed that during aging (18 and 24 months) the [(3)H]-5-HT receptor binding was reduced in hippocampus, hypothalamus and pons-medulla with a decrease in their both Bmax and KD but in cerebral cortex the [(3)H]-5-HT binding was increased with the increase of its only Bmax. The aging-induced changes in [(3)H]-5-HT receptor binding with carnosine (2.0 μg/kg/day, intrathecally, for 21 consecutive days) attenuated in (a) 24-month-aged rats irrespective of the brain regions with the attenuation of its Bmax except hypothalamus where both Bmax and KD were significantly attenuated, (b) hippocampus and hypothalamus of 18-month-aged rats with the attenuation of its Bmax, and restored toward the [(3)H]-5-HT receptor binding that observed in 4-month-young rats. The decrease in pons-medullary [(3)H]-5-HT binding including its Bmax of 18-month-aged rats was promoted with carnosine without any significant change in its cerebral cortex. The [(3)H]-5-HT receptor binding with the same dosages of carnosine in 4-month-young rats (a) increased in the cerebral cortex and hippocampus with the increase in their only Bmax whereas (b) decreased in hypothalamus and pons-medulla with a decrease in their both Bmax and KD. These results suggest that carnosine treatment may (a) play a preventive role in aging-induced brain region-specific changes in serotonergic activity (b) not be worthy in 4-month-young rats in relation to the brain regional serotonergic activity. PMID:26808776

  2. Anti-stress effects of carnosine on restraint-evoked immunocompromise in mice through spleen lymphocyte number maintenance.

    Directory of Open Access Journals (Sweden)

    Yi-Fang Li

    Full Text Available Carnosine (β-alanyl-L-histidine, a naturally occurring dipeptide, has been characterized as a putative neurotransmitter and serves as a reservoir for brain histamine, which could act on histaminergic neurons system to relieve stress-induced damages. However, understanding of the role of carnosine in stress-evoked immunocompromise is limited. In this study, results showed that when mice were subjected to restraint stress, spleen index and the number of spleen lymphocytes including Natural Killer (NK cells were obviously decreased. Results also demonstrated that restraint stress decreased the cytotoxic activity of NK cells per spleen (LU(10/spleen while the activity of a single NK cell (LU(10/10(6 cells was not changed. However, oral administration of carnosine (150 and 300 mg/kg increased spleen index and number of spleen lymphocytes (including NK cells, and elevated the cytotoxic activity of NK cells per spleen in restraint-stressed mice. These results indicated that carnosine ameliorated stress-evoked immunocompromise through spleen lymphocyte number maintenance. Carnosine was further found to reduce stress-induced elevation of plasma corticosterone level. On the other hand, results showed that carnosine and RU486 (a glucocorticoids receptor antagonist treatment prevented the reduction in mitochondrion membrane potential and the release of mitochondrial cytochrome c into cytoplasm, increased Bcl-2/Bax mRNA ratio, as well as decreased terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL-positive cells in spleen lymphocytes of stressed mice. The results above suggested that the maintenance of spleen lymphocyte number by carnosine was related with the inhibition of lymphocytes apoptosis caused by glucocorticoids overflow. The stimulation of lymphocyte proliferation by carnosine also contributed to the maintenance of spleen lymphocyte number in stressed mice. In view of the elevated histamine level, the anti

  3. The synergistic effect of ribose, carnosine, and ascorbic acid on the sensory and physico-chemical characteristics of minced bison meat

    OpenAIRE

    Aliani, Michel; Ryland, Donna; Williamson, Jennifer; Rempel, Natalie

    2013-01-01

    Ingredients such as ascorbic acid used to preserve redness of the raw meat, and carnosine and ribose used for flavor improvement have been incorporated into minced meats to increase consumer acceptance. The objective of this study was to investigate the possible synergistic effect of ascorbic acid, carnosine, and ribose on the sensory and physico-chemical characteristics of minced bison meat. Samples included control (Co) ±1% carnosine (C), 0.1% ascorbic acid (A), 2% ribose (R) (w/w), and com...

  4. Bioactive peptide carnosin protects against lead acetate-induced hepatotoxicity by abrogation of oxidative stress in rats.

    Science.gov (United States)

    Hasanein, Parisa; Kazemian-Mahtaj, Azam; Khodadadi, Iraj

    2016-08-01

    Context Oxidative stress is a common mechanism of liver injury. Carnosine is a dipeptide having strong antioxidant effects. Objectives We investigated the effects of carnosine on lead-induced hepatotoxicity and oxidative stress in rats. Materials and methods Animals received an aqueous solution of lead acetate (500 mg Pb/L in the drinking water) and/or daily oral gavage of carnosine (10 mg/kg) for 8 weeks. Rats were then weighed and used for the biochemical (commercial kits), molecular (standard chemical methods) and histological (microscopic) evaluations. Results Lead-induced oxidative stress in liver tissue was indicated by a significant increase in the level of malondialdehyde (MDA) (8.25 ± 0.15 nmol/mg) as well as decrease in the level of total antioxidant capacity (TAC) (1.72 ± 0.25 μmol/g) and total thiol (SH) groups) 1.9 ± 0.22 μmol/g). Carnosine treatment decreased MDA (4 ± 0.08 nmol/mg), whereas it increased the contents of total thiol (3.25 ± 0.04 μmol/g) and TAC (3.44 ± 0.32 μmol/g) in the lead group. Carnosine also prevented the decreased body weight (p carnosine attenuates liver damage by decreasing necrosis and infiltration of inflammatory cells. Conclusion Carnosine prevented lead-induced hepatotoxicity, indicated by molecular, biochemical and histopathological analyses through inhibiting lipid peroxidation and enhancing antioxidant defence systems. Therefore, carnosine makes a good candidate to protect against the deleterious effect of chronic lead intoxication. PMID:26808926

  5. Daily carnosine and anserine supplementation alters verbal episodic memory and resting state network connectivity in healthy elderly adults

    OpenAIRE

    Jaroslav eRokicki; Lucia eLi; Jun eKaneko; Etsuko eImabayashi; Tatsuhiro eHisatsune; Hiroshi eMatsuda

    2015-01-01

    Carnosine and anserine are strong antioxidants, previously demonstrated to reduce cognitive decline in animal studies. We aimed to investigate their cognitive and neurophysiological effects, using functional MRI, on humans.Thirty-one healthy participants (age 40-78, 10~male/21~female) were recruited to a double-blind placebo-controlled study. Participants were assigned to twice-daily doses of imidazole dipeptide formula ($n = 14$), containing 500~mg (carnosine/anserine, ratio 1/3) or an ident...

  6. Anti-Aggregating Effect of the Naturally Occurring Dipeptide Carnosine on Aβ1-42 Fibril Formation

    OpenAIRE

    Alessandra Aloisi; Amilcare Barca; Alessandro Romano; Sara Guerrieri; Carlo Storelli; Rosaria Rinaldi; Tiziano Verri

    2013-01-01

    Carnosine is an endogenous dipeptide abundant in the central nervous system, where by acting as intracellular pH buffering molecule, Zn/Cu ion chelator, antioxidant and anti-crosslinking agent, it exerts a well-recognized multi-protective homeostatic function for neuronal and non-neuronal cells. Carnosine seems to counteract proteotoxicity and protein accumulation in neurodegenerative conditions, such as Alzheimer's Disease (AD). However, its direct impact on the dynamics of AD-related fibril...

  7. Stretched Gelatin Phantom for Detection of Residual Dipolar Couplings in MR Spectra and Data Analysis of Carnosine

    OpenAIRE

    Karel Bernášek; Marián Grocký; Martin Burian; Jan Lang

    2016-01-01

    Peak splitting due to the residual dipolar coupling (RDC) represents a potentially applicable spectral parameter for diagnostic purposes. Several of the skeletal muscle metabolites were previously reported to display the RDC splitting in in vivo MR spectra. We constructed an in vitro model consisting of mechanically stretched gelatin cylinder soaked with the muscle metabolite carnosine. We describe the preparation procedure of an upscaled 50 mL stretched gelatin sample with carnosine that can...

  8. Daily Carnosine and Anserine Supplementation Alters Verbal Episodic Memory and Resting State Network Connectivity in Healthy Elderly Adults

    OpenAIRE

    Rokicki, Jaroslav; Li, Lucia; Imabayashi, Etsuko; Kaneko, Jun; Hisatsune, Tatsuhiro; Matsuda, Hiroshi

    2015-01-01

    Carnosine and anserine are strong antioxidants, previously demonstrated to reduce cognitive decline in animal studies. We aimed to investigate their cognitive and neurophysiological effects, using functional MRI, on humans. Thirty-one healthy participants (age 40–78, 10 male/21 female) were recruited to a double-blind placebo-controlled study. Participants were assigned to twice-daily doses of imidazole dipeptide formula (n = 14), containing 500 mg (carnosine/anserine, ratio 1/3) or an identi...

  9. Anti-Stress Effects of Carnosine on Restraint-Evoked Immunocompromise in Mice through Spleen Lymphocyte Number Maintenance

    OpenAIRE

    Yi-Fang Li; Rong-Rong He; Bun Tsoi; Xiao-Di Li; Wei-Xi Li; Keiichi Abe; Hiroshi Kurihara

    2012-01-01

    Carnosine (β-alanyl-L-histidine), a naturally occurring dipeptide, has been characterized as a putative neurotransmitter and serves as a reservoir for brain histamine, which could act on histaminergic neurons system to relieve stress-induced damages. However, understanding of the role of carnosine in stress-evoked immunocompromise is limited. In this study, results showed that when mice were subjected to restraint stress, spleen index and the number of spleen lymphocytes including Natural Kil...

  10. Carnosine attenuates early brain injury through its antioxidative and anti-apoptotic effects in a rat experimental subarachnoid hemorrhage model.

    Science.gov (United States)

    Zhang, Zong-yong; Sun, Bao-liang; Yang, Ming-feng; Li, Da-wei; Fang, Jie; Zhang, Shuai

    2015-03-01

    Carnosine (β-alanyl-L-histidine) has been demonstrated to provide antioxidative and anti-apoptotic roles in the animal of ischemic brain injuries and neurodegenerative diseases. The aim of this study was to examine whether carnosine prevents subarachnoid hemorrhage (SAH)-induced early brain injury (EBI) in rats. We found that intraperitoneal administration of carnosine improved neurobehavioral deficits, attenuated brain edema and blood-brain barrier permeability, and decreased reactive oxygen species level at 48 h following SAH in rat models. Carnosine treatment increased tissue copper/zinc superoxide dismutase (CuZn-SOD) and glutathione peroxidase (GSH-Px) enzymatic activities, and reduced post-SAH elevated lactate dehydrogenase (LDH) activity, the concentration of malondialdehyde (MDA), 3-nitrotyrosine (3-NT), 8-hydroxydeoxyguanosine (8-OHDG), interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α) in rats. Furthermore, carnosine treatment attenuated SAH-induced microglia activation and cortical neuron apoptosis. These results indicated that administration of carnosine may provide neuroprotection in EBI following SAH in rat models. PMID:25179154

  11. Anti-aggregating effect of the naturally occurring dipeptide carnosine on aβ1-42 fibril formation.

    Directory of Open Access Journals (Sweden)

    Alessandra Aloisi

    Full Text Available Carnosine is an endogenous dipeptide abundant in the central nervous system, where by acting as intracellular pH buffering molecule, Zn/Cu ion chelator, antioxidant and anti-crosslinking agent, it exerts a well-recognized multi-protective homeostatic function for neuronal and non-neuronal cells. Carnosine seems to counteract proteotoxicity and protein accumulation in neurodegenerative conditions, such as Alzheimer's Disease (AD. However, its direct impact on the dynamics of AD-related fibril formation remains uninvestigated. We considered the effects of carnosine on the formation of fibrils/aggregates of the amyloidogenic peptide fragment Aβ1-42, a major hallmark of AD injury. Atomic force microscopy and thioflavin T assays showed inhibition of Aβ1-42 fibrillogenesis in vitro and differences in the aggregation state of Aβ1-42 small pre-fibrillar structures (monomers and small oligomers in the presence of carnosine. in silico molecular docking supported the experimental data, calculating possible conformational carnosine/Aβ1-42 interactions. Overall, our results suggest an effective role of carnosine against Aβ1-42 aggregation.

  12. Analysis of an H1 receptor-mediated, zinc-potentiated vasoconstrictor action of the histidyl dipeptide carnosine in rabbit saphenous vein

    OpenAIRE

    O'Dowd, Anne; Miller, David J.

    1998-01-01

    The contractile action of the dipeptide carnosine (β-alanyl-L-histidine), active as a Zn·carnosine complex (Zn·Carn), was investigated in isolated rings of rabbit saphenous vein (RSV) and was found to be antagonized by the H1 antagonist mepyramine.Mepyramine-sensitive, histamine-induced contractures in RSV, were smaller (73±0.1%) and less well sustained than carnosine-induced contractures.Schild plot values for mepyramine antagonism were, for carnosine-induced contractures; pA2=7.97±0.12, slo...

  13. Management of the virulent influenza virus infection by oral formulation of nonhydrolized carnosine and isopeptide of carnosine attenuating proinflammatory cytokine-induced nitric oxide production.

    Science.gov (United States)

    Babizhayev, Mark A; Deyev, Anatoly I

    2012-01-01

    Inducible nitric oxide synthase (iNOS) plays an important role in mediating inflammation. In our studies, we found that iNOS-derived NO was significantly increased in the serum samples of 150 patients infected with influenza A virus in comparison with samples of 140 healthy individuals. In human lung epithelial cells, infection with influenza A virus or stimulation with poly(I:C) + interferon-gamma resulted in increased mRNA and protein levels of both interleukin-32 and iNOS, with subsequent release of NO. Activated macrophages are also a source of nitric oxide (NO), which is largely produced by iNOS in response to proinflammatory cytokines. In this review article, the presented findings have many important implications for understanding the Influenza A (H1N1) viral pathogenesis, prevention, and treatment. The direct viral cytotoxicity (referred cytopathic effect) is only a fraction of several types of events induced by virus infection. Nitric oxide and oxygen free radicals such as superoxide anion (O₂⁻˙) are generated markedly in influenza A (including H1N1) virus-infected host boosts, and these molecular species are identified as the potent pathogenic agents. The mutual interaction of NO with O₂⁻˙ resulting in formation of peroxynitrite is operative in the pathogenic mechanism of influenza virus pneumonia. The toxicity and reactivity of oxygen radicals, generated in excessive amounts mediate the overreaction of the host's immune response against the organs or tissues in which viruses are replicating, and this may explain the mechanism of tissue injuries observed in influenza virus infection of various types. The authors revealed the protection that carnosine and its bioavailable nonhydrolized forms provide against peroxynitrite damage and other types of viral injuries in which immunologic interactions are usually involved. Carnosine (beta-alanyl-L-histidine) shows the pharmacologic intracellular correction of NO release which might be one of the

  14. Carnosine and Homocarnosine Degradation Mechanisms by the Human Carnosinase Enzyme CN1: Insights from Multiscale Simulations.

    Science.gov (United States)

    Pavlin, Matic; Rossetti, Giulia; De Vivo, Marco; Carloni, Paolo

    2016-05-17

    The endogenous dipeptide l-carnosine, and its derivative homocarnosine, prevent and reduce several pathologies like amytrophic lateral sclerosis (ALS), Alzheimer's disease, and Parkinson's disease. Their beneficial action is severely hampered because of the hydrolysis by carnosinase enzymes, in particular the human carnosinase, hCN1. This belongs to the metallopeptidase M20 family, where a cocatalytic active site is formed by two Zn(2+) ions, bridged by a hydroxide anion. The protein may exist as a monomer and as a dimer in vivo. Here we used hybrid quantum mechanics/molecular mechanics simulations based on the dimeric apoenzyme's structural information to predict the Michaelis complexes with l-carnosine and its derivative homocarnosine. On the basis of our calculations, we suggest that (i) l-carnosine degradation occurs through a nucleophilic attack of a Zn(2+)-coordinated bridging moiety for both monomer and dimer. This mechanistic hypothesis for hCN1 catalysis differs from previous proposals, while it is in agreement with available experimental data. (ii) The experimentally measured higher affinity of homocarnosine for the enzyme relative to l-carnosine might be explained, at least in part, by more extensive interactions inside the monomeric and dimeric hCN1's active site. (iii) Hydrogen bonds at the binding site, present in the dimer but absent in the monomer, might play a role in the experimentally observed higher activity of the dimeric form. Investigations of the enzymatic reaction are required to establish or disprove this hypothesis. Our results may serve as a basis for the design of potent hCN1 inhibitors. PMID:27105448

  15. Role of Carnosine and Melatonin in Ameliorating Cardiotoxicity of Titanium Dioxide Nanoparticles in the Rats

    Directory of Open Access Journals (Sweden)

    Nouf Al-Rasheed

    2015-08-01

    Full Text Available The aim of this work was to study the possible cardiotoxicity of two different doses of 50 nm nano titanium dioxide (n-TiO2 and the possible modulating effects of the use of two natural antioxidants carnosine and melatonin. The results showed that TiO2- NPs produced deleterious effects on rat cardiac tissue as confirmed by the increased levels of serum myoglobin, troponin-T and CK-MB. Increased levels of serum Inflammatory markers represented by the tumor necrosis factor alpha (TNF-α and Interleukin-6 (IL-6 was also noticed. Caspase3 and IGg were elevated compared to the control group in a dose dependant manner. treatment of the rats with Carnosine or melatonin. along with TiO2- NPs administration significantly improved most of the elevated biochemical markers. It was concluded that the use of Carnosine or melatonin could play a beneficial role against deleterious effects of TiO2- NPs

  16. Attenuation of Some Metabolic Deteriorations Induced by Diabetes Mellitus Using Carnosine

    Science.gov (United States)

    Soliman, K. M.; Mohamed, A. M.; Metwally, N. S.

    The protective ability of carnosine against some metabolic disorders and oxidative stress in Strepotzotocin (STZ) diabetic-induced model was studied. Diabetic rats showed significant increase in serum glucose and cortisol levels indicating disturbance of carbohydrate metabolism, increased triglycerides, total cholesterol, LDL-cholesterol as well as iron level indicating abnormal lipid metabolism and iron overload. Marked increase in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and sorbitol dehydrogenase (SD) were also demonstrated implying impairment of liver function. Concomitantly, the results revealed an impairment of antioxidant status of diabetic animals as evidenced by significant decrease in vitamin E and HDL-C levels. Administration of either two doses of carnosine (10 mg/100 g b.w. or 20 mg/100 g b.w.) two weeks before and after diabetic induction, was effective in ameliorating serum glucose level of diabetic animals and improving the deterioration in the studied parameters. The best results were obtained with the higher dose. No significant changes were noted in serum bilirubin level among the different studied groups. These data suggest that carnosine is a potential multi-protective agent for diabetic complications prevention or therapy.

  17. Oncolytic Adenovirus Loaded with L-carnosine as Novel Strategy to Enhance the Antitumor Activity.

    Science.gov (United States)

    Garofalo, Mariangela; Iovine, Barbara; Kuryk, Lukasz; Capasso, Cristian; Hirvinen, Mari; Vitale, Andrea; Yliperttula, Marjo; Bevilacqua, Maria Assunta; Cerullo, Vincenzo

    2016-04-01

    Oncolytic viruses are able to specifically replicate, infect, and kill only cancer cells. Their combination with chemotherapeutic drugs has shown promising results due to the synergistic action of virus and drugs; the combinatorial therapy is considered a potential clinically relevant approach for cancer. In this study, we optimized a strategy to absorb peptides on the viral capsid, based on electrostatic interaction, and used this strategy to deliver an active antitumor drug. We used L-carnosine, a naturally occurring histidine dipeptide with a significant antiproliferative activity. An ad hoc modified, positively charged L-carnosine was combined with the capsid of an oncolytic adenovirus to generate an electrostatic virus-carnosine complex. This complex showed enhanced antitumor efficacy in vitro and in vivo in different tumor models. In HCT-116 colorectal and A549 lung cancer cell lines, the complex showed higher transduction ratio and infectious titer compared with an uncoated oncolytic adenovirus. The in vivo efficacy of the complex was tested in lung and colon cancer xenograft models, showing a significant reduction in tumor growth. Importantly, we investigated the molecular mechanisms underlying the effects of complex on tumor growth reduction. We found that complex induces apoptosis in both cell lines, by using two different mechanisms, enhancing viral replication and affecting the expression of Hsp27. Our system could be used in future studies also for delivery of other bioactive drugs. Mol Cancer Ther; 15(4); 651-60. ©2016 AACR. PMID:26861248

  18. Zinc L-carnosine protects colonic mucosal injury through induction of heat shock protein 72 and suppression of NF-kappaB activation.

    Science.gov (United States)

    Odashima, Masaru; Otaka, Michiro; Jin, Mario; Wada, Isao; Horikawa, Youhei; Matsuhashi, Tamotsu; Ohba, Reina; Hatakeyama, Natsumi; Oyake, Jinko; Watanabe, Sumio

    2006-11-10

    In this study, we investigated the effects of zinc L-carnosine, an anti-ulcer drug, on acetic acid-induced colonic mucosal injury and the correlation of these effects with expression of 72-kDa heat shock proteins (HSP72) and nuclear factor kappa B (NF-kappaB) activation in rat colonic mucosa in vivo. After intrarectal administration of zinc L-carnosine, the rats received intrarectal infusion of 5% acetic acid (1 ml). The colonic mucosal damage was evaluated by macroscopic assessments 24 h after the intrarectal infusion of acetic acid. Expression of HSP72 in rat colonic mucosa was evaluated by Western blot analysis before and after zinc L-carnosine administration. NF-kappaB activation was evaluated by electrophoretic mobility shift assays (EMSA). Zinc L-carnosine inhibited visible damage in rat colonic mucosa by acetic acid. Expression of HSP72 was significantly increased at 6 h after zinc L-carnosine administration. Furthermore, NF-kappaB activation in colonic mucosa was suppressed 6 h after zinc L-carnosine treatment. These results suggested that zinc L-carnosine protects the colonic mucosa against acetic acid by induction of HSP72 and suppression of NF-kappaB activation and zinc L-carnosine may be a novel therapeutic agent for the therapy of inflammatory bowel disease. PMID:16949620

  19. Zinc carnosine protects against hydrogen peroxide-induced DNA damage in WIL2-NS lymphoblastoid cell line independent of poly (ADP-Ribose) polymerase expression.

    Science.gov (United States)

    Ooi, Theng Choon; Mohammad, Nur Hafiza; Sharif, Razinah

    2014-12-01

    The aim of this study is to investigate the ability of zinc carnosine to protect the human lymphoblastoid (WIL2-NS) cell line from hydrogen peroxide-induced DNA damage. Cells were cultured with medium containing zinc carnosine at the concentrations of 0.4, 4, 16 and 32 μM for 9 days prior to treatment with 30 μM of hydrogen peroxide (30 min). Zinc carnosine at the concentration 16 μM was optimal in protecting cells from hydrogen peroxide-induced cytotoxicity and gave the lowest percentage of apoptotic and necrotic cells. Results showed that zinc carnosine was able to induce glutathione production and protect cells from hydrogen peroxide-induced oxidative stress at all concentration and the highest protection was observed at 32-μM zinc carnosine culture. Cytokinesis-block micronucleus cytome assay showed that cells cultured with 4-32 μM of zinc carnosine showed significant reduction in micronuclei formation, nucleoplasmic bridges and nuclear bud frequencies (p carnosines possess antioxidant properties and are able to reduce hydrogen peroxide-induced DNA damage in vitro independent of poly(ADP-ribose) polymerase. Further studies are warranted to understand the mechanism of protection of zinc carnosine against hydrogen peroxide-induced damage. PMID:25326781

  20. Carnosine inhibits carbonic anhydrase IX-mediated extracellular acidosis and suppresses growth of HeLa tumor xenografts

    International Nuclear Information System (INIS)

    Carbonic anhydrase IX (CA IX) is a transmembrane enzyme that is present in many types of solid tumors. Expression of CA IX is driven predominantly by the hypoxia-inducible factor (HIF) pathway and helps to maintain intracellular pH homeostasis under hypoxic conditions, resulting in acidification of the tumor microenvironment. Carnosine (β-alanyl-L-histidine) is an anti-tumorigenic agent that inhibits the proliferation of cancer cells. In this study, we investigated the role of CA IX in carnosine-mediated antitumor activity and whether the underlying mechanism involves transcriptional and translational modulation of HIF-1α and CA IX and/or altered CA IX function. The effect of carnosine was studied using two-dimensional cell monolayers of several cell lines with endogenous CA IX expression as well as Madin Darby canine kidney transfectants, three-dimensional HeLa spheroids, and an in vivo model of HeLa xenografts in nude mice. mRNA and protein expression and protein localization were analyzed by real-time PCR, western blot analysis, and immunofluorescence staining, respectively. Cell viability was measured by a flow cytometric assay. Expression of HIF-1α and CA IX in tumors was assessed by immunohistochemical staining. Real-time measurement of pH was performed using a sensor dish reader. Binding of CA IX to specific antibodies and metabolon partners was investigated by competitive ELISA and proximity ligation assays, respectively. Carnosine increased the expression levels of HIF-1α and HIF targets and increased the extracellular pH, suggesting an inhibitory effect on CA IX-mediated acidosis. Moreover, carnosine significantly inhibited the growth of three-dimensional spheroids and tumor xenografts compared with untreated controls. Competitive ELISA showed that carnosine disrupted binding between CA IX and antibodies specific for its catalytic domain. This finding was supported by reduced formation of the functional metabolon of CA IX and anion exchanger 2 in the

  1. Antioxidant potential of date (Phoenix dactylifera L.) seed protein hydrolysates and carnosine in food and biological systems.

    Science.gov (United States)

    Ambigaipalan, Priyatharini; Shahidi, Fereidoon

    2015-01-28

    Date seed protein hydrolysates were evaluated for antioxidant activity as well as solubility and water-holding capacity in food and biological model systems. Date seed protein hydrolysates as well as carnosine exhibited >80% of solubility over a pH range of 2-12. The hydrolysates and carnosine at 0.5% (w/w) were also found to be effective in enhancing water-holding capacity and cooking yield in a fish model system, which was nearly similar to sodium tripolyphosphate (STPP; 0.3%, w/w). Incorporation of hydrolysates (200 ppm) in fish model systems resulted in the highest inhibition (30%) of oxidation in comparison to butylated hydroxytoluene (BHT; 9%). In addition, hydrolysates and carnosine inhibited β-carotene oxidation by 75%. The hydrolysates (0.1 mg/mL) inhibited LDL cholesterol oxidation by 60%, whereas carnosine inhibited oxidation by 80% after 12 h of incubation. Additionally, hydrolysates and carnosine effectively inhibited hydroxyl (6 mg/mL) and peroxyl (0.1 mg/mL) radical-induced DNA scission. Therefore, date seed protein hydrolysates could be used as a potential functional food ingredient for health promotion. PMID:25553507

  2. Synthesis, physicochemical characterization, and biological activities of new carnosine derivatives stable in human serum as potential neuroprotective agents.

    Science.gov (United States)

    Bertinaria, Massimo; Rolando, Barbara; Giorgis, Marta; Montanaro, Gabriele; Guglielmo, Stefano; Buonsanti, M Federica; Carabelli, Valentina; Gavello, Daniela; Daniele, Pier Giuseppe; Fruttero, Roberta; Gasco, Alberto

    2011-01-27

    The synthesis and the physicochemical and biological characterization of a series of carnosine amides bearing on the amido group alkyl substituents endowed with different lipophilicity are described. All synthesized products display carnosine-like properties differentiating from the lead for their high serum stability. They are able to complex Cu(2+) ions at physiological pH with the same stoichiometry as carnosine. The newly synthesized compounds display highly significant copper ion sequestering ability and are capable of protecting LDL from oxidation catalyzed by Cu(2+) ions, the most active compounds being the most hydrophilic ones. All the synthesized amides show quite potent carnosine-like HNE quenching activity; in particular, 7d, the member of the series selected for this kind of study, is able to cross the blood-brain barrier (BBB) and to protect primary mouse hippocampal neurons against HNE-induced death. These products can be considered metabolically stable analogues of carnosine and are worthy of additional investigation as potential neuroprotective agents. PMID:21182325

  3. Stretched Gelatin Phantom for Detection of Residual Dipolar Couplings in MR Spectra and Data Analysis of Carnosine

    Directory of Open Access Journals (Sweden)

    Karel Bernášek

    2016-01-01

    Full Text Available Peak splitting due to the residual dipolar coupling (RDC represents a potentially applicable spectral parameter for diagnostic purposes. Several of the skeletal muscle metabolites were previously reported to display the RDC splitting in in vivo MR spectra. We constructed an in vitro model consisting of mechanically stretched gelatin cylinder soaked with the muscle metabolite carnosine. We describe the preparation procedure of an upscaled 50 mL stretched gelatin sample with carnosine that can be used as a phantom for setting-up and testing of spectroscopic measurements of RDC in a MR scanner. We also report on analysis of the RDC splittings in 1H and 13C high resolution MR spectra of carnosine.

  4. Molecular identification of carnosine N-methyltransferase as chicken histamine N-methyltransferase-like protein (hnmt-like.

    Directory of Open Access Journals (Sweden)

    Jakub Drozak

    Full Text Available Anserine (beta-alanyl-N(Pi-methyl-L-histidine, a naturally occurring derivative of carnosine (beta-alanyl-L-histidine, is an abundant constituent of skeletal muscles and brain of many vertebrates. Although it has long been proposed to serve as a proton buffer, radicals scavenger and transglycating agent, its physiological function remains obscure. The formation of anserine is catalyzed by carnosine N-methyltransferase which exhibits unknown molecular identity. In the present investigation, we have purified carnosine N-methyltransferase from chicken pectoral muscle about 640-fold until three major polypeptides of about 23, 26 and 37 kDa coeluting with the enzyme were identified in the preparation. Mass spectrometry analysis of these polypeptides resulted in an identification of histamine N-methyltransferase-like (HNMT-like protein as the only meaningful candidate. Analysis of GenBank database records indicated that the hnmt-like gene might be a paralogue of histamine N-methyltransferase gene, while comparison of their protein sequences suggested that HNMT-like protein might have acquired a new activity. Chicken HNMT-like protein was expressed in COS-7 cells, purified to homogeneity, and shown to catalyze the formation of anserine as confirmed by both chromatographic and mass spectrometry analysis. Both specificity and kinetic studies carried out on the native and recombinant enzyme were in agreement with published data. Particularly, several compounds structurally related to carnosine, including histamine and L-histidine, were tested as potential substrates for the enzyme, and carnosine was the only methyl group acceptor. The identification of the gene encoding carnosine N-methyltransferase might be beneficial for estimation of the biological functions of anserine.

  5. Tuning the self-assembly of the bioactive dipeptide L-carnosine by incorporation of a bulky aromatic substituent

    OpenAIRE

    Castelletto, Valeria; Cheng, Ge; Greenland, Barny W.; Hamley, Ian W.; Harris, Peter J. F.

    2011-01-01

    The dipeptide L-carnosine has a number of important biological properties. Here, we explore the effect of attachment of a bulky hydrophobic aromatic unit, Fmoc [N-(fluorenyl-9-methoxycarbonyl)] on the self-assembly of Fmoc-L-carnosine, i.e., Fmoc-Beta-alanine-histidine (Fmoc-BetaAH). It is shown that Fmoc-BetaAH forms well-defined amyloid fibril containing Beta sheets above a critical aggregation concentration, which is determined from pyrene and ThT fluorescence experiments. Twisted fi...

  6. Effects of Beta-Alanine on Muscle Carnosine and Exercise Performance:A Review of the Current Literature

    OpenAIRE

    Matthew Cooke; Mike Greenwood; Kreider, Richard B; Culbertson, Julie Y.

    2010-01-01

    Muscle carnosine has been reported to serve as a physiological buffer, possess antioxidant properties, influence enzyme regulation, and affect sarcoplasmic reticulum calcium regulation. Beta-alanine (β-ALA) is a non-essential amino acid. β-ALA supplementation (e.g., 2-6 grams/day) has been shown to increase carnosine concentrations in skeletal muscle by 20-80%. Several studies have reported that β-ALA supplementation can increase high-intensity intermittent exercise performance and/or trainin...

  7. Effect of Dietary Supplementation of Blood Meal and Additional Magnesium on Carnosine and Anserine Concentrations of Pig Muscles

    OpenAIRE

    Park, Se Won; Kim, Chan Ho; Kim, Jong Woong; Shin, Hye Seong; Paik, In Kee; Kil, Dong Yong

    2014-01-01

    The objective of this study was to investigate the effect of dietary supplementation of blood meal as a source of L-histidine, and the addition of magnesium (Mg) as a catalyst of carnosine synthetase for the carnosine and anserine concentrations of pig muscles (longissimus dorsi, LD and vastus intermedius, VI). A total of twenty-four pigs with an average body weight of 60.2±4.2 kg were randomly allotted to one of three dietary treatments (eight replicates), during 56 d of the feeding trial. D...

  8. Laccase mediated-synthesis of hydroxycinnamoyl-peptide from ferulic acid and carnosine.

    Science.gov (United States)

    Aljawish, Abdulhadi; Chevalot, Isabelle; Madad, Nidal; Paris, Cédric; Muniglia, Lionel

    2016-06-10

    Carnosine (CAR) dipeptide was functionalized with ferulic acid (FA) as substrate using laccase from Myceliophtora thermophila as biocatalyst. The enzymatic reaction was performed in aqueous medium under mild conditions (pH 7.5, 30°C) as an eco-friendly procedure. Results showed that this enzymatic process led to the synthesis of two new derivatives (P1, P2), from the coupling between CAR and FA derived products. Conditions allowing a high production of P1, P2 derivatives were determined with an optimal ratio of (FA: CAR) of (1:1.6) at optimal time reaction of 8h. Under these optimal conditions, the coupling between CAR and FA-products was demonstrated, resulting in the decrease of -NH2 groups (almost 50%) as quantified via derivatization. Due to the presence of FA in the structure of these new derivatives, they exhibited higher hydrophobic property than carnosine. Structural analyses by mass spectrometry showed that P1 and P2 (FA-CAR) derivatives exhibited the same molecular mass (MM 770g/mol) containing one CAR-molecule and three FA-molecules but with different chemical structures. Furthermore, these derivatives presented improved antioxidant (almost 10 times) and anti-proliferative (almost 18 times) properties in comparison with CAR. Moreover, P1 derivative exhibited higher antioxidant and anti-proliferative activities than P2 derivative, which confirmed the different structures of P1 and P2. These results suggested that the oxidized phenols coupling with carnosine is a promising process to enhance the CAR-properties. PMID:27084055

  9. Carnosine decreased neuronal cell death through targeting glutamate system and astrocyte mitochondrial bioenergetics in cultured neuron/astrocyte exposed to OGD/recovery.

    Science.gov (United States)

    Ouyang, Li; Tian, Yueyang; Bao, Yun; Xu, Huijuan; Cheng, Jiaoyan; Wang, Bingyu; Shen, Yao; Chen, Zhong; Lyu, Jianxin

    2016-06-01

    Previously, we showed that carnosine upregulated the expression level of glutamate transporter 1 (GLT-1), which has been recognized as an important participant in the astrocyte-neuron lactate shuttle (ANLS), with ischemic model in vitro and in vivo. This study was designed to investigate the protective effect of carnosine on neuron/astrocyte co-cultures exposed to OGD/recovery, and to explore whether the ANLS or any other mechanism contributes to carnosine-induced neuroprotection on neuron/astrocyte. Co-cultures were treated with carnosine and exposed to OGD/recovery. Cell death and the extracellular levels of glutamate and GABA were measured. The mitochondrial respiration and glycolysis were detected by Seahorse Bioscience XF96 Extracellular Flux Analyzer. Results showed that carnosine decreased neuronal cell death, increased extracellular GABA level, and abolished the increase in extracellular glutamate and reversed the mitochondrial energy metabolism disorder induced by OGD/recovery. Carnosine also upregulated the mRNA level of neuronal glutamate transporter EAAC1 at 2h after OGD. Dihydrokainate, a specific inhibitor of GLT-1, decreased glycolysis but it did not affect mitochondrial respiration of the cells, and it could not reverse the increase in mitochondrial OXPHOS induced by carnosine in the co-cultures. The levels of mRNAs for monocarboxylate transporter1, 4 (MCT1, 4), which were expressed in astrocytes, and MCT2, the main neuronal MCT, were significantly increased at the early stage of recovery. Carnosine only partly reversed the increased expression of astrocytic MCT1 and MCT4. These results suggest that regulating astrocytic energy metabolism and extracellular glutamate and GABA levels but not the ANLS are involved in the carnosine-induced neuroprotection. PMID:27040711

  10. Dietary supplemental vitamin B6 increases carnosine and anserine concentrations in the heart of rats

    OpenAIRE

    Suidasari, Sofya; HASEGAWA, Tomoko; Yanaka, Noriyuki; Kato, Norihisa

    2015-01-01

    This study was performed to examine the effect of dietary level of vitamin B6 on the concentrations of carnosine and anserine, antioxidants, in the heart of rats. Analysis using UPLC–MS/MS showed that the concentrations of these dipeptides in the 7 and 35 mg pyridoxine HCl/kg groups were significantly higher than those in the 1 mg pyridoxine HCl/kg group, implying the novel role of dietary vitamin B6 as a determinant of the dipeptides favorable for heart.

  11. Could carnosine suppress zinc-mediated proteasome inhibition and neurodegeneration? Therapeutic potential of a non-toxic but non-patentable dipeptide.

    Science.gov (United States)

    Hipkiss, Alan R

    2005-01-01

    Ageing and neurodegenerative conditions are often associated with proteasome dysfunction, possibly mediated by zinc and/or copper ions. Studies have shown that (i) the olfactory lobe is normally enriched in carnosine and zinc, (ii) carnosine can suppress copper and zinc toxicity in olfactory neurones, (iii) olfactory dysfunction is often associated with neurodegenerative conditions and (iv) elevated levels of zinc are found in brains of Alzheimer's patients. It is suggested that nasal administration of carnosine should be explored as a possible way of suppressing zinc/copper-mediated proteasome inhibition and consequent neurodegeneration. PMID:16034682

  12. Influence of genetic knockout of Pept2 on the in vivo disposition of endogenous and exogenous carnosine in wild-type and Pept2 null mice

    OpenAIRE

    Kamal, Mohamed A; Jiang, Huidi; Hu, Yongjun; Keep, Richard F; Smith, David E.

    2009-01-01

    Carnosine (β-alanyl-l-histidine), an endogenous dipeptide substrate of the proton-coupled oligopeptide transporter PEPT2, plays an important role in many physiological processes. This study examined the effect of PEPT2 on the disposition of endogenous and exogenous carnosine in wild-type and Pept2 null mice. After exogenous dosing of [3H]carnosine (1 nmol/g iv bolus), a marked increase was observed in its systemic clearance in Pept2 null mice (0.50 vs. 0.29 ml/min), resulting in a decreased s...

  13. Tuning the self-assembly of the bioactive dipeptide L-carnosine by incorporation of a bulky aromatic substituent.

    Science.gov (United States)

    Castelletto, V; Cheng, G; Greenland, B W; Hamley, I W; Harris, P J F

    2011-03-15

    The dipeptide L-carnosine has a number of important biological properties. Here, we explore the effect of attachment of a bulky hydrophobic aromatic unit, Fmoc [N-(fluorenyl-9-methoxycarbonyl)] on the self-assembly of Fmoc-L-carnosine, i.e., Fmoc-β-alanine-histidine (Fmoc-βAH). It is shown that Fmoc-βAH forms well-defined amyloid fibrils containing β sheets above a critical aggregation concentration, which is determined from pyrene and ThT fluorescence experiments. Twisted fibrils were imaged by cryogenic transmission electron microscopy. The zinc-binding properties of Fmoc-βAH were investigated by FTIR and Raman spectroscopy since the formation of metal ion complexes with the histidine residue in carnosine is well-known, and important to its biological roles. Observed changes in the spectra may reflect differences in the packing of the Fmoc-dipeptides due to electrostatic interactions. Cryo-TEM shows that this leads to changes in the fibril morphology. Hydrogelation is also induced by addition of an appropriate concentration of zinc ions. Our work shows that the Fmoc motif can be employed to drive the self-assembly of carnosine into amyloid fibrils. PMID:21338121

  14. Daily Carnosine and Anserine Supplementation Alters Verbal Episodic Memory and Resting State Network Connectivity in Healthy Elderly Adults.

    Science.gov (United States)

    Rokicki, Jaroslav; Li, Lucia; Imabayashi, Etsuko; Kaneko, Jun; Hisatsune, Tatsuhiro; Matsuda, Hiroshi

    2015-01-01

    Carnosine and anserine are strong antioxidants, previously demonstrated to reduce cognitive decline in animal studies. We aimed to investigate their cognitive and neurophysiological effects, using functional MRI, on humans. Thirty-one healthy participants (age 40-78, 10 male/21 female) were recruited to a double-blind placebo-controlled study. Participants were assigned to twice-daily doses of imidazole dipeptide formula (n = 14), containing 500 mg (carnosine/anserine, ratio 1/3) or an identical placebo (n = 17). Functional MRI and neuropsychological assessments were carried out at baseline and after 3 months of supplementation. We analyzed resting state functional connectivity with the FSL fMRI analysis package. There were no differences in neuropsychological scores between the groups at baseline. After 3 months of supplementation, the carnosine/anserine group had better verbal episodic memory performance and decreased connectivity in the default mode network, the posterior cingulate cortex and the right fronto parietal network, as compared with the placebo group. Furthermore, there was a correlation between the extents of cognitive and neuroimaging changes. These results suggest that daily carnosine/anserine supplementation can impact cognitive function and that network connectivity changes are associated with its effects. PMID:26640437

  15. Hyperglycemia Does Not Affect Iron Mediated Toxicity of Cultured Endothelial and Renal Tubular Epithelial Cells : Influence of L-Carnosine

    NARCIS (Netherlands)

    Zhang, Shiqi; Ntasis, Emmanouil; Kabtni, Sarah; van den Born, Jaap; Navis, Gerjan; Bakker, Stephan J. L.; Kraemer, Bernhard K.; Yard, Benito A.; Hauske, Sibylle J.

    2016-01-01

    Iron has been suggested to affect the clinical course of type 2 diabetes (T2DM) as accompanying increased intracellular iron accumulation may provide an alternative source for reactive oxygen species (ROS). Although carnosine has proven its therapeutic efficacy in rodent models of T2DM, little is kn

  16. Hyperglycemia Does Not Affect Iron Mediated Toxicity of Cultured Endothelial and Renal Tubular Epithelial Cells: Influence of L-Carnosine.

    Science.gov (United States)

    Zhang, Shiqi; Ntasis, Emmanouil; Kabtni, Sarah; van den Born, Jaap; Navis, Gerjan; Bakker, Stephan J L; Krämer, Bernhard K; Yard, Benito A; Hauske, Sibylle J

    2016-01-01

    Iron has been suggested to affect the clinical course of type 2 diabetes (T2DM) as accompanying increased intracellular iron accumulation may provide an alternative source for reactive oxygen species (ROS). Although carnosine has proven its therapeutic efficacy in rodent models of T2DM, little is known about its efficacy to protect cells from iron toxicity. We sought to assess if high glucose (HG) exposure makes cultured human umbilical vein endothelial cells (HUVECs) and renal proximal tubular epithelial cells (PTECs) more susceptible to metal induced toxicity and if this is ameliorated by L-carnosine. HUVECs and PTECs, cultured under normal glucose (5 mM, NG) or HG (30 mM), were challenged for 24 h with FeCl3. Cell viability was not impaired under HG conditions nor did HG increase susceptibility to FeCl3. HG did not change the expression of divalent metal transporter 1 (DMT1), ferroportin (IREG), and transferrin receptor protein 1 (TFRC). Irrespective of glucose concentrations L-carnosine prevented toxicity in a dose-dependent manner, only if it was present during the FeCl3 challenge. Hence our study indicates that iron induced cytotoxicity is not enhanced under HG conditions. L-Carnosine displayed a strong protective effect, most likely by chelation of iron mediated toxicity. PMID:26788523

  17. Hyperglycemia Does Not Affect Iron Mediated Toxicity of Cultured Endothelial and Renal Tubular Epithelial Cells: Influence of L-Carnosine

    Directory of Open Access Journals (Sweden)

    Shiqi Zhang

    2016-01-01

    Full Text Available Iron has been suggested to affect the clinical course of type 2 diabetes (T2DM as accompanying increased intracellular iron accumulation may provide an alternative source for reactive oxygen species (ROS. Although carnosine has proven its therapeutic efficacy in rodent models of T2DM, little is known about its efficacy to protect cells from iron toxicity. We sought to assess if high glucose (HG exposure makes cultured human umbilical vein endothelial cells (HUVECs and renal proximal tubular epithelial cells (PTECs more susceptible to metal induced toxicity and if this is ameliorated by L-carnosine. HUVECs and PTECs, cultured under normal glucose (5 mM, NG or HG (30 mM, were challenged for 24 h with FeCl3. Cell viability was not impaired under HG conditions nor did HG increase susceptibility to FeCl3. HG did not change the expression of divalent metal transporter 1 (DMT1, ferroportin (IREG, and transferrin receptor protein 1 (TFRC. Irrespective of glucose concentrations L-carnosine prevented toxicity in a dose-dependent manner, only if it was present during the FeCl3 challenge. Hence our study indicates that iron induced cytotoxicity is not enhanced under HG conditions. L-Carnosine displayed a strong protective effect, most likely by chelation of iron mediated toxicity.

  18. Daily carnosine and anserine supplementation alters verbal episodic memory and resting state network connectivity in healthy elderly adults

    Directory of Open Access Journals (Sweden)

    Jaroslav eRokicki

    2015-11-01

    Full Text Available Carnosine and anserine are strong antioxidants, previously demonstrated to reduce cognitive decline in animal studies. We aimed to investigate their cognitive and neurophysiological effects, using functional MRI, on humans.Thirty-one healthy participants (age 40-78, 10~male/21~female were recruited to a double-blind placebo-controlled study. Participants were assigned to twice-daily doses of imidazole dipeptide formula ($n = 14$, containing 500~mg (carnosine/anserine, ratio 1/3 or an identical placebo ($n = 17$. Functional MRI and neuropsychological assessments were carried out at baseline and after 3 months of supplementation. We analyzed resting state functional connectivity with the FSL fMRI analysis package. There were no differences in neuropsychological scores between the groups at baseline. After 3 months of supplementation, the carnosine/anserine group had better verbal episodic memory performance and decreased connectivity in the Default Mode Network, the Posterior Cingulate Cortex and the Right Fronto Parietal Network, as compared with the placebo group. Furthermore, there was a correlation between the extents of cognitive and neuroimaging changes. These results suggest that daily carnosine/anserine supplementation can impact cognitive function and that network connectivity changes are associated with its effects.

  19. Effects of carnosine supplementation to an all-plant protein diet for rainbow trout(Oncorhynchus mykiss)

    Science.gov (United States)

    Fish meal may contain “unknown growth factors” that have yet to be identified for their physiological role. Carnosine is a histidine-ß-alanine dipeptide found in muscle and nervous system tissue which has been demonstrated to have biological activity, but its physiological role is not well defined. ...

  20. Zinc, copper, and carnosine attenuate neurotoxicity of prion fragment PrP106-126.

    Science.gov (United States)

    Kawahara, Masahiro; Koyama, Hironari; Nagata, Tetsuya; Sadakane, Yutaka

    2011-07-01

    Prion diseases are progressive neurodegenerative diseases that are associated with the conversion of normal cellular prion protein (PrP(C)) to abnormal pathogenic prion protein (PrP(SC)) by conformational changes. Prion protein is a metal-binding protein that is suggested to be involved in metal homeostasis. We investigated here the effects of trace elements on the conformational changes and neurotoxicity of synthetic prion peptide (PrP106-126). PrP106-126 exhibited the formation of β-sheet structures and enhanced neurotoxicity during the aging process. The co-existence of Zn(2+) or Cu(2+) during aging inhibited β-sheet formation by PrP106-126 and attenuated its neurotoxicity on primary cultured rat hippocampal neurons. Although PrP106-126 formed amyloid-like fibrils as observed by atomic force microscopy, the height of the fibers was decreased in the presence of Zn(2+) or Cu(2+). Carnosine (β-alanyl histidine) significantly inhibited both the β-sheet formation and the neurotoxicity of PrP106-126. Our results suggested that Zn(2+) and Cu(2+) might be involved in the pathogenesis of prion diseases. It is also possible that carnosine might become a candidate for therapeutic treatments for prion diseases. PMID:21442127

  1. Effect of Anserine/Carnosine Supplementation on Verbal Episodic Memory in Elderly People.

    Science.gov (United States)

    Hisatsune, Tatsuhiro; Kaneko, Jun; Kurashige, Hiroki; Cao, Yuan; Satsu, Hideo; Totsuka, Mamoru; Katakura, Yoshinori; Imabayashi, Etsuko; Matsuda, Hiroshi

    2015-01-01

    Our goal in this study was to determine whether or not anserine/carnosine supplementation (ACS) is capable of preserving cognitive function of elderly people. In a double-blind randomized controlled trial, volunteers were randomly assigned to an ACS or placebo group at a 1:1 ratio. The ACS group took 1.0 g of an anserine/carnosine (3:1) formula daily for 3 months. Participants were evaluated by psychological tests before and after the 3-month supplementation period. Thirty-nine healthy elderly volunteers (60-78 years old) completed the follow-up tests. Among the tests, delayed recall verbal memory assessed by the Wechsler Memory Scale-Logical Memory showed significant preservation in the ACS group, compared to the placebo group (p = 0.0128). Blood analysis revealed a decreased secretion of inflammatory cytokines, including CCL-2 and IL-8, in the ACS group. MRI analysis using arterial spin labeling showed a suppression in the age-related decline in brain blood flow in the posterior cingulate cortex area in the ACS group, compared to the placebo group (p = 0.0248). In another randomized controlled trial, delayed recall verbal memory showed significant preservation in the ACS group, compared to the placebo group (p = 0.0202). These results collectively suggest that ACS may preserve verbal episodic memory and brain perfusion in elderly people, although further study is needed. PMID:26682691

  2. Copper(II) complex formation equilibria involving L-carnosine, the role in the catalysis of amino acid ester hydrolisis

    Energy Technology Data Exchange (ETDEWEB)

    Shoukry, E.M.; Shoukry, M.M.; Mahgoub, A.E.; Galal, H.M. [Cairo Univ., Cairo (Egypt). Faculty of Science

    2000-10-01

    The binary and ternary complexes of copper(II) involving carnosine (H{sub 3}L), amino acids and DNA constituents were examined. Copper(II) was found to form CuL and CuLH{sub 1} complexes with carnosine. The ternary complexes of Copper(II) with carnosine and DNA constituents are formed in a stepwise mechanism, whereby carnosine binds to copper(II), then followed by ligation of the DNA constituents. The concentration distribution of the various complex species has been evaluated. The hydrolysis of amino acid ester is catalysed by the Cu-carnosine complex. The rate enhancement compared with the fee ester hydrolysis is investigated in terms of the ester coordination mode. [Italian] Sono stati considerati i complessi binari e ternari del rame(II) con la carnosina (H{sub 3}L), amino acidi e constituenti del DNA. Si e' trovato che il rame(II) forma complessi CuL e CuLH{sub 1} con la carnosina. I complessi ternari di rame(II) con carnosina e constitutenti del DNA si formano con un meccanismo a stadi, prima la carnosina lega il rame e successivamente sono legati i constituenti del DNA. E' stata valutata la distribuzione della concentrazione delle varie specie complesse. Il complesso Cu-carnosina catalizza l'idrolisi degli esteri di aminoacidi. L'incremento di velocita', rispetto all'idrolisi dell'estere libero, e' stato studiato in termini di modo di coordinazione dell'estere.

  3. Carnosine Inhibits the Proliferation of Human Gastric Carcinoma Cells by Retarding Akt/mTOR/p70S6K Signaling

    OpenAIRE

    Zhang, Zhenwei; Miao, Lei; Wu, Xin; Liu, Guangze; Peng, Yuting; Xin, Xiaoming; Jiao, Binghua; Kong, Xiangping

    2014-01-01

    Carnosine (β-alanyl-L-histidine), described as an enigmatic peptide for its antioxidant, anti-aging and especially antiproliferation properties, has been demonstrated to play an anti-tumorigenic role in certain types of cancer. However, its function in human gastric carcinoma remains unclear. In this study, the effect of carnosine on cell proliferation and its underlying mechanisms were investigated in the cultured human gastric carcinoma cells. The mTOR signaling axis molecules were analyzed...

  4. Effect of transition metal binding on the tautomeric equilibrium of the carnosine imidazolic ring

    Science.gov (United States)

    Torreggiani, A.; Fini, G.; Bottura, G.

    2001-05-01

    A Raman study of carnosine (Carn) and its complexes with Cu(II), Zn(II) and Co(II) at different pH values was carried out. At pH 7 and 9, Carn exists in equilibrium between two tautomeric forms. Raman spectroscopy appears to be a useful tool for analysing the tautomeric equilibrium of the imidazole ring of Carn since the sites involved in metal chelation can be identified by some bands (e.g. νC4C5) that change in wavenumber depending on whether the imidazole ring takes the tautomeric form I or II. Form I (N π-H) is predominant in the free ligand, but the metal coordination can affect the tautomeric equilibrium. Although weak compared to those of aromatic residues, the Raman marker bands may be useful in analysing metal-histidine interaction in proteins.

  5. Carnosine and Related Peptides: Therapeutic Potential in Age-Related Disorders.

    Science.gov (United States)

    Cararo, José H; Streck, Emilio L; Schuck, Patricia F; Ferreira, Gustavo da C

    2015-09-01

    Imidazole dipeptides (ID), such as carnosine (β-alanyl-L-histidine), are compounds widely distributed in excitable tissues of vertebrates. ID are also endowed of several biochemical properties in biological tissues, including antioxidant, bivalent metal ion chelating, proton buffering, and carbonyl scavenger activities. Furthermore, remarkable biological effects have been assigned to such compounds in age-related human disorders and in patients whose activity of serum carnosinase is deficient or undetectable. Nevertheless, the precise biological role of ID is still to be unraveled. In the present review we shall discuss some evidences from clinical and basic studies for the utilization of ID as a drug therapy for age-related human disorders. PMID:26425391

  6. Determination of carnosine, anserine, homocarnosine, pentosidine and thiobarbituric acid reactive substances contents in meat from different animal species.

    Science.gov (United States)

    Peiretti, Pier Giorgio; Medana, Claudio; Visentin, Sonja; Giancotti, Valeria; Zunino, Valentina; Meineri, Giorgia

    2011-06-15

    The aim of this research was to determine the content of the histidinic antioxidants, advanced glycation end products (pentosidine) and thiobarbituric acid reactive substance (TBARS) in the meat from different animal species. Carnosine, anserine, homocarnosine and pentosidine were quantified by HPLC/MS, while TBARS was determined by photometric measurements. The total CRCs (carnosine+anserine+homocarnosine) content was in the increasing order: beef

  7. Effects of carnosine on contractile apparatus Ca²⁺ sensitivity and sarcoplasmic reticulum Ca²⁺ release in human skeletal muscle fibers.

    Science.gov (United States)

    Dutka, T L; Lamboley, C R; McKenna, M J; Murphy, R M; Lamb, G D

    2012-03-01

    There is considerable interest in potential ergogenic and therapeutic effects of increasing skeletal muscle carnosine content, although its effects on excitation-contraction (EC) coupling in human muscle have not been defined. Consequently, we sought to characterize what effects carnosine, at levels attained by supplementation, has on human muscle fiber function, using a preparation with all key EC coupling proteins in their in situ positions. Fiber segments, obtained from vastus lateralis muscle of human subjects by needle biopsy, were mechanically skinned, and their Ca(2+) release and contractile apparatus properties were characterized. Ca(2+) sensitivity of the contractile apparatus was significantly increased by 8 and 16 mM carnosine (increase in pCa(50) of 0.073 ± 0.007 and 0.116 ± 0.006 pCa units, respectively, in six type I fibers, and 0.063 ± 0.018 and 0.103 ± 0.013 pCa units, respectively, in five type II fibers). Caffeine-induced force responses were potentiated by 8 mM carnosine in both type I and II fibers, with the potentiation in type II fibers being entirely explicable by the increase in Ca(2+) sensitivity of the contractile apparatus caused by carnosine. However, the potentiation of caffeine-induced responses caused by carnosine in type I fibers was beyond that expected from the associated increase in Ca(2+) sensitivity of the contractile apparatus and suggestive of increased Ca(2+)-induced Ca(2+) release. Thus increasing muscle carnosine content likely confers benefits to muscle performance in both fiber types by increasing the Ca(2+) sensitivity of the contractile apparatus and possibly also by aiding Ca(2+) release in type I fibers, helping to lessen or slow the decline in muscle performance during fatiguing stimulation. PMID:22174397

  8. Effect of carnosine supplementation on apoptosis and irisin, total oxidant and antioxidants levels in the serum, liver and lung tissues in rats exposed to formaldehyde inhalation.

    Science.gov (United States)

    Aydin, Suna; Ogeturk, Murat; Kuloglu, Tuncay; Kavakli, Ahmet; Aydin, Suleyman

    2015-02-01

    The main objective of the study has been to show whether carnosine has positive effects on liver and lung tissues of rats exposed to a range of formaldehyde concentrations, and to explore how irisin expression and antioxidant capacity are altered in these tissues by carnosine supplementation. Sprague-Dawley type male rats were divided into 8 groups with 6 animals in each: (I) Control; no chemical supplementation); (II) sham (100mg/kg/day carnosine); (III) low dose formaldehyde (LDFA) for 5 days/week; (IV) LDFA for 5 days/week and carnosine); (V) moderate dose formaldehyde (MDFA) for 5 days/week); (VI) MDFA for 5 days/week and carnosine; (VII) high dose formaldehyde (HDFA) for 5 days/week; (VIII) and HDFA for 5 days/week and carnosine. Sham and control groups were exposed to normal air. Irisin levels of the serum, liver and lung tissue supernatants were analyzed by ELISA, while the REL method was used to determine total oxidant/antioxidant capacity. Irisin production by the tissues was detected immunohistochemically. Increasing doses of FA decreased serum/tissue irisin and total antioxidant levels relative to the controls, as also to increases in TUNEL expressions, total oxidant level, oxidant and apoptosis index. Irisin expression was detected in hepatocyte and sinusoidal cells of the liver and parenchymal cells of the lung. In conclusion, while FA exposure reduces irisin and total oxidant in the serum, liver and lung tissues in a dose-dependent manner and increases the total antioxidant capacity, carnosine supplementation reduces the oxidative stress and restores the histopathological and biochemical signs. PMID:25541044

  9. Effects of beta-alanine supplementation on brain homocarnosine/carnosine signal and cognitive function: an exploratory study.

    Directory of Open Access Journals (Sweden)

    Marina Yazigi Solis

    Full Text Available Two independent studies were conducted to examine the effects of 28 d of beta-alanine supplementation at 6.4 g d(-1 on brain homocarnosine/carnosine signal in omnivores and vegetarians (Study 1 and on cognitive function before and after exercise in trained cyclists (Study 2.In Study 1, seven healthy vegetarians (3 women and 4 men and seven age- and sex-matched omnivores undertook a brain 1H-MRS exam at baseline and after beta-alanine supplementation. In study 2, nineteen trained male cyclists completed four 20-Km cycling time trials (two pre supplementation and two post supplementation, with a battery of cognitive function tests (Stroop test, Sternberg paradigm, Rapid Visual Information Processing task being performed before and after exercise on each occasion.In Study 1, there were no within-group effects of beta-alanine supplementation on brain homocarnosine/carnosine signal in either vegetarians (p = 0.99 or omnivores (p = 0.27; nor was there any effect when data from both groups were pooled (p = 0.19. Similarly, there was no group by time interaction for brain homocarnosine/carnosine signal (p = 0.27. In study 2, exercise improved cognitive function across all tests (P 0.05 of beta-alanine supplementation on response times or accuracy for the Stroop test, Sternberg paradigm or RVIP task at rest or after exercise.28 d of beta-alanine supplementation at 6.4 g d(-1 appeared not to influence brain homocarnosine/carnosine signal in either omnivores or vegetarians; nor did it influence cognitive function before or after exercise in trained cyclists.

  10. Hyperglycemia Does Not Affect Iron Mediated Toxicity of Cultured Endothelial and Renal Tubular Epithelial Cells: Influence of L-Carnosine

    OpenAIRE

    Shiqi Zhang; Emmanouil Ntasis; Sarah Kabtni; Jaap van den Born; Gerjan Navis; Stephan J L Bakker; Krämer, Bernhard K.; Benito A Yard; Hauske, Sibylle J.

    2015-01-01

    Iron has been suggested to affect the clinical course of type 2 diabetes (T2DM) as accompanying increased intracellular iron accumulation may provide an alternative source for reactive oxygen species (ROS). Although carnosine has proven its therapeutic efficacy in rodent models of T2DM, little is known about its efficacy to protect cells from iron toxicity. We sought to assess if high glucose (HG) exposure makes cultured human umbilical vein endothelial cells (HUVECs) and renal proximal tubul...

  11. Carnosine inhibits carbonic anhydrase IX-mediated extracellular acidosis and suppresses growth of HeLa tumor xenografts

    OpenAIRE

    Ditte, Zuzana; Ditte, Peter; Labudova, Martina; Simko, Veronika; Iuliano, Filippo; Zatovicova, Miriam; Csaderova, Lucia; Pastorekova, Silvia; Pastorek, Jaromir

    2014-01-01

    Background Carbonic anhydrase IX (CA IX) is a transmembrane enzyme that is present in many types of solid tumors. Expression of CA IX is driven predominantly by the hypoxia-inducible factor (HIF) pathway and helps to maintain intracellular pH homeostasis under hypoxic conditions, resulting in acidification of the tumor microenvironment. Carnosine (β-alanyl-L-histidine) is an anti-tumorigenic agent that inhibits the proliferation of cancer cells. In this study, we investigated the role of CA I...

  12. Graphene Oxides Decorated with Carnosine as an Adjuvant To Modulate Innate Immune and Improve Adaptive Immunity in Vivo.

    Science.gov (United States)

    Meng, Chunchun; Zhi, Xiao; Li, Chao; Li, Chuanfeng; Chen, Zongyan; Qiu, Xusheng; Ding, Chan; Ma, Lijun; Lu, Hongmin; Chen, Di; Liu, Guangqing; Cui, Daxiang

    2016-02-23

    Current studies have revealed the immune effects of graphene oxide (GO) and have utilized them as vaccine carriers and adjuvants. However, GO easily induces strong oxidative stress and inflammatory reaction at the site of injection. It is very necessary to develop an alternative adjuvant based on graphene oxide derivatives for improving immune responses and decreasing side effects. Carnosine (Car) is an outstanding and safe antioxidant. Herein, the feasibility and efficiency of ultrasmall graphene oxide decorated with carnosine as an alternative immune adjuvant were explored. OVA@GO-Car was prepared by simply mixing ovalbumin (OVA, a model antigen) with ultrasmall GO covalently modified with carnosine (GO-Car). We investigated the immunological properties of the GO-Car adjuvant in model mice. Results show that OVA@GO-Car can promote robust and durable OVA-specific antibody response, increase lymphocyte proliferation efficiency, and enhance CD4(+) T and CD8(+) T cell activation. The presence of Car in GO also probably contributes to enhancing the antigen-specific adaptive immune response through modulating the expression of some cytokines, including IL-6, CXCL1, CCL2, and CSF3. In addition, the safety of GO-Car as an adjuvant was evaluated comprehensively. No symptoms such as allergic response, inflammatory redness swelling, raised surface temperatures, physiological anomalies of blood, and remarkable weight changes were observed. Besides, after modification with carnosine, histological damages caused by GO-Car in lung, muscle, kidney, and spleen became weaken significantly. This study sufficiently suggest that GO-Car as a safe adjuvant can effectively enhance humoral and innate immune responses against antigens in vivo. PMID:26766427

  13. Carnosine Reduces Oxidative Stress and Reverses Attenuation of Righting and Postural Reflexes in Rats with Thioacetamide-Induced Liver Failure

    OpenAIRE

    Milewski, Krzysztof; Hilgier, Wojciech; Fręśko, Inez; Polowy, Rafał; Podsiadłowska, Anna; Zołocińska, Ewa; Grymanowska, Aneta W.; Robert K Filipkowski; Albrecht, Jan; Zielińska, Magdalena

    2016-01-01

    Cerebral oxidative stress (OS) contributes to the pathogenesis of hepatic encephalopathy (HE). Existing evidence suggests that systemic administration of l-histidine (His) attenuates OS in brain of HE animal models, but the underlying mechanism is complex and not sufficiently understood. Here we tested the hypothesis that dipeptide carnosine (β-alanyl-l-histidine, Car) may be neuroprotective in thioacetamide (TAA)-induced liver failure in rats and that, being His metabolite, may mediate the w...

  14. Intravitreal injection of forskolin, homotaurine, and L-carnosine affords neuroprotection to retinal ganglion cells following retinal ischemic injury

    OpenAIRE

    Russo, Rossella; Adornetto, Annagrazia; Cavaliere, Federica; Varano, Giuseppe Pasquale; Rusciano, Dario; Morrone, Luigi Antonio; Corasaniti, Maria Tiziana; Bagetta, Giacinto; Nucci, Carlo

    2015-01-01

    Purpose Retinal ganglion cell (RGC) death is the final event leading to visual impairment in glaucoma; therefore, identification of neuroprotective strategies able to slow down or prevent the process is one of the main challenges for glaucoma research. The purpose of this study was to evaluate the neuroprotective potential of RGC death induced by the in vivo transient increase in intraocular pressure (IOP) of a combined treatment with forskolin, homotaurine, and L-carnosine. Forskolin (7beta-...

  15. Carnosine as a protective factor in diabetic nephropathy: association with a leucine repeat of the carnosinase gene CNDP1.

    Science.gov (United States)

    Janssen, Bart; Hohenadel, Daniela; Brinkkoetter, Paul; Peters, Verena; Rind, Nina; Fischer, Christine; Rychlik, Ivan; Cerna, Marie; Romzova, Marianna; de Heer, Emile; Baelde, Hans; Bakker, Stephan J L; Zirie, Mahmoud; Rondeau, Eric; Mathieson, Peter; Saleem, Moin A; Meyer, Jochen; Köppel, Hannes; Sauerhoefer, Sibylle; Bartram, Claus R; Nawroth, Peter; Hammes, Hans-Peter; Yard, Benito A; Zschocke, Johannes; van der Woude, Fokko J

    2005-08-01

    The risk of diabetic nephropathy is partially genetically determined. Diabetic nephropathy is linked to a gene locus on chromosome 18q22.3-q23. We aimed to identify the causative gene on chromosome 18 and to study the mechanism by which the product of this gene could be involved in the development of diabetic nephropathy. DNA polymorphisms were determined in 135 case (diabetic nephropathy) and 107 control (diabetes without nephropathy) subjects. The effect of carnosine on the production of extracellular matrix components and transforming growth factor-beta (TGF-beta) after exposure to 5 and 25 mmol/l d-glucose was studied in cultured human podocytes and mesangial cells, respectively. A trinucleotide repeat in exon 2 of the CNDP1 gene, coding for a leucine repeat in the leader peptide of the carnosinase-1 precursor, was associated with nephropathy. The shortest allelic form (CNDP1 Mannheim) was more common in the absence of nephropathy (P = 0.0028, odds ratio 2.56 [95% CI 1.36-4.84]) and was associated with lower serum carnosinase levels. Carnosine inhibited the increased production of fibronectin and collagen type VI in podocytes and the increased production of TGF-beta in mesangial cells induced by 25 mmol/l glucose. Diabetic patients with the CNDP1 Mannheim variant are less susceptible for nephropathy. Carnosine protects against the adverse effects of high glucose levels on renal cells. PMID:16046297

  16. L-carnosine enhanced reproductive potential of the Saccharomyces cerevisiae yeast growing on medium containing glucose as a source of carbon.

    Science.gov (United States)

    Kwolek-Mirek, Magdalena; Molon, Mateusz; Kaszycki, Pawel; Zadrag-Tecza, Renata

    2016-08-01

    Carnosine is an endogenous dipeptide composed of β-alanine and L-histidine, which occurs in vertebrates, including humans. It has a number of favorable properties including buffering, chelating, antioxidant, anti-glycation and anti-aging activities. In our study we used the Saccharomyces cerevisiae yeast as a model organism to examine the impact of L-carnosine on the cell lifespan. We demonstrated that L-carnosine slowed down the growth and decreased the metabolic activity of cells as well as prolonged their generation time. On the other hand, it allowed for enhancement of the yeast reproductive potential and extended its reproductive lifespan. These changes may be a result of the reduced mitochondrial membrane potential and decreased ATP content in the yeast cells. However, due to reduction of the post-reproductive lifespan, L-carnosine did not have an influence on the total lifespan of yeast. In conclusion, L-carnosine does not extend the total lifespan of S. cerevisiae but rather it increases the yeast's reproductive capacity by increasing the number of daughter cells produced. PMID:27040824

  17. The anti-proliferative effect of L-carnosine correlates with a decreased expression of hypoxia inducible factor 1 alpha in human colon cancer cells.

    Directory of Open Access Journals (Sweden)

    Barbara Iovine

    Full Text Available In recent years considerable attention has been given to the use of natural substances as anticancer drugs. The natural antioxidant dipeptide L-carnosine belongs to this class of molecules because it has been proved to have a significant anticancer activity both in vitro and in vivo. Previous studies have shown that L-carnosine inhibits the proliferation of human colorectal carcinoma cells by affecting the ATP and Reactive Oxygen Species (ROS production. In the present study we identified the Hypoxia-Inducible Factor 1α (HIF-1α as a possible target of L-carnosine in HCT-116 cell line. HIF-1α protein is over-expressed in multiple types of human cancer and is the major cause of resistance to drugs and radiation in solid tumours. Of particular interest are experimental data supporting the concept that generation of ROS provides a redox signal for HIF-1α induction, and it is known that some antioxidants are able to suppress tumorigenesis by inhibiting HIF-1α. In the current study we found that L-carnosine reduces the HIF-1α protein level affecting its stability and decreases the HIF-1 transcriptional activity. In addition, we demonstrated that L-carnosine is involved in ubiquitin-proteasome system promoting HIF-1α degradation. Finally, we compared the antioxidant activity of L-carnosine with that of two synthetic anti-oxidant bis-diaminotriazoles (namely 1 and 2, respectively. Despite these three compounds have the same ability in reducing intracellular ROS, 1 and 2 are more potent scavengers and have no effect on HIF-1α expression and cancer cell proliferation. These findings suggest that an analysis of L-carnosine antioxidant pathway will clarify the mechanism underlying the anti-proliferative effects of this dipeptide on colon cancer cells. However, although the molecular mechanism by which L-carnosine down regulates or inhibits the HIF-1α activity has not been yet elucidated, this ability may be promising in treating hypoxia

  18. The anti-proliferative effect of L-carnosine correlates with a decreased expression of hypoxia inducible factor 1 alpha in human colon cancer cells.

    Science.gov (United States)

    Iovine, Barbara; Oliviero, Giorgia; Garofalo, Mariangela; Orefice, Maria; Nocella, Francesca; Borbone, Nicola; Piccialli, Vincenzo; Centore, Roberto; Mazzone, Massimiliano; Piccialli, Gennaro; Bevilacqua, Maria Assunta

    2014-01-01

    In recent years considerable attention has been given to the use of natural substances as anticancer drugs. The natural antioxidant dipeptide L-carnosine belongs to this class of molecules because it has been proved to have a significant anticancer activity both in vitro and in vivo. Previous studies have shown that L-carnosine inhibits the proliferation of human colorectal carcinoma cells by affecting the ATP and Reactive Oxygen Species (ROS) production. In the present study we identified the Hypoxia-Inducible Factor 1α (HIF-1α) as a possible target of L-carnosine in HCT-116 cell line. HIF-1α protein is over-expressed in multiple types of human cancer and is the major cause of resistance to drugs and radiation in solid tumours. Of particular interest are experimental data supporting the concept that generation of ROS provides a redox signal for HIF-1α induction, and it is known that some antioxidants are able to suppress tumorigenesis by inhibiting HIF-1α. In the current study we found that L-carnosine reduces the HIF-1α protein level affecting its stability and decreases the HIF-1 transcriptional activity. In addition, we demonstrated that L-carnosine is involved in ubiquitin-proteasome system promoting HIF-1α degradation. Finally, we compared the antioxidant activity of L-carnosine with that of two synthetic anti-oxidant bis-diaminotriazoles (namely 1 and 2, respectively). Despite these three compounds have the same ability in reducing intracellular ROS, 1 and 2 are more potent scavengers and have no effect on HIF-1α expression and cancer cell proliferation. These findings suggest that an analysis of L-carnosine antioxidant pathway will clarify the mechanism underlying the anti-proliferative effects of this dipeptide on colon cancer cells. However, although the molecular mechanism by which L-carnosine down regulates or inhibits the HIF-1α activity has not been yet elucidated, this ability may be promising in treating hypoxia-related diseases. PMID

  19. Protective effects of L-carnosine on CCl4 -induced hepatic injury in rats.

    Science.gov (United States)

    Alsheblak, Mehyar Mohammad; Elsherbiny, Nehal M; El-Karef, Amro; El-Shishtawy, Mamdouh M

    2016-03-01

    The present study was undertaken to investigate the possible protective effect of L-carnosine (CAR), an endogenous dipeptide of alanine and histidine, on carbon tetrachloride (CCl4)-induced hepatic injury. Liver injury was induced in male Sprague-Dawley rats by intraperitoneal (i.p.) injections of CCl4, twice weekly for six weeks. CAR was administered to rats daily, at dose of 250 mg/kg, i.p. At the end of six weeks, blood and liver tissue specimens were collected. Results show that CAR treatment attenuated the hepatic morphological changes, necroinflammation and fibrosis induced by CCl4, as indicated by hepatic histopathology scoring. In addition, CAR treatment significantly reduced the CCl4-induced elevation of liver-injury parameters in serum. CAR treatment also combatted oxidative stress; possibly by restoring hepatic nuclear factor erythroid 2-related factor 2 (Nrf-2) levels. Moreover, CAR treatment prevented the activation of hepatic stellate cells (HSCs), as indicated by reduced α-smooth muscle actin (α-SMA) expression in the liver, and decreased hepatic inflammation as demonstrated by a reduction in hepatic tumor necrosis factor-α (TNF-α) and restoration of interleukin-10 (IL-10) levels. In conclusion, CCl4-induced hepatic injury was alleviated by CAR treatment. The results suggest that these beneficial, protective effects are due, at least in part, to its anti-oxidant, anti-inflammatory and anti-fibrotic activities. PMID:27094155

  20. Effect of Carnosine in Experimental Arthritis and on Primary Culture Chondrocytes.

    Science.gov (United States)

    Ponist, S; Drafi, F; Kuncirova, V; Mihalova, D; Rackova, L; Danisovic, L; Ondrejickova, O; Tumova, I; Trunova, O; Fedorova, T; Bauerova, K

    2016-01-01

    Carnosine's (CARN) anti-inflammatory potential in autoimmune diseases has been but scarcely investigated as yet. The aim of this study was to evaluate the therapeutic potential of CARN in rat adjuvant arthritis, in the model of carrageenan induced hind paw edema (CARA), and also in primary culture of chondrocytes under H2O2 injury. The experiments were done on healthy animals, arthritic animals, and arthritic animals with oral administration of CARN in a daily dose of 150 mg/kg b.w. during 28 days as well as animals with CARA treated by a single administration of CARN in the same dose. CARN beneficially affected hind paw volume and changes in body weight on day 14 and reduced hind paw swelling in CARA. Markers of oxidative stress in plasma and brain (malondialdehyde, 4-hydroxynonenal, protein carbonyls, and lag time of lipid peroxidation) and also activity of gamma-glutamyltransferase were significantly corrected by CARN. CARN also reduced IL-1alpha in plasma. Suppression of intracellular oxidant levels was also observed in chondrocytes pretreated with CARN. Our results obtained on two animal models showed that CARN has systemic anti-inflammatory activity and protected rat brain and chondrocytes from oxidative stress. This finding suggests that CARN might be beneficial for treatment of arthritic diseases. PMID:26885252

  1. Circulating carnosine dipeptidase 1 associates with weight loss and poor prognosis in gastrointestinal cancer.

    Directory of Open Access Journals (Sweden)

    Peter Arner

    Full Text Available Cancer cachexia (CC is linked to poor prognosis. Although the mechanisms promoting this condition are not known, several circulating proteins have been proposed to contribute. We analyzed the plasma proteome in cancer subjects in order to identify factors associated with cachexia.Plasma was obtained from a screening cohort of 59 patients, newly diagnosed with suspected gastrointestinal cancer, with (n = 32 or without (n = 27 cachexia. Samples were subjected to proteomic profiling using 760 antibodies (targeting 698 individual proteins from the Human Protein Atlas project. The main findings were validated in a cohort of 93 patients with verified and advanced pancreas cancer.Only six proteins displayed differential plasma levels in the screening cohort. Among these, Carnosine Dipeptidase 1 (CNDP1 was confirmed by sandwich immunoassay to be lower in CC (p = 0.008. In both cohorts, low CNDP1 levels were associated with markers of poor prognosis including weight loss, malnutrition, lipid breakdown, low circulating albumin/IGF1 levels and poor quality of life. Eleven of the subjects in the discovery cohort were finally diagnosed with non-malignant disease but omitting these subjects from the analyses did not have any major influence on the results.In gastrointestinal cancer, reduced plasma levels of CNDP1 associate with signs of catabolism and poor outcome. These results, together with recently published data demonstrating lower circulating CNDP1 in subjects with glioblastoma and metastatic prostate cancer, suggest that CNDP1 may constitute a marker of aggressive cancer and CC.

  2. Effects of Beta-Alanine Supplementation on Brain Homocarnosine/Carnosine Signal and Cognitive Function: An Exploratory Study

    OpenAIRE

    Marina Yazigi Solis; Simon Cooper; Hobson, Ruth M; Artioli, Guilherme G.; Otaduy, Maria C.; Hamilton Roschel; Jacques Robertson; Daniel Martin; Vitor S Painelli; Harris, Roger C; Bruno Gualano; Craig Sale

    2015-01-01

    Objectives Two independent studies were conducted to examine the effects of 28 d of beta-alanine supplementation at 6.4 g d-1 on brain homocarnosine/carnosine signal in omnivores and vegetarians (Study 1) and on cognitive function before and after exercise in trained cyclists (Study 2). Methods In Study 1, seven healthy vegetarians (3 women and 4 men) and seven age- and sex-matched omnivores undertook a brain 1H-MRS exam at baseline and after beta-alanine supplementation. In study 2, nineteen...

  3. Effect of Four Weeks of β-alanine Supplementation on Muscle Carnosine and Blood Serum Lactate during Exercise in Male Rats.

    Science.gov (United States)

    Naderi, Alireza; Hemat Far, Ahmad; Willems, Mark E T; Sadeghi, Mehdi

    2016-01-01

    β-alanine (BA) supplementation may increase muscle buffering capacity and affect physiological responses during exercise. We examined the effects of 4 weeks of BA supplementation on muscle carnosine and serum lactate in male rats. Rats (n = 24, age: 2 months, body weight: 265±22 g) were divided into a BA supplementation or control group. Along with aerobic acclimatization exercise (15 m·min(-1), 8-10 min·day(-1), 4 days·week(-1) for 4 weeks), the BA group had access to BA powder in their drinking water (1.8%) with the control group having access to plain water for 4 weeks. After 4 weeks, rats ran on a treadmill at speeds of 15, 20, 25, 30, and 35 m·min(-1), respectively, each for 4 min, in order to measure post-exercise serum lactate. Muscle carnosine and serum lactate levels were measured with high-performance liquid chromatography (HPLC) and enzyme-linked immunosorbant assay (ELISA) procedures, respectively. Following BA supplementation, carnosine content in the m.rectus femoris increased by 117% (p carnosine content and reduces serum lactate; these changes may indicate an adaptation of rat skeletal muscles to postpone peripheral muscle fatigue during high-intensity exercise. PMID:26745664

  4. l-carnosine dipeptide overcomes acquired resistance to 5-fluorouracil in HT29 human colon cancer cells via downregulation of HIF1-alpha and induction of apoptosis.

    Science.gov (United States)

    Iovine, Barbara; Guardia, Francesca; Irace, Carlo; Bevilacqua, Maria Assunta

    2016-08-01

    Hypoxia-inducible factor (HIF-1α) protein is over-expressed in many human cancers and is a major cause of resistance to drugs. HIF-1α up-regulation decreases the effectiveness of several anticancer agents, including 5-fluorouracil (5-FU), because it induces the expression of drug efflux transporters, alters DNA repair mechanisms and modifies the balance between pro- and antiapoptotic factors. These findings suggest that inhibition of HIF-1α activity may sensitize cancer cells to cytotoxic drugs. We previously reported that l-carnosine reduces HIF-1α expression by inhibiting the proliferation of colon cancer cells. In the present study we investigated the effect of l-carnosine on HT29 colon cancer cells with acquired resistance to 5-FU. We found that l-carnosine reduces colon cancer cell viability, decreases HIF-1α and multi-drug resistant protein MDR1-pg expression, and induces apoptosis. Moreover, the l-carnosine/5-FU combination lowers the expression of some chemoresistance markers. The combination index evaluated in vitro on the HT29-5FU cell line by median drug effect analysis reveals a significant synergistic effect. PMID:27234614

  5. Effects of dietary supplementation of carnosine on mitochondrial dysfunction, amyloid pathology, and cognitive deficits in 3xTg-AD mice.

    Directory of Open Access Journals (Sweden)

    Carlo Corona

    Full Text Available BACKGROUND: The pathogenic road map leading to Alzheimer's disease (AD is still not completely understood; however, a large body of studies in the last few years supports the idea that beside the classic hallmarks of the disease, namely the accumulation of amyloid-β (Aβ and neurofibrillary tangles, other factors significantly contribute to the initiation and the progression of the disease. Among them, mitochondria failure, an unbalanced neuronal redox state, and the dyshomeostasis of endogenous metals like copper, iron, and zinc have all been reported to play an important role in exacerbating AD pathology. Given these factors, the endogenous peptide carnosine may be potentially beneficial in the treatment of AD because of its free-radical scavenger and metal chelating properties. METHODOLOGY: In this study, we explored the effect of L-carnosine supplementation in the 3xTg-AD mouse, an animal model of AD that shows both Aβ- and tau-dependent pathology. PRINCIPAL FINDINGS: We found that carnosine supplementation in 3xTg-AD mice promotes a strong reduction in the hippocampal intraneuronal accumulation of Aβ and completely rescues AD and aging-related mitochondrial dysfunctions. No effects were found on tau pathology and we only observed a trend toward the amelioration of cognitive deficits. CONCLUSIONS AND SIGNIFICANCE: Our data indicate that carnosine can be part of a combined therapeutic approach for the treatment of AD.

  6. Carnosine and taurine treatments diminished brain oxidative stress and apoptosis in D-galactose aging model.

    Science.gov (United States)

    Aydın, A Fatih; Çoban, Jale; Doğan-Ekici, Işın; Betül-Kalaz, Esra; Doğru-Abbasoğlu, Semra; Uysal, Müjdat

    2016-04-01

    D-galactose (GAL) has been used as an animal model for brain aging and antiaging studies. GAL stimulates oxidative stress in several tissues including brain. Carnosine (CAR; β-alanil-L-histidine) and taurine (TAU; 2-aminoethanesulfonic acid) exhibit antioxidant properties. CAR and TAU have anti-aging and neuroprotective effects. We investigated the effect of CAR and TAU supplementations on oxidative stress and brain damage in GAL-treated rats. Rats received GAL (300 mg/kg; s.c.; 5 days per week) alone or together with CAR (250 mg/kg/daily; i.p.; 5 days per week) or TAU (2.5% w/w; in rat chow) for 2 months. Brain malondialdehyde (MDA), protein carbonyl (PC) and glutathione (GSH) levels and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), glutathione transferase (GST) and acetylcholinesterase (AChE) activities were determined. Expressions of B cell lymphoma-2 (Bcl-2), Bax and caspase-3 were also evaluated in the brains by immunohistochemistry. GAL treatment increased brain MDA and PC levels and AChE activities. It decreased significantly brain GSH levels, SOD and GSH-Px but not GST activities. GAL treatment caused histopathological changes and increased apoptosis. CAR and TAU significantly reduced brain AChE activities, MDA and PC levels and elevated GSH levels in GAL-treated rats. CAR, but not TAU, significantly increased low activities of SOD and GSH-Px. Both CAR and TAU diminished apoptosis and ameliorated histopathological findings in the brain of GAL-treated rats. Our results indicate that CAR and TAU may be effective to prevent the development of oxidative stress, apoptosis and histopathological deterioration in the brain of GAL-treated rats. PMID:26518192

  7. Oral treatment of pressure ulcers with polaprezinc (zinc L-carnosine complex): 8-week open-label trial.

    Science.gov (United States)

    Sakae, Kensaku; Yanagisawa, Hiroyuki

    2014-06-01

    Polaprezinc (zinc L-carnosine complex) is a tablet commonly prescribed for gastric ulcers in Japan. Recently, we reported the effects of polaprezinc on pressure ulcer healing at 4-week follow-up. We aimed to further evaluate the efficacy and safety of polaprezinc in 8-week treatment for chronic pressure ulcers. Patients with stage II-IV pressure ulcers for ≥ 8 weeks received 150 mg/day polaprezinc (containing 116 mg L-carnosine and 34 mg zinc) per os for a maximum of 8 weeks. We measured the severity of pressure ulcers weekly using the Pressure Ulcer Scale for Healing (PUSH) score and monitored blood biochemistry. Fourteen patients (nine men; 68.4 ± 11.8 years) were enrolled. Pressure ulcer stages were II (one patient; 7 %), III (nine; 64 %), and IV (four; 29 %). The PUSH score improved significantly from 8.1 [95 % CI, 6.0-10.3] at baseline to -1.4 [-4.0 to 1.1] after 8 weeks (P zinc levels increased significantly (P zinc ratios (P < 0.001) decreased significantly. In one patient, preexisting copper deficiency deteriorated. These preliminary data suggest that polaprezinc may be effective and well-tolerated in 8-week treatment of pressure ulcers and could be a candidate for their oral treatment. PMID:24691900

  8. Effects of Beta-Alanine on Muscle Carnosine and Exercise Performance: A Review of the Current Literature

    Directory of Open Access Journals (Sweden)

    Matthew Cooke

    2010-01-01

    Full Text Available Muscle carnosine has been reported to serve as a physiological buffer, possess antioxidant properties, influence enzyme regulation, and affect sarcoplasmic reticulum calcium regulation.Beta-alanine (β-ALA is a non-essential amino acid. β-ALA supplementation (e.g., 2–6 grams/day has been shown to increase carnosine concentrations in skeletal muscle by 20–80%.Several studies have reported that β-ALA supplementation can increase high-intensity intermittent exercise performance and/or training adaptations. Although the specific mechanism remains to be determined, the ergogenicity of β-ALA has been most commonly attributed to an increased muscle buffering capacity.More recently, researchers have investigated the effects of co-ingesting β-ALA with creatine monohydrate to determine whether there may be synergistic and/or additive benefits. This paper overviews the theoretical rationale and potential ergogenic value of β-ALA supplementation with or without creatine as well as provides future research recommendations.

  9. Evidence for rapid inter- and intramolecular chlorine transfer reactions of histamine and carnosine chloramines: implications for the prevention of hypochlorous-acid-mediated damage.

    Science.gov (United States)

    Pattison, David I; Davies, Michael J

    2006-07-01

    Hypochlorous acid (HOCl) is a powerful oxidant generated from H(2)O(2) and Cl(-) by the heme enzyme myeloperoxidase, which is released from activated leukocytes. HOCl possesses potent antibacterial properties, but excessive production can lead to host tissue damage that is implicated in a wide range of human diseases (e.g., atherosclerosis). Histamine and carnosine have been proposed as protective agents against such damage. However, as recent studies have shown that histidine-containing compounds readily form imidazole chloramines that can rapidly chlorinate other targets, it was hypothesized that similar reactions may occur with histamine and carnosine, leading to propagation, rather than prevention, of HOCl-mediated damage. In this study, the reactions of HOCl with histamine, histidine, carnosine, and other compounds containing imidazole and free amine sites were examined. In all cases, rapid formation (k, 1.6 x 10(5) M(-)(1) s(-)(1)) of imidazole chloramines was observed, followed by chlorine transfer to yield more stable, primary chloramines (R-NHCl). The rates of most of these secondary reactions are dependent upon substrate concentrations, consistent with intermolecular mechanisms (k, 10(3)-10(4) M(-)(1) s(-)(1)). However, for carnosine, the imidazole chloramine transfer rates are independent of the concentration, indicative of intramolecular processes (k, 0.6 s(-)(1)). High-performance liquid chromatography studies show that in all cases the resultant R-NHCl species can slowly chlorinate N-alpha-acetyl-Tyr. Thus, the current data indicate that the chloramines formed on the imidazole and free amine groups of these compounds can oxidize other target molecules but with limited efficiency, suggesting that histamine and particularly carnosine may be able to limit HOCl-mediated oxidation in vivo. PMID:16800640

  10. Improved spectral resolution and high reliability of in vivo 1H MRS at 7 T allow the characterization of the effect of acute exercise on carnosine in skeletal muscle

    OpenAIRE

    Just Kukurová, I; Valkovič, L; J. Ukropec; de Courten, B.; Chmelík, M.; Ukropcová, B; Trattnig, S.; Krššák, M.

    2015-01-01

    The aims of this study were to observe the behavior of carnosine peaks in human soleus (SOL) and gastrocnemius (GM) muscles following acute exercise, to determine the relaxation times and to assess the repeatability of carnosine quantification by 1H MRS at 7 T. Relaxation constants in GM and SOL were measured by a stimulated echo acquisition mode (STEAM) localization sequence. For T 1 measurement, an inversion recovery sequence was used. The repeatability of the measurement and the absolute q...

  11. Improved spectral resolution and high reliability of in vivo $^1$H MRS at 7 T allow the characterization of the effect of acute exercise on carnosine in skeletal muscle

    OpenAIRE

    Just Kukurová, I; Valkovič, L; J. Ukropec; de Courten, B.; Chmelík, M.; Ukropcová, B; Trattnig, S.; Krššák, M.

    2016-01-01

    The aims of this study were to observe the behavior of carnosine peaks in human soleus (SOL) and gastrocnemius (GM) muscles following acute exercise, to determine the relaxation times and to assess the repeatability of carnosine quantification by 1H MRS at 7 T. Relaxation constants in GM and SOL were measured by a stimulated echo acquisition mode (STEAM) localization sequence. For T1 measurement, an inversion recovery sequence was used. The repeatability of the measurement and the absolute qu...

  12. Improved spectral resolution and high reliability of in vivo (1) H MRS at 7 T allow the characterization of the effect of acute exercise on carnosine in skeletal muscle.

    Science.gov (United States)

    Just Kukurová, Ivica; Valkovič, Ladislav; Ukropec, Jozef; de Courten, Barbora; Chmelík, Marek; Ukropcová, Barbara; Trattnig, Siegfried; Krššák, Martin

    2016-01-01

    The aims of this study were to observe the behavior of carnosine peaks in human soleus (SOL) and gastrocnemius (GM) muscles following acute exercise, to determine the relaxation times and to assess the repeatability of carnosine quantification by (1) H MRS at 7 T. Relaxation constants in GM and SOL were measured by a stimulated echo acquisition mode (STEAM) localization sequence. For T1 measurement, an inversion recovery sequence was used. The repeatability of the measurement and the absolute quantification of carnosine were determined in both muscles in five healthy volunteers. For absolute quantification, an internal water reference signal was used. The effect of acute exercise on carnosine levels and resonance lines was tested in eight recreational runners/cyclists. The defined carnosine measurement protocol was applied three times - before and twice after (approximately 20 and 40 min) a 1-h submaximal street run and additional toe-hopping. The measured T1 relaxation times for the C2-H carnosine peak at 7 T were 2002 ± 94 and 1997 ± 259 ms for GM and SOL, respectively, and the T2 times were 95.8 ± 9.4 and 81.0 ± 21.8 ms for GM and SOL, respectively. The coefficient of variation of the carnosine quantification measurement was 9.1% for GM and 6.3% for SOL, showing high repeatability, and the intraclass correlation coefficients (ICCs) of 0.93 for GM and 0.98 for SOL indicate the high reliability of the measurement. Acute exercise did not change the concentration of carnosine in the muscle, but affected the shape of the resonance lines, in terms of the shifting and splitting into doublets. Carnosine measurement by (1) H MRS at 7 T in skeletal muscle exhibits high repeatability and reliability. The observed effects of acute exercise were more prominent in GM, probably as a result of the larger portion of glycolytic fibers in this muscle and the more pronounced exercise-induced change in pH. Our results support the application of the MRS-based assessment of

  13. Carbonic anhydrase activators: gold nanoparticles coated with derivatized histamine, histidine, and carnosine show enhanced activatory effects on several mammalian isoforms.

    Science.gov (United States)

    Saada, Mohamed-Chiheb; Montero, Jean-Louis; Vullo, Daniela; Scozzafava, Andrea; Winum, Jean-Yves; Supuran, Claudiu T

    2011-03-10

    Lipoic acid moieties were attached to amine or amino acids showing activating properties against the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1). The obtained lipoic acid conjugates of histamine, L-histidine methyl ester, and L-carnosine methyl ester were attached to gold nanoparticles (NPs) by reaction with Au(III) salts in reducing conditions. The CA activators (CAAs)-coated NPs showed low nanomolar activation (K(A)s of 1-9 nM) of relevant cytosolic, membrane-bound, mitochondrial, and transmembrane CA isoforms, such as CA I, II, IV, VA, VII, and XIV. These NPs also effectively activated CAs ex vivo, in whole blood experiments, with an increase of 200-280% of the CA activity. This is the first example of enzyme activation with nanoparticles and may lead to biomedical applications for conditions in which the CA activity is diminished, such as aging, Alzheimer's disease, or CA deficiency syndrome. PMID:21291238

  14. Analysis of plasma from prostate cancer patients links decreased carnosine dipeptidase 1 levels to lymph node metastasis

    Directory of Open Access Journals (Sweden)

    Ulrika Qundos

    2014-03-01

    Full Text Available There is a need for a better differentiation of aggressive tumors in prostate cancer to design a tailored treatment for each patient, preferably by a minimally invasive analysis of blood samples. In a previous study, we discovered a decrease of plasma levels of carnosine dipeptidase 1 (CNDP1 in association with aggressive prostate cancer. Now this relation has been investigated and characterized further by generating several new antibodies for extended analysis of CNDP1 in plasma. Multi-antibody sandwich assays were developed and applied to 1214 samples from two Swedish cohorts that confirmed decreased levels of CNDP1 in plasma from patients with advanced disease. Therein, data from CNDP1 assays allowed a better differentiation between tumor N stages than clinical tPSA, but did not when classifying T or M stages. Further investigations can now elucidate mechanisms behind decreasing levels of CNDP1 in plasma and primary in regards to lymph node metastasis.

  15. Peptide-lanthanide cation equilibria in aqueous phase. I. Bound shifts for L-carnosine-praseodymium complexes

    Science.gov (United States)

    Mossoyan, J.; Asso, M.; Benlian, D.

    L-Carnosine complexes of Pr 3+ were characterized in aqueous solution by 1H NMR and potentiometric titration. A rigorous treatment of chemical shifts and pH variation data with lanthanide concentration is presented. Two different forms of the peptide ligand, forming simultaneously two complexes, were taken into account. At low pH values the cation is only coordinated at the carboxylate site of the ligand in a weak complex ( β2 = 6) whereas in neutral solution a stronger complex ( β1 = 37) is present as a consequence of the deprotonation of the imidazole ring. The computation of induced bound shifts † 2 and Δ1 for resonating nuclei of the peptide in both forms yields consistent figures. These provide the experimental basis for a conformational model which is usually not obtainable for labile complexes with low stability constants.

  16. Inhibitory effect of the carnosine-gallic acid synthetic peptide on MMP-2 and MMP-9 in human fibrosarcoma HT1080 cells.

    Science.gov (United States)

    Kim, Sung-Rae; Eom, Tae-Kil; Byun, Hee-Guk

    2014-09-01

    Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that degrade extracellular matrix components and play important roles in a variety of biological and pathological processes such as malignant tumor metastasis and invasion. In this study, we constructed carnosine-gallic acid peptide (CGP) to identify a better MMP inhibitor than carnosine. The inhibitory effects of CGP on MMP-2 and MMP-9 were investigated in the human fibrosarcoma (HT1080) cell line. As a result, CGP significantly decreased MMP-2 and MMP-9 expression levels without a cytotoxic effect. Moreover, CGP may inhibit migration and invasion in HT1080 cells through the urokinase plasminogen activator (uPA)-uPA receptor signaling pathways to inhibit MMP-2 and MMP-9. Based on these results, it appears that CGP may play an important role in preventing and treating several MMP-2 and MMP-9-mediated health problems such as metastasis. PMID:24956509

  17. Reactivity, Selectivity, and Reaction Mechanisms of Aminoguanidine, Hydralazine, Pyridoxamine, and Carnosine as Sequestering Agents of Reactive Carbonyl Species: A Comparative Study.

    Science.gov (United States)

    Colzani, Mara; De Maddis, Danilo; Casali, Gaia; Carini, Marina; Vistoli, Giulio; Aldini, Giancarlo

    2016-08-19

    Reactive carbonyl species (RCS) are endogenous or exogenous byproducts involved in the pathogenic mechanisms of different oxidative-based disorders. Detoxification of RCS by carbonyl quenchers is a promising therapeutic strategy. Among the most studied quenchers are aminoguanidine, hydralazine, pyridoxamine, and carnosine; their quenching activity towards four RCS (4-hydroxy-trans-2-nonenal, methylglyoxal, glyoxal, and malondialdehyde) was herein analyzed and compared. Their ability to prevent protein carbonylation was evaluated in vitro by using an innovative method based on high-resolution mass spectrometry (HRMS). The reactivity of the compounds was RCS dependent: carnosine efficiently quenched 4-hydroxy-trans-2-nonenal, pyridoxamine was particularly active towards malondialdehyde, aminoguanidine was active towards methylglyoxal and glyoxal, and hydralazine efficiently quenched all RCS. Reaction products were generated in vitro and were characterized by HRMS. Molecular modeling studies revealed that the reactivity was controlled by specific stereoelectronic parameters that could be used for the rational design of improved carbonyl quenchers. PMID:26891408

  18. Analysis of products of animal origin in feeds by determination of carnosine and related dipeptides by high-performance liquid chromatography.

    Science.gov (United States)

    Schönherr, Jens

    2002-03-27

    Products of animal origin such as meat meal were commonly used as sources of protein and amino acids for the production of compound feeds. Because the feeding of such products is prohibited in Germany, the official feedstuff control of the government must evaluate feeds for the forbidden use of products of animal origin. Microscope examination is the official method to prove animal-originated adulterations of feeds. This paper proposes a high-performance liquid chromatography method for the determination of the dipeptide carnosine and related dipeptides (anserine and balenine) and shows the dependence of the contents of anserine, balenine, and carnosine in compound feeds on the content of meat meal in feeds. The presented method can complete and confirm the result of the microscopic method for evidence of components of animal origin in feeds. PMID:11902938

  19. Natural antioxidant L-carnosine inhibits LPO intensification in structures of the auditory analyzer under conditions of chronic exposure to aminoglycoside antibiotics.

    Science.gov (United States)

    Zhuravskii, S G; Aleksandrova, L A; Sirot, V S; Ivanov, S A

    2004-10-01

    Intragastric administration of L-carnosine suspension to Wistar-Kyoto rats 3 days before and after 7-day course of intraperitoneal injections of ototoxic aminoglycoside antibiotic kanamycin compensated expenditures of tissue antioxidant systems and significantly eliminated kanamycin-induced intensification of MDA production in tissues of the membrane part of the cochlea and in the auditory cortex of the temporal lobe. L-NAME (competitive NO synthase inhibitor) also inhibited LPO, increased total antioxidant activity, and decreased ototoxicity of kanamycin, which confirms the contribution of NO into LPO intensification under conditions of aminoglycoside treatment. Inhibition of pathological intensification of LPO processes and increase in total antioxidant activity under conditions of induced acute aminoglycoside ototoxicity characterizes L-carnosine as a highly effective otoprotector. PMID:15665945

  20. Prevention of radiation esophagitis by polaprezinc (zinc L-carnosine) in patients with non-small cell lung cancer who received chemoradiotherapy

    OpenAIRE

    Yanase, Komei; Funaguchi, Norihiko; Iihara, Hirotoshi; Yamada, Maya; Kaito, Daizo; Endo, Junki; Ito, Fumitaka; Ohno, Yasushi; Tanaka, Hidekazu; Itoh, Yoshinori; Minatoguchi, Shinya

    2015-01-01

    Background: Concurrent chemoradiotherapy (CCRT) plays an important role in multimodality therapy for non-small cell lung cancer. However, esophagitis often develops as a complication of CCRT, causing treatment delays and reducing the patient’s quality of life. We examined the efficacy of polaprezinc (PZ), zinc L-carnosine used for the therapy of gastric ulcer, against the onset of esophagitis caused by CCRT for lung cancer. Patients and Methods: Patients who concurrently underwent chemotherap...

  1. The neurotoxic effect of clindamycin - induced gut bacterial imbalance and orally administered propionic acid on DNA damage assessed by the comet assay: protective potency of carnosine and carnitine

    OpenAIRE

    El-Ansary, Afaf; Shaker, Ghada H; El-Gezeery, Amina R; Al-Ayadhi, Laila

    2013-01-01

    Background Comet assay is a quick method for assessing DNA damage in individual cells. It allows the detection of single and double DNA strand breaks, which represent the direct effect of some damaging agents. This study uses standard comet quantification models to compare the neurotoxic effect of orally administered propionic acid (PA) to that produced as a metabolite of bacterial overgrowth induced by clindamycin. Additionally, the protective effect of carnosine and carnitine as natural die...

  2. EFFECT OF Β-ALANINE AND L-HISTIDINE ON CONCENTRATION OF CARNOSINE IN MUSCLE TISSUE AND OXIDATIVE STABILITY OF CHICKEN MEAT

    Directory of Open Access Journals (Sweden)

    Gordana Kralik

    2015-09-01

    Full Text Available This paper presents the results of two separate experiments, each involving 75 chickens of Cobb 500 provenience, divided into three experimental groups. During the last three weeks of fattening, chickens were fed finisher diets supplemented with amino acids β-alanine (0%, 0.5% and 1% and L-histidine (0%, 0.3% and 0.5% in different portions. After chickens have been slaughtered, 10 samples of breast tissue were taken from each group for carnosine content determination in muscle tissue and lipid oxidation expressed as TBARS. Analysis of THE results referring to carnosine concentration in breast muscle proved that supplementation of 0.5% L-histidine affected the carnosine concentration increase in breast muscles from 941.58 µg/g of tissue (H1 to 1186.06 µg/g of tissue (H3, while supplementation of 1% β-alanine influenced the increase in carnosine concentration from 756.15 µg/g of tissue (A1 to 911.01 µg/g of tissue (A3. Supplementation of amino acids did not have effects on TBARS values, but oxidation values decreased along with the supplementation of higher amounts of amino acids to diets, which was particularly expressed in samples stored for 60 days at -20°C. The experimental group H3 (0.5% L-histidine exhibited 30.54% lower value of lipid oxidation than the control one H1 (0% L-histidine, while the group with 1% β-alanine (A3 had lipid oxidation value by 17.65% lower than the control group A1 (0% β-alanine.

  3. Modulation of PARP-1 and PARP-2 expression by L-carnosine and trehalose after LPS and INFγ-induced oxidative stress.

    Science.gov (United States)

    Spina-Purrello, Vittoria; Giliberto, Salvatrice; Barresi, Vincenza; Nicoletti, Vincenzo G; Giuffrida Stella, Anna Maria; Rizzarelli, Enrico

    2010-12-01

    Poly(ADP-ribose) polymerases (PARPs) play a crucial role in DNA damage surveillance through their nick sensor functions. Since PARPs' over activation leads to an excessive consumption of NAD(+) and ATP depletion, these enzymes also are involved in the early events of programmed cell death as well as in necrosis. In order to verify the protective action of L: -carnosine and trehalose against NO induced cell death, in the present study we examined their effects on the expression of PARP-1, PARP-2 and iNOS in primary rat astrocyte and oligodendrocyte cells, treated with lipopolysaccharide (LPS) and interferon gamma (INFγ), through semi-quantitative PCR and western analysis. To further characterize the molecular mechanisms underlying L-carnosine and trehalose action, we measured cell viability, nitrite production and LDH release. The data obtained clearly demonstrate that in the stress model employed L-carnosine and trehalose down regulate PARP-1 and PARP-2 expression in both cell phenotypes, thus suggesting their possible application in clinical trials. PMID:21053069

  4. Preparation of 99mTc-Carnosine and 99mTcO-(V-DMSA Complexes,Biological Distribution, and Estimation of Their Gene Anti- PolymorphismsInduced by -Irradiation

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    E.A. EL-Ghany, F. Marzouk, Samy A. Abd El-Azim1, M.H. Awwad2

    2007-12-01

    Full Text Available Background: Two chelating agents (Carnosine and DMSA were used to study their labeling conditions with technetium-99m followed by biological distribution investigation. Molecular studies were done via PCR/RFLP analysis of angiotensin II subtype II receptor gene for monitoring their antioxidant activity through free iron chelation leading to inhibition of Fenton reaction. Material and methods: Carnosine was labeled by mixing 4 mg with 30 mg glucose and 25 g SnCl2.2H2O, followed by pertechnetate and stand at room temperature for 60 minutes. Minor modification was done to prepare 99mTc(V-DMSA tracer in one step, by adding pertechnetate solution to the lyophilized kit contains 1mg DMSA, 0.1 mg SnCl2.2H2O, and 30 mg glucose at pH 9. The biodistribution of the two tracers in normal and tumor-induced mice. The molecular investigation of the anti-oxidant activity of both carnosine and DMSA in 6 Gy -irradiated rats using the anti-inflammatory angiotensin II subtype II receptor gene (AT2RG as indicator. Results: Carnosine and DMSA were labeled with Technetium-99m yielding 85% and 97%, respectively the ability of both tracers to localize in tumor sites but the priority to the 99mTc (V-DMSA. Molecular studies showed strong antioxidant activity of carnosine but not enough to block radiation induced oxidative stress and Moderate antioxidant activity of DMSA was achieved by chelating free iron and iron released through oxidative stress. Maximum protection was achieved through the dual action of both DMSA and carnosine. Conclusion: moderate and high labeling yield were achieved for both 99mTc(VDMSA and 99mTc-canosine respectively with higher selectivity of the former to tumor sites and maximum protection were achieved by the dual action of both chelating agents

  5. L-carnosine modulates respiratory burst and reactive oxygen species production in neutrophil biochemistry and function: may oral dosage form of non-hydrolized dipeptide L-carnosine complement anti-infective anti-influenza flu treatment, prevention and self-care as an alternative to the conventional vaccination?

    Science.gov (United States)

    Babizhayev, Mark A; Deyev, Anatoliy I; Yegorov, Yegor E

    2014-05-01

    Influenza A is a viral disease of global dimension, presenting with high morbidity and mortality in annual epidemics, and in pandemics which are of infrequent occurrence but which have very high attack rates. Influenza vaccines of the future must be directed toward use of conserved group-specific viral antigens, such as are present in transitional proteins which are exposed during the fusion of virus to the host cell. Influenza probes revealed a continuing battle for survival between host and parasite in which the host population updates the specificity of its pool of humoral immunity by contact with and response to infection with the most recent viruses which possess altered antigenic specificity in their hemagglutinin (HA) ligand. It is well known that the HA protein is found on the surface of the influenza virus particle and is responsible for binding to receptors on host cells and initiating infection. Polymorphonuclear neutrophils (PMN) have been reported to be involved in the initial host response to influenza A virus (IAV). Early after IAV infection, neutrophils infiltrate the airway probably due to release of chemokines that attract PMN. Clearly, severe IAV infection is characterized by increased neutrophil influx into the lung or upper respiratory tract. Carnosine (β-alanyl-L-histidine) and anserine (N-β-alanyl-1-methyl-L-histidine) are found in skeletal muscle of most vertebrates, including those used for food; for example, 100 g of chicken breast contains 400 mg (17.6 mmol/L) of carnosine and 1020 mg (33.6 mmol/l) of anserine. Carnosine-stimulated respiratory burst in neutrophils is a universal biological mechanism of influenza virus destruction. Our own studies revealed previously unappreciated functional effects of carnosine and related histidine containing compounds as a natural biological prevention and barrier against Influenza virus infection, expand public understanding of the antiviral properties of imidazole-containing dipeptide based

  6. Zinc-L-carnosine binds to molecular chaperone HSP70 and inhibits the chaperone activity of the protein.

    Science.gov (United States)

    Haga, Asami; Okamoto, Tomoya; Yamada, Shintaroh; Kubota, Toshihiko; Sanpei, Ann; Takahashi, Shota; Nakayama, Masahiro; Nagai, Miki; Otaka, Michiro; Miyazaki, Toshio; Nunomura, Wataru; Grave, Ewa; Itoh, Hideaki

    2013-09-01

    In this study, we have investigated the specific binding proteins of Zinc-L-carnosine (Polaprezinc) using Polaprezinc-affinity column chromatography in vitro. A protein having a 70-kDa molecular mass was eluted by the linear gradient of 0-1.0 mM Polaprezinc from the affinity column and the protein was identified as the molecular chaperone HSP70 by immunoblotting. The chaperone activity of HSP70 was completely suppressed by Polaprezinc. The ATPase activity of HSP70 was affected to some extent by the reagent. In the circular dichroism (CD) spectrum, the secondary structure of HSP70 was changed in the presence of Polaprezinc, i.e. it decreased in the α-helix. We have determined the Polaprezinc-binding domain of HSP70 by using recombinant HSP70N- and C-domains. Although Polaprezinc could bind to both the N-terminal and the C-terminal of HSP70, the HSP70N-domain has a high affinity to the drug. Regarding the peptide cleavage of the HSP70N- and C-domains with proteinase K, the intact HSP70N still remained in the presence of Polaprezinc. On the other hand, the quantity of the intact C-domain slightly decreased under the same conditions along with the newly digested small peptides appeared. It has been suggested that Polaprezinc binds to HSP70 especially in the N-domains, suppresses the chaperone activity and delays an ATPase activities of HSP70. PMID:23687308

  7. Aging, proteotoxicity, mitochondria, glycation, NAD+ and carnosine: possible inter-relationships and resolution of the oxygen paradox

    Directory of Open Access Journals (Sweden)

    Alan R Hipkiss

    2010-03-01

    Full Text Available It is suggested that NAD+ availability strongly affects cellular aging and organism lifespan: low NAD+ availability increases intracellular levels of glycolytic triose phosphates (glyceraldehyde-3-phosphate and dihydroxyacetone-phosphate which, if not further metabolized, decompose spontaneously into methylglyoxal (MG, a glycating agent and source of protein and mitochondrial dysfunction and reactive oxygen species (ROS. MG-damaged proteins and other aberrant polypeptides can induce ROS generation, promote mitochondrial dysfunction and inhibit proteasomal activity. Upregulation of mitogenesis and mitochondrial activity by increased aerobic exercise, or dietary manipulation, helps to maintain NAD+ availability and thereby decreases MG-induced proteotoxicity. These proposals can explain the apparent paradox whereby aging is seemingly caused by increased ROS-mediated macromolecular damage but is ameliorated by increased aerobic activity. It is also suggested that increasing mitochondrial activity decreases ROS generation, while excess numbers of inactive mitochondria are deleterious due to increased ROS generation. The muscle- and brain-associated dipeptide, carnosine, is an intracellular buffer which can delay senescence in cultured human fibroblasts and delay aging in senescence-accelerated mice. Carnosine’s ability to react with MG and possibly other deleterious carbonyl compounds, and scavenge various ROS, may account for its protective ability towards ischemia and ageing.

  8. The membrane-stabilizing action of zinc carnosine (Z-103) in stress-induced gastric ulceration in rats

    Energy Technology Data Exchange (ETDEWEB)

    Cho, C.H.; Luk, C.T.; Ogle, C.W. (Univ. of Hong Kong (Hong Kong))

    1991-01-01

    Zinc compounds have been shown to antagonize various types of gastric ulceration in rats. Zinc carnosine (Z-103), a newly developed agent was, therefore, examined for its antiulcer effect in stress-induced ulceration and also its membrane stabilizing action in rat stomachs. Cold-restraint stress induced severe hemorrhagic lesions together with increased mast cell degranulation and {beta}-glucuronidase release in the gastric glandular mucosa. A-103 pretreatment with a single oral dose reversed these actions in a dose-dependent manner. When the compound was incubated in concentrations of 10{sup {minus}7}, 10{sup {minus}6}, 10{sup {minus}5} or 10{sup {minus}4} M, with isolated hepatic lysosomes, it significantly reduced the spontaneous release of {beta}-glucuronidase in the medium. The present study not only demonstrates the antiulcer effect of Z-103 but also indicates that the protective action is likely to be mediated by its membrane-stabilizing action on mast cells and lysosomes in the gastric glandular mucosa.

  9. Chemical relevance of the copper(II)— L-carnosine system in aqueous solution: A thermodynamic and spectrophotometric study

    Science.gov (United States)

    Daniele, Pier G.; Prenesti, Enrico; Zelano, Vincenzo; Ostacoli, Giorgio

    1993-08-01

    The copper(II)— L-carnosine (L -) system has been re-investigated in aqueous solution, at I = 0.1 mol dm -1, different temperatures (5⩽ t⩽45°C) and with metal to ligand ratios ranging from 3:1 to 1:3. Both potentiometry and visible spectrophotometry were employed. From an overall consideration of all experiments, [CuLH] 2+, [CuL] +, [CuLH -1]°, [Cu 2L 2H -2]° and [Cu 2LH -1] 2+ were recognized as the species which provide the best interpretation of experimental data. The complex formation constants, determined at different temperatures, allowed us to obtain reliable values of Δ H° and good estimates of Δ C° p. From visible spectrophotometric measurements, carried out at different pH and metal to ligand ratios, it was possible to calculate the electronic spectrum of each complex formed in solution. A structure is also proposed for each species, on the basis of thermodynamic and spectral results.

  10. Protective effects of carnosine alone and together with alpha-tocopherol on lipopolysaccharide (LPS) plus ethanol-induced liver injury.

    Science.gov (United States)

    Kalaz, Esra Betül; Aydın, A Fatih; Doğan-Ekici, Işın; Çoban, Jale; Doğru-Abbasoğlu, Semra; Uysal, Müjdat

    2016-03-01

    The aim of this study was to investigate the effect of carnosine (CAR) alone and together with vitamin E (Vit E) on alcoholic steatohepatitis (ASH) in rats. ASH was induced by ethanol (3 times; 5 g/kg; 12 h intervals, via gavage), followed by a single dose of lipopolysaccharide (LPS; 10 mg/kg; i.p.). CAR (250 mg/kg; i.p.) and Vit E (200 mg D-α-tocopherol/kg; via gavage) were administered 30 min before and 90 min after the LPS injection. CAR treatment lowered high serum transaminase activities together with hepatic histopathologic improvements in rats with ASH. Reactive oxygen species formation, malondialdehyde levels, myeloperoxidase activities and transforming growth factor β1 (TGF-β1) and collagen 1α1 (COL1A1) expressions were observed to decrease. These improvements were more remarkable in CAR plus Vit E-treated rats. Our results indicate that CAR may be effective in suppressing proinflammatory, prooxidant, and profibrotic factors in the liver of rats with ASH. PMID:26773358

  11. The Expression of Carnosine and Its Effect on the Antioxidant Capacity of Longissimus dorsi Muscle in Finishing Pigs Exposed to Constant Heat Stress

    OpenAIRE

    Yang, Peige; Hao, Yue; Feng, Jinghai; Lin, Hai; Feng, Yuejin; Wu, Xin; Xin YANG; Gu, Xianhong

    2014-01-01

    The objective of this study was to assess the effects of constant high ambient temperatures on meat quality, antioxidant capacity, and carnosine expression in longissimus dorsi muscle of finishing pigs. Castrated 24 male DLY (crossbreeds between Landrace×Yorkshire sows and Duroc boars) pigs were allocated to one of three treatments: constant ambient temperature at 22°C and ad libitum feeding (CON, n = 8); constant high ambient temperature at 30°C and ad libitum feeding (H30, n = 8); and const...

  12. Effects of Dietary L-carnosine and Alpha-lipoic Acid on Growth Performance, Blood Thyroid Hormones and Lipid Profiles in Finishing Pigs

    OpenAIRE

    Bao, Yinghui; Gao, Chunqi; Hao, Wenbo; Ji, Cheng; Zhao, Lihong; Zhang, Jianyun; Liu, Tao; Ma, Qiugang

    2015-01-01

    The present study was conducted to determine the effects of L-carnosine (LC) and/or alpha-lipoic acid (ALA) supplementation on growth performance, blood thyroid hormones and lipid profiles in finishing pigs. A total of 40 (Landrace×Yorkshire) pigs with an initial body weight of 57.93±3.14 kg were randomly allocated to 4 experimental diets using a 2×2 factorial arrangement with 2 LC supplemental levels (0 or 0.1%) and 2 ALA supplemental levels (0 or 0.03%) in basal diets. The results showed th...

  13. Modulation of inhibitory glycine receptors in cultured embryonic mouse hippocampal neurons by zinc, thiol containing redox agents and carnosine.

    Science.gov (United States)

    Thio, L L; Zhang, H X

    2006-01-01

    Modulation of inhibitory glycine receptors by zinc (Zn(2+)) and endogenous redox agents such as glutathione may alter inhibition in the mammalian brain. Despite the abundance of Zn(2+) in the hippocampus and its ability to modulate glycine receptors, few studies have examined Zn(2+) modulation of hippocampal glycine receptors. Whether redox agents modulate hippocampal glycine receptors also remains unknown. This study examined Zn(2+) and redox modulation of glycine receptor-mediated currents in cultured embryonic mouse hippocampal neurons using whole-cell recordings. Zn(2+) concentrations below 10 microM potentiated currents elicited by low glycine, beta-alanine, and taurine concentrations by 300-400%. Zn(2+) concentrations above 300 microM produced nearly complete inhibition. Potentiating Zn(2+) concentrations shifted the dose-response curves for the three agonists to the left and decreased the Hill coefficient for glycine and beta-alanine but not taurine. Inhibiting Zn(2+) concentrations shifted the dose-response curves for glycine and beta-alanine to the right but reduced the maximum taurine response. Histidine residues may participate in potentiation because diethyl pyrocarbonate and pH 5.4 diminished Zn(2+) enhancement of glycine currents. pH 5.4 diminished Zn(2+) block of glycine currents, but diethyl pyrocarbonate did not. These findings indicate that separate sites mediate Zn(2+) potentiation and inhibition. The redox agents glutathione, dithiothreitol, tris(2-carboxyethyl)phosphine, and 5,5'-dithiobis(2-nitrobenzoic acid) did not alter glycine currents by a redox mechanism. However, glutathione and dithiothreitol interfered with the effects of Zn(2+) on glycine currents by chelating it. Carnosine had similar effects. Thus, Zn(2+) and thiol containing redox agents that chelate Zn(2+) modulate hippocampal glycine receptors with the mechanism of Zn(2+) modulation being agonist dependent. PMID:16515845

  14. Expression and characterization of the biofilm-related and carnosine-hydrolyzing aminoacylhistidine dipeptidase from Vibrio alginolyticus.

    Science.gov (United States)

    Wang, Ting-Yi; Chen, Yi-Chin; Kao, Liang-Wei; Chang, Chin-Yuan; Wang, Yu-Kuo; Liu, Yen-Hsi; Feng, Jen-Min; Wu, Tung-Kung

    2008-10-01

    The biofilm-related and carnosine-hydrolyzing aminoacylhistidine dipeptidase (pepD) gene from Vibrio alginolyticus was cloned and sequenced. The recombinant PepD protein was produced and biochemically characterized and the putative active-site residues responsible for metal binding and catalysis were identified. The recombinant enzyme, which was identified as a homodimeric dipeptidase in solution, exhibited broad substrate specificity for Xaa-His and His-Xaa dipeptides, with the highest activity for the His-His dipeptide. Sequence and structural homologies suggest that the enzyme is a member of the metal-dependent metallopeptidase family. Indeed, the purified enzyme contains two zinc ions per monomer. Reconstitution of His.Tag-cleaved native apo-PepD with various metal ions indicated that enzymatic activity could be optimally restored when Zn2+ was replaced with other divalent metal ions, including Mn2+, Co2+, Ni2+, Cu2+ and Cd2+, and partially restored when Zn2+ was replaced with Mg2+. Structural homology modeling of PepD also revealed a 'catalytic domain' and a 'lid domain' similar to those of the Lactobacillus delbrueckii PepV protein. Mutational analysis of the putative active-site residues supported the involvement of His80, Asp119, Glu150, Asp173 and His461 in metal binding and Asp82 and Glu149 in catalysis. In addition, individual substitution of Glu149 and Glu150 with aspartic acid resulted in the partial retention of enzymatic activity, indicating a functional role for these residues on the catalysis and zinc ions, respectively. These effects may be necessary either for the activation of the catalytic water molecule or for the stabilization of the substrate-enzyme tetrahedral intermediate. Taken together, these results may facilitate the design of PepD inhibitors for application in antimicrobial treatment and antibody-directed enzyme prodrug therapy. PMID:18783432

  15. Carnosine Reduces Oxidative Stress and Reverses Attenuation of Righting and Postural Reflexes in Rats with Thioacetamide-Induced Liver Failure.

    Science.gov (United States)

    Milewski, Krzysztof; Hilgier, Wojciech; Fręśko, Inez; Polowy, Rafał; Podsiadłowska, Anna; Zołocińska, Ewa; Grymanowska, Aneta W; Filipkowski, Robert K; Albrecht, Jan; Zielińska, Magdalena

    2016-02-01

    Cerebral oxidative stress (OS) contributes to the pathogenesis of hepatic encephalopathy (HE). Existing evidence suggests that systemic administration of L-histidine (His) attenuates OS in brain of HE animal models, but the underlying mechanism is complex and not sufficiently understood. Here we tested the hypothesis that dipeptide carnosine (β-alanyl-L-histidine, Car) may be neuroprotective in thioacetamide (TAA)-induced liver failure in rats and that, being His metabolite, may mediate the well documented anti-OS activity of His. Amino acids [His or Car (100 mg/kg)] were administrated 2 h before TAA (i.p., 300 mg/kg 3× in 24 h intervals) injection into Sprague-Dawley rats. The animals were thus tested for: (i) brain prefrontal cortex and blood contents of Car and His, (ii) amount of reactive oxygen species (ROS), total antioxidant capacity (TAC), GSSG/GSH ratio and thioredoxin reductase (TRx) activity, and (iii) behavioral changes (several models were used, i.e. tests for reflexes, open field, grip test, Rotarod). Brain level of Car was reduced in TAA rats, and His administration significantly elevated Car levels in control and TAA rats. Car partly attenuated TAA-induced ROS production and reduced GSH/GSSG ratio, whereas the increase of TRx activity in TAA brain was not significantly modulated by Car. Further, Car improved TAA-affected behavioral functions in rats, as was shown by the tests of righting and postural reflexes. Collectively, the results support the hypothesis that (i) Car may be added to the list of neuroprotective compounds of therapeutic potential on HE and that (ii) Car mediates at least a portion of the OS-attenuating activity of His in the setting of TAA-induced liver failure. PMID:26801175

  16. Potential Antifibrotic and Angiostatic Impact of Idebenone, Carnosine and Vitamin E in Nano-Sized Titanium Dioxide-Induced Liver Injury

    Directory of Open Access Journals (Sweden)

    Samy A. Abdelazim

    2015-04-01

    Full Text Available Background/Aim: The present study investigated the in vitro and in vivo effects of individual and combined doses of idebenone, carnosine and vitamin E on ameliorating some of the biochemical indices of nano-sized titanium dioxide (n-TiO2 in mice liver. Methods: The in vitro cytotoxic effect of nano-sized anatase TiO2 (21 nm on hepatic cell lines (HepG 2 was investigated. Additionally, n-TiO2 was orally administered (150 mg/kg/day for 2 weeks, followed by a daily intragastric gavage of the aforementioned antioxidants for 1 month. Results: n-TiO2 induced significant cytotoxicity in hepatic cell lines and elevated the levels of serum alanine aminotransferase (ALT, aspartate aminotransferase (AST, hepatic total antioxidant capacity (TAC and nitrite/nitrate (NOx levels. Meanwhile, glutathione-S-transferase (GST activity was significantly reduced. Moreover, RT-PCR and western blot analysis showed that n-TiO2 significantly altered the mRNA and protein expressions of transforming growth factor-beta (TGF-β1 and Smad-2, as well as vascular endothelium growth factor (VEGF. Histopathological examination of hepatic tissue reinforced these results.Conclusion: Idebenone, carnosine and vitamin E ameliorated the deviated parameters with the combination regimen demonstrating the most pronounced effect. Oxidative stress, liver fibrosis and angiogenesis may be implicated in n-TiO2-induced liver toxicity.

  17. Study on Extraction Process of Carnosine by Double Enzyme Hydrolysis%双酶法提取肌肽的工艺研究

    Institute of Scientific and Technical Information of China (English)

    王海生; 伍曾利; 李介钟

    2012-01-01

    With beef as raw material,extracting carnosine by pepsin and trypsin double enzymatic was made.The results showed that the best process conditions of orthogonal experiment were pepsin 2.0%,and the digested time 7 h;trypsin 2.0%,and the digested time 4 h.%以牛肉为原料,采用胃蛋白酶、胰蛋白酶双酶法提取肌肽。结果表明,通过正交试验获得的最佳提取工艺为:胃蛋白酶用量为2.0%,其酶解时间为7 h;胰蛋白酶用量为2.0%,其酶解时间为4 h。

  18. The effect of production system and age on levels of iron, taurine, carnosine, coenzyme Q(10), and creatine in beef muscles and liver.

    Science.gov (United States)

    Purchas, R W; Busboom, J R

    2005-08-01

    Samples of longissimus (LL) and triceps brachii (TB) muscles from Angus-cross heifers finished either on a high-concentrate ration in Washington, USA, (US cattle, n=15) or on pasture in New Zealand (NZ cattle, n=16) were assessed for composition characteristics. Half of the NZ cattle were of a similar age to the US cattle (NZAge) and half were of a similar weight (NZWt). Iron concentration was higher in TB (20.9 vs. 17.5μgg(-1); Pcarnosine, creatine and creatinine, as expected for a muscle with a more aerobic metabolism. These differences were magnified for the even more aerobic cheek muscle. Differences between the two NZ groups were small, but muscles from the US cattle contained less taurine, carnosine, coenzyme Q(10), and creatinine. Reasons for these differences in various meat components for similar cattle from different production systems are not clear. PMID:22063884

  19. Evidence for an essential role of intradimer interaction in catalytic function of carnosine dipeptidase II using electrospray-ionization mass spectrometry.

    Science.gov (United States)

    Okumura, Nobuaki; Tamura, Jun; Takao, Toshifumi

    2016-02-01

    Carnosine dipeptidase II (CN2/CNDP2) is an M20 family metallopeptidase that hydrolyses various dipeptides including β-alanyl-L-histidine (carnosine). Crystallographic analysis showed that CN2 monomer is composed of one catalytic and one dimerization domains, and likely to form homodimer. In this crystal, H228 residue of the dimerization domain interacts with the substrate analogue bestatin on the active site of the dimer counterpart, indicating that H228 is involved in enzymatic reaction. In the present study, the role of intradimer interaction of CN2 in its catalytic activity was investigated using electrospray-ionization time-of-flight mass spectrometry (ESI-TOF MS). First, a dimer interface mutant I319K was prepared and shown to be present as a folded monomer in solution as examined by using ESI-TOF MS. Since the mutant was inactive, it was suggested that dimer formation is essential to its enzymatic activity. Next, we prepared H228A and D132A mutant proteins with different N-terminal extended sequences, which enabled us to monitor dimer exchange reaction by ESI-TOF MS. The D132A mutant is a metal ligand mutant and also inactive. But the activity was partially recovered time-dependently when H228A and D132A mutant proteins were incubated together. In parallel, H228A/D132A heterodimer was formed as detected by ESI-TOF MS, indicating that interaction of a catalytic center with H228 residue of the other subunit is essential to the enzymatic reaction. These results provide evidence showing that intradimer interaction of H228 with the reaction center of the dimer counterpart is essential to the enzymatic activity of CN2. PMID:26549037

  20. Separation of N-derivatized di- and tri-peptide stereoisomers by micro-liquid chromatography using a quinidine-based monolithic column - Analysis of l-carnosine in dietary supplements.

    Science.gov (United States)

    Wang, Qiqin; Sánchez-López, Elena; Han, Hai; Wu, Huihui; Zhu, Peijie; Crommen, Jacques; Marina, Maria Luisa; Jiang, Zhengjin

    2016-01-01

    In the present study, a new analytical methodology was developed enabling the enantiomeric determination of N-derivatized di- and tri-peptides in dietary supplements using chiral micro-LC on a monolithic column consisting of poly(O-9-[2-(methacryloyloxy)-ethylcarbamoyl]-10,11-dihydroquinidine-co-2-hydroxyethyl methacrylate-co-ethylene dimethacrylate) (poly(MQD-co-HEMA-co-EDMA)). After optimization of the mobile phase conditions, a baseline resolution of the stereoisomers of 24 out of 53 N-derivatized di- and tri-peptides was obtained. 3,5-Dinitrobenzoyl- and 3,5-dichlorobenzoyl-peptide stereoisomers were separated with exceptionally high selectivity and resolution. The monolithic column was then applied to the quantitative analysis of l-carnosine and its enantiomeric impurity in three different commercial dietary supplements. Method validation demonstrated satisfactory results in terms of linearity, precision, selectivity, accuracy and limits of detection and quantification. The determined amounts of l-carnosine in commercial formulations were in agreement with the labeled content for all analyzed samples, and the enantiomeric impurity was found to be below the limit of detection (LOD), showing the potential of the poly(MQD-co-HEMA-co-EDMA) monolithic column as a reliable tool for the quality control of l-carnosine in dietary supplements by micro-LC. PMID:26410182

  1. Protective substances against zinc-induced neuronal death after ischemia: carnosine as a target for drug of vascular type of dementia.

    Science.gov (United States)

    Kawahara, Masahiro; Konoha, Keiko; Nagata, Tetsuya; Sadakane, Yutaka

    2007-06-01

    Recent studies have indicated the significance of zinc in neurodegeneration after transient global ischemia. After ischemia, excess glutamate and zinc, which are released in the synaptic clefts, cause the apoptotic death of the target neurons, and finally lead the pathogenesis of vascular type of dementia. Considering the removal of zinc using zinc-sensitive chelators was effective in the prevention of neuronal death after transient global ischemia, it is highly possible that substances which protect against zinc-induced neuronal death will become a candidate for drugs of vascular type of dementia. Based on this 'zinc hypothesis', we have searched for such substances among various agricultural products including fruits, vegetables, and fishes using our developed in vitro screening system. Among tested, we found that carnosine (beta-alanyl histidine) protected against zinc-induced death of cultured neurons, and have applied for the patent as a drug of ischemia-induced neuronal death and the treatment/prevention for vascular type of dementia (application No. 2006-145857) in Japan. Here, we review the perspective of protective substances of zinc-induced neuronal death as a drug of vascular type of dementia based on our studies and other numerous studies. PMID:18221226

  2. Glycation of the muscle-specific enolase by reactive carbonyls: effect of temperature and the protection role of carnosine, pyridoxamine and phosphatidylserine.

    Science.gov (United States)

    Pietkiewicz, Jadwiga; Bronowicka-Szydełko, Agnieszka; Dzierzba, Katarzyna; Danielewicz, Regina; Gamian, Andrzej

    2011-03-01

    Reactive carbonyls such as 4-hydroxy-2-nonenal (4-HNE), trans-2-nonenal (T2 N), acrolein (ACR) can react readily with nucleophilic protein sites forming of advanced glycation end-products (AGE). In this study, the human and pig muscle-specific enolase was used as a protein model for in vitro modification by 4-HNE, T2 N and ACR. While the human enolase interaction with reactive α-oxoaldehyde methylglyoxal (MOG) was demonstrated previously, the effect of 4-HNE, T2N and ACR has not been identified yet. Altering in catalytic function were observed after the enzyme incubation with these active compounds for 1-24 h at 25, 37 and 45 °C. The inhibition degree of enolase activity occurred in following order: 4-HNE > ACR > MOG > T2N and inactivation of pig muscle-specific enolase was more effective relatively to human enzyme. The efficiency of AGE formation depends on time and incubation temperature with glycating agent. More amounts of insoluble AGE were formed at 45 °C. We found that pyridoxamine and natural dipeptide carnosine counteracted AGE formation and protected enolase against the total loss of catalytic activity. Moreover, we demonstrated for the first time that phosphatidylserine may significantly protect enolase against decrease of catalytic activity in spite of AGE production. PMID:21347838

  3. Skin beautification with oral non-hydrolized versions of carnosine and carcinine: Effective therapeutic management and cosmetic skincare solutions against oxidative glycation and free-radical production as a causal mechanism of diabetic complications and skin aging.

    Science.gov (United States)

    Babizhayev, Mark A; Deyev, Anatoliy I; Savel'yeva, Ekaterina L; Lankin, Vadim Z; Yegorov, Yegor E

    2012-10-01

    Advanced glycation Maillard reaction end products (AGEs) are causing the complications of diabetes and skin aging, primarily via adventitious and cross-linking of proteins. Long-lived proteins such as structural collagen are particularly implicated as pathogenic targets of AGE processes. The formation of α-dicarbonyl compounds represents an important step for cross-linking proteins in the glycation or Maillard reaction. The purpose of this study was to investigate the contribution of glycation coupled to the glycation free-radical oxidation reactions as markers of protein damage in the aging of skin tissue proteins and diabetes. To elucidate the mechanism for the cross-linking reaction, we studied the reaction between a three-carbon α-dicarbonyl compound, methylglyoxal, and amino acids using EPR spectroscopy, a spectrophotometric kinetic assay of superoxide anion production at the site of glycation and a chemiluminescence technique. The transglycating activity, inhibition of transition metal ions peroxidative catalysts, resistance to hydrolysis of carnosine mimetic peptide-based compounds with carnosinase and the protective effects of carnosine, carcinine and related compounds against the oxidative damage of proteins and lipid membranes were assessed in a number of biochemical and model systems. A 4-month randomized, double-blind, controlled study was undertaken including 42 subjects where the oral supplement of non-hydrolized carnosine (Can-C Plus® formulation) was tested against placebo for 3 months followed by a 1-month supplement-free period for both groups to assess lasting effects. Assessment of the age-related skin parameters and oral treatment efficacy measurements included objective skin surface evaluation with Visioscan® VC 98 and visual assessment of skin appearance parameters. The results together confirm that a direct one-electron transfer between a Schiff base methylglyoxal dialkylimine (or its protonated form) and methylglyoxal is responsible for

  4. Zinc-carnosine and vitamin E supplementation does not ameliorate gastrointestinal side effects associated with ciclosporin therapy of canine atopic dermatitis.

    Science.gov (United States)

    Wilson, Laura S; Rosenkrantz, Wayne S; Roycroft, Linda M

    2011-02-01

    Chelated zinc-carnosine and vitamin E [GastriCalm(®) (GCM); Teva Animal Health] is marketed as an anti-emetic supplement for dogs to assist the repair of damaged stomach and intestinal mucosa. The purpose of this prospective, double-blinded, placebo-controlled trial was to determine whether GCM reduced the frequency of vomiting, diarrhoea and appetite changes during initiation of ciclosporin (Atopica(®); Novartis Animal Health) therapy for the treatment of canine atopic dermatitis. Sixty privately owned dogs diagnosed with atopic dermatitis were randomly assigned to GCM (n=30) or placebo (n=30) groups. All dogs received ∼ 5 mg/kg ciclosporin (range, 3.5-5.8 mg/kg) once daily. Dogs <13.6 kg received half a tablet of GCM or placebo; dogs ≥ 13.6 kg received one tablet once daily. GastriCalm(®) or placebo was administered 30 min prior to eating, and the ciclosporin was administered 2 h after feeding. Owners recorded episodes of vomiting, diarrhoea and appetite changes. Dogs were examined on days 0 and 14. Forty-one of 60 dogs (68.3%) had at least one episode of vomiting, diarrhoea or appetite change, leaving nine placebo dogs (30%) and ten GCM dogs (33.3%) free of adverse events (AE). Twenty-seven of 60 dogs (45%) vomited, and 15 of 60 (25%) had diarrhoea. There was no significant difference in episodes of individual AEs, but the placebo group had a significantly lower total AE score (summation of episodes of appetite change, vomiting and diarrhoea; P=0.022). Small dogs (<6.82 kg) had significantly fewer total AEs in both treatment groups and tolerated ciclosporin better than larger dogs (P<0.05). PMID:20586994

  5. Evidence for a dipolar-coupled AM system in carnosine in human calf muscle from in vivo 1H NMR spectroscopy

    Science.gov (United States)

    Schröder, Leif; Bachert, Peter

    2003-10-01

    Spin systems with residual dipolar couplings such as creatine, taurine, and lactate in skeletal muscle tissue exhibit first-order spectra in in vivo 1H NMR spectroscopy at 1.5 T because the coupled protons are represented by (nearly) symmetrized eigenfunctions. The imidazole ring protons (H2, H4) of carnosine are suspected to form also a coupled system. The ring's stiffness could enable a connectivity between these anisochronous protons with the consequence of second-order spectra at low field strength. Our purpose was to study whether this deviation from the Paschen-Back condition can be used to detect the H2-H4 coupling in localized 1D 1H NMR spectra obtained at 1.5 T (64 MHz) from the human calf in a conventional whole-body scanner. As for the hydrogen hyperfine interaction, a Breit-Rabi equation was derived to describe the transition from Zeeman to Paschen-Back regime for two dipolar-coupled protons. The ratio of the measurable coupling strength ( Sk) and the difference in resonance frequencies of the coupled spins (Δ ω) induces quantum-state mixing of various degree upon definition of an appropriate eigenbase of the coupled spin system. The corresponding Clebsch-Gordan coefficients manifest in characteristic energy corrections in the Breit-Rabi formula. These additional terms were used to define an asymmetry parameter of the line positions as a function of Sk and Δ ω. The observed frequency shifts of the resonances were found to be consistent with this parameter within the accuracy achievable in in vivo NMR spectroscopy. Thus it was possible to identify the origin of satellite peaks of H2, H4 and to describe this so far not investigated type of residual dipolar coupling in vivo.

  6. Zinc Carnosine Inhibits Lipopolysaccharide-Induced Inflammatory Mediators by Suppressing NF-κb Activation in Raw 264.7 Macrophages, Independent of the MAPKs Signaling Pathway.

    Science.gov (United States)

    Ooi, Theng Choon; Chan, Kok Meng; Sharif, Razinah

    2016-08-01

    This study aimed to investigate the role of the mitogen-activated protein kinases (MAPKs) signaling pathway in the anti-inflammatory effects of zinc carnosine (ZnC) in lipopolysaccharide (LPS)-induced RAW 264.7 cells. Cells were pretreated with ZnC (0-100 μM) for 2 h prior to the addition of LPS (1 μg/ml). Following 24 h of treatment, ZnC was found not to be cytotoxic to RAW 264.7 cells up to the concentration of 100 μM. Our current findings showed that ZnC did not protect RAW 264.7 cells from LPS-induced "respiratory burst". Significant increment in intracellular glutathione (GSH) level and reduction in thiobarbituric acid reactive substances (TBARS) concentration can only be observed in cell pretreated with high doses of ZnC only (50 and 100 μM for GSH and 100 μM only for TBARS). On the other hand, pretreatment of cells with ZnC was able to inhibit LPS-induced inducible nitric oxide synthase and cyclooxygenase-2 expression significantly. Furthermore, results from immunoblotting showed that ZnC was able to suppress nuclear factor-kappaB (NF-κB) activation, and highest suppression can be observed at 100 μM of ZnC pretreatment. However, pretreatment of ZnC did not inhibit the early activation of MAPKs. In conclusion, pretreatment with ZnC was able to inhibit the expression of inflammatory mediators in LPS-induced RAW 264.7 cells, mainly via suppression of NF-κB activation, and is independent of the MAPKs signaling pathway. PMID:26749414

  7. Evaluation of radioprotective effect of carnosine (beta- alanyl-1- histidine on the wound healing in rats Avaliação do efeito radioprotetor da carnosina (beta-alanil-1- histidina no processo de cicatrização em ratos

    Directory of Open Access Journals (Sweden)

    Rosana Aramaki Tanaka

    2005-09-01

    Full Text Available The purpose of this study was to evaluate the radioprotective effect of carnosine (beta- alanyl-1-histidine on the wound healing in rats. Therefore, 48 male rats were submitted to a surgical procedure to perform a rectangular wound in the anterior-dorsal region. The animals were divided into 4 experimental groups randomly chosen: control; irradiated; carnosine irradiated and carnosine group. The irradiated and carnosine irradiated group were exposed to a dose (6Gy of gamma irradiation, in the whole body, 72 hours after surgery. The carnosine and carnosine irradiated groups, in addition to the surgical procedure and the irradiation, received two doses of carnosine aqueous solution, the first one being injected 48 hours after surgery, and the second one 1 hour and 30 minutes before irradiation. The tissue repair of the 4 groups was evaluated at 4, 7, 14, and 21 days after inflicting the wound, by morphological, histochemical and histophysical methods. At all examined periods, it could be observed that the animals from the carnosine irradiated group presented a better developed granulation tissue than the irradiated group and closely similar to that of the control group. Thus, under the experimental conditions used, it was possible to conclude that carnosine is an effective radioprotective substance.O objetivo deste estudo foi avaliar o efeito radioprotetor da carnosina (beta-alanil-1-histidina no processo de cicatrização em ratos. Para isto, 48 ratos machos foram submetidos a um procedimento cirúrgico para realização de uma ferida retangular na região dorsal anterior. Os animais foram divididos aleatoriamente em 4 grupos experimentais: controle, irradiado, carnosina irradiado e carnosina. Os grupos carnosina e carnosina irradiado foram exposto a uma dose de corpo todo de 6 Gy de radiação gama, 72 horas após a cirurgia para confecção da ferida. O grupo carnosina e carnosina irradiado, adicionalmente, ao procedimento cirúrgico e a

  8. The effect of zinc sulphate and zinc carnosine on genome stability and cytotoxicity in the WIL2-NS human lymphoblastoid cell line.

    Science.gov (United States)

    Sharif, Razinah; Thomas, Philip; Zalewski, Peter; Graham, Robin D; Fenech, Michael

    2011-02-28

    Zinc (Zn) is an essential cofactor required by numerous enzymes that are essential for cell metabolism and the maintenance of DNA integrity. We investigated the effect of Zn deficiency or excess on genomic instability events and determined the optimal concentration of two Zn compounds that minimize DNA-damage events. The effects of Zn sulphate (ZnSO(4)) and Zn carnosine (ZnC) on cell proliferation were investigated in the WIL2-NS human lymphoblastoid cell line. DNA damage was determined by the use of both the comet assay and the cytokinesis-block micronucleus cytome (CBMN-Cyt) assay. Zn-deficient medium (0μM) was produced using Chelex treatment, and the two Zn compounds (i.e. ZnSO(4) and ZnC) were tested at concentrations of 0.0, 0.4, 4.0, 16.0, 32.0 and 100.0μM. Results from an MTT assay showed that cell growth and viability were decreased in Zn-depleted cells (0μM) as well as at 32μM and 100μM for both Zn compounds (P<0.0001). DNA strand-breaks, as measured by the comet assay, were found to be increased in Zn-depleted cells compared with the other treatment groups (P<0.05). The CBMN-Cyt assay showed a significant increase in the frequency of both apoptotic and necrotic cells under Zn-deficient conditions (P<0.0001). Elevated frequencies of micronuclei (MNi), nucleoplasmic bridges (NPBs) and nuclear buds (NBuds) were induced in Zn-depleted cells (P<0.0001), whereas genome damage was reduced in supplemented cultures for both Zn compounds at 4μM and 16μM, possibly suggesting that these concentrations may be optimal for genome stability. The potential protective effect of ZnSO(4) and ZnC was also investigated following exposure to 1.0Gy γ-radiation. Culture in medium containing these compounds at 4-32μM prior to irradiation displayed significantly reduced frequencies of MNi, NPBs and NBuds compared with cells maintained in 0μM medium (P<0.0001). Expression of γ-H2AX and 8-oxoguanine glycosylase measured by western blotting was increased in Zn

  9. Bioactivation antioxidant and transglycating properties of N-acetylcarnosine autoinduction prodrug of a dipeptide L-carnosine in mucoadhesive drug delivery eye-drop formulation: powerful eye health application technique and therapeutic platform.

    Science.gov (United States)

    Babizhayev, Mark A

    2012-06-01

    A considerable interest in N-acetylcarnosine ocular drug design for eye health is based on clinical strategies to improve ocular drug delivery through metabolic enzymatic activation. Human biology aspects of ocular N-acetylcarnosine deacetylation during its pass through the cornea to the aqueous humor and dipeptide hydrolyzing enzymes are characterized. Novel approaches to ocular drug delivery increasing intraocular bioavailability of N-acetylcarnosine biologically activated metabolite carnosine become an integral development ensuring prolonged retention of the medication in the mucoadhesive precorneal area and facilitating transcorneal penetration of the natural dipeptide with the corneal promoters. A comprehensive list of techniques for peptide drug design, synthesis, purification, and biological analyses was considered: liquid chromatography (LC), high performance liquid chromatography (HPLC), (1) H and (13) C nuclear magnetic resonance (NMR), electrospray ionization (ESI) mass spectroscopy, and spectrophotometry. The antioxidant activity of therapeutics-targeted molecules was studied in aqueous solution and in a lipid membrane environment. A deglycation therapeutic system was developed involving removal, by transglycation of sugar or aldehyde moieties from Schiff bases by histidyl-hydrazide compounds or aldehyde scavenger L-carnosine. Clinical studies included ophthalmoscopy, visual acuity (VA), halometer disability glare tests, slit-image, and retro-illumination photography. N-acetylcarnosine 1% lubricant eye drops are considered as an auto-induction prodrug and natural ocular redox state balance therapies with implications in prevention and treatment of serious eye diseases that involve pathways of continuous oxidative damage to ocular tissues(cataracts, primary open-angle glaucoma, age-related macular degeneration) and sight-threatening glycosylation processes (diabetic retinopathy and consequent visual impairment) important for public health. The results of

  10. A Dietary Supplement Containing Cinnamon, Chromium and Carnosine Decreases Fasting Plasma Glucose and Increases Lean Mass in Overweight or Obese Pre-Diabetic Subjects: A Randomized, Placebo-Controlled Trial.

    Directory of Open Access Journals (Sweden)

    Yuejun Liu

    Full Text Available Preventing or slowing the progression of prediabetes to diabetes is a major therapeutic issue.Our aim was to evaluate the effects of 4-month treatment with a dietary supplement containing cinnamon, chromium and carnosine in moderately obese or overweight pre-diabetic subjects, the primary outcome being change in fasting plasma glucose (FPG level. Other parameters of plasma glucose homeostasis, lipid profile, adiposity and inflammatory markers were also assessed.In a randomized, double-blind, placebo-controlled study, 62 subjects with a FPG level ranging from 5.55 to 7 mmol/L and a body mass index ≥ 25 kg/m(2, unwilling to change their dietary and physical activity habits, were allocated to receive a 4-month treatment with either 1.2 g/day of the dietary supplement or placebo. Patients were followed up until 6 months post-randomization.Four-month treatment with the dietary supplement decreased FPG compared to placebo (-0.24 ± 0.50 vs +0.12 ± 0.59 mmol/L, respectively, p = 0.02, without detectable significant changes in HbA1c. Insulin sensitivity markers, plasma insulin, plasma lipids and inflammatory markers did not differ between the treatment groups. Although there were no significant differences in changes in body weight and energy or macronutrient intakes between the two groups, fat-free mass (% increased with the dietary supplement compared to placebo (p = 0.02. Subjects with a higher FPG level and a milder inflammatory state at baseline benefited most from the dietary supplement.Four-month treatment with a dietary supplement containing cinnamon, chromium and carnosine decreased FPG and increased fat-free mass in overweight or obese pre-diabetic subjects. These beneficial effects might open up new avenues in the prevention of diabetes.ClinicalTrials.gov NCT01530685.

  11. Preparation, Spectrochemical, and Computational Analysis of L-Carnosine (2-[(3-Aminopropanoylamino]-3-(1H-imidazol-5-ylpropanoic Acid and Its Ruthenium (II Coordination Complexes in Aqueous Solution

    Directory of Open Access Journals (Sweden)

    Myalo Sabela

    2011-12-01

    Full Text Available This study reports the synthesis and characterization of novel ruthenium (II complexes with the polydentate dipeptide, L-carnosine (2-[(3-aminopropanoylamino]-3-(1H-imidazol-5-ylpropanoic acid. Mixed-ligand complexes with the general composition [MLp(Clq(H2Or]·xH2O (M = Ru(II; L = L-carnosine; p = 3 − q; r = 0–1; and x = 1–3 were prepared by refluxing aqueous solutions of the ligand with equimolar amounts of ruthenium chloride (black-alpha form at 60 °C for 36 h. Physical properties of the complexes were characterized by elemental analysis, DSC/TGA, and cyclic voltammetry. The molecular structures of the complexes were elucidated using UV-Vis, ATR-IR, and heteronuclear NMR spectroscopy, then confirmed by density function theory (DFT calculations at the B3LYP/LANL2DZ level. Two-dimensional NMR experiments (1H COSY, 13C gHMBC, and 15N gHMBC were also conducted for the assignment of chemical shifts and calculation of relative coordination-induced shifts (RCIS by the complex formed. According to our results, the most probable coordination geometries of ruthenium in these compounds involve nitrogen (N1 from the imidazole ring and an oxygen atom from the carboxylic acid group of the ligand as donor atoms. Additional thermogravimetric and electrochemical data suggest that while the tetrahedral-monomer or octahedral-dimer are both possible structures of the formed complexes, the metal in either structure occurs in the (2+ oxidation state. Resulting RCIS values indicate that the amide-carbonyl, and the amino-terminus of the dipeptide are not involved in chelation and these observations correlate well with theoretical shift predictions by DFT.

  12. 肌肽与维生素 E对育肥猪肉品质和抗氧化性能的影响%Effects of Carnosine and Vitamin E on Meat Quality and Antioxidant Capacity of Growing-Finishing Pigs

    Institute of Scientific and Technical Information of China (English)

    田莹; 刘显军; 边连全; 陈静

    2014-01-01

    本试验旨在研究肌肽与维生素E单独及联合使用对育肥猪肉品质和抗氧化性能的影响。试验采用2因素2×3析因设计,设3个肌肽水平(0、50、100 mg/kg),2个维生素E水平(0、200 mg/kg),选择90头体重约为70 kg的“杜×长×大”三元杂交育肥猪,按体重相近、性别比例相同原则,随机分为6组,每组3个重复,每个重复5头猪。预试期为7 d,试验期为42 d。结果表明:1)饲粮中添加肌肽能显著提高屠宰后45 min肌肉的pH和降低贮存48 h肌肉的滴水损失( P<0.05),极显著提高屠宰24 h后肌肉的pH和降低贮存24 h肌肉的滴水损失( P<0.01);维生素E能极显著降低贮存24和48 h 肌肉的滴水损失(P<0.01),二者均能显著改善肉色(P<0.05)。肌肽与维生素 E 在改善肉色和降低贮存24 h 肌肉的滴水损失上存在互作效应( P<0.05),且联合添加优于单独添加。2)饲粮中添加肌肽可显著提高育肥猪血清总抗氧化能力(T-AOC)及总超氧化物歧化酶(T-SOD)和过氧化氢酶(CAT)活性(P<0.05),极显著提高谷胱甘肽过氧化物酶( GSH-Px)活性( P<0.01),维生素E可极显著提高育肥猪血清T-AOC及T-SOD和GSH-Px活性(P<0.01)。在提高血清的T-AOC和GSH-Px活性上,二者存在显著互作效应( P<0.05),且联合添加优于单独添加。3)肌肽可显著降低贮存24 h背最长肌的丙二醛( MDA)含量( P<0.05),极显著降低贮存48、72和96 h背最长肌的MDA含量( P<0.01);维生素E可极显著降低贮存24、48、72和96 h背最长肌的MDA含量(P<0.01),且肌肽与维生素E 对贮存48 h背最长肌的MDA含量存在显著互作效应(P<0.05)。综上,饲粮中添加100 mg/kg的肌肽、200 mg/kg的维生素E为最优组合。%A 2 × 3 ( carnosine × vitamin E ) mulitiple-factor experiment was conducted to investigate the effects of the dietary supplementation with the carnosine and vitamin E on meat quality and antioxidant capacity of growing-finishing pigs. In the test, 90

  13. Preparation and clinical evaluation of a novel lozenge containing polaprezinc, a zinc-L-carnosine, for prevention of oral mucositis in patients with hematological cancer who received high-dose chemotherapy.

    Science.gov (United States)

    Hayashi, Hiroko; Kobayashi, Ryo; Suzuki, Akio; Yamada, Yuto; Ishida, Masayuki; Shakui, Toshinobu; Kitagawa, Junichi; Hayashi, Hideki; Sugiyama, Tadashi; Takeuchi, Hirofumi; Tsurumi, Hisashi; Itoh, Yoshinori

    2016-08-01

    We previously reported that oral ingestion of polaprezinc, a zinc-L-carnosine, suspended in sodium alginate solution prevents oral mucositis in patients receiving radiotherapy or high-dose chemotherapy. In the present study, we developed a novel preparation of polaprezinc and evaluated clinical effect of the lozenge preparation in patients receiving high-dose chemotherapy for hematopoietic stem cell transplantation. The preparation contained 18.75 mg polaprezinc in a tablet and showed an excellent uniformity and stability up to 24 weeks after storage under room temperature. The incidence rate of grade ≥ 2 oral mucositis was 74 % in patients without premedication, whereas the rate was remarkably reduced in patients receiving the suspension (23 %) or lozenge (13 %) of polaprezinc (P < 0.01). The use of non-opioid analgesic drugs such as anti-inflammatory agents and local anesthetics for oral pain was also greatly reduced by polaprezinc suspension or its lozenge (16 % for suspension and 13 % for lozenge compared with 89 % with no premedication, P < 0.01). These findings suggest that polaprezinc lozenge is simple to apply and highly effective for prevention of oral mucositis associated with high-dose chemotherapy for hematopoietic stem cell transplantation. PMID:27418192

  14. Non-hydrolyzed in digestive tract and blood natural L-carnosine peptide ("bioactivated Jewish penicillin") as a panacea of tomorrow for various flu ailments: signaling activity attenuating nitric oxide (NO) production, cytostasis, and NO-dependent inhibition of influenza virus replication in macrophages in the human body infected with the virulent swine influenza A (H1N1) virus.

    Science.gov (United States)

    Babizhayev, Mark A; Deyev, Anatoliy I; Yegorov, Yegor E

    2013-01-01

    in excessive amounts mediate the overreaction of the host's immune response against the organs or tissues in which viruses are replicating, and this may explain the mechanism of tissue injuries observed in influenza virus infection of various types. In this article, the types of protection of carnosine in its bioavailable non-hydrolyzed forms in formulations are considered against reactive oxygen radical species-dependent injury, peroxynitrite damage, and other types of viral injuries in which impaired immune responses to viral pathogens are usually involved. Carnosine (β-alanyl-L-histidine) shows the pharmacological intracellular correction of NO release, which might be one of the important factors of natural immunity in controlling the initial stages of influenza A virus infection (inhibition of virus replication) and virus-induced regulation of cytokine gene expression. The protective effects of orally applied non-hydrolyzed formulated species of carnosine include at least the direct interaction with NO, inhibition of cytotoxic NO-induced proinflammatory condition, and attenuation of the effects of cytokines and chemokines that can exert profound effects on inflammatory cells. These data are consistent with the hypothesis that natural products, such as chicken soup and chicken breast extracts rich in carnosine and its derivative anserine (β-alanyl-1-methyl-L-histidine), could contribute to the pathogenesis and prevention of influenza virus infections and cold but have a limitation due to the susceptibility to enzymatic hydrolysis of dipeptides with serum carnosinase and urine excretion after oral ingestion of a commercial chicken extract. The formulations of non-hydrolyzed in digestive tract and blood natural carnosine peptide and isopeptide (γ-glutamyl-carnosine) products, manufactured at the cGMP-certified facility and patented by the authors, have promise in the control and prevention of influenza A (H1N1) virus infection, cough, and cold. PMID:23425625

  15. An urea, arginine and carnosine based cream (Ureadin Rx Db ISDIN shows greater efficacy in the treatment of severe xerosis of the feet in Type 2 diabetic patients in comparison with glycerol-based emollient cream. A randomized, assessor-blinded, controlled trial

    Directory of Open Access Journals (Sweden)

    Federici Adalberto

    2012-09-01

    Full Text Available Abstract Background Xerosis is a common skin disorder frequently observed in diabetic patients. An effective hydration of foot skin in diabetics is a relevant preventive strategy in order to maintain a healthy foot. Urea is considered an effective hydrating and emollient topical product. The aim of the present study was to evaluate the efficacy of topical urea 5% with arginine and carnosine (Ureadin Rx Db, ISDIN Spain (UC in comparison with glycerol-based emollient topical product (Dexeryl, Pierre Fabre (EC, in Type 2 diabetic patients. Methods We assessed the effect of UC on skin hydration in a randomized, evaluator-blinded comparative study in 40 type II diabetic patients, aged 40–75 years, treated with UC or the comparator for 28 days with a twice-daily application. The principal outcomes were the Dryness Area Severity Index (DASI Score and the Visual Analogue Score (VAS for skin dryness evaluated at baseline and at the end of study period by an investigator unaware of treatment allocation. Results UC induced significantly greater hydration than EC with an 89% reduction in DASI score (from 1.6 to 0.2; p  Conclusion Application of urea 5%, arginine and carnosine cream increases skin hydration and alleviates the condition of skin dryness in Type 2 diabetic patients in comparison with a control glycerol-based emollient product. (Dutch Trials Register trial number 3328.

  16. 肌肽对抗坏血酸-半胱氨酸模式反应形成香味化合物的影响%Effect of carnosine on aroma compounds generation from Maillard reaction of ascorbic acid and cysteine

    Institute of Scientific and Technical Information of China (English)

    刘应煊; 余爱农; 肖儒兰

    2012-01-01

    The identification of aroma compounds,formed from the model reactions of ascorbic acid and cysteine at pH 8.00 and(140±2)℃ for 2h,was performed using a solid-phase microextraction-gas chromatography-mass spectrometry(SPME-GC-MS) technique.The effect of carnosine on aroma compounds was investigated.Forty-seven aroma compounds were identified and showed that sulfur-containing compounds such as alicyclic S compounds,thiophenes and thienothiophenes were the most abundant compounds.Other compounds identified were furans,thiazoles and pyrazines.The addition of carnosine into the reaction mixture in general caused a reduction or disappearance in content of some sulfur-containing compounds.On the other hand,it facilitated the generation of several nitrogen-containing volatiles such as methylpyrazine,ethylpyrazine,2,6-dimethylpyrazine and other alkyl pyrazines.The results suggested that carnosine inhibited the thermal degradation of Cys to some extent.Furthermore,carnosine acted as a nitrogenous source to facilitate the formation of nitrogen-containing compounds,possibly by degradation to form ammonia.%以固相微萃取-气相色谱-质谱联用(SPME-GC-MS)技术对抗坏血酸与半胱氨酸(ASA-Cys)的模式反应产物进行鉴定,研究了肌肽对模式反应形成香味化合物的影响。呋喃、吡嗪、噻吩、噻唑、噻吩并噻吩及脂环硫化物在内的47个香味化合物被鉴定出来,其中,含硫化合物如脂环硫化物、噻吩、噻吩并噻吩是最主要的香味成分。肌肽加入到模式体系中,一方面使一些含硫化合物的产量显著降低,甚至消失;另一方面却促进了几个含氮化合物如甲基吡嗪,乙基吡嗪,2,6-二甲基吡嗪及其它烷基吡嗪的生成。这表明在模式反应中,肌肽抑制了Cys的热降解,同时暗示了肌肽作为氮源在热降解时很可能生成了NH3,NH3与H2S和ASA降解产物发生竞争反应形成含氮化合物如烷基吡嗪,从而导致含硫化合物的产量降低。

  17. Diabetic nephropathy : pathology, genetics and carnosine metabolism

    NARCIS (Netherlands)

    Mooyaart, Antien Leonora

    2011-01-01

    My thesis concerns different aspects of diabetic nephropathy. A pathologic classification of diabetic nephropathy is developed, a meta-analyis of genes in diabetic nephropathy is developed and the other chapters are about the CNDP1 gene in relation to kidney disease, mainly diabetic nephropathy.

  18. Biomarkers and special features of oxidative stress in the anterior segment of the eye linked to lens cataract and the trabecular meshwork injury in primary open-angle glaucoma: challenges of dual combination therapy with N-acetylcarnosine lubricant eye drops and oral formulation of nonhydrolyzed carnosine.

    Science.gov (United States)

    Babizhayev, Mark A

    2012-02-01

    analogs, beta-blockers, or local carbonic anhydrase inhibitors, these effects were markedly reduced. Oxidative stress can induce characteristic glaucomatous TM changes, and these oxidative stress-induced TM changes can be minimized by the use of antioxidants and IOP-lowering substances. It is tempting to speculate that the prevention of oxidative stress exposure to the TM may help to reduce the progression of POAG. The author's laboratory has developed and patented the dual combination therapy with N-acetylcarnosine lubricant eye drops and oral formulation of nonhydrolyzed carnosine in ripe cataracts and POAG. The specific regimen for the treatment in each stage of age-related ophthalmic disease has been taken up. In the treatment of POAG, this dual therapy can be combined with conventional antiglaucoma therapy with beta-blocking and/or adrenergic agonist medicines providing the significant IOP-lowering effect and significant increase in outflow facility. The developed therapy is a prominent management care of the glaucomatous neurodegeneration. PMID:21883446

  19. Effects of Zinc Carnosine on AKP,BGP and E2 in Cage Layers with Low-calcium Osteoporosis%肌肽锌对低钙性骨质疏松笼养蛋鸡 AKP、BGP 及 E2的影响

    Institute of Scientific and Technical Information of China (English)

    吕文亭; 王鹏; 刘春凌; 利凯; 杨永红

    2015-01-01

    选用250只24周龄健康海兰褐蛋鸡,随机分为5组,每组50只。对照组饲喂基础日粮(含钙3.55%),低钙组饲喂低钙日粮(含钙1.95%),试验Ⅰ、Ⅱ、Ⅲ组分别于低钙日粮中添加10、30、50 mg/kg 肌肽锌,试验期60 d,定期采集血样,观察肌肽锌对低钙性骨质疏松笼养蛋鸡碱性磷酸酶(AKP)、骨钙素(BGP)及雌二醇(E2)的影响。结果显示,AKP 和 BGP 随肌肽锌添加剂量的增加而降低,20 d 和40 d 时,试验Ⅰ组血清中 AKP 和 BGP 显著低于低钙组(P <0.05),试验Ⅱ、Ⅲ组血清中 AKP 和 BGP 均极显著低于低钙组(P <0.01),试验Ⅲ组血清中 AKP 和 BGP 均极显著低于试验Ⅰ组(P <0.01)、显著低于试验Ⅱ组(P <0.05);60 d 时,试验Ⅰ、Ⅱ、Ⅲ组血清中 AKP 和 BGP 均极显著低于低钙组(P <0.01),试验Ⅲ组血清中AKP 和 BGP 均极显著低于试验Ⅰ组(P <0.01),试验Ⅲ组血清中 BGP 显著低于试验Ⅱ组(P <0.05);各组E2随日龄的增长而降低,整个试验期,低钙组血清中 E2均显著低于对照组(P <0.05),其余各组无显著差异(P >0.05)。结果表明,在低钙日粮中添加50 mg/kg 肌肽锌能更好地改善低钙性骨质疏松笼养蛋鸡血清中骨代谢重要标志物和相关激素的水平,明显降低骨吸收,缓解笼养蛋鸡骨质疏松的程度。%The experiment was conducted to study the effects of zinc carnosine (ZnC)on AKP,BGP and E2 in cage layers with low-calcium osteoporosis.250 24-week-old hyline brown laying hens were randomly di-vided into 5 groups with 50 per group.The control group was fed with a basal diet (containing calcium 3. 55%),low calcium group was fed with a low-calcium diet (containing calcium 1.95%),and three test groups were given with the low-calcium diet added with 10,30,50 mg/kg ZnC,respectively.The experi-ment lasted for 60 days

  20. Carnosine prevents necrotic and apoptotic death of rat thymocytes via ouabain sensitive Na/K-ATPase

    OpenAIRE

    Smolyaninova, Larisa V.; Dergalev, Alexander A.; Kulebyakin, Konstantin Y.; Carpenter, David O.; Boldyrev, Alexander A.

    2012-01-01

    It is known that ouabain, a selective inhibitor of Na/K-ATPase, can cause not only activation of signal cascades, which regulate the cell viability, but also can cause free radical accumulation, which can evoke the oxidative stress. We have shown that nanomolar concentrations of ouabain result in the temporary increase in the level of intracellular free radicals but the millimolar concentration of ouabain induces a stable intracellular accumulation of free radicals in rat thymocytes. The incr...

  1. Phytosome-hyaluronic acid systems for ocular delivery of L-carnosine

    OpenAIRE

    Abdelkader H; Longman, MR; Alany RG; Pierscionek B

    2016-01-01

    Hamdy Abdelkader,1,2 Michael R Longman,1 Raid G Alany,1,3 Barbara Pierscionek4 1Drug Discovery, Delivery and Patient Care (DDDPC) Theme, School of Life Sciences, Pharmacy and Chemistry, Kingston University London, Kingston Upon Thames, London, UK; 2Department of Pharmaceutics, Faculty of Pharmacy, Minia University, Mina, Egypt; 3School of Pharmacy, The University of Auckland, Auckland, New Zealand; 4Vision Cognition and Neuroscience Theme, Faculty of Science, Engineering and Computing, Kings...

  2. Carnosine supplementation to an all-plant protein diet for rainbow trout (Oncorhynchus mykiss).

    Science.gov (United States)

    Fishmeal may contain “unknown growth factors” that have yet to be identified for their physiological role. As fishmeal levels in rainbow trout (Oncorhynchus mykiss) feeds are reduced, the dietary loss of these compounds may contribute to growth reductions. One such compound, identified in fishmeal...

  3. Effect of Carnosine in Experimental Arthritis and on Primary Culture Chondrocytes

    Directory of Open Access Journals (Sweden)

    S. Ponist

    2016-01-01

    Full Text Available Carnosine’s (CARN anti-inflammatory potential in autoimmune diseases has been but scarcely investigated as yet. The aim of this study was to evaluate the therapeutic potential of CARN in rat adjuvant arthritis, in the model of carrageenan induced hind paw edema (CARA, and also in primary culture of chondrocytes under H2O2 injury. The experiments were done on healthy animals, arthritic animals, and arthritic animals with oral administration of CARN in a daily dose of 150 mg/kg b.w. during 28 days as well as animals with CARA treated by a single administration of CARN in the same dose. CARN beneficially affected hind paw volume and changes in body weight on day 14 and reduced hind paw swelling in CARA. Markers of oxidative stress in plasma and brain (malondialdehyde, 4-hydroxynonenal, protein carbonyls, and lag time of lipid peroxidation and also activity of gamma-glutamyltransferase were significantly corrected by CARN. CARN also reduced IL-1alpha in plasma. Suppression of intracellular oxidant levels was also observed in chondrocytes pretreated with CARN. Our results obtained on two animal models showed that CARN has systemic anti-inflammatory activity and protected rat brain and chondrocytes from oxidative stress. This finding suggests that CARN might be beneficial for treatment of arthritic diseases.

  4. Simple enzymatic procedure for l‐carnosine synthesis: whole‐cell biocatalysis and efficient biocatalyst recycling

    OpenAIRE

    Heyland, Jan; Antweiler, Nicolai; Lutz, Jochen; Heck, Tobias; Geueke, Birgit; Kohler, Hans‐Peter E.; Blank, Lars M.; Schmid, Andreas

    2009-01-01

    Summary β‐Peptides and their derivates are usually stable to proteolysis and have an increased half‐life compared with α‐peptides. Recently, β‐aminopeptidases were described as a new enzyme class that enabled the enzymatic degradation and formation of β‐peptides. As an alternative to the existing chemical synthesis routes, the aim of the present work was to develop a whole‐cell biocatalyst for the synthesis and production of β‐peptides using this enzymatic activity. For the optimization of th...

  5. Carnosine as a protective factor in diabetic nephropathy - Association with a leucine repeat of the carnosinase gene CNDP1

    NARCIS (Netherlands)

    Janssen, B; Hohenadel, D.; Brinkkoetter, P.; Peters, V.; Rind, N.; Fischer, C.; Rychlik, I.; Cerna, M.; Romzova, M.; de Heer, E.; Baelde, H.; Bakker, Stephan; Zirie, M.; Rondeau, E.; Mathieson, P.; Saleem, M.A.; Meyer, J.; Koppel, H.; Sauerhoefer, S.; Bartram, C.R.; Nawroth, P.; Hammes, H.P.; Yard, B.A.; Zschocke, J.; van der Woude, F.J.

    2005-01-01

    The risk of diabetic nephropathy is partially genetically determined. Diabetic nephropathy is linked to a gene locus on chromosome 18q22.3-q23. We aimed to identify the causative gene on chromosome 18 and to study the mechanism by which the product of this gene could be involved in the development o

  6. Muscle interstitial potassium kinetics during intense exhaustive exercise

    DEFF Research Database (Denmark)

    Nordsborg, Nikolai; Mohr, Magni; Pedersen, Lasse Dannemann;

    2003-01-01

    was assessed by measurement of carnosine in the dialysate, because carnosine is only expected to be found intracellularly. Changes in [K+]i could be reproduced, when exhaustive leg exercise was performed on two different days, with a between-day difference of approximately 0.5 mM at rest and 1.5 mM at...... <0.05). The dialysate content of carnosine was elevated by exercise, but low-intensity exercise resulted in higher dialysate carnosine concentrations than subsequent intense exercise. Furthermore, no relationship was found between carnosine concentrations and [K+]i. Thus the present data suggest that...

  7. Polaprezinc (Zinc L-carnosine) is a potent inducer of anti-oxidative stress enzyme, heme oxygenase (HO)-1 - a new mechanism of gastric mucosal protection.

    Science.gov (United States)

    Ueda, Kazuki; Ueyama, Takashi; Oka, Masashi; Ito, Takao; Tsuruo, Yoshihiro; Ichinose, Masao

    2009-07-01

    Heme oxygenase (HO)-1 is implicated in cytoprotection in various organs. We tested a possibility that polaprezinc (PZ), an anti-ulcer drug, could induce HO-1 in the gastric mucosa. Male 6-week-old Wistar rats were intragastrically administered PZ. Gastric expression of HO-1 was assessed by real time RT-PCR and western blotting, and localization of HO-1 was observed by in situ hybridization and immunohistochemistry. The levels of HO-1 mRNA were increased in a dose-dependent manner. The levels of HO-1 mRNA were increased 4-fold by PZ at the dose of 200 mg/kg at 3 h as compared with control levels. The levels of immunoreactive HO-1 were increased 3-fold at 6 h. Signals for HO-1 mRNA and immunoreactivity were detected strongly in the surface gastric mucosal cells and moderately in the gastric macrophages. Treatment with an HO-1 inhibitor, stannous mesoporphyrin (SnMP) significantly worsened the HCl-induced acute gastric mucosal lesions and increased the apoptosis of mucosal cells. Mucosal lesions were decreased by pretreatment with PZ, while they were increased by co-administration with SnMP. These data indicate for the first time that PZ is an effective inducer of HO-1 in the stomach. PZ-induced HO-1 functions as a part of the mucosal protective effects of PZ. PMID:19542683

  8. Effects of Dietary Supplementation of Carnosine on Mitochondrial Dysfunction, Amyloid Pathology, and Cognitive Deficits in 3xTg-AD Mice

    OpenAIRE

    Carlo Corona; Valerio Frazzini; Elena Silvestri; Rossano Lattanzio; Rossana La Sorda; Mauro Piantelli; Canzoniero, Lorella M. T.; Domenico Ciavardelli; Enrico Rizzarelli; Stefano L Sensi

    2011-01-01

    BACKGROUND: The pathogenic road map leading to Alzheimer's disease (AD) is still not completely understood; however, a large body of studies in the last few years supports the idea that beside the classic hallmarks of the disease, namely the accumulation of amyloid-β (Aβ) and neurofibrillary tangles, other factors significantly contribute to the initiation and the progression of the disease. Among them, mitochondria failure, an unbalanced neuronal redox state, and the dyshomeostasis of endoge...

  9. Development of a model based on oncolytic adenovirus loaded with L-carnosine as a drug delivery system for cancer therapy

    OpenAIRE

    Garofalo, Mariangela

    2015-01-01

    Oncolytic viruses are viruses that are able to replicate specifically and infect and destroy only tumor cells. Many clinical studies have shown that the oncolytic approach alone could not efficiently destroy the large tumor mass, thus by limiting an efficacy virotherapy. Combination of oncolytic adenoviruses (Ads) and chemotherapeutic drugs has shown promising therapeutic results due to the synergistic action of virus and drug and is considered as a potential approach for cancer therapy. In t...

  10. Existence of carcinine, a histamine-related compound, in mammalian tissues

    Energy Technology Data Exchange (ETDEWEB)

    Flancbaum, L.; Brotman, D.N.; Fitzpatrick, J.C.; Van Es, Theodorus; Kasziba, E.; Fisher, H. (Rutgers Univ., New Brunswick, NJ (USA))

    1990-01-01

    Carcinine ({beta}-alanylhistamine) was synthesized in vitro from histamine and {beta}-alanine. It was detected quantitatively using an HPLC method previously described for the quantification of the related compounds histamine, histidine, carnosine and 3-methylhistamine. Carcinine was identified in several tissues of the rat, guinea pig, mouse and human, and was then shown to be metabolically related in vivo to histamine, histidine, carnosine and 3-methylhistamine through radioisotopic labeling. The results demonstrate that carcinine may be concurrently quantitated using the same HPLC method as that used to measure histamine, histidine, carnosine and 3-methylhistamine. These findings suggest a role for carcinine in the carnosine-histidine-histamine metabolic pathway and the mammalian physiologic response to stress.

  11. A Mutant of Mycobacterium smegmatis Defective in Dipeptide Transport

    OpenAIRE

    Bhatt, Achal; Green, Renee; Coles, Roswell; Condon, Michael; Connell, Nancy D.

    1998-01-01

    A mutant of Mycobacterium smegmatis unable to use the dipeptide carnosine (β-alanyl-l-histidine) as a sole carbon or nitrogen source was isolated. Carnosinase activity and the ability to grow on β-Ala and/or l-His were similar in the mutant and the wild type. However, the mutant showed significant impairment in the uptake of carnosine. This study is the first description of a peptide utilization mutant of a mycobacterium.

  12. Pharmacological influence on processes of adjuvant arthritis: Effect of the combination of an antioxidant active substance with methotrexate.

    Science.gov (United States)

    Drafi, Frantisek; Bauerova, Katarina; Kuncirova, Viera; Ponist, Silvester; Mihalova, Danica; Fedorova, Tatiana; Harmatha, Juraj; Nosal, Radomir

    2012-06-01

    Oxygen metabolism has an important role in the pathogenesis of rheumatoid arthritis. A certain correlation was observed between oxidative stress, arthritis and the immune system. Reactive oxygen species produced in the course of cellular oxidative phosphorylation and by activated phagocytic cells during oxidative burst, exceed the physiological buffering capacity and result in oxidative stress. The excessive production of ROS can damage protein, lipids, nucleic acids, and matrix components. Patients with rheumatoid arthritis have an altered antioxidant defense capacity barrier. In the present study the effect of substances with antioxidative properties, i.e. pinosylvin and carnosine, was determined in monotherapy for the treatment of adjuvant arthritis (AA). Moreover carnosine was evaluated in combination therapy with methotrexate. Rats with AA were administered first pinosylvin (30 mg/kg body mass daily per os), second carnosine (150 mg/kg body mass daily per os) in monotherapy for a period of 28 days. Further, rats with AA were administered methotrexate (0.3 mg/kg body mass 2-times weekly per os), and a combination of methotrexate+carnosine, with the carnosine dose being the same as in the previous experiment. Parameters, i.e. changes in hind paw volume and arthritic score were determined in rats as indicators of destructive arthritis-associated clinical changes. Plasmatic levels of TBARS and lag time of Fe(2+)-induced lipid peroxidation (tau-FeLP) in plasma and brain were specified as markers of oxidation. Plasmatic level of CRP and activity of γ-glutamyltransferase (GGT) in spleen and joint were used as inflammation markers. In comparison to pinosylvin, administration of carnosine monotherapy led to a significant decrease in the majority of the parameters studied. In the combination treatment with methotrexate+carnosine most parameters monitored were improved more remarkably than by methotrexate alone. Carnosine can increase the disease-modifying effect of

  13. Beta-alanine supplementation in high-intensity exercise.

    Science.gov (United States)

    Harris, Roger C; Sale, Craig

    2012-01-01

    Glycolysis involves the oxidation of two neutral hydroxyl groups on each glycosyl (or glucosyl) unit metabolised, yielding two carboxylic acid groups. During low-intensity exercise these, along with the remainder of the carbon skeleton, are further oxidised to CO(2) and water. But during high-intensity exercise a major portion (and where blood flow is impaired, then most) is accumulated as lactate anions and H(+). The accumulation of H(+) has deleterious effects on muscle function, ultimately impairing force production and contributing to fatigue. Regulation of intracellular pH is achieved over time by export of H(+) out of the muscle, although physicochemical buffers in the muscle provide the first line of defence against H(+) accumulation. In order to be effective during high-intensity exercise, buffers need to be present in high concentrations in muscle and have pK(a)s within the intracellular exercise pH transit range. Carnosine (β-alanyl-L-histidine) is ideal for this role given that it occurs in millimolar concentrations within the skeletal muscle and has a pK(a) of 6.83. Carnosine is a cytoplasmic dipeptide formed by bonding histidine and β-alanine in a reaction catalysed by carnosine synthase, although it is the availability of β-alanine, obtained in small amounts from hepatic synthesis and potentially in greater amounts from the diet that is limiting to synthesis. Increasing muscle carnosine through increased dietary intake of β-alanine will increase the intracellular buffering capacity, which in turn might be expected to increase high-intensity exercise capacity and performance where this is pH limited. In this study we review the role of muscle carnosine as an H(+) buffer, the regulation of muscle carnosine by β-alanine, and the available evidence relating to the effects of β-alanine supplementation on muscle carnosine synthesis and the subsequent effects of this on high-intensity exercise capacity and performance. PMID:23075550

  14. 肌肽锌对低钙性骨质疏松笼养蛋鸡骨组织结构和形态计量学的影响%Effects of zinc carnosine on the structure of bone tissue and bone histomorphometry in the cage layer with osteoporosis from low calcium

    Institute of Scientific and Technical Information of China (English)

    吕文亭; 王鹏; 利凯; 刘春凌; 杨永红

    2015-01-01

    为了研究肌肤锌(ZnC)对低钙性骨质疏松笼养蛋鸡骨组织结构和形态计量学的影响,试验采用250只24周龄健康海兰褐蛋鸡,随机分为5组(每组50只),对照组饲喂基础日粮(含钙3.55%),低钙组饲喂低钙日粮(含钙1.95%),试验Ⅰ、Ⅱ、Ⅲ组分别于低钙日粮中添加10,30,50 mg/kg ZnC,试验期60 d.试验结束后,每组剖杀10只鸡,取左胫骨中段作骨组织结构检查和形态计量学测定.结果表明:与对照组相比,低钙组中胫骨皮质骨上出现许多吸收腔,在吸收腔内和髓质骨小梁周围破骨细胞明显增多,骨吸收增强,导致骨质疏松;与低钙组相比,试验Ⅱ组中胫骨皮质骨上吸收腔减少,试验Ⅲ组中胫骨皮质骨上未见吸收腔,在试验Ⅱ组皮质骨外表面和吸收腔内及试验Ⅲ组皮质骨外表面均可见大量骨原细胞和成骨细胞,试验Ⅱ、Ⅲ组髓质骨小梁表面也可见大量成骨细胞,骨形成明显增强.与低钙组相比,试验Ⅱ、Ⅲ组的骨小梁面积、骨小梁面积百分比、骨小梁厚度均极显著增加(P<0.01),骨小梁分离度极显著降低(P<0.01);试验Ⅱ组的骨小梁周长、骨小梁数量高于低钙组,但差异不显著(P>0.05),而试验Ⅲ组的骨小梁周长、骨小梁数量均极显著增加(P<0.01).说明在低钙日粮中添加50 mg/kg ZnC能有效改善低钙性骨质疏松笼养蛋鸡的骨组织结构和形态计量学指标,明显减少骨量流失,对笼养蛋鸡骨质疏松症产生积极的防治作用.

  15. Aging risk factors and Parkinson's disease: contrasting roles of common dietary constituents.

    Science.gov (United States)

    Hipkiss, Alan R

    2014-06-01

    Aging is a Parkinson's disease (PD) risk factor. It is suggested here that certain dietary components may either contribute to or ameliorate PD risk. There is evidence, which indicates that excessive carbohydrate (glucose or fructose) catabolism is a cause of mitochondrial dysfunction in PD, one consequence is increased production of methylglyoxal (MG). However, other dietary components (carnosine and certain plant extracts) not only scavenge MG but can also influence some of the biochemical events (signal transduction, stress protein synthesis, glycation, and toxin generation) associated with PD pathology. As double blind, placebo-controlled carnosine supplementation studies have revealed beneficial outcomes in humans, it is suggested that MG scavengers such as carnosine be further explored for their therapeutic potential toward PD. PMID:24388766

  16. Metabolomic elucidation of pork from different crossbreds

    DEFF Research Database (Denmark)

    Bertram, Hanne Christine S.; Straadt, Ida Krestine; Clausen, Morten Rahr;

    )-based metabolomics. Several metabolites including amino acids, organic acids and nucleotides were identified in the obtained proton NMR spectra. Breed-specific differences in the level of several metabolites including inosine, carnosine and lactate were found. Sensory analysis of the cooked pork was performed, and...... correlations between individual metabolites and sensory attributes were elucidated. A high content of carnosine in the meat was associated with a low value of many sensory attributes related to meat flavor/taste. Surprsingly, IMP and inosine were in general not correlated with sensory attributes related to...

  17. Role of Natural Antioxidants in the Modulation of Plasma Amino Acid Pattern in Rats Exposed to Hemic Hypoxia

    Directory of Open Access Journals (Sweden)

    Nouf Mohamed Al-Rasheed

    2015-10-01

    Full Text Available ABSTRACTThe aim of this work was to investigate whether the free radical scavengers, L-arginine (L-arg and/or carnosine, either alone, or in combination would modulate tissue injury induced by hypoxia by measuring Fischer's ratio [concentrations of branched chain amino acids (BCAAs/aromatic amino acids]. Decreased Fischer's ratios and increased malondialdehyde (MDA led to pathogeneses of many diseases. Rats were injected with sodium nitrite (60 mg/kg to establish hypoxia. They were treated with L-arg, (200 mg/ kg and/or carnosine (200 mg/ kg and their combination 24 and 1 h prior to sodium nitrite intoxication. The results revealed that hypoxia significantly decreased hemoglobin, arginine, citrulline and proline and increased sLDH, MDA , ammonia , urea, BCAAs (valine, leucine and isoleucine and aromatic amino acids (phenylalanine and tyrosine . The Fischer's ratio was decreased compared with the control; the administration of the aforementioned antioxidants ameliorated most of the previously altered parameters. It was concluded that Fischer's ratio was a valuable tool for understanding the pathology of hemic hypoxia, evaluating the degree of the modulatory effect of various natural antioxidants and the synergy between L-arg and carnosine in ameliorating the effect of sodium nitrite on amino acids pattern. Thus, it could be recommended to administer the combination of L-arg and carnosine in the areas of high altitudes to combat the hazard effect of hypoxia on hemoglobin concentration and MDA level.

  18. Central administration of dipeptides, beta-alanyl-BCAAs, induces hyperactivity in chicks

    Directory of Open Access Journals (Sweden)

    Denbow D Michael

    2007-05-01

    Full Text Available Abstract Background Carnosine (β-alanyl-L-histidine is a putative neurotransmitter and has a possible role in neuron-glia cell interactions. Previously, we reported that carnosine induced hyperactivity in chicks when intracerebroventricularly (i.c.v. administered. In the present study, we focused on other β-alanyl dipeptides to determine if they have novel functions. Results In Experiment 1, i.c.v. injection of β-alanyl-L-leucine, but not β-alanyl-glycine, induced hyperactivity behavior as observed with carnosine. Both carnosine and β-alanyl-L-leucine stimulated corticosterone release. Thus, dipeptides of β-alanyl-branched chain amino acids were compared in Experiment 2. The i.c.v. injection of β-alanyl-L-isoleucine caused a similar response as β-alanyl-L-leucine, but β-alanyl-L-valine was somewhat less effective than the other two dipeptides. β-Alanyl-L-leucine strongly stimulated, and the other two dipeptides tended to stimulate, corticosterone release. Conclusion These results suggest that central β-alanyl-branched chain amino acid stimulates activity in chicks through the hypothalamus-pituitary-adrenal axis. We named β-alanyl-L-leucine, β-alanyl-L-isoleucine and β-alanyl-L-valine as Excitin-1, Excitin-2 and Excitin-3, respectively.

  19. Profiling histidine dipeptides in plasma and urine after ingesting beef, chicken or chicken broth in humans

    Science.gov (United States)

    Reactive carbonyl species (RCS), oxidation products of polyunsaturated fatty acids, protein & sugars, play a role in the etiology of certain chronic diseases. Our previous studies revealed that histidine-dipeptides such as carnosine and anserine detoxify cytotoxic carbonyls such as 4-hydroxy-trans-...

  20. Role of histidyl dipeptides in contractile function of fast and slow motor units in rat skeletal muscle.

    Science.gov (United States)

    Kaczmarek, Dominik; Łochyński, Dawid; Everaert, Inge; Pawlak, Maciej; Derave, Wim; Celichowski, Jan

    2016-07-01

    The physiological role of the muscle histidyl dipeptides carnosine and anserine in contractile function of various types of muscle fibers in vivo is poorly understood. Ten adult male Wistar rats were randomly assigned to two groups: control and supplemented for 10 wk with beta-alanine, the precursor of carnosine (∼640 mg·kg body wt(-1)·day(-1)). Thereafter, contractile properties and fatigability of isolated fast fatigable (FF), fast resistant to fatigue (FR), and slow motor units (MUs) from the medial gastrocnemius were determined in deeply anaesthetized animals. The fatigue resistance was tested with a 40-Hz fatigue protocol followed by a second protocol at 40 Hz in fast and 20 Hz in slow units. In the supplemented rats, histidyl dipeptide concentrations significantly increased (P carnosine increased by 94% in the white portion. The twitch force of FF units and maximum tetanic force of FR units were significantly increased (P Carnosine and anserine seem to play an important yet divergent role in various MUs. PMID:27197862

  1. New concept in nutrition for the maintenance of the aging eye redox regulation and therapeutic treatment of cataract disease; synergism of natural antioxidant imidazole-containing amino acid-based compounds, chaperone, and glutathione boosting agents: a systemic perspective on aging and longevity emerged from studies in humans.

    Science.gov (United States)

    Babizhayev, Mark A

    2010-01-01

    Cataract, opacification of the lens, is one of the commonest causes of loss of useful vision during aging, with an estimated 16 million people world-wide affected. The role of nutritional supplementation in prevention of onset or progression of ocular disease is of interest to health care professionals and patients. The aging eye seems to be at considerable risk from oxidative stress. This review outlines the potential role of the new nutritional strategy on redox balance in age-related eye diseases and detail how the synergism and interaction of imidazole-containing amino acid-based compounds (nonhydrolized L-carnosine, histidine), chaperone agents (such as, L-carnosine, D-pantethine), glutathione-boosting agents (N-acetylcysteine, vitamin E, methionine), and N-acetylcarnosine eye drops plays key roles in the function and maintenance of the redox systems in the aging eye and in the treatment of human cataract disease. A novel patented oral health supplement is presented which enhances the anticataract activity of eye drops and activates functional visual acuity. The clinical data demonstrate the effectiveness and safety of a combined oral health care treatment with amino acids possessing chaperone-like activity with N-acetylcarnosine lubricant eye drops. L-carnosine and N-acetylcarnosine protected the chaperone activity of alpha-crystallin and reduced the increased posttranslational modifications of lens proteins. Biological activities of the nonhydrolyzed carnosine in the oral formulation are based on its antioxidant and antiglycating (transglycating) action that, in addition to heavy metal chelation and pH-buffering ability, makes carnosine an essential factor for preventing sight-threatening eye disorders having oxidative stress in their pathogenesis, neurodegeneration, and accumulation of senile features. The findings suggest that synergism is required between carnosine or other imidazole-containing compounds and reduced glutathione in tissues and cells for

  2. Biochemical, Biomedical and Metabolic Aspects of Imidazole-Containing Dipeptides with the Inherent Complexity to Neurodegenerative Diseases and Various States of Mental Well-Being: A Challenging Correction and Neurotherapeutic Pharmaceutical Biotechnology for Treating Cognitive Deficits, Depression and Intellectual Disabilities.

    Science.gov (United States)

    Babizhayev, Mark A

    2014-01-01

    The activities of carnosine (β-alanyl-L-histidine), carnosine imidazole containing dipeptide based derivatives (N-acetylcarnosine, carcinine, homocarnosine) and a carnosine degrading enzyme (serum carnosinase (EC 3.4.13.20); [human tissue carnosinase (EC 3.4.13.3), CN2 (CNDP2)] ) activities have been discrepantly linked to neuropathophysiological processes. Approximately 82% of the U.S. population will experience normal age-related cognitive decline, as compared to the precipitous losses that are associated with dementing disorders. Interventions designed to promote health and function through everyday activity and specific pharmaco-nutritional therapeutic treatments may enhance brain plasticity in key regions that support executive function. Cognitive health is multidimensional cascade of functions. It encompasses an array of functions, including general intellectual ability, memory, language, allowing a person to interact effectively and appropriately with the environment. The risk factors for reduced physical and cognitive functions in elderly people, as identified in longitudinal studies, relate to comorbidities, critical care situations, physical and psychosocial health, environmental conditions, social circumstances, nutrition, and lifestyle. Depression and dementia are both common in older adults; cognitive functioning declines slightly with normal aging; depression itself can be associated with cognitive impairment and dementia. In this study the role of carnosine and related neuron specific naturally-occurring endogenous imidazole-containing dipeptide pharmacoperones (N-acetylcarnosine, carcinine) is revealed presently in a surprisingly large amounts in long-lived human tissues to correct conformational abnormalities leading to distinct neurodegeneration and age-related disease states, treating cognitive deficits, depression and intellectual disabilities. Carnosine serves as a physiological buffering agent and a metal ion (e.g., zinc and copper) chelator

  3. A new method for non-invasive estimation of human muscle fiber type composition.

    Directory of Open Access Journals (Sweden)

    Audrey Baguet

    Full Text Available BACKGROUND: It has been established that excellence in sports with short and long exercise duration requires a high proportion of fast-twitch (FT or type-II fibers and slow-twitch (ST or type-I fibers, respectively. Until today, the muscle biopsy method is still accepted as gold standard to measure muscle fiber type composition. Because of its invasive nature and high sampling variance, it would be useful to develop a non-invasive alternative. METHODOLOGY: Eighty-three control subjects, 15 talented young track-and-field athletes, 51 elite athletes and 14 ex-athletes volunteered to participate in the current study. The carnosine content of all 163 subjects was measured in the gastrocnemius muscle by proton magnetic resonance spectroscopy ((1H-MRS. Muscle biopsies for fiber typing were taken from 12 untrained males. PRINCIPAL FINDINGS: A significant positive correlation was found between muscle carnosine, measured by (1H-MRS, and percentage area occupied by type II fibers. Explosive athletes had ∼30% higher carnosine levels compared to a reference population, whereas it was ∼20% lower than normal in typical endurance athletes. Similar results were found in young talents and ex-athletes. When active elite runners were ranked according to their best running distance, a negative sigmoidal curve was found between logarithm of running distance and muscle carnosine. CONCLUSIONS: Muscle carnosine content shows a good reflection of the disciplines of elite track-and-field athletes and is able to distinguish between individual track running distances. The differences between endurance and sprint muscle types is also observed in young talents and former athletes, suggesting this characteristic is genetically determined and can be applied in early talent identification. This quick method provides a valid alternative for the muscle biopsy method. In addition, this technique may also contribute to the diagnosis and monitoring of many conditions and

  4. Biopolymeric receptor for peptide recognition by molecular imprinting approach—Synthesis, characterization and application

    International Nuclear Information System (INIS)

    The present work is focused on the development of a biocompatible zwitterionic hydrogel for various applications in analytical chemistry. Biopolymer chitosan was derivatized to obtain a series of zwitterionic hydrogel samples. Free amino groups hanging on the biopolymeric chain were reacted with γ-butyrolactone to quaternize the N-centers of polymeric chain. N,N-methylene-bis-acrylamide acts as a crosslinker via Michael-type addition in the subsequent step and facilitated gelation of betainized chitosan. These biopolymeric hydrogel samples were fully characterized by FTIR, 1H NMR, 13C NMR spectra, SEM and XRD. Hydrogels were further characterized for their swelling behavior at varying parameters. The extent of swelling was perceived to be dictated by solvent composition such as pH, ionic strength and temperature. This valuable polymeric format is herein chosen to design an artificial receptor for dipeptide ‘carnosine’, which has adequate societal significance to be analytically determined, by molecular imprinting. Electrostatic interactions along with complementary H-bonding and other hydrophobic interactions inducing additional synergetic effect between the template (carnosine) and the imprinted polymer led to the formation of imprinted sites. The MIP was able to selectively and specifically take up carnosine from aqueous solution quantitatively. Thus prepared MIPs were characterized by FTIR spectroscopy, SEM providing evidence for the quality and quantity of imprinted gels. The binding studies showed that the MIP illustrated good recognition for carnosine as compared to non-imprinted polymers (NIPs). Detection limit was estimated as 3.3 μg mL−1. Meanwhile, selectivity experiments demonstrated that imprinted gel had a high affinity to carnosine in the presence of close structural analogues (interferrants). - Highlights: • Development of a biocompatible zwitterionic hydrogel • A series of chitosan-derived zwitterionic hydrogel samples • Polymeric

  5. Biopolymeric receptor for peptide recognition by molecular imprinting approach—Synthesis, characterization and application

    Energy Technology Data Exchange (ETDEWEB)

    Singh, Lav Kumar; Singh, Monika; Singh, Meenakshi, E-mail: meenakshi_s4@rediffmail.com

    2014-12-01

    The present work is focused on the development of a biocompatible zwitterionic hydrogel for various applications in analytical chemistry. Biopolymer chitosan was derivatized to obtain a series of zwitterionic hydrogel samples. Free amino groups hanging on the biopolymeric chain were reacted with γ-butyrolactone to quaternize the N-centers of polymeric chain. N,N-methylene-bis-acrylamide acts as a crosslinker via Michael-type addition in the subsequent step and facilitated gelation of betainized chitosan. These biopolymeric hydrogel samples were fully characterized by FTIR, {sup 1}H NMR, {sup 13}C NMR spectra, SEM and XRD. Hydrogels were further characterized for their swelling behavior at varying parameters. The extent of swelling was perceived to be dictated by solvent composition such as pH, ionic strength and temperature. This valuable polymeric format is herein chosen to design an artificial receptor for dipeptide ‘carnosine’, which has adequate societal significance to be analytically determined, by molecular imprinting. Electrostatic interactions along with complementary H-bonding and other hydrophobic interactions inducing additional synergetic effect between the template (carnosine) and the imprinted polymer led to the formation of imprinted sites. The MIP was able to selectively and specifically take up carnosine from aqueous solution quantitatively. Thus prepared MIPs were characterized by FTIR spectroscopy, SEM providing evidence for the quality and quantity of imprinted gels. The binding studies showed that the MIP illustrated good recognition for carnosine as compared to non-imprinted polymers (NIPs). Detection limit was estimated as 3.3 μg mL{sup −1}. Meanwhile, selectivity experiments demonstrated that imprinted gel had a high affinity to carnosine in the presence of close structural analogues (interferrants). - Highlights: • Development of a biocompatible zwitterionic hydrogel • A series of chitosan-derived zwitterionic hydrogel samples

  6. Diabetes mellitus: novel insights, analysis and interpretation of pathophysiology and complications management with imidazole-containing peptidomimetic antioxidants.

    Science.gov (United States)

    Babizhayev, Mark A; Lankin, Vadim Z; Savel'Yeva, Ekaterina L; Deyev, Anatoliy I; Yegorov, Yegor E

    2013-12-01

    Patients suffering from the severe complications associated with both insulin- (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM): nephropathy, retinopathy, neuropathy, and atherosclerosis are still largely left without a prospect of an efficient treatment. Chronic hyperglycaemia, the primary clinical manifestation of diabetes, is associated with development of certain of the diabetic complications. The accelerated formation of advanced glycation end-products (AGEs) due to elevated glycemia has repeatedly been reported as a central pathogenic factor in the development of diabetic microvascular complications. Glucose and α-dicarbonyl compounds chemically attach to proteins and nucleic acids without the aid of enzymes. Initially, chemically reversible Schiff base and Amadori product adducts form in proportion to glucose concentration. The major biological effects of excessive nonenzymatic glycosylation are leading to increased free radical production and compromised free radical inhibitory and scavenger systems, inactivation of enzymes; inhibition of regulatory molecule binding; crosslinking of glycosylated proteins and trapping of soluble proteins by glycosylated extracellular matrix (both may progress in the absence of glucose); decreased susceptibility to proteolysis; abnormalities of nucleic acid function; altered macromolecular recognition and endocytosis; and increased immunogenicity. The discovery of chemical agents that can inhibit deleterious glycation reactions is potentially of great therapeutic benefit to all diabetes-associated pathologies. This study demonstrates the progress in development of patented carnosine mimetics resistant in formulations to enzymatic hydrolysis with human carnosinases that are acting as a universal form of antioxidant, deglycating and transglycating agents that inhibit sugar-mediated protein cross-linking, chelate or inactivate a number of transition metal ions (including ferrous and copper ions), possess lipid

  7. The potential of a niacinamide dominated cosmeceutical formulation on fibroblast activity and wound healing in vitro.

    Science.gov (United States)

    Wessels, Quenton; Pretorius, Etheresia; Smith, Celeste M; Nel, Hugo

    2014-04-01

    Knowledge on the intrinsic mechanisms involved in wound healing provides opportunity for various therapeutic strategies. The manipulation of dermal fibroblast proliferation and differentiation might prove to beneficially augment wound healing. This study evaluated the combined effects of niacinamide, L-carnosine, hesperidin and Biofactor HSP(®) on fibroblast activity. The effects on fibroblast collagen production, cellular proliferation, migration and terminal differentiation were assessed. In addition, the authors determined the effects on in vitro wound healing. The optimal concentrations of actives were determined in vitro. Testing parameters included microscopic morphological cell analysis, cell viability and proliferation determination, calorimetric collagen detection and in vitro wound healing dynamics. Results show that 0·31 mg/ml niacinamide, 0·10 mg/ml L-carnosine, 0·05 mg/ml hesperidin and 5·18 µg/ml Biofactor HSP® proved optimal in vitro. The results show that fibroblast collagen synthesis was increased alongside with cellular migration and proliferation. PMID:22892041

  8. Computational design of effective, bioinspired HOCl antioxidants: the role of intramolecular Cl+ and H+ shifts.

    Science.gov (United States)

    Karton, Amir; O'Reilly, Robert J; Pattison, David I; Davies, Michael J; Radom, Leo

    2012-11-21

    The enzyme myeloperoxidase generates significant amounts of hypochlorous acid (HOCl) at sites of inflammation to inflict oxidative damage upon invading pathogens. However, excessive production of this potent oxidant is associated with numerous inflammatory diseases. Recent kinetic measurements suggest that the endogenous antioxidant carnosine is an effective HOCl scavenger. On the basis of computational modeling, we suggest a possible mechanism for this antioxidant activity. We find that a unique structural relationship between three adjacent functional groups (imidazole, carboxylic acid, and terminal amine) enables an intramolecular chlorine transfer to occur. In particular, two sequential proton shifts are coupled with a Cl(+) shift converting the kinetically favored product (chlorinated at the imidazole nitrogen) into the thermodynamically favored product (chlorinated at the terminal amine) effectively trapping the chlorine. We proceed to design systems that share similar structural features to those of carnosine but with even greater HOCl-scavenging capabilities. PMID:23148773

  9. Concentration of antioxidants in two muscles of mature dairy cows from Azores.

    Science.gov (United States)

    Roseiro, L C; Santos, C; Gonçalves, H; Moniz, C; Afonso, I; Tavares, M; da Ponte, D J B

    2014-02-01

    This study evaluated the concentrations of α-tocopherol, β-carotene, creatine, carnosine, anserine and coenzyme Q10 in Longissimus dorsi (Ld) and Gluteus medius (Gm) muscles of culled dairy cows and the impact of age, production status before slaughter (dry-off vs lactating) and carcass weight on them. The effects of applying a finishing feeding regimen before slaughter were also examined. Gm muscle presented higher levels (P0.05). The finishing feeding promoted higher mean concentrations of anserine and creatine but lower carnosine values (P>0.05) than directly slaughtered dry-off cows. The variation between muscles and from animal-to-animal makes it difficult to exactly define the antioxidant status of the dairy cow's meat. PMID:24211545

  10. The Molecular Mechanisms of Zinc Neurotoxicity and the Pathogenesis of Vascular Type Senile Dementia

    OpenAIRE

    Masahiro Kawahara; Dai Mizuno

    2013-01-01

    Zinc (Zn) is an essential trace element that is abundantly present in the brain. Despite its importance in normal brain functions, excess Zn is neurotoxic and causes neurodegeneration following transient global ischemia and plays a crucial role in the pathogenesis of vascular-type dementia (VD). We have investigated the molecular mechanisms of Zn-induced neurotoxicity using immortalized hypothalamic neurons (GT1–7 cells) and found that carnosine (β-alanyl histidine) and histidine (His) inhibi...

  11. Zinc Supplementation with Polaprezinc Protects Mouse Hepatocytes against Acetaminophen-Induced Toxicity via Induction of Heat Shock Protein 70

    OpenAIRE

    Nishida, Tadashi; Ohata, Shuzo; Kusumoto, Chiaki; Mochida, Shinsuke; Nakada, Junya; Inagaki, Yoshimi; Ohta, Yoshiji; Matsura, Tatsuya

    2009-01-01

    Polaprezinc, a chelate compound consisting of zinc and l-carnosine, is clinically used as a medicine for gastric ulcers. It has been shown that induction of heat shock protein (HSP) is involved in protective effects of polaprezinc against gastric mucosal injury. In the present study, we investigated whether polaprezinc and its components could induce HSP70 and prevent acetaminophen (APAP) toxicity in mouse primary cultured hepatocytes. Hepatocytes were treated with polaprezinc, zinc sulfate o...

  12. Effectiveness of polaprezinc for low-dose aspirin-induced small-bowel mucosal injuries as evaluated by capsule endoscopy: a pilot randomized controlled study

    OpenAIRE

    Watari, Ikue; Oka, Shiro; Tanaka, Shinji; Aoyama, Taiki; Imagawa, Hiroki; Shishido, Takayoshi; Yoshida, Shigeto; Chayama, Kazuaki

    2013-01-01

    Background Treatment of low-dose aspirin (LDA)-induced small-bowel injury has not been established. Polaprezinc, a chelate of zinc and L-carnosine, may be efficacious for such injury. We conducted a pilot randomized controlled study to investigate whether polaprezinc is effective against LDA-induced small-bowel injuries. Methods Consecutive patients under long-term (>3 months) LDA treatment and who agreed to participate in our study underwent initial capsule endoscopy (CE). Patients with LDA-...

  13. Crystal Structure and Mutational Analysis of Aminoacylhistidine Dipeptidase from Vibrio alginolyticus Reveal a New Architecture of M20 Metallopeptidases*

    OpenAIRE

    Chang, Chin-Yuan; Hsieh, Yin-Cheng; Wang, Ting-Yi; Chen, Yi-Chin; Wang, Yu-Kuo; Chiang, Ting-Wei; Chen, Yi-Ju; Chang, Cheng-Hsiang; Chen, Chun-Jung; Wu, Tung-Kung

    2010-01-01

    Aminoacylhistidine dipeptidases (PepD, EC 3.4.13.3) belong to the family of M20 metallopeptidases from the metallopeptidase H clan that catalyze a broad range of dipeptide and tripeptide substrates, including l-carnosine and l-homocarnosine. Homocarnosine has been suggested as a precursor for the neurotransmitter γ-aminobutyric acid (GABA) and may mediate the antiseizure effects of GABAergic therapies. Here, we report the crystal structure of PepD from Vibrio alginolyticus and the results of ...

  14. Heat shock protein 70-dependent protective effect of polaprezinc on acetylsalicylic acid-induced apoptosis of rat intestinal epithelial cells

    OpenAIRE

    Qin, Ying; NAITO, Yuji; Handa, Osamu; Hayashi, Natsuko; Kuki, Aiko; Mizushima, Katsura; Omatsu, Tatsushi; Tanimura, Yuko; Morita, Mayuko; Adachi, Satoko; Fukui, Akifumi; Hirata, Ikuhiro; Kishimoto, Etsuko; Nishikawa, Taichiro; Uchiyama, Kazuhiko

    2011-01-01

    Protection of the small intestine from mucosal injury induced by nonsteroidal anti-inflammatory drugs including acetylsalicylic acid is a critical issue in the field of gastroenterology. Polaprezinc an anti-ulcer drug, consisting of zinc and L-carnosine, provides gastric mucosal protection against various irritants. In this study, we investigated the protective effect of polaprezinc on acetylsalicylic acid-induced apoptosis of the RIE1 rat intestinal epithelial cell line. Confluent rat intest...

  15. Examination of Association with Candidate Genes for Diabetic Nephropathy in a Mexican American Population

    OpenAIRE

    Kim, Sulgi; Abboud, Hanna E.; Pahl, Madeleine V.; Tayek, John; Snyder, Susan; Tamkin, James; Alcorn, Harry; Ipp, Eli; Nast, Cynthia C.; Elston, Robert C.; Iyengar, Sudha K.; Adler, Sharon G.

    2010-01-01

    Background and objectives: Diabetic nephropathy (DN) is a multifactorial complication characterized by persistent proteinuria in susceptible individuals with type 1 and type 2 diabetes. Disease burden in people of Mexican-American descent is particularly high, but there are only a few studies that characterize genes for DN in this ethnic group. Two genes, carnosine dipeptidase 1 (CNDP1) and engulfment and cell motility 1 (ELMO1) previously showed association with DN in other ethnic groups. CN...

  16. 肌肽的研究进展

    Institute of Scientific and Technical Information of China (English)

    胡新旭; 赵丽红; 张勇; 高书锋; 周映华; 张德元; 刘惠知

    2013-01-01

    肌肽(丙氨酰组氨酸,L-Carnosine,β-alanyl-L-histidine)是一种天然二肽,抗氧化性能极强,具备多种生物活性功能。1肌肽的物理化学性质和生物学特性1.1肌肽的基本物化特性

  17. Individual variability in human blood metabolites identifies age-related differences

    OpenAIRE

    Chaleckis, Romanas; MURAKAMI, Itsuo; Takada, Junko; Kondoh, Hiroshi; Yanagida, Mitsuhiro

    2016-01-01

    Human blood provides a rich source of information about metabolites that reflects individual differences in health, disease, diet, and lifestyle. The coefficient of variation for human blood metabolites enriched in red blood cells or plasma was quantified after careful preparation. We identified 14 age-related metabolites. Metabolites that decline strikingly in the elderly include antioxidants and compounds involved in high physical activity, including carnosine, UDP-acetyl-glucosamine, ophth...

  18. Study of molecular mechanisms of UV-induced aggregation of crystallins and possibility of maintaining eye lens transparency

    Science.gov (United States)

    Soustov, L. V.; Chelnokov, E. V.; Bityurin, N. M.; Kiselev, A. L.; Nemov, V. V.; Sergeev, Yu. V.; Ostrovsky, M. A.

    2006-03-01

    The effect of D-pantethine and L-carnosine on the rate of UV-induced (XeC1 laser λ = 308 nm) aggregation of a mixture of βL-crystallin and α-crystallin is studied. We also demonstrate that the suggested by us combination of short-chain peptides shows better protective properties with respect to UV-induced aggregation than known anti-cataract agents.

  19. Muscle histidine-containing dipeptides are elevated by glucose intolerance in both rodents and men.

    Directory of Open Access Journals (Sweden)

    Sanne Stegen

    Full Text Available Muscle carnosine and its methylated form anserine are histidine-containing dipeptides. Both dipeptides have the ability to quench reactive carbonyl species and previous studies have shown that endogenous tissue levels are decreased in chronic diseases, such as diabetes.Rodent study: Skeletal muscles of rats and mice were collected from 4 different diet-intervention studies, aiming to induce various degrees of glucose intolerance: 45% high-fat feeding (male rats, 60% high-fat feeding (male rats, cafeteria feeding (male rats, 70% high-fat feeding (female mice. Body weight, glucose-tolerance and muscle histidine-containing dipeptides were assessed. Human study: Muscle biopsies were taken from m. vastus lateralis in 35 males (9 lean, 8 obese, 9 prediabetic and 9 newly diagnosed type 2 diabetic patients and muscle carnosine and gene expression of muscle fiber type markers were measured.Diet interventions in rodents (cafeteria and 70% high-fat feeding induced increases in body weight, glucose intolerance and levels of histidine-containing dipeptides in muscle. In humans, obese, prediabetic and diabetic men had increased muscle carnosine content compared to the lean (+21% (p>0.1, +30% (p<0.05 and +39% (p<0.05, respectively. The gene expression of fast-oxidative type 2A myosin heavy chain was increased in the prediabetic (1.8-fold, p<0.05 and tended to increase in the diabetic men (1.6-fold, p = 0.07, compared to healthy lean subjects.Muscle histidine-containing dipeptides increases with progressive glucose intolerance, in male individuals (cross-sectional. In addition, high-fat diet-induced glucose intolerance was associated with increased muscle histidine-containing dipeptides in female mice (interventional. Increased muscle carnosine content might reflect fiber type composition and/or act as a compensatory mechanism aimed at preventing cell damage in states of impaired glucose tolerance.

  20. Olfactory dysfunction and cognitive impairment in age-related neurodegeneration: prevalence related to patient selection, diagnostic criteria and therapeutic treatment of aged clients receiving clinical neurology and community-based care.

    Science.gov (United States)

    Babizhayev, Mark A; Deyev, Anatoliy I; Yegorov, Yegor E

    2011-11-01

    A decrease in olfactory function with age has been attributed to a variety of factors including normal anatomical and physiological changes in aging, surgery, trauma, environmental factors, medications and disease. Olfactory impairment has also been associated with neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease. Deficits in these chemical senses cannot only reduce the pleasure and comfort from food, but represent risk factors for nutritional and immune deficiencies as well as adherence to specific dietary regimens. Therapy is limited, but one should be aware of the existing medical and surgical treatment modalities. Reactive oxygen and nitrogen species, copper and zinc ions, glycating agents and reactive aldehydes, protein cross-linking and proteolytic dysfunction may all contribute to neurodegeneration, olfactory dysfunction, AD. Carnosine (beta-alanyl- L-histidine) is a naturally-occurring, pluripotent, homeostatic transglycating agent. The olfactory lobe is normally enriched in carnosine and zinc. Loss of olfactory function and oxidative damage to olfactory tissue are early symptoms of AD. Protein and lipid oxidation and glycation are integral components of the AD pathophysiology. Carnosine can suppress amyloidbeta peptide toxicity, inhibit production of oxygen free-radicals, scavenge hydroxyl radicals and reactive aldehydes, and suppresses protein glycation. The observations suggest that patented non-hydrolyzed carnosine lubricant drug delivery or perfume toilet water formulations combined with related moiety amino acid structures, such as beta-alanine, should be explored for therapeutic potential towards olfactory dysfunction, AD and other neurodegenerative disorders. "The olfactory system, anatomically, is right in the middle of the part of the brain that's very important for memory. There are strong neural connections between the two." ~ Donald Wilson. PMID:22082323

  1. Polaprezinc Protects Mice against Endotoxin Shock

    OpenAIRE

    Ohata, Shuzo; Moriyama, Chihiro; Yamashita, Atsushi; Nishida, Tadashi; Kusumoto, Chiaki; Mochida, Shinsuke; Minami, Yukari; Nakada, Junya; Shomori, Kohei; Inagaki, Yoshimi; Ohta, Yoshiji; Matsura, Tatsuya

    2010-01-01

    Polaprezinc (PZ), a chelate compound consisting of zinc and l-carnosine (Car), is an anti-ulcer drug developed in Japan. In the present study, we investigated whether PZ suppresses mortality, pulmonary inflammation, and plasma nitric oxide (NO) and tumor necrosis factor (TNF)-α levels in endotoxin shock mice after peritoneal injection of lipopolysaccharide (LPS), and how PZ protects against LPS-induced endotoxin shock. PZ pretreatment inhibited the decrease in the survival rate of mice after ...

  2. Inhibitory Effects of Polaprezine on the Inflammatory Response to Helicobacter pylori

    OpenAIRE

    Handa, Osamu; Yoshida, Norimasa; TANAKA, Yukiko; Ueda, Miho; Ishikawa, Takeshi; Takagi, Tomohisa; Matsumoto, Naoyuki; Naito, Yuji; Yoshikawa, Toshikazu

    2002-01-01

    Helicobacter pylori-infected gastrointestinal mucosa is frequently infiltrated by polymorphonuclear leukocytes (PMN) and monocytes, and these invading cells have been implicated in gastrointestinal mucosal inflammation. To clarify the efficacy of polaprezinc, a chelate compound consisting of zinc and L-carnosine, against H pylori-induced inflammation including PMN infiltration, the in vitro effects of this drug on interleukin (IL)-8 production by an established gastric cancer cell line (MKN 4...

  3. β-Alanine supplementation enhances human skeletal muscle relaxation speed but not force production capacity.

    OpenAIRE

    Hannah, R; Stannard, R. L.; Minshull, C; Artioli, G. G.; Harris, R. C.; Sale, C.

    2015-01-01

    β-Alanine (BA) supplementation improves human exercise performance. One possible explanation for this is an enhancement of muscle contractile properties, occurring via elevated intramuscular carnosine resulting in improved calcium sensitivity and handling. This study investigated the effect of BA supplementation on in vivo contractile properties and voluntary neuromuscular performance. Twenty-three men completed two experimental sessions, pre- and post-28 days supplementation with 6.4 g/day o...

  4. Traditional reactive carbonyl scavengers do not prevent the carbonylation of brain proteins induced by acute glutathione depletion

    OpenAIRE

    Zheng, J; Bizzozero, O. A.

    2010-01-01

    This study investigated the effect of reactive carbonyl species (RCS)-trapping agents on the formation of protein carbonyls during depletion of brain glutathione (GSH). To this end, rat brain slices were incubated with the GSH-depletor diethyl maleate in the absence or presence of chemically different RCS scavengers (hydralazine, methoxylamine, aminoguanidine, pyridoxamine, carnosine, taurine and z-histidine hydrazide). Despite their strong reactivity towards the most common RCS, none of the ...

  5. Zinc Supplementation with Polaprezinc Protects Mouse Hepatocytes against Acetaminophen-Induced Toxicity via Induction of Heat Shock Protein 70.

    Science.gov (United States)

    Nishida, Tadashi; Ohata, Shuzo; Kusumoto, Chiaki; Mochida, Shinsuke; Nakada, Junya; Inagaki, Yoshimi; Ohta, Yoshiji; Matsura, Tatsuya

    2010-01-01

    Polaprezinc, a chelate compound consisting of zinc and l-carnosine, is clinically used as a medicine for gastric ulcers. It has been shown that induction of heat shock protein (HSP) is involved in protective effects of polaprezinc against gastric mucosal injury. In the present study, we investigated whether polaprezinc and its components could induce HSP70 and prevent acetaminophen (APAP) toxicity in mouse primary cultured hepatocytes. Hepatocytes were treated with polaprezinc, zinc sulfate or l-carnosine at the concentration of 100 microM for 9 h, and then exposed to 10 mM APAP. Polaprezinc or zinc sulfate increased cellular HSP70 expression. However, l-carnosine had no influence on it. Pretreatment of the cells with polaprezinc or zinc sulfate significantly suppressed cell death as well as cellular lipid peroxidation after APAP treatment. In contrast, pretreatment with polaprezinc did not affect decrease in intracellular glutathione after APAP. Furthermore, treatment with KNK437, an HSP inhibitor, attenuated increase in HSP70 expression induced by polaprezinc, and abolished protective effect of polaprezinc on cell death after APAP. These results suggested that polaprezinc, in particular its zinc component, induces HSP70 expression in mouse primary cultured hepatocytes, and inhibits lipid peroxidation after APAP treatment, resulting in protection against APAP toxicity. PMID:20104264

  6. The molecular mechanisms of zinc neurotoxicity and the pathogenesis of vascular type senile dementia.

    Science.gov (United States)

    Mizuno, Dai; Kawahara, Masahiro

    2013-01-01

    Zinc (Zn) is an essential trace element that is abundantly present in the brain. Despite its importance in normal brain functions, excess Zn is neurotoxic and causes neurodegeneration following transient global ischemia and plays a crucial role in the pathogenesis of vascular-type dementia (VD). We have investigated the molecular mechanisms of Zn-induced neurotoxicity using immortalized hypothalamic neurons (GT1-7 cells) and found that carnosine (β-alanyl histidine) and histidine (His) inhibited Zn2+-induced neuronal death. A DNA microarray analysis revealed that the expression of several genes, including metal-related genes (metallothionein and Zn transporter 1), endoplasmic reticulum (ER)-stress related genes (GADD34, GADD45, and p8), and the calcium (Ca)-related gene Arc (activity-related cytoskeleton protein), were affected after Zn exposure. The co-existence of carnosine or His inhibited the expression of GADD34, p8, and Arc, although they did not influence the expression of the metal-related genes. Therefore, ER-stress and the disruption of Ca homeostasis may underlie the mechanisms of Zn-induced neurotoxicity, and carnosine might be a possible drug candidate for the treatment of VD. PMID:24213606

  7. Eff ects of natural antioxidants on colour stability, lipid oxidation and metmyoglobin reducing activity in raw beef patties

    Directory of Open Access Journals (Sweden)

    Fang Liu

    2015-03-01

    Full Text Available Background. Minced meats undergo oxidative changes and develop rancidity more quickly than intact muscle since grinding exposes more of the muscle surface to air and microbial contamination. Due to concerns about toxicological safety of synthetic antioxidants, recent studies have put more focus on natural antioxidant compounds derived from food components. Material and methods. The effects of four natural antioxidants (vitamin E, carnosine, grape seed extract and tea catechins on oxidative processes and metmyoglobin reducing activity in raw beef patties during refrigerated (4°C storage were investigated and the results were compared with butylated hydroxyanisole treatment patties. The correlation of lipid oxidation, colour and metmyoglobin reducing activity of beef patties were also studied. Results. Samples treated with carnosine had the highest redness values on the eighth day. Tea catechins, vitamin E and grape seed extract showed higher protective effect against lipid oxidation than carnosine. Metmyoglobin reducing activity increased greatly in all samples during the storage. Signifi cant correlation between redness value and lipid oxidation was demonstrated, while a weak correlation between metmyoglobin reducing activity and any other parameters was shown.

  8. Mechanical Stress Promotes Cisplatin-Induced Hepatocellular Carcinoma Cell Death

    Directory of Open Access Journals (Sweden)

    Laila Ziko

    2015-01-01

    Full Text Available Cisplatin (CisPt is a commonly used platinum-based chemotherapeutic agent. Its efficacy is limited due to drug resistance and multiple side effects, thereby warranting a new approach to improving the pharmacological effect of CisPt. A newly developed mathematical hypothesis suggested that mechanical loading, when coupled with a chemotherapeutic drug such as CisPt and immune cells, would boost tumor cell death. The current study investigated the aforementioned mathematical hypothesis by exposing human hepatocellular liver carcinoma (HepG2 cells to CisPt, peripheral blood mononuclear cells, and mechanical stress individually and in combination. HepG2 cells were also treated with a mixture of CisPt and carnosine with and without mechanical stress to examine one possible mechanism employed by mechanical stress to enhance CisPt effects. Carnosine is a dipeptide that reportedly sequesters platinum-based drugs away from their pharmacological target-site. Mechanical stress was achieved using an orbital shaker that produced 300 rpm with a horizontal circular motion. Our results demonstrated that mechanical stress promoted CisPt-induced death of HepG2 cells (~35% more cell death. Moreover, results showed that CisPt-induced death was compromised when CisPt was left to mix with carnosine 24 hours preceding treatment. Mechanical stress, however, ameliorated cell death (20% more cell death.

  9. The Molecular Mechanisms of Zinc Neurotoxicity and the Pathogenesis of Vascular Type Senile Dementia

    Directory of Open Access Journals (Sweden)

    Masahiro Kawahara

    2013-11-01

    Full Text Available Zinc (Zn is an essential trace element that is abundantly present in the brain. Despite its importance in normal brain functions, excess Zn is neurotoxic and causes neurodegeneration following transient global ischemia and plays a crucial role in the pathogenesis of vascular-type dementia (VD. We have investigated the molecular mechanisms of Zn-induced neurotoxicity using immortalized hypothalamic neurons (GT1-7 cells and found that carnosine (β-alanyl histidine and histidine (His inhibited Zn2+-induced neuronal death. A DNA microarray analysis revealed that the expression of several genes, including metal-related genes (metallothionein and Zn transporter 1, endoplasmic reticulum (ER-stress related genes (GADD34, GADD45, and p8, and the calcium (Ca-related gene Arc (activity-related cytoskeleton protein, were affected after Zn exposure. The co-existence of carnosine or His inhibited the expression of GADD34, p8, and Arc, although they did not influence the expression of the metal-related genes. Therefore, ER-stress and the disruption of Ca homeostasis may underlie the mechanisms of Zn-induced neurotoxicity, and carnosine might be a possible drug candidate for the treatment of VD.

  10. NI (II AND PB (II INHIBIT THE ENZYMATIC ACTIVITY OF DNA IN AN ELECTRON TRANSFER REACTION

    Directory of Open Access Journals (Sweden)

    B FARZAMI

    2002-03-01

    Full Text Available Introduction. Ni and Pb are metals with several suggested mechanisms for their toxicity on the biological systems. We have recently investigated involvement of DNA in an electron transfer reaction as an enzyme. In this reaction non- fluorescent dichlorofluorescin (LDCF is converted to the dichlorofluorescein (DCF in the presence of peroxides and hematin. Methods. The fluorometric technique was used in this study. The pH effect on the reaction rate was investigated. The results showed that DCF has the maximum emission on tris buffer 0.05 Mat pH 8.4. Results. DNA and carnosine catalyze the reaction, which proceeds by the electron transfer mechanism. The presence of carnosine is necessary for the catalytic action of DNA as a cofactor. Ni (II and Pb (11 are the potent inhibitors of the reaction. The kinetic parameters and determined in the presence and absence of the above ligands. Discussion. DNA, which has the electrical properties only in the double helical forms, acts as a catalyst in the conversion of LDCF to DCF. The existence of the carnosine, an endogenous dipeptide with antioxidant and free radical scavenging roles, is an important factor for the progress of the reaction. Both Ni (11 and Pb (II inhibit the reaction. These metals could act as the electron pool to cause inhibition in such electron transfer reaction. This phenomenon could be related to the carcinogenic effect of these metals.

  11. [The effect of antioxidants on in vivo and in vitro methemoglobin formation in erytrocytes of patients with Parkinson`s disease].

    Science.gov (United States)

    Makletsova, M G; Rikhireva, G T; Poleshuk, V V; Grjakalov, K V; Timerbaeva, S L; Fedorova, T N

    2016-01-01

    Methemoglobin formation was examined in erytrocytes of 16 patients with Parkinson`s disease (PD) (stage 3-4 by the Hoehn and Yahr scale). The patients receiving levodopa-containing drugs (madopar, nakom) were also treated with intramuscular injections of mexidol (daily dose 100 mg/day) for 14 days. Control group included 12 clinically healthy persons. The erythrocyte methemoglobin content was determined by electronic paramagnetic resonance (EPR) using the EPR signal intensity with g-factor 6.0. The methemoglobin content was significantly higher in erythrocytes of PD patients than in healthy donors. The complex therapy with mexidol normalized the methemoglobin content in erythrocytes of PD patients. Incubation in vitro of erythrocytes of donors and PD patients with acrolein increased the methemoglobin content, while incubation with carnosine normalized the methemoglobin content in erythrocytes of PD patients. Prophylactic (i.e. before acrolein addition) and therapeutic administration of carnosine to the incubation system with acrolein decreased the methemoglobin content to its initial level. Results of this study suggest that inclusion of the antioxidants mexidol and carnosine in the scheme of basic therapy of PD may reduce side effects associated with methemoglobinemia. PMID:27143379

  12. Natural Antioxidants Improve Red Blood Cell “Survival” in Non-Leukoreduced Blood Samples

    Directory of Open Access Journals (Sweden)

    Yuliya V Kucherenko

    2015-03-01

    Full Text Available Background: Blood collected in an anticoagulant can be kept refrigerated in an unmodified state within 5 - 6 weeks. Oxidative damage is considered to be a one of the major factors contributing to the development of storage lesions. Lipid and membrane proteins oxidation results in changes in cation gradients that affect the cell survival. Aim: In the present study we used the natural antioxidants and ion channels blockers (L-carnosine, spermine, phloretin and their mixtures to prolong “survival” of red blood cells (RBCs, measured as the lack of PS exposure and cell hemolysis, in the Alsever's preservative solution upon hypothermic storage. Results: We show that the mixture of carnosine (20 mM, spermine (20 µM and phloretin (100 µM effectively blunted phosphatidylserine (PS exposure, Ca2+ accumulation and RBCs hemolysis in non-leukoreduced low (∼2% hematocrit samples after 36 days of storage as well as after 1 day of post-storage incubation of the stored cells in physiological saline solution. In addition, a slight but significant decrease in PS exposure was observed in non-leukoreduced high (∼20% hematocrit samples after 36 days of storage with the mixture of substances. Conclusion: We conclude that the use of the mixture of natural antioxidants (carnosine, spermine, and phloretin as an additive to blood preservative solution provides better RBCs storage and “survival”.

  13. The Effect of Camosine on Collagen Content in Rat Cardiac Fibroblast Under High Glucose Condition%肌肽对高糖环境下心肌成纤维细胞胶原表达的影响

    Institute of Scientific and Technical Information of China (English)

    闫俊霞; 郑海霞; 毕惠梅; 崔云霞; 房绍红; 周宏博

    2012-01-01

    目的:探讨肌肽对高糖环境下心肌成纤维细胞中胶原生成的影响及作用机制.方法:原代培养心肌成纤维细胞,将细胞分为正常糖组(NG,5.5mmol/L glucose)、高糖组(HG,25mmol/L glucose)、高糖+10mmol/L肌肽组、高糖+20mmol/L肌肽组、高糖+40mmol/L肌肽组、高糖+SB组(HG+10 μmol/L SB203580)、高糖+PD组(HG+10 μmol/L PD98059).ELISA检测胶原Ⅰ、Ⅲ的含量,Western blot检测TGF-β1、p-p38 MAPK和p-ERK(1/2)等蛋白的表达.结果:与正常糖组相比,高糖组中胶原Ⅰ和胶原Ⅲ含量增加(P<0.01);TGF-β1、p-p38和p-ERK等表达增加(P<0.01);与高糖组相比,高糖+肌肽组中胶原Ⅰ、Ⅲ、TGF-β1、p-p38、和p-ERK等均降低(P<0.05);高糖+SB组和高糖+PD组中胶原Ⅰ、Ⅲ表达减少(P<0.05).结论:肌肽对心肌成纤维细胞中胶原生成具有抑制作用,且通过MAPK通路实现.%Objective: To investigate the effect and mechanism of carnosine on collagen content in rat cardiac fibroblasts under high glucose condition. Methods: The rat cardiac fibroblasts were divided into seven groups, NG group (5.5mmol/L glucose), HG group (25mmol/L glucose), HG+10mmol/L carnosine group, HG+20mmol/L carnosine group, HG+40mmol/L carnosine group, HG+SB group (HG+10 μmol/LSB203580 ), HG+PD group (HG+10 μmol/L PD98059 ). The collagen Ⅰ and Ⅲ contents were detected by ELISA , and Western blotting was used to detect the protein expression level of TGF-β1, p-p38 MAPK and p-ERK (1/2). Results: By the end of the experiment, compared with NG group, the expression level of collagen Ⅰ and collagen Ⅲ were significantly higher in the HG group (P<0.01); The protein expression level of TGF-β1, p-p38, p-ERK were also significantly higher in the HG group (P<0.01). However, after supplement the carnosine, the level of collagen Ⅰ , collagen Ⅲ, TGF-β1, p-p38 and p-ERK were significantly reduced in HG+Car group than HG group (P<0.05); Compared with HG group, the collagen Ⅰ and

  14. Repeated Supramaximal Exercise-Induced Oxidative Stress: Effect of β-Alanine Plus Creatine Supplementation

    Science.gov (United States)

    Belviranli, Muaz; Okudan, Nilsel; Revan, Serkan; Balci, Serdar; Gokbel, Hakki

    2016-01-01

    Background: Carnosine is a dipeptide formed from the β-alanine and histidine amino acids and found in mainly in the brain and muscle, especially fast twitch muscle. Carnosine and creatine has an antioxidant effect and carnosine accounts for about 10% of the muscle's ability to buffer the H+ ions produced by exercise. Objectives: The aim of the study was to investigate the effects of beta alanine and/or creatine supplementation on oxidant and antioxidant status during repeated Wingate tests (WTs). Patients and Methods: Forty four sedentary males participated in the study. Participants performed three 30s WTs with 2 minutes rest between exercise bouts. After the first exercise session, the subjects were assigned to one of four groups: Placebo, Creatine, Beta-alanine and Beta-alanine plus creatine. Participants ingested twice per day for 22 consecutive days, then four times per day for the following 6 days. After the supplementation period the second exercise session was applied. Blood samples were taken before and immediately after the each exercise session for the analysis of oxidative stress and antioxidant markers. Results: Malondialdehyde levels and superoxide dismutase activities were affected by neither supplementation nor exercise. During the pre-supplementation session, protein carbonyl reduced and oxidized glutathione (GSH and GSSG) levels increased immediately after the exercise. However, during the post-supplementation session GSH and GSSG levels increased in beta-alanine and beta-alanine plus creatine groups immediately after the exercise compared to pre-exercise. In addition, during the post-supplementation session total antioxidant capacity increased in beta-alanine group immediately after the exercise. Conclusions: Beta-alanine supplementation has limited antioxidant effect during the repeated WTs.

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

    Science.gov (United States)

    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. PMID:26306846

  16. Zinc deficiency or excess within the physiological range increases genome instability and cytotoxicity, respectively, in human oral keratinocyte cells

    OpenAIRE

    Sharif, Razinah; Thomas, Philip; Zalewski, Peter; Fenech, Michael

    2011-01-01

    Zinc (Zn) is an essential component of Zn-finger proteins and acts as a cofactor for enzymes required for cellular metabolism and in the maintenance of DNA integrity. The study investigated the genotoxic and cytotoxic effects of Zn deficiency or excess in a primary human oral keratinocyte cell line and determined the optimal concentration of two Zn compounds (Zn Sulphate (ZnSO4) and Zn Carnosine (ZnC)) to minimise DNA damage. Zn-deficient medium (0 μM) was produced using Chelex treatment, and...

  17. Nutritional Strategies to Modulate Intracellular and Extracellular Buffering Capacity During High-Intensity Exercise

    OpenAIRE

    Lancha Junior, Antonio Herbert; de Salles Painelli, Vitor; Saunders, Bryan; Artioli, Guilherme Giannini

    2015-01-01

    Intramuscular acidosis is a contributing factor to fatigue during high-intensity exercise. Many nutritional strategies aiming to increase intra- and extracellular buffering capacity have been investigated. Among these, supplementation of beta-alanine (~3–6.4 g/day for 4 weeks or longer), the rate-limiting factor to the intramuscular synthesis of carnosine (i.e. an intracellular buffer), has been shown to result in positive effects on exercise performance in which acidosis is a contributing fa...

  18. Localized double-quantum-filtered 1H NMR spectroscopy

    Science.gov (United States)

    Thomas, M. A.; Hetherington, H. P.; Meyerhoff, D. J.; Twieg, D. B.

    The image-guided in vivo spectroscopic (ISIS) pulse sequence has been combined with a double-quantum-filter scheme in order to obtain localized and water-suppressed 1H NMR spectra of J-coupled metabolites. The coherence-transfer efficiency associated with the DQ filter for AX and A 3X spin systems is described. Phantom results of carnosine, alanine, and ethanol in aqueous solution are presented. For comparison, the 1H NMR spectrum of alanine in aqueous solution with the binomial (1331, 2662) spin-echo sequence is also shown.

  19. ENDOR study of VO/sup 2 +/-imidazole complexes in frozen aqueous solution

    Energy Technology Data Exchange (ETDEWEB)

    Mulks, C.F.; Kirste, B.; van Willigen, H.

    1982-11-03

    Complexes formed between the oxovanadium(IV) cation and imidazole, carnosine, and histidine have been studied with ENDOR. It is shown that the technique gives information on proton and nitrogen hyperfine coupling components as well as /sup 14/N quadrupole splittings. The data provide insight into the geometric structure of the complexes. The results presented indicate that ENDOR studies of VO/sup 2 +/ binding to more complex systems of biological interest (such as proteins) can be used to identify binding to histidine moieties. Furthermore, such studies could be of help in establishing the binding site geometry.

  20. International society of sports nutrition position stand: Beta-Alanine.

    Science.gov (United States)

    Trexler, Eric T; Smith-Ryan, Abbie E; Stout, Jeffrey R; Hoffman, Jay R; Wilborn, Colin D; Sale, Craig; Kreider, Richard B; Jäger, Ralf; Earnest, Conrad P; Bannock, Laurent; Campbell, Bill; Kalman, Douglas; Ziegenfuss, Tim N; Antonio, Jose

    2015-01-01

    The International Society of Sports Nutrition (ISSN) provides an objective and critical review of the mechanisms and use of beta-alanine supplementation. Based on the current available literature, the conclusions of the ISSN are as follows: 1) Four weeks of beta-alanine supplementation (4-6 g daily) significantly augments muscle carnosine concentrations, thereby acting as an intracellular pH buffer; 2) Beta-alanine supplementation currently appears to be safe in healthy populations at recommended doses; 3) The only reported side effect is paraesthesia (tingling), but studies indicate this can be attenuated by using divided lower doses (1.6 g) or using a sustained-release formula; 4) Daily supplementation with 4 to 6 g of beta-alanine for at least 2 to 4 weeks has been shown to improve exercise performance, with more pronounced effects in open end-point tasks/time trials lasting 1 to 4 min in duration; 5) Beta-alanine attenuates neuromuscular fatigue, particularly in older subjects, and preliminary evidence indicates that beta-alanine may improve tactical performance; 6) Combining beta-alanine with other single or multi-ingredient supplements may be advantageous when supplementation of beta-alanine is high enough (4-6 g daily) and long enough (minimum 4 weeks); 7) More research is needed to determine the effects of beta-alanine on strength, endurance performance beyond 25 min in duration, and other health-related benefits associated with carnosine. PMID:26175657

  1. Hyper-beta-alaninemia associated with beta-aminoaciduria and gamma-aminobutyricaciduaia, somnolence and seizures.

    Science.gov (United States)

    Scriver, C R; Pueschel, S; Davies, E

    1966-03-24

    Hyper-beta-alaninemia was found in a somnolent, convulsing infant. Hyper-beta-aminoaciduria (beta-ala, betaAIB and taurine) was also observed, varying directly with plasma beta-alanine concentration. The beta-aminoaciduria is explained by the interaction between beta-alanine and a specific cellular-transport system with preference for beta-amino compounds. Gamma-aminobutyricaciduria was also observed, its excretion being independent of beta-alanine levels. Dietary modifications, pyridoxine, pantothenic acid and antibiotic therapy were not beneficial. Post-mortem tissues had elevated levels of beta-alanine and carnosine; GABA levels in brain were probably elevated for the age of the patient. A proposed block in beta-alanine-alpha-ketoglutarate transaminase would expand the free beta-alanine pool, thus increasing tissue carnosine. beta-Alanine is a central-nervous-system depressant. Associated inhibition of GABA transaminase and displacement of GABA from central-nervous-system binding sites would produce GABAuria and convulsions. PMID:17926374

  2. Analysis of human muscle extracts by proton NMR

    International Nuclear Information System (INIS)

    Perchloric acid extracts were prepared from pooled human muscle biopsies from patients diagnosed with scoliosis (SCOL) and cerebral palsy (CP). After neutralization with KOH and removal of perchlorate, the extracts were concentrated by freeze drying and dissolved in 2H2O to contain 120 O.D. units at 280 nm per 0.5 ml. 1H NMR spectroscopy was performed with the 5 mm probe of a Varian XL300 instrument. Creatine, lactate, carnosine, and choline were the major resonances in the one-dimensional spectra of both extracts. With creatine as reference, 2.5-fold more lactate was found in SCOL than in CP, and a much smaller difference was also found in their carnosine content. Two-dimensional COSY comparison revealed several differences between the two extracts. Taurine, N-acetyl glutamate, glycerophosphoryl choline (or phosphoryl choline) and an unidentified spot were present only in the extract from SCOL but not in that from CP. On the other hand, aspartate, hydroxy-proline, carnitine and glycerophosphoryl ethanolamine were only present in CP but absent in SCOL. Alanine, cysteine, lysine and arginine appeared in both extracts without an apparent intensity difference

  3. Self-Assemblies of novel molecules, VECAR

    Science.gov (United States)

    Shrestha, Bijay; Kim, Hye-Young; Lee, Soojin; Novak, Brian; Moldovan, Dorel

    2015-03-01

    VECAR is a newly synthesized molecule, which is an amphiphilic antioxidant molecule that consists of two molecular groups, vitamin-E and Carnosine, linked by a hydrocarbon chain. The hydrocarbon chain is hydrophobic and both vitamin-E and Carnosine ends are hydrophilic. In the synthesis process, the length of the hydrophobic chain of VECAR molecules can vary from the shortest (n =0) to the longest (n =18), where n indicates the number of carbon atoms in the chain. We conducted MD simulation studies of self-assembly of VECAR molecules in water using GROMACS on LONI HPC resources. Our study shows that there is a strong correlation between the shape and atomistic structure of the self-assembled nano-structures (SANs) and the chain-length (n) of VECAR molecules. We will report the results of data analyses including the atomistic structure of each SANs and the dynamic and energetic mechanisms of their formation as function of time. In summary, both VECAR molecules of chain-length n =18 and 9 form worm-like micelles, which may be used as a drug delivery system. This research is supported by the Louisiana Board of Regents-RCS Grant (LEQSF(2012-15)-RD-A-19).

  4. The effect of beta-alanine supplementation on neuromuscular fatigue in elderly (55–92 Years: a double-blind randomized study

    Directory of Open Access Journals (Sweden)

    Cramer Joel T

    2008-11-01

    Full Text Available Abstract Background Ageing is associated with a significant reduction in skeletal muscle carnosine which has been linked with a reduction in the buffering capacity of muscle and in theory, may increase the rate of fatigue during exercise. Supplementing beta-alanine has been shown to significantly increase skeletal muscle carnosine. The purpose of this study, therefore, was to examine the effects of ninety days of beta-alanine supplementation on the physical working capacity at the fatigue threshold (PWCFT in elderly men and women. Methods Using a double-blind placebo controlled design, twenty-six men (n = 9 and women (n = 17 (age ± SD = 72.8 ± 11.1 yrs were randomly assigned to either beta-alanine (BA: 800 mg × 3 per day; n = 12; CarnoSyn™ or Placebo (PL; n = 14 group. Before (pre and after (post the supplementation period, participants performed a discontinuous cycle ergometry test to determine the PWCFT. Results Significant increases in PWCFT (28.6% from pre- to post-supplementation were found for the BA treatment group (p Conclusion We suggest that BA supplementation, by improving intracellular pH control, improves muscle endurance in the elderly. This, we believe, could have importance in the prevention of falls, and the maintenance of health and independent living in elderly men and women.

  5. Analysis of human muscle extracts by proton NMR

    Energy Technology Data Exchange (ETDEWEB)

    Venkatasubramanian, P.N.; Barany, M.; Arus, C.

    1986-03-01

    Perchloric acid extracts were prepared from pooled human muscle biopsies from patients diagnosed with scoliosis (SCOL) and cerebral palsy (CP). After neutralization with KOH and removal of perchlorate, the extracts were concentrated by freeze drying and dissolved in /sup 2/H/sub 2/O to contain 120 O.D. units at 280 nm per 0.5 ml. /sup 1/H NMR spectroscopy was performed with the 5 mm probe of a Varian XL300 instrument. Creatine, lactate, carnosine, and choline were the major resonances in the one-dimensional spectra of both extracts. With creatine as reference, 2.5-fold more lactate was found in SCOL than in CP, and a much smaller difference was also found in their carnosine content. Two-dimensional COSY comparison revealed several differences between the two extracts. Taurine, N-acetyl glutamate, glycerophosphoryl choline (or phosphoryl choline) and an unidentified spot were present only in the extract from SCOL but not in that from CP. On the other hand, aspartate, hydroxy-proline, carnitine and glycerophosphoryl ethanolamine were only present in CP but absent in SCOL. Alanine, cysteine, lysine and arginine appeared in both extracts without an apparent intensity difference.

  6. Effect of heat stress on the serum concentrations of free amino acids and some of their metabolites in growing pigs.

    Science.gov (United States)

    Morales, A; Cota, S E M; Ibarra, N O; Arce, N; Htoo, J K; Cervantes, M

    2016-07-01

    Exposure to heat stress (HS) may affect the intestinal epithelia of pigs, resulting in impaired digestive and absorptive capacity. The serum concentration (SC) of free AA in pigs can be used as indicators of their availability. This study was conducted with 12 crossbred (Landrace × Hampshire × Duroc) pigs (29.0 ± 2.8 kg initial BW) distributed into 2 groups to analyze the SC of free AA and some AA metabolites in pigs exposed to HS conditions. The treatments were pigs housed under natural HS conditions in a room with no ambient temperature control (23.6 to 37.6°C, HS) and pigs housed at thermoneutral conditions (24 ± 2°C), feed restricted to a level similar to that of their HS counterparts. All pigs received a wheat-soybean meal diet. Blood samples were collected at both the absorptive (2.5 h after a meal) and postabsorptive (10.0 h after a meal) phase. At the absorptive phase, the SC of free Arg, Leu, Lys, Phe, Thr, and Trp were lower ( carnosine, ornithine (Orn), and Tau were lower ( carnosine and sarcosine ( < 0.05) decreased in HS pigs. The results of this study show a marked and differential effect of HS on the SC of AA. These data indicate that HS negatively affects the digestive and absorptive capacity of pigs and that the metabolism of some AA is modified in pigs to counteract the negative effects of the HS. PMID:27482670

  7. Separation and detection of amino acid metabolites of Escherichia coli in microbial fuel cell with CE.

    Science.gov (United States)

    Wang, Wei; Ma, Lihong; Lin, Ping; Xu, Kaixuan

    2016-07-01

    In this work, CE-LIF was employed to investigate the amino acid metabolites produced by Escherichia coli (E. coli) in microbial fuel cell (MFC). Two peptides, l-carnosine and l-alanyl-glycine, together with six amino acids, cystine, alanine, lysine, methionine, tyrosine, arginine were separated and detected in advance by a CE-LIF system coupled with a homemade spontaneous injection device. The injection device was devised to alleviate the effect of electrical discrimination for analytes during sample injection. All analytes could be completely separated within 8 min with detection limits of 20-300 nmol/L. Then this method was applied to analyze the substrate solution containing amino acid metabolites produced by E. coli. l-carnosine, l-alanyl-glycine, and cystine were used as the carbon, nitrogen, and sulfur source for the E. coli culture in the MFC to investigate the amino acid metabolites during metabolism. Two MFCs were used to compare the activity of metabolism of the bacteria. In the sample collected at the running time 200 h of MFC, the amino acid methionine was discovered as the metabolite with the concentrations 23.3 μg/L. PMID:27121957

  8. Separation of Key Biogenic Amines by Capillary Electrophoresis and Determination of Possible Indicators of Sport Fatigue in Athlete's Urine.

    Science.gov (United States)

    He, Lili; Ren, Jie; Shi, Zhihao; Xu, Zhongqi

    2016-09-01

    This article aims to build up a simple, rapid and accurate capillary zone electrophoresis (CZE) method for the separation of biogenic amines (BAs). Here, 10 key BAs (phenethylamine, histamine, tryptamine, tyramine, 5-hydroxytryptamine, octopamine, dopamine, norepinephrine, epinephrine and carnosine) owning significant functions were chosen for method development. The baseline separation and identification of 10 standards of the mixture by CZE were eventually achieved in 150.0 mmol/L phosphate buffer (Na2HPO4-NaH2PO4) containing 1.0 mmol/L borax at a pH of 6.1. The addition of borax was found effective for improving the isomeric separation of octopamine and dopamine. The proposed method allowed the limits of detections of BAs to be in the range of 0.2-1.2 µmol/L at UV detection (200 nm); the relative standard deviation of the migration time and the peak area were in the ranges 0.08-0.12 and 2.74-4.63% (n = 5), respectively. Formaldehyde (a possible antiseptic in urine) and five main matrices in urine were studied for the identification of BAs. Finally, profiling of BAs in actual urine from athletes was carried out. Currently, only phenethylamine, norepinephrine and carnosine were designated by spiking the standards. In addition, their variation in athletes' urine has been checked at different states of sport fatigue with the goal of obtaining possible indicators of sport fatigue. PMID:27139740

  9. Carnosinases, Their Substrates and Diseases

    Directory of Open Access Journals (Sweden)

    Francesco Bellia

    2014-02-01

    Full Text Available Carnosinases are Xaa-His dipeptidases that play diverse functions throughout all kingdoms of life. Human isoforms of carnosinase (CN1 and CN2 under appropriate conditions catalyze the hydrolysis of the dipeptides carnosine (β-alanyl-L-histidine and homocarnosine (γ-aminobutyryl-L-histidine. Alterations of serum carnosinase (CN1 activity has been associated with several pathological conditions, such as neurological disorders, chronic diseases and cancer. For this reason the use of carnosinase levels as a biomarker in cerebrospinal fluid (CSF has been questioned. The hydrolysis of imidazole-related dipeptides in prokaryotes and eukaryotes is also catalyzed by aminoacyl-histidine dipeptidases like PepD (EC 3.4.13.3, PepV (EC 3.4.13.19 and anserinase (EC 3.4.13.5. The review deals with the structure and function of this class of enzymes in physiological and pathological conditions. The main substrates of these enzymes, i.e., carnosine, homocarnosine and anserine (β-alanyl-3-methyl-L-histidine will also be described.

  10. Inhibitory effect of polaprezinc on the inflammatory response to Helicobacter pylori.

    Science.gov (United States)

    Handa, Osamu; Yoshida, Norimasa; Tanaka, Yukiko; Ueda, Miho; Ishikawa, Takeshi; Takagi, Tomohisa; Matsumoto, Naoyuki; Naito, Yuji; Yoshikawa, Toshikazu

    2002-11-01

    Helicobacter pylori-infected gastrointestinal mucosa is frequently infiltrated by polymorphonuclear leukocytes (PMN) and monocytes, and these invading cells have been implicated in gastrointestinal mucosal inflammation. To clarify the efficacy of polaprezinc, a chelate compound consisting of zinc and L-carnosine, against H pylori-induced inflammation including PMN infiltration, the in vitro effects of this drug on interleukin (IL)-8 production by an established gastric cancer cell line (MKN 45 cells) and on PMN-endothelial cell adhesive interactions was investigated. Polaprezinc and zinc sulphate inhibited IL-8 production by MKN 45 cells in response to stimulation with H pylori water extract (HPE) in a dose-dependent manner from 10(-7) M to 10(-5) M. In addition, the expression of CD11b and CD18 on PMN and PMN-dependent adhesion to endothelial cells elicited by HPE was inhibited by polaprezinc and zinc sulphate in a concentration-dependent manner. L-carnosine did not have any effects on IL-8 production or PMN-endothelial cell interactions. These results suggest that polaprezinc, mainly the zinc component, may inhibit H pylori-induced PMN-mediated gastric inflammation by attenuating CD11b/CD18 expression on PMN and IL-8 production from gastric epithelial cells. PMID:12464972

  11. Induction of type 1 interferon receptor by zinc in U937 cells.

    Science.gov (United States)

    Nagamine, Takeaki; Nakajima, Kastuyuki; Takada, Hisashi; Sekine, Yoshitaka; Suzuki, Kazuhiro

    2009-06-01

    This study aims to determine whether zinc enhances interferon (IFN)-alpha activity in U937 cells. Type 1 IFN2 receptor (IFNAR2) protein in U937 cells was measured by flow cytometry. After 24h of exposure to zinc chloride or polaprezinc (a chelate of zinc and L-carnosine) at concentrations ranging from 50 to 200 microM, histograms showing anti-IFNAR2 antibody-positive cells shifted to a higher FITC intensity. Zinc chloride and polaprezinc increased IFNAR2 mRNA levels approximately 30% and 40%, respectively, compared to the control. L-carnosine alone did not alter IFNAR2 mRNA or protein levels. Cellular levels of 2'-5' oligoadenylate synthetases (OAS) were markedly increased by IFN-alpha, and the increase was significantly accelerated by polaprezinc. However, polaprezinc alone did not increase 2'-5'OAS levels. The finding suggests that zinc, especially polaprezinc, enhances the expression of INFAR2 in U937 cells, thereby inducing production of the anti-viral protein 2'-5'OAS. PMID:19362011

  12. The effects of polaprezinc on radiation-induced taste alterations

    International Nuclear Information System (INIS)

    The effects of polaprezinc (an insoluble zinc complex of L-carnosine) on taste abnormalities were investigated in 22 patients receiving radiation therapy to head and neck malignancies. The total doses to the tongue were 25.5-46.0 Gy (mean, 37.9 Gy). All patients received 75 mg of polaprezinc two times a day with an interval of 0-1,561 days (mean, 305.3 days) after the completion of radiation therapy. The duration of the drug administration was 25-353 days (mean, 96.9 days). Twenty patients (90.9%) were aware of an improvement of a partial or complete loss of taste. Polaprezinc is effective in improving loss of taste after radiation therapy. (author)

  13. Possible new antiaging strategies related to neuroendocrine-immune interactions.

    Science.gov (United States)

    Mocchegiani, Eugenio; Malavolta, Marco

    2008-01-01

    The aging process demonstrates gradual and spontaneous changes, resulting in maturation through childhood, puberty and young adulthood, and then decline through middle and late age. However, animals and humans are capable of reaching the extreme limit of life span characteristic for the species with a very efficient network of antiaging mechanisms. Among them, neuroendocrine-immune interactions play a pivotal role. The loss of the capacity of the organism in remodeling the neuroendocrine-immune response leads to the appearance of age-associated pathologies. We herein report some substances which can be proposed as new antiaging strategies because of their capacity to remodel some biological functions in old animals and humans. These substances are: L-deprenyl, leptin, ghrelin, carnosine and NO donors. Their role as possible antiaging strategies in healthy people in relation to neuroendocrine-immune responses and zinc ion bioavailability is reported and discussed. PMID:19047810

  14. Effect of ethanol consumption during gestation on maternal-fetal amino acid metabolism in the rat

    International Nuclear Information System (INIS)

    The distribution of 14C-alpha-aminoisobutyric acid (AIB), administered intravenously, in maternal, fetal and placental tissues was examined in the rat on gestation-day 21. Ethanol consumption during gestation (day 6 through 21) significantly reduced the uptake of AIB by the placenta and fetus while exerting no influence on maternal tissue AIB uptake. The concentration of fetal plasma free histidine was decreased 50% as a result of maternal ethanol ingestion, but the free histidine level of maternal plasma was not altered. Since no effect on protein content of fetal tissue could be detected, it is speculated that reduced histidine to the fetus might significantly alter the amounts of histamine and carnosine formed via their precursor. The significance of these findings in relation to the Fetal Alcohol Syndrome is discussed

  15. The Effect of Chicken Extract on Mood, Cognition and Heart Rate Variability

    Directory of Open Access Journals (Sweden)

    Hayley Young

    2015-01-01

    Full Text Available Chicken extract, which is rich in anserine and carnosine, has been widely taken in Asian countries as a traditional remedy with various aims, including attenuation of psychological fatigue. The effects of consuming BRAND’S Essence of Chicken (EOC or a placebo on 46 young adults’ responses to a standard psychological “stressor” were considered. Heart rate variability (HRV, cortisol responses, mood and cognition were measured at baseline and after ten days supplementation. EOC resulted in feeling less anxious, depressed and confused and more agreeable and clearheaded. A decrease in HRV was observed after EOC but only in females. Cognition and cortisol levels were not influenced by EOC. Findings suggest that EOC may be a promising supplement to improve mood in a healthy population.

  16. The effects of polaprezinc on radiation-induced taste alterations

    Energy Technology Data Exchange (ETDEWEB)

    Nakamura, Katsumasa; Togao, Osamu [Kyushu Univ., Fukuoka (Japan). Graduate School of Medical Sciences; Shikama, Naoto (and others)

    2001-06-01

    The effects of polaprezinc (an insoluble zinc complex of L-carnosine) on taste abnormalities were investigated in 22 patients receiving radiation therapy to head and neck malignancies. The total doses to the tongue were 25.5-46.0 Gy (mean, 37.9 Gy). All patients received 75 mg of polaprezinc two times a day with an interval of 0-1,561 days (mean, 305.3 days) after the completion of radiation therapy. The duration of the drug administration was 25-353 days (mean, 96.9 days). Twenty patients (90.9%) were aware of an improvement of a partial or complete loss of taste. Polaprezinc is effective in improving loss of taste after radiation therapy. (author)

  17. [Zinc and gastrointestinal disorders].

    Science.gov (United States)

    Higashimura, Yasuki; Takagi, Tomohisa; Naito, Yuji

    2016-07-01

    Zinc, an essential trace element, affects immune responses, skin metabolism, hormone composition, and some sensory function, so that the deficiency presents various symptoms such as immunodeficiency and taste obstacle. Further, the zinc deficiency also considers as a risk of various diseases. Recent reports demonstrated that -20% of the Japanese population was marginally zinc deficiency, and over 25% of the global population is at high risk of zinc deficiency. In gastrointestinal disorders, zinc plays an important role in the healing of mucosal and epithelial damage. In fact, polaprezinc, a chelate compound of zinc and L-carnosine, has been used for the treatment of gastric ulcer and gastritis. We describe here the therapeutic effect of zinc on gastrointestinal disorders. PMID:27455800

  18. Effect of ethanol consumption during gestation on maternal-fetal amino acid metabolism in the rat

    Energy Technology Data Exchange (ETDEWEB)

    Lin, G.W.

    1981-01-01

    The distribution of /sup 14/C-alpha-aminoisobutyric acid (AIB), administered intravenously, in maternal, fetal and placental tissues was examined in the rat on gestation-day 21. Ethanol consumption during gestation (day 6 through 21) significantly reduced the uptake of AIB by the placenta and fetus while exerting no influence on maternal tissue AIB uptake. The concentration of fetal plasma free histidine was decreased 50% as a result of maternal ethanol ingestion, but the free histidine level of maternal plasma was not altered. Since no effect on protein content of fetal tissue could be detected, it is speculated that reduced histidine to the fetus might significantly alter the amounts of histamine and carnosine formed via their precursor. The significance of these findings in relation to the Fetal Alcohol Syndrome is discussed.

  19. Use of antioxidants to reduce lipid oxidation and off-odor volatiles of irradiated pork homogenates and patties.

    Science.gov (United States)

    Nam, K C; Ahn, D U

    2003-01-01

    Pork homogenates and patties treated with antioxidants (200 μM, final) were irradiated with an electron beam. Lipid oxidation of the pork homogenates and patties were determined at day 0 and 5 and volatile compounds were analyzed soon after irradiation. Ionizing radiation accelerated lipid oxidation and produced S-containing volatiles in pork homogenates and patties. Addition of an antioxidant (sesamol, gallate, Trolox, or α-tocopherol) and their combinations decreased, but carnosine did not affect the production of off-odor volatiles and lipid oxidation of pork homogenates and patties by irradiation. Antioxidant combinations showed distinct beneficial reduction in lipid oxidation of aerobically packaged irradiated pork patties. The effect of antioxidant combinations in reducing sulfur volatiles of irradiated pork patties was clearer under vacuum than aerobic conditions. PMID:22061977

  20. Does chronic glycolysis accelerate aging? Could this explain how dietary restriction works?

    Science.gov (United States)

    Hipkiss, Alan R

    2006-05-01

    The mechanisms by which dietary restriction (DR) suppresses aging are not understood. Suppression of glycolysis by DR could contribute to controlling senescence. Many glycolytic intermediates can glycate proteins and other macromolecules. Methyglyoxal (MG), formed from dihydroxyacetone- and glyceraldehyde-3-phosphates, rapidly glycates proteins, damages mitochondria, and induces a prooxidant state to create a senescent-like condition. Ad libitum-fed and DR animals differ in mitochondrial activity and glycolytic flux rates. Persistent glycolysis in the unrestricted condition would increase the intracellular load of glycating agents (e.g., MG) and increase ROS generation by inactive mitochondria. Occasional glycolysis during DR would decrease MG and reactive oxygen species (ROS) production and could be hormetic, inducing synthesis of glyoxalase-1 and anti-glycating agents (carnosine and polyamines). PMID:16804012

  1. Individual variability in human blood metabolites identifies age-related differences

    Science.gov (United States)

    Murakami, Itsuo; Takada, Junko; Kondoh, Hiroshi; Yanagida, Mitsuhiro

    2016-01-01

    Metabolites present in human blood document individual physiological states influenced by genetic, epigenetic, and lifestyle factors. Using high-resolution liquid chromatography-mass spectrometry (LC-MS), we performed nontargeted, quantitative metabolomics analysis in blood of 15 young (29 ± 4 y of age) and 15 elderly (81 ± 7 y of age) individuals. Coefficients of variation (CV = SD/mean) were obtained for 126 blood metabolites of all 30 donors. Fifty-five RBC-enriched metabolites, for which metabolomics studies have been scarce, are highlighted here. We found 14 blood compounds that show remarkable age-related increases or decreases; they include 1,5-anhydroglucitol, dimethyl-guanosine, acetyl-carnosine, carnosine, ophthalmic acid, UDP-acetyl-glucosamine, N-acetyl-arginine, N6-acetyl-lysine, pantothenate, citrulline, leucine, isoleucine, NAD+, and NADP+. Six of them are RBC-enriched, suggesting that RBC metabolomics is highly valuable for human aging research. Age differences are partly explained by a decrease in antioxidant production or increasing inefficiency of urea metabolism among the elderly. Pearson’s coefficients demonstrated that some age-related compounds are correlated, suggesting that aging affects them concomitantly. Although our CV values are mostly consistent with those CVs previously published, we here report previously unidentified CVs of 51 blood compounds. Compounds having moderate to high CV values (0.4–2.5) are often modified. Compounds having low CV values, such as ATP and glutathione, may be related to various diseases because their concentrations are strictly controlled, and changes in them would compromise health. Thus, human blood is a rich source of information about individual metabolic differences. PMID:27036001

  2. High Levels of Dietary Supplement Vitamins A, C and E are Absorbed in the Small Intestine and Protect Nutrient Transport Against Chronic Gamma Irradiation.

    Science.gov (United States)

    Roche, Marjolaine; Neti, Prasad V S V; Kemp, Francis W; Azzam, Edouard I; Ferraris, Ronaldo P; Howell, Roger W

    2015-11-01

    We examined nutrient transport in the intestines of mice exposed to chronic low-LET 137Cs gamma rays. The mice were whole-body irradiated for 3 days at dose rates of 0, 0.13 and 0.20 Gy/h, for total dose delivery of 0, 9.6 or 14.4 Gy, respectively. The mice were fed either a control diet or a diet supplemented with high levels of vitamins A, C and E. Our results showed that nutrient transport was perturbed by the chronic irradiation conditions. However, no apparent alteration of the macroscopic intestinal structures of the small intestine were observed up to day 10 after initiating irradiation. Jejunal fructose uptake measured in vitro was strongly affected by the chronic irradiation, whereas uptake of proline, carnosine and the bile acid taurocholate in the ileum was less affected. D-glucose transport did not appear to be inhibited significantly by either 9.6 or 14.4 Gy exposure. In the 14.4 Gy irradiated groups, the diet supplemented with high levels of vitamins A, C and E increased intestinal transport of fructose compared to the control diet (day 10; t test, P = 0.032), which correlated with elevated levels of vitamins A, C and E in the plasma and jejunal enterocytes. Our earlier studies with mice exposed acutely to 137Cs gamma rays demonstrated significant protection for transport of fructose, glucose, proline and carnosine. Taken together, these results suggest that high levels of vitamins A, C and E dietary supplements help preserve intestinal nutrient transport when intestines are irradiated chronically or acutely with low-LET gamma rays. PMID:26484399

  3. Antioxidant status of turkey breast meat and blood after feeding a diet enriched with histidine.

    Science.gov (United States)

    Kopec, W; Wiliczkiewicz, A; Jamroz, D; Biazik, E; Pudlo, A; Hikawczuk, T; Skiba, T; Korzeniowska, M

    2016-01-01

    The objective of this study was to investigate the effects of 1) spray dried blood cells rich in histidine and 2) pure histidine added to feed on the antioxidant status and concentration of carnosine related components in the blood and breast meat of female turkeys. The experiment was performed on 168 Big7 turkey females randomly assigned to 3 dietary treatments: control; control with the addition of 0.18% L-histidine (His); and control with the addition of spray dried blood cells (SDBC). Birds were raised for 103 d on a floor with sawdust litter, with drinking water and feed ad libitum. The antioxidant status of blood plasma and breast muscle was analyzed by ferric reducing ability (FRAP) and by 2,2-Azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and 1,1-Diphenyl-2-picrylhydrazyl (DPPH) radicals scavenging ability. The activity of antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) was analyzed in the blood and breast meat, with the content of carnosine and anserine quantified by HPLC. Proximate analysis as well as amino acid profiling were carried out for the feed and breast muscles. Growth performance parameters also were calculated. Histidine supplementation of the turkey diet resulted in increased DPPH radical scavenging capacity in the breast muscles and blood, but did not result in higher histidine dipeptide concentrations. The enzymatic antioxidant system of turkey blood was affected by the diet with SDBC. In the plasma, the SDBC addition increased both SOD and GPx activity, and decreased GPx activity in the erythrocytes. Feeding turkeys with an SDBC containing diet increased BW and the content of isoleucine and valine in breast muscles. PMID:26574038

  4. A combined enrichment and aptamer pulldown assay for Francisella tularensis detection in food and environmental matrices.

    Directory of Open Access Journals (Sweden)

    Elise A Lamont

    Full Text Available Francisella tularensis, a Gram-negative bacterium and causative agent of tularemia, is categorized as a Class A select agent by the Centers for Disease Control and Prevention due to its ease of dissemination and ability to cause disease. Oropharyngeal and gastrointestinal tularemia may occur due to ingestion of contaminated food and water. Despite the concern to public health, little research is focused on F. tularensis detection in food and environmental matrices. Current diagnostics rely on host responses and amplification of F. tularensis genetic elements via Polymerase Chain Reaction; however, both tools are limited by development of an antibody response and limit of detection, respectively. During our investigation to develop an improved culture medium to aid F. tularensis diagnostics, we found enhanced F. tularensis growth using the spent culture filtrate. Addition of the spent culture filtrate allowed for increased detection of F. tularensis in mixed cultures of food and environmental matrices. Ultraperformance liquid chromatography (UPLC/MS analysis identified several unique chemicals within the spent culture supernatant of which carnosine had a matching m/z ratio. Addition of 0.625 mg/mL of carnosine to conventional F. tularensis medium increased the growth of F. tularensis at low inoculums. In order to further enrich F. tularensis cells, we developed a DNA aptamer cocktail to physically separate F. tularensis from other bacteria present in food and environmental matrices. The combined enrichment steps resulted in a detection range of 1-106 CFU/mL (starting inoculums in both soil and lettuce backgrounds. We propose that the two-step enrichment process may be utilized for easy field diagnostics and subtyping of suspected F. tularensis contamination as well as a tool to aid in basic research of F. tularensis ecology.

  5. Individual variability in human blood metabolites identifies age-related differences.

    Science.gov (United States)

    Chaleckis, Romanas; Murakami, Itsuo; Takada, Junko; Kondoh, Hiroshi; Yanagida, Mitsuhiro

    2016-04-19

    Metabolites present in human blood document individual physiological states influenced by genetic, epigenetic, and lifestyle factors. Using high-resolution liquid chromatography-mass spectrometry (LC-MS), we performed nontargeted, quantitative metabolomics analysis in blood of 15 young (29 ± 4 y of age) and 15 elderly (81 ± 7 y of age) individuals. Coefficients of variation (CV = SD/mean) were obtained for 126 blood metabolites of all 30 donors. Fifty-five RBC-enriched metabolites, for which metabolomics studies have been scarce, are highlighted here. We found 14 blood compounds that show remarkable age-related increases or decreases; they include 1,5-anhydroglucitol, dimethyl-guanosine, acetyl-carnosine, carnosine, ophthalmic acid, UDP-acetyl-glucosamine,N-acetyl-arginine,N6-acetyl-lysine, pantothenate, citrulline, leucine, isoleucine, NAD(+), and NADP(+) Six of them are RBC-enriched, suggesting that RBC metabolomics is highly valuable for human aging research. Age differences are partly explained by a decrease in antioxidant production or increasing inefficiency of urea metabolism among the elderly. Pearson's coefficients demonstrated that some age-related compounds are correlated, suggesting that aging affects them concomitantly. Although our CV values are mostly consistent with those CVs previously published, we here report previously unidentified CVs of 51 blood compounds. Compounds having moderate to high CV values (0.4-2.5) are often modified. Compounds having low CV values, such as ATP and glutathione, may be related to various diseases because their concentrations are strictly controlled, and changes in them would compromise health. Thus, human blood is a rich source of information about individual metabolic differences. PMID:27036001

  6. The effects of 10 weeks of resistance training combined with beta-alanine supplementation on whole body strength, force production, muscular endurance and body composition.

    Science.gov (United States)

    Kendrick, Iain P; Harris, Roger C; Kim, Hyo Jeong; Kim, Chang Keun; Dang, Viet H; Lam, Thanh Q; Bui, Toai T; Smith, Marcus; Wise, John A

    2008-05-01

    Carnosine (Carn) occurs in high concentrations in skeletal muscle is a potent physico-chemical buffer of H+ over the physiological range. Recent research has demonstrated that 6.4 g x day(-1) of beta-alanine (beta-ala) can significantly increase skeletal muscle Carn concentrations (M-[Carn]) whilst the resultant change in buffering capacity has been shown to be paralleled by significant improvements in anaerobic and aerobic measures of exercise performance. Muscle carnosine increase has also been linked to increased work done during resistance training. Prior research has suggested that strength training may also increase M-[Carn] although this is disputed by other studies. The aim of this investigation is to assess the effect of 10 weeks resistance training on M-[Carn], and, secondly, to investigate if increased M-[Carn] brought about through beta-ala supplementation had a positive effect on training responses. Twenty-six Vietnamese sports science students completed the study. The subjects completed a 10-week resistance-training program whilst consuming 6.4 g x day(-1) of beta-ala (beta-ALG) or a matched dose of a placebo (PLG). Subjects were assessed prior to and after training for whole body strength, isokinetic force production, muscular endurance, body composition. beta-Alanine supplemented subjects increased M-[Carn] by 12.81 +/- 7.97 mmol x kg(-1) dry muscle whilst there was no change in PLG subjects. There was no significant effect of beta-ala supplementation on any of the exercise parameters measured, mass or % body fat. In conclusion, 10 weeks of resistance training alone did not change M-[Carn]. PMID:18175046

  7. A transient increase in lipid peroxidation primes preadipocytes for delayed mitochondrial inner membrane permeabilization and ATP depletion during prolonged exposure to fatty acids.

    Science.gov (United States)

    Rogers, Carlyle; Davis, Barbara; Neufer, P Darrell; Murphy, Michael P; Anderson, Ethan J; Robidoux, Jacques

    2014-02-01

    Preadipocytes are periodically subjected to fatty acid (FA) concentrations that are potentially cytotoxic. We tested the hypothesis that prolonged exposure of preadipocytes of human origin to a physiologically relevant mix of FAs leads to mitochondrial inner membrane (MIM) permeabilization and ultimately to mitochondrial crisis. We found that exposure of preadipocytes to FAs led to progressive cyclosporin A-sensitive MIM permeabilization, which in turn caused a reduction in MIM potential, oxygen consumption, and ATP synthetic capacity and, ultimately, death. Additionally, we showed that FAs induce a transient increase in intramitochondrial reactive oxygen species (ROS) and lipid peroxide production, lasting roughly 30 and 120min for the ROS and lipid peroxides, respectively. MIM permeabilization and its deleterious consequences including mitochondrial crisis and cell death were prevented by treating the cells with the mitochondrial FA uptake inhibitor etomoxir, the mitochondrion-selective superoxide and lipid peroxide antioxidants MitoTempo and MitoQ, or the lipid peroxide and reactive carbonyl scavenger l-carnosine. FAs also promoted a delayed oxidative stress phase. However, the beneficial effects of etomoxir, MitoTempo, and l-carnosine were lost by delaying the treatment by 2h, suggesting that the initial phase was sufficient to prime the cells for the delayed MIM permeabilization and mitochondrial crisis. It also suggested that the second ROS production phase is a consequence of this loss in mitochondrial health. Altogether, our data suggest that approaches designed to diminish intramitochondrial ROS or lipid peroxide accumulation, as well as MIM permeabilization, are valid mechanism-based therapeutic avenues to prevent the loss in preadipocyte metabolic fitness associated with prolonged exposure to elevated FA levels. PMID:24269897

  8. N-Acetylcarnosine sustained drug delivery eye drops to control the signs of ageless vision: Glare sensitivity, cataract amelioration and quality of vision currently available treatment for the challenging 50,000-patient population

    Directory of Open Access Journals (Sweden)

    Mark A Babizhayev

    2008-10-01

    Full Text Available Mark A Babizhayev1, Leslie Burke2, Philip Micans3, Stuart P Richer4,51Innovative Vision Products, Inc., County of New Castle, Delaware, USA; 2Wise Choice Products LLC, London, England, United Kingdom; 3IAS Group, Sark, United Kingdom; 4Eye Clinic DVA Medical Center, North Chicago, Illinois, USA; 5Department of Family and Preventive Medicine, Rosalind Franklin University of Medicine and Science, North Chicago, Illinois, USABackground: Innovative Vision Products, Inc. (IVP’s scientists developed the lubricant eye drops (Can-C™ designed as 1% N-acetylcarnosine (NAC prodrug of L-carnosine containing a mucoadhesive cellulose-based compound combined with corneal absorption promoters in a sustained drug delivery system. Only the natural L-isomeric form of NAC raw material was specifically synthesized at the cGMP facility and employed for the manufacturing of Can-C™ eye drops.Objective and study design: In the present clinical study the authors assessed vision before and after 9 month term of topical ocular administration of NAC lubricant eye drops or placebo in 75 symptomatic patients with age-related uncomplicated cataracts in one or both eyes, with acuity in one eye of 20/40 or worse (best-corrected distance, and no previous cataract surgery in either eye and no other ocular abnormality and 72 noncataract subjects ranged in age from 54 to 78 years.Setting: Subjects in these subsample groups have reported complaints of glare and wanted to administer eye drops to get quick eye relief and quality of vision for their daily activities including driving and computer works. Following 9 months of treatment with NAC lubricant eye drops, most patients’ glare scores were improved or returned to normal in disability glare tests with Halometer DG. Improvement in disability glare was accompanied with independent improvement in acuity. Furthermore, patients with the poorest pretreatment vision were as likely to regain certain better visual function after 9

  9. Proton-dependent zinc release from intracellular ligands.

    Science.gov (United States)

    Kiedrowski, Lech

    2014-07-01

    In cultured cortical and hippocampal neurons when intracellular pH drops from 6.6 to 6.1, yet unclear intracellular stores release micromolar amounts of Zn(2+) into the cytosol. Mitochondria, acidic organelles, and/or intracellular ligands could release this Zn(2+) . Although exposure to the protonophore FCCP precludes reloading of the mitochondria and acidic organelles with Zn(2+) , FCCP failed to compromise the ability of the intracellular stores to repeatedly release Zn(2+) . Therefore, Zn(2+) -releasing stores were not mitochondria or acidic organelles but rather intracellular Zn(2+) ligands. To test which ligands might be involved, the rate of acid-induced Zn(2+) release from complexes with cysteine, glutathione, histidine, aspartate, glutamate, glycine, and carnosine was investigated; [Zn(2+) ] was monitored in vitro using the ratiometric Zn(2+) -sensitive fluorescent probe FuraZin-1. Carnosine failed to chelate Zn(2+) but did chelate Cu(2+) ; the remaining ligands chelated Zn(2+) and upon acidification were releasing it into the medium. However, when pH was decreasing from 6.6 to 6.1, only zinc-cysteine complexes rapidly accelerated the rate of Zn(2+) release. The zinc-cysteine complexes also released Zn(2+) when a histidine-modifying agent, diethylpyrocarbonate, was applied at pH 7.2. Since the cytosolic zinc-cysteine complexes can contain micromolar amounts of Zn(2+) , these complexes may represent the stores responsible for an acid-induced intracellular Zn(2+) release. This study aimed at identifying intracellular stores which release Zn(2+) when pHi drops from 6.6 to 6.1. It was found that these stores are not mitochondria or acidic organelles, but rather intracellular Zn(2+) ligands. When the pH was decreasing from 6.6 to 6.1, only zinc-cysteine complexes showed a rapid acceleration in the rate of Zn(2+) release. Therefore, the stores responsible for an acid-induced intracellular Zn(2+) release in neurons may be the cytosolic zinc-cysteine complexes

  10. Polaprezinc prevents oral mucositis associated with radiochemotherapy in patients with head and neck cancer.

    Science.gov (United States)

    Watanabe, Tomoko; Ishihara, Masashi; Matsuura, Katsuhiko; Mizuta, Keisuke; Itoh, Yoshinori

    2010-10-15

    Oral mucositis is frequent but serious adverse event associated with radiotherapy or radiochemotherapy in head and neck cancer severely impairs health-related quality of life, leading to poor prognosis due to discontinuation of the therapy. Although a number of compounds have been tested for prophylaxis of oral mucositis, few of them are satisfactory. We investigated the effect of polaprezinc (zinc L-carnosine), a gastric mucosal protective drug, on radiochemotherapy-induced oral mucositis, pain, xerostomia and taste disturbance in patients with head and neck cancer. Patients were randomly assigned to receive polaprezinc (n = 16) or azulene oral rinse as the control (n = 15). The incidence rates of mucositis, pain, xerostomia and taste disturbance were all markedly lower in polaprezinc group than in control. Moreover, the use of analgesics was significantly (p = 0.003) less frequent and the amount of food intake was significantly (p = 0.002) higher in polaprezinc group than in control. On the other hand, tumor response rate in patients with neoadjuvant radiochemotherapy was not significantly affected by polaprezinc, in which the response rate (complete plus partial response) was 88% for polaprezinc and 92% for control (p = 1.000). Therefore, it is highly assumable that polaprezinc is potentially useful for prevention of oral mucositis and improvement of quality of life without reducing the tumor response. PMID:20104529

  11. Protection by polaprezinc against radiation-induced apoptosis in rat jejunal crypt cells

    International Nuclear Information System (INIS)

    Polaprezinc, an anti-ulcer drug, is a chelate compound consisting of zinc and L-carnosine. Polaprezinc has been shown to prevent gastric mucosal injury. The anti ulcer effects of polaprezinc have been ascribed to its antioxidative property. The effect of polaprezinc on ionizing radiation-induced apoptosis was studied in the jejunal epithelial crypt cells of rats. Seven-to eight week-old Wistar rats, which were treated with 100 mg/kg of polaprezinc orally 1 h before irradiation or 2% carboxymethyl cellulose sodium in controls, were exposed to whole body X-ray irradiation at 2 Gy. The number of apoptotic cells per jejunum crypt was counted in haematoxylin and eosin stained sections at 0-6 h after irradiation. TdT-mediated dUTP-biotin nick end-labeling (TUNEL) positive cells and immunopositive cells for active caspase-3 per crypt were also counted. Accumulation of p53, p21WAF1/CIP1 and Bax expression in the jejunum after irradiation were examined by Western blot analyses. Polaprezinc treatment given prior to radiation resulted in a significant reduction in numbers of apoptotic cells, TUNEL positive cells and active caspase-3 immunopositive cells in jejunal crypt cells. Polaprezinc treatment resulted in decreases of p53 accumulation, p21WAF1/CIP1 and Bax expression after irradiation. Polaprezinc has a protective effect against ionizing radiation induced apoptosis in rat jejunal crypt cells. (author)

  12. Disruption of zinc homeostasis and the pathogenesis of senile dementia.

    Science.gov (United States)

    Kawahara, Masahiro; Mizuno, Dai; Koyama, Hironari; Konoha, Keiko; Ohkawara, Susumu; Sadakane, Yutaka

    2014-02-01

    Zinc (Zn) is an essential trace element that is abundantly present in the brain. Although Zn plays crucial roles in learning and memory, numerous studies have indicated that the disruption of Zn homeostasis, namely both depletion and excess Zn, causes severe damage to neurons and is linked with various neurodegenerative diseases including Alzheimer's disease and vascular dementia. Here, we review the current understanding of the role of Zn in the pathogenesis of these neurodegenerative diseases. Based on our findings and other numerous studies, Zn acts as a contributor to Alzheimer's disease in the oligomerization, and as a protector in the neurotoxicity of Alzheimer's β-amyloid protein. Furthermore, Zn plays a central role in ischemia-induced neuronal death and the pathogenesis of vascular dementia. Involvement of Ca(2+) dyshomeostasis and endoplasmic reticulum (ER) stress in the mechanism of Zn-induced neurotoxicity are suggested. We also discuss the possible role of carnosine (β-alanyl histidine), a dipeptide that is present in the brain, as a protective substance for neuronal injury. PMID:24247360

  13. Effect of polaprezinc on taste disorders in zinc-deficient rats.

    Science.gov (United States)

    Hamano, Hiroki; Yoshinaga, Koji; Eta, Runa; Emori, Yutaka; Kawasaki, Daisuke; Iino, Yuka; Sawada, Miwa; Kuroda, Hiroyuki; Takei, Mineo

    2006-01-01

    The effect of polaprezinc, a chelate compound consisting of zinc ion and L-carnosine, on abnormalities of taste sensation induced by feeding a zinc-deficient diet to rats was examined by using the two-bottle preference test (quinine hydrochloride as a bitter taste and sodium chloride as a salty taste). Rats were fed either a zinc-deficient or a zinc-sufficient diet. The zinc-deficient diet increased the preference for both taste solutions, while polaprezinc (at doses of 3 and 10 mg/kg) restored the altered taste preferences. We also evaluated the proliferation of taste bud cells using 5-bromo-2'-deoxyuridine (BrdU). The BrdU incorporation into taste bud cells was significantly reduced in rats fed a zinc-deficient diet compared with rats fed a zinc-sufficient diet (from 50.8% to 45.0%, pzinc deficiency induces the delayed of proliferation of taste bud cells, while polaprezinc improves cell proliferation. In conclusion, polaprezinc had a therapeutic effect in a rat model of abnormal taste sensation. Its mechanism of action was suggested to involve improvement of the decrease in taste bud cell proliferation caused by zinc deficiency. PMID:17473379

  14. [Development of polaprezinc research].

    Science.gov (United States)

    Takei, Mineo

    2012-01-01

    Zinc, one of essential trace elements, functions as a structural component in more than 300 different enzymes in the human body, playing crucial roles in performing a number of functions, including protein and DNA synthesis. Also hereditary or dietary zinc deficiency leading to pathological changes such as growth retardation, skin symptoms and taste disorders in human has been well investigated. Polaprezinc (Promac(®), Zeria Pharmaceutical Co., Ltd.), a chelate compound consisting of zinc and L-carnosine, is a zinc-related medicine approved for the first time in Japan, which has been clinically used to treat gastric ulcers. Its mechanism of action is believed to oxygen radical scavenging, anti-oxidation, and acceleration of wound healing. Further, as zinc deficiency is known to be a primary cause of taste disorders, a clinical phase III study is in progress to determine taste disorders as a new indication of polaprezinc. The pharmacological action of polaprezinc, however, on taste disorders remains unclear. So we examined the effect of polaprezinc on taste disorders induced by feeding rats a zinc-deficient diet and clarified its mechanism of action in restoring the reduced zinc content in the lingual epithelium and improving delayed cell proliferation of taste bud cells due to zinc deficiency. In this review, we primarily make reference to our own data on the pharmacological action of polaprezinc on taste disorders and introduce recent research on the effects of polaprezinc in treating other diseases. PMID:22382829

  15. Protection by polaprezinc against radiation-induced apoptosis in rat jejunal crypt cells.

    Science.gov (United States)

    Matsuu-Matsuyama, Mutsumi; Shichijo, Kazuko; Okaichi, Kumio; Nakayama, Toshiyuki; Nakashima, Masahiro; Uemura, Takashi; Niino, Daisuke; Sekine, Ichiro

    2008-07-01

    Polaprezinc, an anti-ulcer drug, is a chelate compound consisting of zinc and L-carnosine. Polaprezinc has been shown to prevent gastric mucosal injury. The anti ulcer effects of polaprezinc have been ascribed to its antioxidative property. The effect of polaprezinc on ionizing radiation-induced apoptosis was studied in the jejunal epithelial crypt cells of rats. Seven-to eight week-old Wistar rats, which were treated with 100 mg/kg of polaprezinc orally 1h before irradiation or 2% carboxymethyl cellulose sodium in controls, were exposed to whole body X-ray irradiation at 2 Gy. The number of apoptotic cells per jejunum crypt was counted in haematoxylin and eosin stained sections at 0-6 h after irradiation. TUNEL positive cells and immunopositive cells for active caspase-3 per crypt were also counted. Accumulation of p53, p21(WAF1/CIP1) and Bax expression in the jejunum after irradiation were examined by Western blot analyses. Polaprezinc treatment given prior to radiation resulted in a significant reduction in numbers of apoptotic cells, TUNEL positive cells and active caspase-3 immunopositive cells in jejunal crypt cells. Polaprezinc treatment resulted in decreases of p53 accumulation, p21(WAF1/CIP1) and Bax expression after irradiation. Polaprezinc has a protective effect against ionizing radiation induced apoptosis in rat jejunal crypt cells. PMID:18413982

  16. The seasonal fluctuation of plasma amino acids in aquarium-maintained bottlenose dolphins (Tursiops truncatus).

    Science.gov (United States)

    Miyaji, Kazuki; Ohta, Mitsuaki; Nagao, Kenji; Ohtani, Nobuyo; Bannai, Makoto

    2012-07-01

    Although there has been extensive research on plasma amino acid profiles of mammals, there is currently a lack of information on seasonal differences in the concentrations of plasma amino acids specifically in cetaceans. The present study examined the response of the plasma amino acids to seasonal changes in the culture environment after controlling for the effect of sex and age. Significant seasonal changes in plasma carnosine (P=0.012), cystine (P=0.0014), isoleucine (P=0.0042), methionine (P=0.002), ornithine (P=0.0096), and taurine (P=0.032) were observed. These amino acids were mainly related to capacity for exercise, ammonia detoxification, thermoregulation, and osmoregulation. We proposed that optimizing plasma amino acids levels by supplementation of amino acids should be of considerable benefit for aquarium-maintained bottlenose dolphins. This study constitutes a first step towards improving our understanding of the metabolism of aquarium-maintained bottlenose dolphins. We also revealed that the ratio of tryptophan to large neutral amino acids significantly declined (P=0.0076), suggesting reduction in serotonin synthesis in winter and autumn. Although further studies are needed, this finding implied that bottlenose dolphins could produce behavioral changes seasonally by the alteration of serotonin activity. To better understand the metabolic machinery for amino acids that facilitate the adaptation of marine mammals to their environments, it is essential to continue monitoring of and further investigations into relationships between plasma amino acids and specific environmental factors. PMID:22333514

  17. Metabolic profile of dystrophic mdx mouse muscles analyzed with in vitro magnetic resonance spectroscopy (MRS).

    Science.gov (United States)

    Martins-Bach, Aurea B; Bloise, Antonio C; Vainzof, Mariz; Rahnamaye Rabbani, Said

    2012-10-01

    Duchenne muscular dystrophy (DMD) is a recessive X-linked form of muscular dystrophy characterized by progressive and irreversible degeneration of the muscles. The mdx mouse is the classical animal model for DMD, showing similar molecular and protein defects. The mdx mouse, however, does not show significant muscle weakness, and the diaphragm muscle is significantly more degenerated than skeletal muscles. In this work, (1)H magnetic resonance spectroscopy (MRS) was used to study the metabolic profile of quadriceps and diaphragm muscles from mdx and control mice. Using principal components analysis (PCA), the animals were separated into groups according to age and lineages. The classification was compared to histopathological analysis. Among the 24 metabolites identified from the nuclear MR spectra, only 19 were used by the PCA program for classification purposes. These can be important key biomarkers associated with the progression of degeneration in mdx muscles and with natural aging in control mice. Glutamate, glutamine, succinate, isoleucine, acetate, alanine and glycerol were increased in mdx samples as compared to control mice, in contrast to carnosine, taurine, glycine, methionine and creatine that were decreased. These results suggest that MRS associated with pattern recognition analysis can be a reliable tool to assess the degree of pathological and metabolic alterations in the dystrophic tissue, thereby affording the possibility of evaluation of beneficial effects of putative therapies. PMID:22673895

  18. Composition and quality differences between the longissimus and infraspinatus muscles for several groups of pasture-finished cattle.

    Science.gov (United States)

    Purchas, R W; Zou, M

    2008-10-01

    Samples of longissimus (LT) and infraspinatus (IS) muscles from five contrasting groups of pasture-finished cattle (n=7/group) were assessed for quality and composition characteristics in order to determine whether features of pasture-finished beef reported previously apply across different muscles and different classes of cattle. The cattle were not raised together or slaughtered at the same time. Wagyu-cross steers had the highest intramuscular fat levels, particularly in the LT, followed by Angus steers, Charolais-cross steers and Belgian Blue-cross steers, with the lowest levels for Friesian bulls. Relative to the LT, the IS muscle had longer sarcomeres, higher cooking losses, higher concentrations of vitamin E, and lower myofibrillar fragmentation indexes, while its ultimate pH was slightly higher but less variable. Beef from Wagyu-cross steers had the highest chroma values and the lowest shear values, while Friesian bull beef was darkest and least tender. Intramuscular fatty acid composition and concentrations of bioactive compounds such as coenzyme Q(10) and carnosine, were similar to those reported previously for cattle finished on New Zealand pastures although taurine levels were lower. Generally concentrations of bioactive compounds differed more between muscles and groups than between cattle finished on pasture or grain as reported previously. PMID:22063355

  19. Radiation-induced changes in the patterns of free ninhydrin-reactive substances of meat

    International Nuclear Information System (INIS)

    Samples of minced lean beef and pork, breast muscle of chicken, and white meat of carp packed in polyethylene/Hostaphan bags were irradiated in the presence of air at about 250C with 10-MeV electrons. The doses applied were for beef 0.5-20 Mrad, and for other meat samples 10 Mrad. In the dose range of 0-5 Mrad, no statistically significant changes in the composition of the free amino acids and similar compounds usually present in beef were found. In the dose range between 10 and 20 Mrad a tendency towards small losses in such components became obvious. In beef samples irradiated at doses >= 0.5 Mrad a new substance (Y) appeared distinctly in the zone of the basic amino-acids. This compound was detected by two independent methods, column chromatography and high-voltage electrophoresis. The yellow colour of the band appearing above carnosine in the pherogram was striking. Substance Y was also found after irradiation of pork and chicken meat. At a dose of 10 Mrad the concentration of Y in white chicken meat was nearly three times higher than in beef and pork. After irradiation of white carp muscle no Y, but another new basic compound (X) was observed. In the pherograms it appeared as a brwonish-red band above β-alanine. (orig./AJ)

  20. Ergothioneine, histidine, and two naturally occurring histidine dipeptides as radioprotectors against gamma-irradiation inactivation of bacteriophages T4 and P22

    International Nuclear Information System (INIS)

    Bacteriophages P22, T4+, and T4os (osmotic shock-resistant mutant with altered capsids) were diluted in 0.85% NaCl and exposed to gamma irradiation (2.79 Gy/min) at room temperature (24 degrees C). T4+ was more sensitive to inactivation than was P22, and the T4os mutant was even more sensitive than T4+. Catalase exhibited a strong protective effect and superoxide dismutase a weaker protection, indicating that H2O2 or some product derived therefrom was predominant in causing inactivation of plaque formation. Low but significant (0.1-0.3 mM) reduced glutathione (GSH) enhanced phage inactivation, but a higher (1 mM) GSH concentration protected. A similar effect was found for the polyamine, spermidine. In contrast, 0.1 mM L-ergothioneine (2-thiol-L-histidine betaine) exhibited strong protection and 1 mM afforded essentially complete protection. L-Ergothioneine is present in millimolar concentrations in some fungi and is conserved up to millimolar concentrations in critical tissues when consumed by man. L-Histidine and two histidine-containing dipeptides, carnosine and anserine, protected at a concentration of 1 mM, a level at which they are present in striated muscles of various animals

  1. Proton MRS in neurological disorders

    International Nuclear Information System (INIS)

    Proton magnetic resonance spectroscopy (1H MRS) permits the acquisition of the signal arising from several brain metabolites. At long echo-time (TE) 1H MRS can detect N-acetyl-aspartate containing compounds, choline containing compounds, creatine+phosphocreatine and lactate. At short TE, lipids, tryglicerides, alanine, glutamate, glutamine, GABA, scyllo-inositol, glucose, myo-inositol, carnosine and histydine are visible. 1H MRS can be performed with single-voxel, multivoxel, single slice and multislice techniques. With single voxel 1H MRS it is possible to measure metabolites relaxation time, which allows the measurement of metabolite concentrations. This technique can be useful in the study of focal lesions in the central nervous system (CNS) such as epilepsy (pre-surgical identification of epileptic focus), brain tumors (evaluation of recurrence and radiation necrosis), stroke, multiple sclerosis, etc. Single slice and multislice 1H MRS imaging (1H MRSI) can be performed only at long TE and permits the mapping of the brain metabolites distribution which makes them particularly useful in studying diffuse diseases and heterogeneous lesions of the CNS. 1H MRS can also be useful in the evaluation of 'ischemic penumbra' of stroke; developmental (myelin and neuronal dysgenesis); head trauma (evaluation of cerebral damage not visible with MRI); degenerative disorders (identification of microscopic pathology not visible with MRI); and metabolic diseases (metabolic disturbances with specific metabolic patterns)

  2. Metabolomic study of plasma from female mink (Neovison vison) with low and high residual feed intake during restrictive and ad libitum feeding.

    Science.gov (United States)

    Hedemann, Mette Skou; Damgaard, Birthe Marie

    2012-12-01

    Metabolite profiling may elucidate changes in metabolic pathways under various physiological or nutritional conditions. In the present study two groups of female mink characterised as having a high (16 mink) or low (14 mink) residual feed intake were investigated during restrictive and ad libitum feeding. Blood samples were collected three times during the experimental period; during restrictive feeding, and four days and three weeks after the change to ad libitum feeding. Plasma samples were subjected to liquid chromatography mass spectrometry non-targeted metabolomics. Subjecting data to principal component analysis showed that there was no grouping of the data according to the residual feed intake. In contrast, data were clearly grouped according to feeding level. Identification of the metabolites responsible for this grouping showed that the plasma level of metabolites related to mobilisation of energy was high during restrictive feeding, e.g. betaine, carnitine, and creatine. During ad libitum feeding the plasma level of metabolites that can be characterised as biomarkers of meat intake (creatinine, carnosine, 1- and 3 methylhistidine) was high. The plasma level of lysophosphatidylcholine species was highest after four days of ad libitum feeding suggesting a short term imbalance in the transport or metabolism of these metabolites when changing the feeding level. PMID:23123310

  3. Crystallization and preliminary crystallographic study of carnosinase CN2 from mice

    Energy Technology Data Exchange (ETDEWEB)

    Yamashita, Tetsuo; Unno, Hideaki; Ujita, Sayuri; Otani, Hiroto; Okumura, Nobuaki; Hashida-Okumura, Akiko; Nagai, Katsuya; Kusunoki, Masami, E-mail: kusunoki@protein.osaka-u.ac.jp [Institute for Protein Research, Osaka University, 3-2 Yamada-oka, Suita, Osaka 565-0871 (Japan)

    2006-10-01

    Mouse carnosinase was crystallized in complex with Zn{sup 2+} or Mn{sup 2+} and the complexes are undergoing structure determination by the MAD method. Mammalian tissues contain several histidine-containing dipeptides, of which l-carnosine is the best characterized and is found in various tissues including the brain and skeletal muscles. However, the mechanism for its biosynthesis and degradation have not yet been fully elucidated. Crystallographic study of carnosinase CN2 from mouse has been undertaken in order to understand its enzymatic mechanism from a structural viewpoint. CN2 was crystallized by the hanging-drop vapour-diffusion technique using PEG 3350 as a precipitant. Crystals were obtained in complex with either Mn{sup 2+} or Zn{sup 2+}. Both crystals of CN2 belong to the monoclinic space group P2{sub 1} and have almost identical unit-cell parameters (a = 54.41, b = 199.77, c = 55.49 Å, β = 118.52° for the Zn{sup 2+} complex crystals). Diffraction data were collected to 1.7 and 2.3 Å for Zn{sup 2+} and Mn{sup 2+} complex crystals, respectively, using synchrotron radiation. Structure determination is ongoing using the multiple-wavelength anomalous diffraction (MAD) method.

  4. Proton MRS in neurological disorders

    Energy Technology Data Exchange (ETDEWEB)

    Bonavita, S.; Di Salle, F.; Tedeschi, G

    1999-05-01

    Proton magnetic resonance spectroscopy ({sup 1}H MRS) permits the acquisition of the signal arising from several brain metabolites. At long echo-time (TE) {sup 1}H MRS can detect N-acetyl-aspartate containing compounds, choline containing compounds, creatine+phosphocreatine and lactate. At short TE, lipids, tryglicerides, alanine, glutamate, glutamine, GABA, scyllo-inositol, glucose, myo-inositol, carnosine and histydine are visible. {sup 1}H MRS can be performed with single-voxel, multivoxel, single slice and multislice techniques. With single voxel {sup 1}H MRS it is possible to measure metabolites relaxation time, which allows the measurement of metabolite concentrations. This technique can be useful in the study of focal lesions in the central nervous system (CNS) such as epilepsy (pre-surgical identification of epileptic focus), brain tumors (evaluation of recurrence and radiation necrosis), stroke, multiple sclerosis, etc. Single slice and multislice {sup 1}H MRS imaging ({sup 1}H MRSI) can be performed only at long TE and permits the mapping of the brain metabolites distribution which makes them particularly useful in studying diffuse diseases and heterogeneous lesions of the CNS. {sup 1}H MRS can also be useful in the evaluation of 'ischemic penumbra' of stroke; developmental (myelin and neuronal dysgenesis); head trauma (evaluation of cerebral damage not visible with MRI); degenerative disorders (identification of microscopic pathology not visible with MRI); and metabolic diseases (metabolic disturbances with specific metabolic patterns)

  5. Are fish fed with cyanobacteria safe, nutritious and delicious? A laboratory study

    Science.gov (United States)

    Liang, Hualei; Zhou, Wenshan; Zhang, Yulei; Qiao, Qin; Zhang, Xuezhen

    2015-10-01

    Toxic cyanobacterial blooms, which produce cyclic heptapeptide toxins known as microcystins, are worldwide environmental problems. On the other hand, the cyanobacteria protein (30-50%) has been recommended as substitute protein for aquaculture. The present laboratory study verified the feasibility of cyanobacteria protein substitution and risk assessment. Goldfish were fed diets supplemented lyophilised cyanobacteria powder for 16 weeks with the various doses: 0% (control), 10%, 20%, 30% and 40%. Low doses (10% and 20%) promoted growth whereas high doses (30% and 40%) inhibited growth. In cyanobacteria treated fish, the proximate composition of ash, crude fat content and crude protein content decreased in 16 weeks; the saturated fatty acid (SFA) content significantly increased; the n-3 polyunsaturated fatty acid content, collagen content and muscle pH significantly decreased; cooking loss percents increased significantly. Muscle fiber diameter and myofibril length were negatively correlation. Additionally, flavour compounds (e.g., amino acids, nucleotides, organic acids and carnosine) changed significantly in the treated fish, and odour compounds geosmin and 2-methylisoborneol increased significantly. The estimated daily intake (EDI) of microcystins in muscle was close to or exceeded the World Health Organization (WHO) tolerable daily intake (TDI), representing a great health risk. Cyanobacterie is not feasible for protein sources use in aquaculture.

  6. Ultraviolet spectrophotometric characterization of copper(II) complexes with imidazole N-methyl derivatives of ?-histidine in aqueous solution

    Science.gov (United States)

    Prenesti, Enrico; Berto, Silvia; Daniele, Pier Giuseppe

    2003-01-01

    In this study we considered π-methyl- L-histidine (π-methis) and τ-methyl- L-histidine (τ-methis) as ligands for copper(II) ion, in order to clarify, by means of ultraviolet (UV) spectroscopy in aqueous solution ( T=25 °C, I=0.1 M), some aspects of the co-ordination mode with respect to other ligands of a previous study in which copper(II) complexes of L-histidine, N-acetyl- L-histidine, histamine, L-histidine methyl ester or carnosine were investigated. Particularly, UV spectra (300-400 nm) were recorded on solutions at various pH values, containing each binary system Cu-L; afterwards, an UV absorption spectrum for single complexes was calculated, taking into account the chemical model previously assessed, in order to fulfil a correct spectrum-structure correlation. The problem related to the eventual superimposition of the CT shoulder (≈330 nm) to copper(II) of OH - and imidazole pyridine nitrogen groups were now solved by means of a comparison of the UV spectra of dimer species formed by both π-methis or τ-methis. Finally, copper(II) complex formation with 2,2'-bipyridine was taken into account to compare the behaviour of pyridine (from 2,2'-bipyridine) and pyridine imidazole nitrogens (from π-methis or τ-methis) with respect to the UV charge transfer process to copper(II) ion.

  7. ESI-MS and theoretical study on the coordination structures and reaction modes of the diperoxovanadate complexes containing histidine-like ligands

    Science.gov (United States)

    Yu, Xian-Yong; Xu, Xin; Chen, Zhong

    2008-01-01

    In order to study the coordination structures and the reaction modes of diperoxovanadate complexes in the gas phase, the interaction between K3[OV(O2)2(C2O4)]·H2O and a series of histidine-like ligands has been investigated by the combination of the electrospray ionization-mass spectrometry (ESI-MS) and the density functional theory (DFT) calculations. The experimental results proved the formation of both [OV(O2)2L]- (L = all histidine-like ligands) and [OV(O2)2L'2]- (L' = histidine and carnosine only) species. DFT calculations at the level of B3LYP/6-31+G* showed that [OV(O2)2L'2]- is a hexa-coordinated complex, instead of a hepta-coordinated complex as proposed before. The unique coordination mode in the gas phase is for one ligand to bind to the oxygen atoms via hydrogen binding, rather than both ligands to the metal center. The L'2 dimer formation and the maintenance of the hydrogen bonding within the dimer during the complex formation are two important factors that enhance the abundance of the [OV(O2)2L'2]- species. The calculated bonding enthalpy and free energy changes provided an explanation on the reaction modes of the interaction systems, in agreement with the observations of the ESI-MS experiments.

  8. Ergothioneine, histidine, and two naturally occurring histidine dipeptides as radioprotectors against gamma-irradiation inactivation of bacteriophages T4 and P22

    Energy Technology Data Exchange (ETDEWEB)

    Hartman, P.E.; Hartman, Z.; Citardi, M.J.

    1988-05-01

    Bacteriophages P22, T4+, and T4os (osmotic shock-resistant mutant with altered capsids) were diluted in 0.85% NaCl and exposed to gamma irradiation (2.79 Gy/min) at room temperature (24 degrees C). T4+ was more sensitive to inactivation than was P22, and the T4os mutant was even more sensitive than T4+. Catalase exhibited a strong protective effect and superoxide dismutase a weaker protection, indicating that H/sub 2/O/sub 2/ or some product derived therefrom was predominant in causing inactivation of plaque formation. Low but significant (0.1-0.3 mM) reduced glutathione (GSH) enhanced phage inactivation, but a higher (1 mM) GSH concentration protected. A similar effect was found for the polyamine, spermidine. In contrast, 0.1 mM L-ergothioneine (2-thiol-L-histidine betaine) exhibited strong protection and 1 mM afforded essentially complete protection. L-Ergothioneine is present in millimolar concentrations in some fungi and is conserved up to millimolar concentrations in critical tissues when consumed by man. L-Histidine and two histidine-containing dipeptides, carnosine and anserine, protected at a concentration of 1 mM, a level at which they are present in striated muscles of various animals.

  9. Enhanced topical delivery of tacrolimus by a carbomer hydrogel formulation with transcutol P.

    Science.gov (United States)

    Lee, Sang Gon; Kang, Jong Bu; Kim, Sung Rae; Kim, Chae Jin; Yeom, Dong Woo; Yoon, Ho Yub; Kwak, Seong Shin; Choi, Young Wook

    2016-10-01

    Tacrolimus (TAC), a non-steroidal anti-inflammatory and immunosuppressive agent, is used for the treatment of atopic dermatitis (AD) and skin immune diseases. TAC-loaded topical hydrogel formulations composed of carbomer, carnosine, transcutol P (diethylene glycol monoethyl ether) and humectant were prepared. For comparison, TAC-loaded topical cream-type formulations were also prepared and commercially available TAC ointment was used as a reference. A drug release study in vitro revealed that the total amount of TAC released from hydrogels over 24 h was approximately 30 times greater than that for the reference formulation. Compared to the reference ointment and creams, carbomer gel formulations showed higher skin permeation and retention of TAC (significantly different at p < 0.05), especially those with more than 10% of transcutol P. Therefore, carbomer gel formulations with sufficient levels of transcutol P are good candidates for skin delivery of TAC and have potential as therapeutic agents for the treatment of AD or immune skin disorders. PMID:26925849

  10. Comparison of Bioactive Compounds and Quality Traits of Breast Meat from Korean Native Ducks and Commercial Ducks.

    Science.gov (United States)

    Lee, Hyun Jung; Jayasena, Dinesh D; Kim, Sun Hyo; Kim, Hyun Joo; Heo, Kang Nyung; Song, Ji Eun; Jo, Cheorun

    2015-01-01

    The aim of this research was to compare the bioactive compound content and quality traits of breast meat from male and female Korean native ducks (KND) and commercial ducks (CD, Cherry Valley). Meat from three 6-wk old birds of each sex from KND and CD were evaluated for carcass and breast weights, pH, color, cooking loss, shear force, and bioactive compound (creatine, carnosine, anserine, betaine, and L-carnitine) content. KND showed significantly higher carcass weights than CD whereas no such difference (p>0.05) was found between male and female ducks. The breed and sex had no significant effects on the breast weight, pH value, and shear force. However, KND had significantly lower cooking loss values than did CD. Creatine, anserine, and L-carnitine contents were significantly higher in KND than in CD and were predominant in female ducks compared to males. The results of this study provide rare information regarding the amounts and the determinants of several bioactive compounds in duck meat, which can be useful for selection and breeding programs, and for popularizing indigenous duck meat. PMID:26761808

  11. Hyperfine structure analysis in magnetic resonance spectroscopy: from astrophysical measurements towards endogenous biosensors in human tissue; Hyperfeinstruktur-Analyse in der Magnetresonanzspektroskopie: von astrophysikalischen Messungen zu endogenen Biosensoren in menschlichem Gewebe

    Energy Technology Data Exchange (ETDEWEB)

    Schroeder, L. [Deutsches Krebsforschungszentrum, Heidelberg (Germany). Medizinische Physik in der Radiologie; California Univ., Berkeley, CA (United States). Dept. of Chemistry; Lawrence Berkeley National Lab., Berkeley, CA (United States). Dept. of Chemistry

    2007-07-01

    The hyperfine interaction of two spins is a well studied effect in atomic systems. Magnetic resonance experiments demonstrate that the detectable dipole transitions are determined by the magnetic moments of the constituents and the external magnetic field. Transferring the corresponding quantum mechanics to molecular bound nuclear spins allows for precise prediction of NMR spectra obtained from metabolites in human tissue. This molecular hyperfine structure has been neglected so far in in vivo NMR spectroscopy but contains useful information, especially when studying molecular dynamics. This contribution represents a review of the concept of applying the Breit-Rabi formalism to coupled nuclear spins and discusses the immobilization of different metabolites in anisotropic tissue revealed by 1H NMR spectra of carnosine, phosphocreatine and taurine. Comparison of atomic and molecular spin systems allows for statements on the biological constraints for direct spin-spin interactions. Moreover, the relevance of hyperfine effects on the line shapes of multiplets of indirectly-coupled spin systems with more than two constituents can be predicted by analyzing quantum mechanical parameters. As an example, the superposition of eigenstates of the AMX system of adenosine 5'-triphosphate and its application for better quantification of 31P-NMR spectra will be discussed. (orig.)

  12. Effects of Rice Bran, Flax Seed, and Sunflower Seed on Growth Performance, Carcass Characteristics, Fatty Acid Composition, Free Amino Acid and Peptide Contents, and Sensory Evaluations of Native Korean Cattle (Hanwoo).

    Science.gov (United States)

    Choi, Chang Bon; Kwon, Hana; Kim, Sung Il; Yang, Un Mok; Lee, Ju Hwan; Park, Eun Kyu

    2016-02-01

    This study was conducted to evaluate the effect of dietary supplementation with rice bran, flax seed, or sunflower seed to finishing native Korean cattle (Hanwoo) on growth performances, carcass characteristics, fatty acid composition, free amino acid and peptide contents, and sensory evaluations of Longissimus muscle (LM). A total of 39 Hanwoo steers (average age of 22.2 mo and average body weight (BW) of 552.2 kg) were randomly divided into Control, rice bran (RB), flax seed (FS), or Sunflower seed (SS) groups. The steers were group fed for 273 d until they reached an average age of 31.2 mo. Final BW was 768.2, 785.8, 786.2, and 789.0 kg, and average daily gain was 0.79, 0.85, 0.82, and 0.84 kg for the Control, RS, FS, and SS groups, respectively (p>0.05). Fat thickness of the FS group (19.8 mm) was greater (p0.05) scores for flavor, umami, and overall palatability in sensory evaluations. In conclusion, supplementation of flax seed to diets of finishing Hanwoo steers improved sensory evaluations which might have been caused by increases in flavor related amino acids such as methionine, glutamic acid and α-AAA and peptides, anserine and carnosine, and their complex reactions. PMID:26732444

  13. Solubilisation of myosin in a solution of low ionic strength L-histidine: Significance of the imidazole ring.

    Science.gov (United States)

    Chen, Xing; Zou, Yufeng; Han, Minyi; Pan, Lihua; Xing, Tong; Xu, Xinglian; Zhou, Guanghong

    2016-04-01

    Myosin, a major muscle protein, can be solubilised in a low ionic strength solution containing L-histidine (His). To elucidate which chemical constituents in His are responsible for this solubilisation, we investigated the effects of 5mM His, imidazole (Imi), L-α-alanine (Ala), 1-methyl-L-histidine (M-his) and L-carnosine (Car) on particle properties of myosin suspensions and conformational characteristics of soluble myosin at low ionic strength (1 mM KCl, pH 7.5). His, Imi and Car, each containing an imidazole ring, were able to induce a myosin suspension, which had small particle size species and high absolute zeta potential, thus increasing the solubility of myosin. His, Imi and Car affected the tertiary structure and decreased the α-helix content of soluble myosin. Therefore, the imidazole ring of His appeared to be the significant chemical constituent in solubilising myosin at low ionic strength solution, presumably by affecting its secondary structure. PMID:26593463

  14. Fortified Extract of Red Berry, Ginkgo biloba, and White Willow Bark in Experimental Early Diabetic Retinopathy

    Directory of Open Access Journals (Sweden)

    Claudio Bucolo

    2013-01-01

    Full Text Available Diabetic retinopathy is a complex condition where inflammation and oxidative stress represent crucial pathways in the pathogenesis of the disease. Aim of the study was to investigate the effects of a fortified extract of red berries, Ginkgo biloba and white willow bark containing carnosine and α-lipoic acid in early retinal and plasma changes of streptozotocin-induced diabetic rats. Diabetes was induced by a single streptozotocin injection in Sprague Dawley rats. Diabetics and nondiabetic (control rats were treated daily with the fortified extract for the ten days. Retina samples were collected and analyzed for their TNF-α and VEGF content. Moreover, plasma oxidative stress was evaluated by thiobarbituric acid reacting substances (TBARS. Increased TNF-α and VEGF levels were observed in the retina of diabetic rats. Treatment with the fortified extract significantly lowered retinal cytokine levels and suppressed diabetes-related lipid peroxidation. These data demonstrate that the fortified extract attenuates the degree of retinal inflammation and plasma lipid peroxidation preserving the retina in early diabetic rats.

  15. Metabonomic profiling of serum and urine by (1H NMR-based spectroscopy discriminates patients with chronic obstructive pulmonary disease and healthy individuals.

    Directory of Open Access Journals (Sweden)

    Lingling Wang

    Full Text Available Chronic obstructive pulmonary disease (COPD has seriously impacted the health of individuals and populations. In this study, proton nuclear magnetic resonance ((1H NMR-based metabonomics combined with multivariate pattern recognition analysis was applied to investigate the metabolic signatures of patients with COPD. Serum and urine samples were collected from COPD patients (n = 32 and healthy controls (n = 21, respectively. Samples were analyzed by high resolution (1H NMR (600 MHz, and the obtained spectral profiles were then subjected to multivariate data analysis. Consistent metabolic differences have been found in serum as well as in urine samples from COPD patients and healthy controls. Compared to healthy controls, COPD patients displayed decreased lipoprotein and amino acids, including branched-chain amino acids (BCAAs, and increased glycerolphosphocholine in serum. Moreover, metabolic differences in urine were more significant than in serum. Decreased urinary 1-methylnicotinamide, creatinine and lactate have been discovered in COPD patients in comparison with healthy controls. Conversely, acetate, ketone bodies, carnosine, m-hydroxyphenylacetate, phenylacetyglycine, pyruvate and α-ketoglutarate exhibited enhanced expression levels in COPD patients relative to healthy subjects. Our results illustrate the potential application of NMR-based metabonomics in early diagnosis and understanding the mechanisms of COPD.

  16. Nutraceutical intervention reverses the negative effects of blood from aged rats on stem cells.

    Science.gov (United States)

    Bickford, Paula C; Kaneko, Yuji; Grimmig, Bethany; Pappas, Colleen; Small, Brent; Sanberg, Cyndy D; Sanberg, Paul R; Tan, Jun; Douglas Shytle, R

    2015-10-01

    Aging is associated with a decline in function in many of the stem cell niches of the body. An emerging body of literature suggests that one of the reasons for this decline in function is due to cell non-autonomous influences on the niche from the body. For example, studies using the technique of parabiosis have demonstrated a negative influence of blood from aged mice on muscle satellite cells and neurogenesis in young mice. We examined if we could reverse this effect of aged serum on stem cell proliferation by treating aged rats with NT-020, a dietary supplement containing blueberry, green tea, vitamin D3, and carnosine that has been shown to increase neurogenesis in aged rats. Young and aged rats were administered either control NIH-31 diet or one supplemented with NT-020 for 28 days, and serum was collected upon euthanasia. The serum was used in cultures of both rat hippocampal neural progenitor cells (NPCs) and rat bone marrow-derived mesenchymal stem cells (MSCs). Serum from aged rats significantly reduced cell proliferation as measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and 5-bromo-2'-deoxyuridine (BrdU) assays in both NPCs and MSCs. Serum from aged rats treated with NT-020 was not different from serum from young rats. Therefore, NT-020 rescued the effect of serum from aged rats to reduce stem cell proliferation. PMID:26410618

  17. AGES in brain ageing: AGE-inhibitors as neuroprotective and anti-dementia drugs?

    Science.gov (United States)

    Dukic-Stefanovic, S; Schinzel, R; Riederer, P; Münch, G

    2001-01-01

    In Alzheimer's disease, age-related cellular changes such as compromised energy production and increased radical formation are worsened by the presence of AGEs as additional, AD specific stress factors. Intracellular AGEs (most likely derived from methylglyoxal) crosslink cytoskeletal proteins and render them insoluble. These aggregates inhibit cellular functions including transport processes and contribute to neuronal dysfunction and death. Extracellular AGEs, which accumulate in ageing tissue (but most prominently on long-lived protein deposits like the senile plaques) exert chronic oxidative stress on neurons. In addition, they activate glial cells to produce free radicals (superoxide and NO) and neurotoxic cytokines such as TNF-alpha. Drugs, which inhibit the formation of AGEs by specific chemical mechanisms (AGE-inhibitors), including aminoguanidine, carnosine, tenilsetam, OPB-9195 and pyridoxamine, attenuate the development of (AGE-mediated) diabetic complications. Assuming that 'carbonyl stress' contributes significantly to the progression of Alzheimer's disease, AGE-inhibitors might also become interesting novel therapeutic drugs for treatment of AD. PMID:11708614

  18. [The significance of free radicals and antioxidants due to the load induced by sport activity].

    Science.gov (United States)

    Holecek, V; Liska, J; Racek, J; Rokyta, R

    2004-01-01

    Sport performance is followed by a high production of free radicals. The main reasons are reperfusion after the previous imbalance between the increased need of the organism and the ability of blood supply by oxygen, increased production of ATP, decomposition of the cells particularly white blood cells, oxidation of the purin basis from DNA, stress, output of epinephrine release of free iron, increased temperature in the muscle and its inflammation, and the reception of free radicals from external environment. Peroxidation of lipids, proteins, DNA and other compounds follows the previous biochemical steps. Antioxidants are consumed by free radicals, antioxidative enzymes are released into blood plasma, intracellular calcium is increased, the production of nitric oxide rises, the levels of hydrogen peroxide and hypochlorous acid increase. These penetrate through the membranes and oxidatively damage the tissues. Training improves the ability of the organism to balance the increased load of free radicals. The damage can be lowered by the application of a mixture of antioxidants, the most important are vitamin C, A, E, glutathione, selenium, carnosine, eventually bioflavonoids and ginkgo biloba. The lack of antioxidants can significantly diminish the sport performance and therefore the supplementation with antioxidants is for top sportsmen but also for aged people advisable. PMID:15709642

  19. Vitagenes, dietary antioxidants and neuroprotection in neurodegenerative diseases.

    Science.gov (United States)

    Calabrese, Vittorio; Cornelius, Carolin; Mancuso, Cesare; Barone, Eugenio; Calafato, Stella; Bates, Timothy; Rizzarelli, Enrico; Kostova, Albena T Dinkova

    2009-01-01

    The ability of a cell to counteract stressful conditions, known as cellular stress response, requires the activation of pro-survival pathways and the production of molecules with anti-oxidant, anti-apoptotic or pro-apoptotic activities. Among the cellular pathways conferring protection against oxidative stress, a key role is played by vitagenes, which include heat shock proteins (Hsps) heme oxygenase-1 and Hsp70, as well as the thioredoxin/thioredoxin reductase system. Heat shock response contributes to establish a cytoprotective state in a wide variety of human diseases, including inflammation, cancer, aging and neurodegenerative disorders. Given the broad cytoprotective properties of the heat shock response there is now strong interest in discovering and developing pharmacological agents capable of inducing stress responses. Dietary antioxidants, such as curcumin, L-carnitine/acetyl-L-carnitine and carnosine have recently been demonstrated in vitro to be neuroprotective through the activation of hormetic pathways, including vitagenes. In the present review we discuss the importance of vitagenes in the cellular stress response and analyse, from a pharmacological point of view, the potential use of dietary antioxidants in the treatment of neurodegenerative disorders in humans. PMID:19273073

  20. Neuroprotective actions of a histidine analogue in models of ischemic stroke.

    Science.gov (United States)

    Tang, Sung-Chun; Arumugam, Thiruma V; Cutler, Roy G; Jo, Dong-Gyu; Magnus, Tim; Chan, Sic L; Mughal, Mohamed R; Telljohann, Richard S; Nassar, Matthew; Ouyang, Xin; Calderan, Andrea; Ruzza, Paolo; Guiotto, Andrea; Mattson, Mark P

    2007-05-01

    Histidine is a naturally occurring amino acid with antioxidant properties, which is present in low amounts in tissues throughout the body. We recently synthesized and characterized histidine analogues related to the natural dipeptide carnosine, which selectively scavenge the toxic lipid peroxidation product 4-hydroxynonenal (HNE). We now report that the histidine analogue histidyl hydrazide is effective in reducing brain damage and improving functional outcome in a mouse model of focal ischemic stroke when administered intravenously at a dose of 20 mg/kg, either 30 min before or 60 min and 3 h after the onset of middle cerebral artery occlusion. The histidine analogue also protected cultured rat primary neurons against death induced by HNE, chemical hypoxia, glucose deprivation, and combined oxygen and glucose deprivation. The histidine analogue prevented neuronal apoptosis as indicated by decreased production of cleaved caspase-3 protein. These findings suggest a therapeutic potential for HNE-scavenging histidine analogues in the treatment of stroke and related neurodegenerative conditions. PMID:17254011

  1. Muscle energetics during explosive activities and potential effects of nutrition and training.

    Science.gov (United States)

    Sahlin, Kent

    2014-11-01

    The high-energy demand during high-intensity exercise (HIE) necessitates that anaerobic processes cover an extensive part of the adenosine triphosphate (ATP) requirement. Anaerobic energy release results in depletion of phosphocreatine (PCr) and accumulation of lactic acid, which set an upper limit of anaerobic ATP production and thus HIE performance. This report focuses on the effects of training and ergogenic supplements on muscle energetics and HIE performance. Anaerobic capacity (i.e. the amount of ATP that can be produced) is determined by the muscle content of PCr, the buffer capacity and the volume of the contracting muscle mass. HIE training can increase buffer capacity and the contracting muscle mass but has no effect on the concentration of PCr. Dietary supplementation with creatine (Cr), bicarbonate, or beta-alanine has a documented ergogenic effect. Dietary supplementation with Cr increases muscle Cr and PCr and enhances performance, especially during repeated short periods of HIE. The ergogenic effect of Cr is related to an increase in temporal and spatial buffering of ATP and to increased muscle buffer capacity. Bicarbonate loading increases extracellular buffering and can improve performance during HIE by facilitating lactic acid removal from the contracting muscle. Supplementation with beta-alanine increases the content of muscle carnosine, which is an endogenous intracellular buffer. It is clear that performance during HIE can be improved by interventions that increase the capacity of anaerobic ATP production, suggesting that energetic constraints set a limit for performance during HIE. PMID:25355190

  2. Modulation of the antioxidant activity of HO* scavengers by albumin binding: a 19F-NMR study.

    Science.gov (United States)

    Aime, Silvio; Digilio, Giuseppe; Bruno, Erik; Mainero, Valentina; Baroni, Simona; Fasano, Mauro

    2003-08-01

    The interaction between different HO(z.rad;) radical scavengers in a three-component antioxidant system has been investigated by means of 19F-NMR spectroscopy. This system is composed of bovine serum albumin (BSA), trolox, and N-(4-hydroxyphenyl)-trifluoroacetamide (CF(3)PAF). The antioxidant capacity of BSA and trolox has been assessed by measuring the amount of trifluoroacetamide (TFAM) arising from the radical mediated decomposition of CF(3)PAF. When assayed separately, both trolox and BSA behaved as antioxidants, as they were effective to protect CF(3)PAF from HO* radical-mediated decomposition. By contrast, trolox enhanced the production of TFAM in the presence of BSA, thus behaving as a pro-oxidant. Urate, carnosine, glucose, and propylgallate showed antioxidant properties both with or without BSA. CF(3)PAF and trolox were found to bind to BSA with association constants in the order of 5 x 10(3)M(-1) and to compete for the same binding sites. These results have been discussed in terms of BSA-catalysed cross-reactions between trolox-derived secondary radicals and CF(3)PAF. PMID:12878205

  3. Silica-based cerium (III) chloride nanoparticles prevent the fructose-induced glycation of α-crystallin and H₂O₂-induced oxidative stress in human lens epithelial cells.

    Science.gov (United States)

    Yang, Jin; Cai, Lei; Zhang, Sen; Zhu, Xiangjia; Zhou, Peng; Lu, Yi

    2014-03-01

    This study aimed to investigate whether silica-cerium (III) chloride (CeCl3) nanoparticles could inhibit the formation of advanced glycation end-products (AGEs) and reduce oxidative stress. Silica-CeCl3 nanoparticles were synthesised by adsorption and embedment with micro-silica materials, forming uniform nanoparticles with a diameter of approximately 130 nm. Chaperone activity assays and AGEs formation assays, and intracellular reactive assays were adopted in this study to evaluate CeCl3 nanoparticles effect. UV-visible spectrometry showed that silica-CeCl3 nanoparticles at low concentrations rapidly formed tentatively stable conjugations with α-crystallin, greatly enhancing the chaperone activity of α-crystallin. Moreover, silica-CeCl3 nanoparticles markedly inhibited the fructose-induced glycation of α-crystallin, showing an advantage over the control drugs aminoguanidine and carnosine. Silica-CeCl3 nanoparticles also reduced intracellular reactive oxygen species production and restored glutathione levels in H2O2-treated human lens epithelial cells. These findings suggest that silica-CeCl3 may be used as a novel agent for the prevention of cataractogenesis. PMID:23828754

  4. Traditional reactive carbonyl scavengers do not prevent the carbonylation of brain proteins induced by acute glutathione depletion.

    Science.gov (United States)

    Zheng, J; Bizzozero, O A

    2010-03-01

    This study investigated the effect of reactive carbonyl species (RCS)-trapping agents on the formation of protein carbonyls during depletion of brain glutathione (GSH). To this end, rat brain slices were incubated with the GSH-depletor diethyl maleate in the absence or presence of chemically different RCS scavengers (hydralazine, methoxylamine, aminoguanidine, pyridoxamine, carnosine, taurine and z-histidine hydrazide). Despite their strong reactivity towards the most common RCS, none of the scavengers tested, with the exception of hydralazine, prevented protein carbonylation. These findings suggest that the majority of protein-associated carbonyl groups in this oxidative stress paradigm do not derive from stable lipid peroxidation products like malondialdehyde (MDA), acrolein and 4-hydroxynonenal (4-HNE). This conclusion was confirmed by the observation that the amount of MDA-, acrolein- and 4-HNE-protein adducts does not increase upon GSH depletion. Additional studies revealed that the efficacy of hydralazine at preventing carbonylation was due to its ability to reduce oxidative stress, most likely by inhibiting mitochondrial production of superoxide and/or by scavenging lipid free radicals. PMID:20001647

  5. Polaprezinc Protects Mice against Endotoxin Shock.

    Science.gov (United States)

    Ohata, Shuzo; Moriyama, Chihiro; Yamashita, Atsushi; Nishida, Tadashi; Kusumoto, Chiaki; Mochida, Shinsuke; Minami, Yukari; Nakada, Junya; Shomori, Kohei; Inagaki, Yoshimi; Ohta, Yoshiji; Matsura, Tatsuya

    2010-05-01

    Polaprezinc (PZ), a chelate compound consisting of zinc and l-carnosine (Car), is an anti-ulcer drug developed in Japan. In the present study, we investigated whether PZ suppresses mortality, pulmonary inflammation, and plasma nitric oxide (NO) and tumor necrosis factor (TNF)-alpha levels in endotoxin shock mice after peritoneal injection of lipopolysaccharide (LPS), and how PZ protects against LPS-induced endotoxin shock. PZ pretreatment inhibited the decrease in the survival rate of mice after LPS injection. PZ inhibited the increases in plasma NO as well as TNF-alpha after LPS. Compatibly, PZ suppressed LPS-induced inducible NO synthase mRNA transcription in the mouse lungs. PZ also improved LPS-induced lung injury. However, PZ did not enhance the induction of heat shock protein (HSP) 70 in the mouse lungs after LPS. Pretreatment of RAW264 cells with PZ suppressed the production of NO and TNF-alpha after LPS addition. This inhibition likely resulted from the inhibitory effect of PZ on LPS-mediated nuclear factor-kappaB (NF-kappaB) activation. Zinc sulfate, but not Car, suppressed NO production after LPS. These results indicate that PZ, in particular its zinc subcomponent, inhibits LPS-induced endotoxin shock via the inhibition of NF-kappaB activation and subsequent induction of proinflammatory products such as NO and TNF-alpha, but not HSP induction. PMID:20490319

  6. NMR metabolomic profiling reveals new roles of SUMOylation in DNA damage response.

    Science.gov (United States)

    Cano, Kristin E; Li, Yi-Jia; Chen, Yuan

    2010-10-01

    Post-translational modifications by the Small Ubiquitin-like Modifier (SUMO) family of proteins have been established as critical events in the cellular response to a wide range of DNA damaging reagents and radiation; however, the detailed mechanism of SUMOylation in DNA damage response is not well understood. In this study, we used a nuclear magnetic resonance (NMR) spectroscopy-based metabolomics approach to examine the effect of an inhibitor of SUMO-mediated protein-protein interactions on MCF7 breast cancer cell response to radiation. Metabolomics is sensitive to changes in cellular functions and thus provides complementary information to other biological studies. The peptide inhibitor (SUMO interaction motif mimic, SIM) and a control peptide were stably expressed in MCF-7 cell line. Metabolite profiles of the cell lines before and after radiation were analyzed using solution NMR methods. Various statistical methods were used to isolate significant changes. Differences in the amounts of glutamine, aspartate, malate, alanine, glutamate and NADH between the SIM-expressing and control cells suggest a role for SUMOylation in regulating mitochondrial function. This is also further verified following the metabolism of (13)C-labeled glutamine. The inability of the cells expressing the SIM peptide to increase production of the antioxidants carnosine and glutathione after radiation damage suggests an important role of SUMOylation in regulating the levels of antioxidants that protect cells from free radicals and reactive oxygen species generated by radiation. This study reveals previously unknown roles of SUMOylation in DNA damage response. PMID:20695451

  7. Lipid peroxidation and cataracts: N-acetylcarnosine as a therapeutic tool to manage age-related cataracts in human and in canine eyes.

    Science.gov (United States)

    Babizhayev, Mark A; Deyev, Anatoly I; Yermakova, Valentina N; Brikman, Igor V; Bours, Johan

    2004-01-01

    primary (diene conjugates, cetodienes) lipid peroxidation (LPO) products, while in later stages there is a prevalence of LPO fluorescent end-products. A reliable increase in oxiproducts of fatty acyl content of lenticular lipids was shown by a direct gas chromatography technique producing fatty acid fluorine-substituted derivatives. The lens opacity degree correlates with the level of the LPO fluorescent end-product accumulation in its tissue, accompanied by sulfhydryl group oxidation of lens proteins due to a decrease of reduced glutathione concentration in the lens. The injection of LPO products into the vitreous has been shown to induce cataract. It is concluded that peroxide damage of the lens fibre membranes may be the initial cause of cataract development. N-acetylcarnosine (as the ophthalmic drug Can-C), has been found to be suitable for the nonsurgical prevention and treatment of age-related cataracts. This molecule protects the crystalline lens from oxidative stress-induced damage, and in a recent clinical trial it was shown to produce an effective, safe and long-term improvement in sight. When administered topically to the eye in the form of Can-C, N-acetylcarnosine functions as a time-release prodrug form of L-carnosine resistant to hydrolysis with carnosinase. N-acetylcarnosine has potential as an in vivo universal antioxidant because of its ability to protect against oxidative stress in the lipid phase of biological cellular membranes and in the aqueous environment by a gradual intraocular turnover into L-carnosine. In our study the clinical effects of a topical solution of N-acetylcarnosine (Can-C) on lens opacities were examined in patients with cataracts and in canines with age-related cataracts. These data showed that N-acetylcarnosine is effective in the management of age-related cataract reversal and prevention both in human and in canine eyes. PMID:15139774

  8. A novel high resolution MS approach for the screening of 4-hydroxy-trans-2-nonenal sequestering agents.

    Science.gov (United States)

    Colzani, Mara; Criscuolo, Angela; De Maddis, Danilo; Garzon, Davide; Yeum, Kyung-Jin; Vistoli, Giulio; Carini, Marina; Aldini, Giancarlo

    2014-03-01

    An in vitro high resolution mass spectrometry (MS) method was set-up to test the ability of compounds, mixtures and extracts to inhibit protein carbonylation induced by reactive carbonyl species (RCS). The method consists of incubating the protein target (ubiquitin) with 4-hydroxy-trans-2-nonenal (HNE) in the presence and absence of the tested compound. After 24h of incubation, the reaction is stopped and the protein is analyzed by high-resolution MS. The extent of protein carbonylation is determined by measuring the area of the +11 multicharged peak of the HNE adduct in respect to the native form. The method was validated by measuring the effect of well-known RCS sequestering agents, namely aminoguanidine, pyridoxamine, hydralazine and carnosine, yielding a good reproducibility and the possibility to be automatable. All the compounds were found to dose-dependently inhibit the protein carbonylation with the following order of potency carnosine≈hydralazine≫aminoguanidine>pyridoxamine, as determined by calculating the UC50 values, that is the concentration required to inhibit ubiquitin carbonylation by 50%. A good correlation was found with the results obtained by measuring HNE consumption using an HPLC method optimized by a mobile phase set at pH 7.4, in order to stabilize the eluted adducts. The MS approach was then applied to test the effect of two selected natural extracts on protein carbonylation, i.e. green coffee bean extract and procyanidins from Vitis vinifera. In summary, this paper reports a validated and highly reproducible MS method to test the ability of pure compounds as well as natural extracts to act as protein carbonylation inhibitors. PMID:24463041

  9. Characteristic metabolism of free amino acids in cetacean plasma: cluster analysis and comparison with mice.

    Directory of Open Access Journals (Sweden)

    Kazuki Miyaji

    Full Text Available From an evolutionary perspective, the ancestors of cetaceans first lived in terrestrial environments prior to adapting to aquatic environments. Whereas anatomical and morphological adaptations to aquatic environments have been well studied, few studies have focused on physiological changes. We focused on plasma amino acid concentrations (aminograms since they show distinct patterns under various physiological conditions. Plasma and urine aminograms were obtained from bottlenose dolphins, pacific white-sided dolphins, Risso's dolphins, false-killer whales and C57BL/6J and ICR mice. Hierarchical cluster analyses were employed to uncover a multitude of amino acid relationships among different species, which can help us understand the complex interrelations comprising metabolic adaptations. The cetacean aminograms formed a cluster that was markedly distinguishable from the mouse cluster, indicating that cetaceans and terrestrial mammals have quite different metabolic machinery for amino acids. Levels of carnosine and 3-methylhistidine, both of which are antioxidants, were substantially higher in cetaceans. Urea was markedly elevated in cetaceans, whereas the level of urea cycle-related amino acids was lower. Because diving mammals must cope with high rates of reactive oxygen species generation due to alterations in apnea/reoxygenation and ischemia-reperfusion processes, high concentrations of antioxidative amino acids are advantageous. Moreover, shifting the set point of urea cycle may be an adaptation used for body water conservation in the hyperosmotic sea water environment, because urea functions as a major blood osmolyte. Furthermore, since dolphins are kept in many aquariums for observation, the evaluation of these aminograms may provide useful diagnostic indices for the assessment of cetacean health in artificial environments in the future.

  10. Can cognitive deterioration associated with Down syndrome be reduced?

    Science.gov (United States)

    Thiel, R; Fowkes, S W

    2005-01-01

    Individuals with Down syndrome have signs of possible brain damage prior to birth. In addition to slowed and reduced mental development, they are much more likely to have cognitive deterioration and develop dementia at an earlier age than individuals without Down syndrome. Some of the cognitive impairments are likely due to post-natal hydrogen peroxide-mediated oxidative stress caused by overexpression of the superoxide dismutase (SOD-1) gene, which is located on the triplicated 21st chromosome and known to be 50% overexpressed. However, some of this disability may also be due to early accumulation of advanced protein glycation end-products, which may play an adverse role in prenatal and postnatal brain development. This paper suggests that essential nutrients such as folate, vitamin B6, vitamin C, vitamin E, selenium, and zinc, as well as alpha-lipoic acid and carnosine may possibly be partially preventive. Acetyl-L-carnitine, aminoguanidine, cysteine, and N-acetylcysteine are also discussed, but have possible safety concerns for this population. This paper hypothesizes that nutritional factors begun prenatally, in early infancy, or later may prevent or delay the onset of dementia in the Down syndrome population. Further examination of these data may provide insights into nutritional, metabolic and pharmacological treatments for dementias of many kinds. As the Down syndrome population may be the largest identifiable group at increased risk for developing dementia, clinical research to verify the possible validity of the prophylactic use of anti-glycation nutrients should be performed. Such research might also help those with glycation complications associated with diabetes or Alzheimer's. PMID:15617860

  11. Polaprezinc attenuates cyclophosphamide-induced cystitis and related bladder pain in mice.

    Science.gov (United States)

    Murakami-Nakayama, Masahiro; Tsubota, Maho; Hiruma, Saki; Sekiguchi, Fumiko; Matsuyama, Kenji; Kimura, Takeshi; Moriyama, Masahiro; Kawabata, Atsufumi

    2015-02-01

    Cav3.2 T-type Ca(2+) channels targeted by H2S, a gasotransmitter, participate in cyclophosphamide-induced cystitis and bladder pain. Given that zinc selectively inhibits Cav3.2 among T-channel isoforms and also exhibits antioxidant activity, we examined whether polaprezinc (zinc-l-carnosine), a medicine for peptic ulcer treatment and zinc supplementation, reveals preventive or therapeutic effects on bladder inflammation and/or pain in the mouse with cyclophosphamide-induced cystitis, a model for interstitial cystitis. Systemic administration of cyclophosphamide caused cystitis-related symptoms including increased bladder weight and vascular permeability, and histological signs of bladder edema, accompanied by bladder pain-like nociceptive behavior/referred hyperalgesia. All these symptoms were significantly attenuated by oral preadministration of polaprezinc at 400 mg/kg. The same dose of polaprezinc also prevented the increased malondialdehyde level, an indicator of lipid peroxidation, and protein upregulation of cystathionine-γ-lyase, an H2S-generating enzyme, but not occludin, a tight junction-related membrane protein, in the bladder tissue of cyclophosphamide-treated mice. Oral posttreatment with polaprezinc at 30-100 mg/kg reversed the nociceptive behavior/referred hyperalgesia in a dose-dependent manner without affecting the increased bladder weight. Together, our data show that zinc supplementation with polaprezinc prevents the cyclophosphamide-induced cystitis probably through the antioxidant activity, and, like T-channel blockers, reverses the established cystitis-related bladder pain in mice, suggesting novel therapeutic usefulness of polaprezinc. PMID:25727961

  12. Crystal structure and mutational analysis of aminoacylhistidine dipeptidase from Vibrio alginolyticus reveal a new architecture of M20 metallopeptidases.

    Science.gov (United States)

    Chang, Chin-Yuan; Hsieh, Yin-Cheng; Wang, Ting-Yi; Chen, Yi-Chin; Wang, Yu-Kuo; Chiang, Ting-Wei; Chen, Yi-Ju; Chang, Cheng-Hsiang; Chen, Chun-Jung; Wu, Tung-Kung

    2010-12-10

    Aminoacylhistidine dipeptidases (PepD, EC 3.4.13.3) belong to the family of M20 metallopeptidases from the metallopeptidase H clan that catalyze a broad range of dipeptide and tripeptide substrates, including L-carnosine and L-homocarnosine. Homocarnosine has been suggested as a precursor for the neurotransmitter γ-aminobutyric acid (GABA) and may mediate the antiseizure effects of GABAergic therapies. Here, we report the crystal structure of PepD from Vibrio alginolyticus and the results of mutational analysis of substrate-binding residues in the C-terminal as well as substrate specificity of the PepD catalytic domain-alone truncated protein PepD(CAT). The structure of PepD was found to exist as a homodimer, in which each monomer comprises a catalytic domain containing two zinc ions at the active site center for its hydrolytic function and a lid domain utilizing hydrogen bonds between helices to form the dimer interface. Although the PepD is structurally similar to PepV, which exists as a monomer, putative substrate-binding residues reside in different topological regions of the polypeptide chain. In addition, the lid domain of the PepD contains an "extra" domain not observed in related M20 family metallopeptidases with a dimeric structure. Mutational assays confirmed both the putative di-zinc allocations and the architecture of substrate recognition. In addition, the catalytic domain-alone truncated PepD(CAT) exhibited substrate specificity to l-homocarnosine compared with that of the wild-type PepD, indicating a potential value in applications of PepD(CAT) for GABAergic therapies or neuroprotection. PMID:20819954

  13. Heat shock protein 70-dependent protective effect of polaprezinc on acetylsalicylic acid-induced apoptosis of rat intestinal epithelial cells.

    Science.gov (United States)

    Qin, Ying; Naito, Yuji; Handa, Osamu; Hayashi, Natsuko; Kuki, Aiko; Mizushima, Katsura; Omatsu, Tatsushi; Tanimura, Yuko; Morita, Mayuko; Adachi, Satoko; Fukui, Akifumi; Hirata, Ikuhiro; Kishimoto, Etsuko; Nishikawa, Taichiro; Uchiyama, Kazuhiko; Ishikawa, Takeshi; Takagi, Tomohisa; Yagi, Nobuaki; Kokura, Satoshi; Yoshikawa, Toshikazu

    2011-11-01

    Protection of the small intestine from mucosal injury induced by nonsteroidal anti-inflammatory drugs including acetylsalicylic acid is a critical issue in the field of gastroenterology. Polaprezinc an anti-ulcer drug, consisting of zinc and L-carnosine, provides gastric mucosal protection against various irritants. In this study, we investigated the protective effect of polaprezinc on acetylsalicylic acid-induced apoptosis of the RIE1 rat intestinal epithelial cell line. Confluent rat intestinal epithelial cells were incubated with 70 µM polaprezinc for 24 h, and then stimulated with or without 15 mM acetylsalicylic acid for a further 15 h. Subsequent cellular viability was quantified by fluorometric assay based on cell lysis and staining. Acetylsalicylic acid-induced cell death was also qualified by fluorescent microscopy of Hoechst33342 and propidium iodide. Heat shock proteins 70 protein expression after adding polaprezinc or acetylsalicylic acid was assessed by western blotting. To investigate the role of Heat shock protein 70, Heat shock protein 70-specific small interfering RNA was applied. Cell viability was quantified by fluorometric assay based on cell lysis and staining and apoptosis was analyzed by fluorescence-activated cell sorting. We found that acetylsalicylic acid significantly induced apoptosis of rat intestinal epithelial cells in a dose- and time-dependent manner. Polaprezinc significantly suppressed acetylsalicylic acid-induced apoptosis of rat intestinal epithelial cells at its late phase. At the same time, polaprezinc increased Heat shock protein 70 expressions of rat intestinal epithelial cells in a time-dependent manner. However, in Heat shock protein 70-silenced rat intestinal epithelial cells, polaprezinc could not suppress acetylsalicylic acid -induced apoptosis at its late phase. We conclude that polaprezinc-increased Heat shock protein 70 expression might be an important mechanism by which polaprezinc suppresses acetylsalicylic

  14. Expression of HSP72 in the gastric mucosa is regulated by gastric acid in rats-Correlation of HSP72 expression with mucosal protection

    International Nuclear Information System (INIS)

    Background and aim: The real mechanism of adaptive cytoprotection in the gastric mucosa is not well established. In the present study, we investigated the effect of acid suppressing agents on a 72-kDa heat shock protein (HSP72) expression, which is known as endogenous cytoprotective factor, in the gastric mucosa. Also, the association of gastric mucosal protective function against HCl-challenge was compared between HSP72-induced and -reduced group. Materials and methods: Expression of HSP72 was measured by Western blotting in the gastric mucosa before and after administration of famotidine or omeprazole. The gastric mucosal protective function against 0.6 N HCl was compared between control group and HSP72-reduced group. Also, the effect of increased expression of gastric HSP72 by additional administration of zinc sulfate or zinc L-carnosine, which is known as HSP72-inducer, on mucosal protective function was studied. Results: HSP72 expression in the gastric mucosa was reduced by acid suppressing agents. The lowest expression level of HSP72 was observed 12 h (famotidine, H2-receptor antagonist) or 48 h (omeprazole, proton pump inhibitor) after administration. The gastric mucosal protective ability against 0.6 N HCl was also reduced when HSP72 expression was decreased by famotidine or omeprazole. This phenomenon was reversed by HSP72 induction by additional administration of zinc derivatives. Conclusion: Our results might indicate that the expression of HSP72 in the gastric mucosa is physiologically regulated by gastric acid, and that HSP72 induction could be important in view of mucosal protection especially when HSP72 expression is reduced by administration of acid suppressing agents such as proton pump inhibitor or H2 receptor antagonist

  15. A review of traditional and novel treatments for seizures in autism spectrum disorder: findings from a systematic review and expert panel.

    Science.gov (United States)

    Frye, Richard E; Rossignol, Daniel; Casanova, Manuel F; Brown, Gregory L; Martin, Victoria; Edelson, Stephen; Coben, Robert; Lewine, Jeffrey; Slattery, John C; Lau, Chrystal; Hardy, Paul; Fatemi, S Hossein; Folsom, Timothy D; Macfabe, Derrick; Adams, James B

    2013-01-01

    Despite the fact that seizures are commonly associated with autism spectrum disorder (ASD), the effectiveness of treatments for seizures has not been well studied in individuals with ASD. This manuscript reviews both traditional and novel treatments for seizures associated with ASD. Studies were selected by systematically searching major electronic databases and by a panel of experts that treat ASD individuals. Only a few anti-epileptic drugs (AEDs) have undergone carefully controlled trials in ASD, but these trials examined outcomes other than seizures. Several lines of evidence point to valproate, lamotrigine, and levetiracetam as the most effective and tolerable AEDs for individuals with ASD. Limited evidence supports the use of traditional non-AED treatments, such as the ketogenic and modified Atkins diet, multiple subpial transections, immunomodulation, and neurofeedback treatments. Although specific treatments may be more appropriate for specific genetic and metabolic syndromes associated with ASD and seizures, there are few studies which have documented the effectiveness of treatments for seizures for specific syndromes. Limited evidence supports l-carnitine, multivitamins, and N-acetyl-l-cysteine in mitochondrial disease and dysfunction, folinic acid in cerebral folate abnormalities and early treatment with vigabatrin in tuberous sclerosis complex. Finally, there is limited evidence for a number of novel treatments, particularly magnesium with pyridoxine, omega-3 fatty acids, the gluten-free casein-free diet, and low-frequency repetitive transcranial magnetic simulation. Zinc and l-carnosine are potential novel treatments supported by basic research but not clinical studies. This review demonstrates the wide variety of treatments used to treat seizures in individuals with ASD as well as the striking lack of clinical trials performed to support the use of these treatments. Additional studies concerning these treatments for controlling seizures in individuals

  16. Influence of different histidine sources and zinc supplementation of broiler diets on dipeptide content and antioxidant status of blood and meat.

    Science.gov (United States)

    Kopeć, W; Jamroz, D; Wiliczkiewicz, A; Biazik, E; Pudlo, A; Hikawczuk, T; Skiba, T; Korzeniowska, M

    2013-01-01

    1. The objective of this study was to investigate how a diet containing spray-dried blood cells (SDBC) (4%) with or without zinc (Zn) would affect the concentration of two histidine heterodipeptides and the antioxidant status of broiler blood and breast muscles. 2. The study was carried out on 920 male Flex chickens randomly assigned to 4 dietary treatments: I - control, II - diet I with SDBC, III - diet I with SDBC and supplemented with Zn and IV - diet I supplemented with L-histidine. Birds were raised on floor littered with wood shavings, given free access to water and fed ad libitum. Performance indices were measured on d 1, 21 and 42. 3. The activity of antioxidant enzymes superoxide dismutase, catalase and glutathione peroxidase was analysed in plasma, erythrocytes and muscle tissue. The total antioxidant capacity of plasma and breast muscles was measured by 2,2-azinobis-(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging ability, as well as by ferric reducing antioxidant power (FRAP). Carnosine/anserine content of meat and plasma were determined using HPLC. Diets and breast muscles were analysed for amino acid profile and selected microelement content. 4. Histidine supplementation of the diet increased glutathione peroxidase activity in plasma and superoxide dismutase activity in erythrocytes. Moreover, the addition of SDBC or pure histidine in the diet increased histidine dipeptide content and activated enzymatic and non-enzymatic antioxidant systems in chicken blood and muscles. However, it led to lower growth performance indices. 5. The enrichment of broiler diets with Zn increased the antioxidant potential and the activity of superoxide dismutase in plasma, which was independent of the histidine dipeptide concentration. Zn supplementation combined with SDBC in a broiler diet led to the increase of superoxide dismutase and glutathione peroxidase activity, but it did not affect the radical

  17. β-alanine supplementation improves isometric endurance of the knee extensor muscles

    Directory of Open Access Journals (Sweden)

    Sale Craig

    2012-06-01

    Full Text Available Abstract Background We examined the effect of four weeks of β-alanine supplementation on isometric endurance of the knee extensors at 45% maximal voluntary isometric contraction (MVIC. Methods Thirteen males (age 23 ± 6 y; height 1.80 ± 0.05 m; body mass 81.0 ± 10.5 kg, matched for pre-supplementation isometric endurance, were allocated to either a placebo (n = 6 or β-alanine (n = 7; 6.4 g·d-1 over 4 weeks supplementation group. Participants completed an isometric knee extension test (IKET to fatigue, at an intensity of 45% MVIC, before and after supplementation. In addition, two habituation tests were completed in the week prior to the pre-supplementation test and a further practice test was completed in the week prior to the post-supplementation test. MVIC force, IKET hold-time, and impulse generated were recorded. Results IKET hold-time increased by 9.7 ± 9.4 s (13.2% and impulse by 3.7 ± 1.3 kN·s-1 (13.9% following β-alanine supplementation. These changes were significantly greater than those in the placebo group (IKET: t(11 = 2.9, p ≤0.05; impulse: t(11 = 3.1, p ≤ 0.05. There were no significant changes in MVIC force in either group. Conclusion Four weeks of β-alanine supplementation at 6.4 g·d-1 improved endurance capacity of the knee extensors at 45% MVIC, which most likely results from improved pH regulation within the muscle cell as a result of elevated muscle carnosine levels.

  18. Radiation-induced changes in the patterns of free ninhydrin-reactive substances of meat

    International Nuclear Information System (INIS)

    Samples of minced lean beef and pork, breast muscle of chicken, and white meat of carp packed in polyethylene/Hostaphan bags were irradiated in the presence of air at about 250C with 10-MeV electrons. The doses applied were for beef 0.5-20 Mrad, and for other meat samples 10 Mrad. In the dose range of 0-5 Mrad, no statistically significant changes in the composition of the free amino acids and similar compounds usually present in beef were found. In the dose range between 10 and 20 Mrad a tendency towards small losses in such components became obvious. In beef samples irradiated at doses >= 0.5 Mrad a new substance (Y) appeared distinctly in the zone of the basic amino-acids. This compound was detected by two independent methods, column chromatography and high-voltage electrophoresis. The yellow colour of the band appearing above carnosine in the pherogram was striking. Substance Y was also found after irradiation of pork and chicken meat. At a dose of 10 Mrad the concentration of Y in white chicken meat was nearly three times higher than in beef and pork. After irradiation of white carp muscle no Y, but another new basic compound (X) was observed. In the pherograms it appeared as a brownish-red band above β-alanine. The irradiation products X and Y may be used to find out whether meat of animals as used in this investigation had been exposed to radiation, if doses of 0.5 Mrad or higher were applied. (orig.)

  19. Acute effects of taurine on sarcoplasmic reticulum Ca2+ accumulation and contractility in human type I and type II skeletal muscle fibers.

    Science.gov (United States)

    Dutka, T L; Lamboley, C R; Murphy, R M; Lamb, G D

    2014-10-01

    Taurine occurs in high concentrations in muscle and is implicated in numerous physiological processes, yet its effects on many aspects of contractility remain unclear. Using mechanically skinned segments of human vastus lateralis muscle fibers, we characterized the effects of taurine on sarcoplasmic reticulum (SR) Ca2+ accumulation and contractile apparatus properties in type I and type II fibers. Prolonged myoplasmic exposure (>10 min) to taurine substantially increased the rate of accumulation of Ca2+ by the SR in both fiber types, with no change in the maximum amount accumulated; no such effect was found with carnosine. SR Ca2+ accumulation was similar with 10 or 20 mM taurine, but was significantly slower at 5 mM taurine. Cytoplasmic taurine (20 mM) had no detectable effects on the responsiveness of the Ca2+ release channels in either fiber type. Taurine caused a small increase in Ca2+ sensitivity of the contractile apparatus in type I fibers, but type II fibers were unaffected; maximum Ca(2+)-activated force was unchanged in both cases. The effects of taurine on SR Ca2+ accumulation (1) only became apparent after prolonged cytoplasmic exposure, and (2) persisted for some minutes after complete removal of taurine from the cytoplasm, consistent with the hypothesis that the effects were due to an action of taurine from inside the SR. In summary, taurine potentiates the rate of SR Ca2+ uptake in both type I and type II human fibers, possibly via an action from within the SR lumen, with the degree of potentiation being significantly reduced at low physiological taurine levels. PMID:25123198

  20. Nutritional Strategies to Modulate Intracellular and Extracellular Buffering Capacity During High-Intensity Exercise.

    Science.gov (United States)

    Lancha Junior, Antonio Herbert; Painelli, Vitor de Salles; Saunders, Bryan; Artioli, Guilherme Giannini

    2015-11-01

    Intramuscular acidosis is a contributing factor to fatigue during high-intensity exercise. Many nutritional strategies aiming to increase intra- and extracellular buffering capacity have been investigated. Among these, supplementation of beta-alanine (~3-6.4 g/day for 4 weeks or longer), the rate-limiting factor to the intramuscular synthesis of carnosine (i.e. an intracellular buffer), has been shown to result in positive effects on exercise performance in which acidosis is a contributing factor to fatigue. Furthermore, sodium bicarbonate, sodium citrate and sodium/calcium lactate supplementation have been employed in an attempt to increase the extracellular buffering capacity. Although all attempts have increased blood bicarbonate concentrations, evidence indicates that sodium bicarbonate (0.3 g/kg body mass) is the most effective in improving high-intensity exercise performance. The evidence supporting the ergogenic effects of sodium citrate and lactate remain weak. These nutritional strategies are not without side effects, as gastrointestinal distress is often associated with the effective doses of sodium bicarbonate, sodium citrate and calcium lactate. Similarly, paresthesia (i.e. tingling sensation of the skin) is currently the only known side effect associated with beta-alanine supplementation, and it is caused by the acute elevation in plasma beta-alanine concentration after a single dose of beta-alanine. Finally, the co-supplementation of beta-alanine and sodium bicarbonate may result in additive ergogenic gains during high-intensity exercise, although studies are required to investigate this combination in a wide range of sports. PMID:26553493

  1. Anti-Oxidative and Anti-Inflammation Activities of Pork Extracts.

    Science.gov (United States)

    Gil, Juae; Kim, Dongwook; Yoon, Seok-Ki; Ham, Jun-Sang; Jang, Aera

    2016-01-01

    This study was conducted to evaluate the antioxidative and anti-inflammatory effects of boiled pork powder (BPP) and hot water extract powder (HWEP) from 4 cuts of meat from Landrace × Yorkshire × Duroc (LYD). The highest DPPH radical scavenging activities determined were from BPP of Boston butt (13.65 M TE) and HWEP of loin (19.40 M TE) and ham (21.45 M TE). The 2,2-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical scavenging activities of BPP from shoulder ham (39.28 M TE) and ham (39.43 M TE) were higher than those of other meat cuts, while HWEP of ham exhibited the highest ABTS radical scavenging activity. A higher oxygen radical absorbance capacity was determined for BPP from ham (198.35 M TE) and in HWEP from loin (204.07 M TE), Boston butt (192.85 M TE), and ham (201.36 M TE). Carnosine content of BPP and HWEP from loin and were determined to be 106.68 and 117.77 mg/g on a dry basis, respectively. The anserine content of BPP (5.26 mg/g, dry basis) and HWEP (6.79 mg/g, dry basis) of shoulder ham exhibited the highest value as compared to the extracts from the other meat cuts. The viability of RAW 264.7 cells was increased with increasing HWEP from loin and ham treatment. In addition, the expression of IL-6 and TNF-α was significantly reduced by HWEP from loin and ham, in a dose dependent manner. These results suggested that boiled pork and hot water extract of pork have antioxidative and cytokine inhibitory effects. PMID:27194938

  2. A review of traditional and novel treatments for seizures in autism spectrum disorder: Findings from a systematic review and expert panel.

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    Richard Eugene Frye

    2013-09-01

    Full Text Available Despite the fact that seizures are commonly associated with autism spectrum disorder (ASD, the effectiveness of treatments for seizures has not been well studied in individuals with ASD. This manuscript reviews both traditional and novel treatments for seizures associated with ASD. Studies were selected by systematically searching major electronic databases and by a panel of experts that treat ASD individuals. Only a few anti-epileptic drugs (AEDs have undergone carefully controlled trials in ASD, but these trials examined outcomes other than seizures. Several lines of evidence point to valproate, lamotrigine and levetiracetam as the most effective and tolerable AEDs for individuals with ASD. Limited evidence supports the use of traditional non-AED treatments, such as the ketogenic and modified Atkins diet, multiple subpial transections and immunomodulation and neurofeedback treatments. Although specific treatments may be more appropriate for specific genetic and metabolic syndromes associated with ASD and seizures, there are few studies which have documented the effectiveness of treatments for seizures for specific syndromes. Limited evidence supports L-carnitine, multivitamins and N-acetyl-L-cysteine in mitochondrial disease and dysfunction, folinic acid in cerebral folate abnormalities and early treatment with vigabatrin in tuberous sclerosis complex. Finally, there is limited evidence for a number of novel treatments, particularly magnesium with pyridoxine, omega-3 fatty acids, the gluten-free casein-free diet and transcranial magnetic simulation. Zinc and L-carnosine are potential novel treatments supported by basic research but not clinical studies. This review demonstrates the wide variety of treatments used to treat seizures in individuals with ASD as well as the striking lack of clinical trials performed to support the use these treatments. Additional studies concerning these treatments for controlling seizures in individuals with ASD

  3. Proteins with altered levels in plasma from glioblastoma patients as revealed by iTRAQ-based quantitative proteomic analysis.

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    Poonam Gautam

    Full Text Available Glioblastomas (GBMs are the most common and lethal primary tumors of the central nervous system with high level of recurrence despite aggressive therapy. Tumor-associated proteins/peptides may appear in the plasma of these patients as a result of disruption of the blood-brain barrier in them, raising the scope for development of plasma-based tests for diagnosis and monitoring the disease. With this objective, we analyzed the levels of proteins present in the plasma from GBM patients using an iTRAQ based LC-MS/MS approach. Analysis with pooled plasma specimens from the patient and healthy control samples revealed high confidence identification of 296 proteins, of which 61 exhibited a fold-change ≥1.5 in the patient group. Forty-eight of them contained signal sequence. A majority have been reported in the differentially expressed transcript or protein profile of GBM tissues; 6 have been previously studied as plasma biomarkers for GBM and 16 for other types of cancers. Altered levels of three representative proteins-ferritin light chain (FTL, S100A9, and carnosinase 1 (CNDP1-were verified by ELISA in a test set of ten individual plasma specimens. FTL is an inflammation marker also implicated in cancer, S100A9 is an important member of the Ca(2+ signaling cascade reported to be altered in GBM tissue, and CNDP1 has been reported for its role in the regulation of the levels of carnosine, implicated as a potential drug for GBM. These and other proteins in the dataset may form useful starting points for further clinical investigations for the development of plasma-based biomarker panels for GBM.

  4. The influence of a single nucleotide polymorphism within CNDP1 on susceptibility to diabetic nephropathy in Japanese women with type 2 diabetes.

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    Mahiro Kurashige

    Full Text Available BACKGROUND: Several linkage analyses have mapped a susceptibility locus for diabetic nephropathy to chromosome 18q22-23, and polymorphisms within the carnosine dipeptidase 1 gene (CNDP1, located on 18q22.3, have been shown to be associated with diabetic nephropathy in European subjects with type 2 diabetes. However, the association of this locus with diabetic nephropathy has not been evaluated in the Japanese population. In this study, we examined the association of polymorphisms within the CNDP1/CNDP 2 locus with diabetic nephropathy in Japanese subjects with type 2 diabetes. METHODOLOGY/PRINCIPAL FINDINGS: We genotyped a leucine repeat polymorphism (D18S880 that is within CNDP1 along with 29 single nucleotide polymorphisms (SNPs in the CNDP1/CNDP2 locus for 2,740 Japanese subjects with type 2 diabetes (1,205 nephropathy cases with overt nephropathy or with end-stage renal disease [ESRD], and 1,535 controls with normoalbuminuria. The association of each polymorphism with diabetic nephropathy was analysed by performing logistic regression analysis. We did not observe any association between D18S880 and diabetic nephropathy in Japanese subjects with type 2 diabetes. None of the 29 SNPs within the CNDP1/CNDP2 locus were associated with diabetic nephropathy, but a subsequent sex-stratified analysis revealed that 1 SNP in CNDP1 was nominally associated with diabetic nephropathy in women (rs12604675-A; p = 0.005, odds ratio [OR] = 1.76, 95% confidence interval [CI], 1.19-2.61. Rs12604675 was associated with overt proteinuria (p = 0.002, OR = 2.18, 95% CI, 1.32-3.60, but not with ESRD in Japanese women with type 2 diabetes. CONCLUSIONS/SIGNIFICANCE: Rs12604675-A in CNDP1 may confer susceptibility to overt proteinuria in Japanese women with type 2 diabetes.

  5. Composition of free and peptide-bound amino acids in beef chuck, loin, and round cuts.

    Science.gov (United States)

    Wu, G; Cross, H R; Gehring, K B; Savell, J W; Arnold, A N; McNeill, S H

    2016-06-01

    Meat is a food for humans. However, beef consumption in the United States has steadily declined by >14% over the past decade due to a variety of factors, including insufficient knowledge of animal protein. This study quantified all proteinogenic AA as well as nutritionally and physiologically significant nonproteinogenic AA and small peptides in beef cuts from 3 subprimals (chuck, round, and loin). Beef carcasses ( = 10) were selected at 3 commercial packing plants in the United States. Retail-cut samples were analyzed for the nitrogenous substances after acid, alkaline, or enzymatic hydrolysis and after deproteinization. In these chuck, round, and loin cuts, total amounts of glutamate (free plus peptide bound) were the highest (69-75 mg/g dry weight) followed by lysine, leucine, arginine, and glutamine in descending order. This is the first study to determine aspartate, asparagine, glutamate, and glutamine in meat proteins of any animal species. In all the beef samples evaluated, glutamine was the most abundant free AA (4.0-5.7 mg/g dry weight) followed by taurine, alanine, glutamate, and β-alanine. Additionally, samples from all beef cuts had high concentrations of anserine, carnosine, and glutathione, which were 2.8 to 3.7, 15.2 to 24.2, and 0.68 to 0.79 mg/g dry weight, respectively. Beef top loin steaks appear to provide higher protein nutrition values than top round steaks and under blade roasts, but all are excellent sources of proteinogenic AA as well as antioxidant AA and peptides to improve human growth, development, and health. Our findings may help guide future decisions regarding human and animal nutrition. PMID:27285936

  6. Brain type carnosinase in dementia: a pilot study

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    Papaioannou Alexandra

    2007-11-01

    Full Text Available Abstract Background The pathological processes underlying dementia are poorly understood and so are the markers which identify them. Carnosinase is a dipeptidase found almost exclusively in brain and serum. Carnosinase and its substrate carnosine have been linked to neuropathophysiological processes. Methods Carnosinase activity was measured by a flourometric method in 37 patients attending a Geriatric Outpatient Clinic. There were 17 patients without dementia, 13 had Alzheimer's disease (AD and 7 had mixed dementia (MD. Results The range of serum carnosinase activity for patients without dementia was 14.5 – 78.5 μmol/ml/h. There was no difference in carnosinase activity between patients without dementia (40.3 ± 15.2 μmol/ml/h and patients with AD (44.4 ± 12.4 μmol/ml/h or MD (26.6 ± 15 μmol/ml/h. However, levels in the MD group were significantly lower than the AD group (p = 0.01. This difference remained significant after adjusting for gender, MMSE score, exercise, but not age, one at a time and all combined. The effect of other medical conditions did not remove the significance between the AD and MD groups. The MD group, but not the AD group, demonstrated a significant trend with carnosinase activity decreasing with duration of disease (from first recorded date of diagnosis to date of blood collection (r = -0.76, p = 0.049. There was no association with carnosinase activity and MMSE score in the AD or MD group. Both AD and MD patients on any dementia medication (donepezil, galantamine, memantine had higher carnosinase activity compared to those not taking a dementia medication. Carnosinase activity was higher in patients who regularly exercised (n = 20 compared to those who did not exercise regularly (n = 17(p = 0.006. Conclusion This exploratory study has shown altered activities of the enzyme carnosinase in patients with dementia.

  7. [The role of nonenzymatic glycation and glyco-oxidation in the development of diabetic vascular complications].

    Science.gov (United States)

    Jakus, V

    2003-05-01

    Hyperglycaemia is considered to be the key causal factor in the development of diabetic complications. Poor glycemic control a significant changes of erythrocyte membrane fluidity, erythrocyte deformability and antioxidant status. Nonenzymatic glycation and glycoxidation with cascade of free radical reactions, oxidative and carbonyl stress may play an important role in the development diabetic micro- and macrovascular complications. The serum levels of specific and nonspecific advanced glycation end products (s-AGEs) have been found elevated in type 1 and type 2 diabetic patients. Levels of s-AGEs. may serve as useful biochemical marker for monitoring progression of diabetic complications and pathological processes. Accumulation of AGEs on tissue proteins increases with pathogenesis of diabetic complications and atherosclerosis. AGEs are believed to induce cellular oxidative stress through the interaction with specific cellular receptors. Carbonyl stress-induced tissue damage is caused by AGE precursors formed by hyperglycaemia, hyperlipidemia, nonenzymatic glycation, peroxidation of lipids and metabolis processes. The toxic effects of AGE precursors can not be directly antagonized by antioxidants. Only a small number of biological carbonyl scavengers like glutathione have been identified to date. For therapeutic intervention, nucleophilic compounds as aminoguanidine, pyridoxamine, OPB-9195, 2,3-diaminophenazone, carnosine and tenilsetam give promising results. These potential therapeutics have been proposed to trap AGE precursors. Studies in vitro showed that these AGE inhibitors have also the antioxidant and chelating activity. Angiotensin converting enzyme (ACE) and angiotensin II receptor antagonists also significantly attenuate AGE production. These drugs do not trap AGE precursors, but impact on the production of AGE precursors by chelating transition metals and inhibiting various oxidative steps in the process of glycoxidation, including the formation of

  8. Nasal toxicity, carcinogenicity, and olfactory uptake of metals.

    Science.gov (United States)

    Sunderman, F W

    2001-01-01

    Occupational exposures to inhalation of certain metal dusts or aerosols can cause loss of olfactory acuity, atrophy of the nasal mucosa, mucosal ulcers, perforated nasal septum, or sinonasal cancer. Anosmia and hyposmia have been observed in workers exposed to Ni- or Cd-containing dusts in alkaline battery factories, nickel refineries, and cadmium industries. Ulcers of the nasal mucosa and perforated nasal septum have been reported in workers exposed to Cr(VI) in chromate production and chrome plating, or to As(III) in arsenic smelters. Atrophy of the olfactory epithelium has been observed in rodents following inhalation of NiSO4 or alphaNi3S2. Cancers of the nose and nasal sinuses have been reported in workers exposed to Ni compounds in nickel refining, cutlery factories, and alkaline battery manufacture, or to Cr(VI) in chromate production and chrome plating. In animals, several metals (eg, Al, Cd, Co, Hg, Mn, Ni, Zn) have been shown to pass via olfactory receptor neurons from the nasal lumen through the cribriform plate to the olfactory bulb. Some metals (eg, Mn, Ni, Zn) can cross synapses in the olfactory bulb and migrate via secondary olfactory neurons to distant nuclei of the brain. After nasal instillation of a metal-containing solution, transport of the metal via olfactory axons can occur rapidly, within hours or a few days (eg, Mn), or slowly over days or weeks (eg, Ni). The olfactory bulb tends to accumulate certain metals (eg, Al, Bi, Cu, Mn, Zn) with greater avidity than other regions of the brain. The molecular mechanisms responsible for metal translocation in olfactory neurons and deposition in the olfactory bulb are unclear, but complexation by metal-binding molecules such as carnosine (beta-alanyl-L-histidine) may be involved. PMID:11314863

  9. Telomere length is a biomarker of cumulative oxidative stress, biologic age, and an independent predictor of survival and therapeutic treatment requirement associated with smoking behavior.

    Science.gov (United States)

    Babizhayev, Mark A; Savel'yeva, Ekaterina L; Moskvina, Svetlana N; Yegorov, Yegor E

    2011-11-01

    Globally, tobacco use is associated with 5 million deaths per annum and is regarded as one of the leading causes of premature death. Major chronic disorders associated with smoking include cardiovascular diseases, several types of cancer, and chronic obstructive pulmonary disease (lung problems). Cigarette smoking (CS) generates a cumulative oxidative stress, which may contribute to the pathogenesis of chronic diseases. Mainstream and side stream gas-phase smoke each have about the same concentration of reactive free radical species, about 1 × 10(16) radicals per cigarette (or 5 × 10(14) per puff). This effect is critical in understanding the biologic effects of smoke. Several lines of evidence suggest that cigarette smoke constituents can directly activate vascular reactive oxygen species production. In this work we present multiple evidence that CS provide the important risk factors in many age-related diseases, and is associated with increased cumulative and systemic oxidative stress and inflammation. The cited processes are marked by increased white blood cell (leucocytes, WBCs) turnover. The data suggest an alteration of the circulating WBCs by CS, resulting in increased adherence to endothelial cells. Telomeres are complex DNA-protein structures located at the end of eukaryotic chromosomes. Telomere length shortens with biologic age in all replicating somatic cells. It has been shown that tobacco smoking enhances telomere shortening in circulating human WBCs. Telomere attrition (expressed in WBCs) can serve as a biomarker of the cumulative oxidative stress and inflammation induced by smoking and, consequently, show the pace of biologic aging. We originally propose that patented specific oral formulations of nonhydrolized carnosine and carcinine provide a powerful tool for targeted therapeutic inhibition of cumulative oxidative stress and inflammation and protection of telomere attrition associated with smoking. The longitudinal studies of the clinical

  10. PARP-1 inhibitors DPQ and PJ-34 negatively modulate proinflammatory commitment of human glioblastoma cells.

    Science.gov (United States)

    Scalia, Marina; Satriano, Cristina; Greca, Rossana; Stella, Anna Maria Giuffrida; Rizzarelli, Enrico; Spina-Purrello, Vittoria

    2013-01-01

    Poly(ADP-ribose) polymerases (PARPs) are recognized as key regulators of cell survival or death. PARP-1 is essential to the repair of DNA single-strand breaks via the base excision repair pathway. The enzyme may be overactivated in response to inflammatory cues, thus depleting cellular energy pools and eventually causing cell death. Accordingly, PARP-1 inhibitors, acting by competing with its physiological substrate NAD(+), have been proposed to play a protective role in a wide range of inflammatory and ischemia/reperfusion-associated diseases. Recently, it has also been reported that PARP-1 regulates proinflammatory mediators, including cytokines, chemokines, adhesion molecules, and enzymes (e.g., iNOS). Furthermore, PARP-1 has been shown to act as a coactivator of NF-κB- and other transcription factors implicated in stress/inflammation, as AP-1, Oct-1, SP-1, HIF, and Stat-1. To further substantiate this hypothesis, we tested the biomolecular effects of PARP-1 inhibitors DPQ and PJ-34 on human glioblastoma cells, induced to a proinflammatory state with lipopolysaccharide and Interferon-γ. PARP-1 expression was evaluated by laser scanning confocal microscopy immunofluorescence (LSM); nitrite production, LDH release and cell viability were also determined. LSM of A-172, SNB-19 and CAS-1 cells demonstrated that DPQ and PJ-34 downregulate PARP-1 expression; they also cause a decrease of LDH release and nitrite production, while increasing cell viability. Similar effects were caused in all three cell lines by N-mono-methyl-arginine, a well known iNOS inhibitor, and by L-carnosine and trehalose, two antioxidant molecules. These results demonstrate that, similar to other well characterized drugs, DPQ and PJ-34 reduce cell inflammation and damage that follow PARP-1 overexpression, while they increase cell survival: this suggests their potential exploitation in clinical Medicine. PMID:23011206

  11. New insights in dihydropyrimidine dehydrogenase deficiency: a pivotal role for beta-aminoisobutyric acid?

    Science.gov (United States)

    Van Kuilenburg, André B P; Stroomer, Alida E M; Van Lenthe, Henk; Abeling, Nico G G M; Van Gennip, Albert H

    2004-04-01

    DPD (dihydropyrimidine dehydrogenase) constitutes the first step of the pyrimidine degradation pathway, in which the pyrimidine bases uracil and thymine are catabolized to beta-alanine and the R-enantiomer of beta-AIB (beta-aminoisobutyric acid) respectively. The S-enantiomer of beta-AIB is predominantly derived from the catabolism of valine. It has been suggested that an altered homoeostasis of beta-alanine underlies some of the clinical abnormalities encountered in patients with a DPD deficiency. In the present study, we demonstrated that only a slightly decreased concentration of beta-alanine was present in the urine and plasma, whereas normal levels of beta-alanine were present in the cerebrospinal fluid of patients with a DPD deficiency. Therefore the metabolism of beta-alanine-containing peptides, such as carnosine, may be an important factor involved in the homoeostasis of beta-alanine in patients with DPD deficiency. The mean concentration of beta-AIB was approx. 2-3-fold lower in cerebrospinal fluid and urine of patients with a DPD deficiency, when compared with controls. In contrast, strongly decreased levels (10-fold) of beta-AIB were present in the plasma of DPD patients. Our results demonstrate that, under pathological conditions, the catabolism of valine can result in the production of significant amounts of beta-AIB. Furthermore, the observation that the R-enantiomer of beta-AIB is abundantly present in the urine of DPD patients suggests that significant cross-over exists between the thymine and valine catabolic pathways. PMID:14705962

  12. β-Alanine supplementation enhances human skeletal muscle relaxation speed but not force production capacity.

    Science.gov (United States)

    Hannah, Ricci; Stannard, Rebecca Louise; Minshull, Claire; Artioli, Guilherme Giannini; Harris, Roger Charles; Sale, Craig

    2015-03-01

    β-Alanine (BA) supplementation improves human exercise performance. One possible explanation for this is an enhancement of muscle contractile properties, occurring via elevated intramuscular carnosine resulting in improved calcium sensitivity and handling. This study investigated the effect of BA supplementation on in vivo contractile properties and voluntary neuromuscular performance. Twenty-three men completed two experimental sessions, pre- and post-28 days supplementation with 6.4 g/day of BA (n = 12) or placebo (PLA; n = 11). During each session, force was recorded during a series of knee extensor contractions: resting and potentiated twitches and octet (8 pulses, 300 Hz) contractions elicited via femoral nerve stimulation; tetanic contractions (1 s, 1-100 Hz) via superficial muscle stimulation; and maximum and explosive voluntary contractions. BA supplementation had no effect on the force-frequency relationship, or the force responses (force at 25 and 50 ms from onset, peak force) of resting or potentiated twitches, and octet contractions (P > 0.05). Resting and potentiated twitch electromechanical delay and time-to-peak tension were unaffected by BA supplementation (P > 0.05), although half-relaxation time declined by 7-12% (P < 0.05). Maximum and explosive voluntary forces were unchanged after BA supplementation. BA supplementation had no effect on evoked force responses, implying that altered calcium sensitivity and/or release are not the mechanisms by which BA supplementation influences exercise performance. The reduced half-relaxation time with BA supplementation might, however, be explained by enhanced reuptake of calcium, which has implications for the efficiency of muscle contraction following BA supplementation. PMID:25539942

  13. Effect of advanced glycation end-products on cell proliferation and cell death.

    Science.gov (United States)

    Peterszegi, G; Molinari, J; Ravelojaona, V; Robert, L

    2006-09-01

    The effect of advanced glycation end products (AGE-s) was studied on the proliferation and cell death of human skin fibroblasts in culture. Several AGE-products were prepared from proteins, a peptide and amino acids, using Glucose or Fructose, with or without Fe2+. The AGE preparations increased cell death at the 7th day, after only 72 hours of incubation. Some of these glycation products modified also proliferation. This effect of AGE-s was even maintained without these products in fresh medium for a second period of incubation up to 10 days from the start of the experiment. In order to explore the role of AGE-receptors, especially of AGE-receptor and of growth factor receptors (fibroblast and epidermal growth factors receptors), antibodies to these receptors were added to cell cultures and their effect on both cell death and proliferation were determined as for the AGE-s. These anti-receptor antibodies imitated to some extent the results obtained with AGE-s, producing increase of cell death and proliferation, followed above a certain concentration of antibodies by a decrease and a new increase or plateau. This might correspond to the internalization of the receptors followed by a re-expression on the cell membrane. The role of receptor-mediated Reactive Oxygen Species-production was also explored using scavengers: N-acetyl-cysteine (NAC), L-Carnosine, superoxide dismutase (SOD) and Catalase. Several of these scavengers decreased cell death, suggesting that Reactive Oxygen Species-production is partially involved in the observed phenomena. PMID:16919894

  14. Effect of neuroprotective drugs on gene expression in G93A/SOD1 mice.

    Science.gov (United States)

    Ignacio, Sheila; Moore, Dan H; Smith, Andrew P; Lee, Nancy M

    2005-08-01

    Gene expression analysis is a powerful tool that has been used to define the pathological processes underlying many diseases. Several laboratories, including our own, have used this approach to identify molecular abnormalities in the G93A/SOD1 mouse, an animal model of amyotrophic lateral sclerosis (ALS). Here, we report the results of analysis of an expanded panel of genes throughout the entire lifetime in the spinal cord of these animals. In addition to upregulation of microglia/neuroinflammatory genes identified previously, we observed upregulation of metallothionein-I and -II (MT-I, MT-II). MT-I and MT-II play an important role in disposition of zinc ion, and other studies have also indicated their levels are altered in development of motor neuron disease in these animals. We also analyzed the effect on these expression profiles of several candidate drugs that have been shown to have neuroprotective effects in vivo or in vitro. That is, we asked whether administration to the G93A/SOD1 mice of any of these drugs could reverse the alterations in gene expression patterns that occur as the animals develop. The mice were given daily doses of these drugs when they were 9-11 weeks old, at a stage early in development of motor neuron disease, continuing for 5 weeks, at which time they were sacrificed. Treatment of the mice with l-carnosine, a dipeptide that scavenges free radicals and chelates zinc, did not affect expression of any of the genes altered in these animals. However, it did upregulate 3 genes unaffected by the presence of the G93A/SOD1 mutation: glial fibrillary acidic protein (GFAP), stroma-derived factor-1 (SDF-1), and excitatory amino acid transporter-2 (EAAT2). In contrast, metallothionein-III (MT-III) was downregulated. Treatment of the animals with baicalein, an herbal extract with anti-inflammatory and numerous other effects, downregulated the microglia markers CD68, CD80, and CD86, all of which were upregulated in untreated mutant animals. Baicalein

  15. Carbonic anhydrase activators: X-ray crystal structure of the adduct of human isozyme II with L-histidine as a platform for the design of stronger activators.

    Science.gov (United States)

    Temperini, Claudia; Scozzafava, Andrea; Puccetti, Luca; Supuran, Claudiu T

    2005-12-01

    Activation of the carbonic anhydrase (CA, EC 4.2.1.1) isoforms hCA I, II, and IV with l-histidine and some of its derivatives has been investigated by kinetic and X-ray crystallographic methods. l-His was a potent activator of isozymes I and IV (activation constants in the range of 4-33microM), and a moderate hCA II activator (activation constant of 113microM). Both carboxy- as well as amino-substituted l-His derivatives, such as the methyl ester or the dipeptide carnosine (beta-Ala-His), acted as more efficient activators as compared to l-His. The X-ray crystallographic structure of the hCA II-l-His adduct showed the activator to be anchored at the entrance of the active site cavity, participating in an extended network of hydrogen bonds with the amino acid residues His64, Asn67, and Gln92 and, with three water molecules connecting it to the zinc-bound water. Although the binding site of l-His is similar to that of histamine, the first CA activator for which the X-ray crystal structure has been reported in complex with hCA II (Briganti, F.; Mangani, S.; Orioli, P.; Scozzafava, A.; Vernaglione, G.; Supuran, C. T. Biochemistry1997, 36, 10384) there are important differences of binding between the two structurally related activators, since histamine interacts among others with Asn67 and Gln92 (similarly to l-His), but also with Asn62 and not His64, whereas the number of water molecules connecting them to the zinc-bound water is different (two for histamine, three for l-His). Furthermore, the imidazole moieties of the two activators adopt different conformations when bound to the enzyme active site. Since neither the amino- nor carboxy moieties of l-His participate in interactions with amino acid moieties of the active site, they can be derivatized for obtaining more potent activators, with pharmacological applications for the enhancement of synaptic efficacy. This may constitute a novel approach for the treatment of Alzheimer's disease, aging, and other conditions in

  16. Zinc deficiency or excess within the physiological range increases genome instability and cytotoxicity, respectively, in human oral keratinocyte cells.

    Science.gov (United States)

    Sharif, Razinah; Thomas, Philip; Zalewski, Peter; Fenech, Michael

    2012-04-01

    Zinc (Zn) is an essential component of Zn-finger proteins and acts as a cofactor for enzymes required for cellular metabolism and in the maintenance of DNA integrity. The study investigated the genotoxic and cytotoxic effects of Zn deficiency or excess in a primary human oral keratinocyte cell line and determined the optimal concentration of two Zn compounds (Zn Sulphate (ZnSO(4)) and Zn Carnosine (ZnC)) to minimise DNA damage. Zn-deficient medium (0 μM) was produced using Chelex treatment, and the two Zn compounds ZnSO(4) and ZnC were tested at concentrations of 0.0, 0.4, 4.0, 16.0, 32.0 and 100.0 μM. Cell viability was decreased in Zn-depleted cells (0 μM) as well as at 32 μM and 100 μM for both Zn compounds (P < 0.0001) as measured via the MTT assay. DNA strand breaks, as measured by the comet assay, were found to be increased in Zn-depleted cells compared with the other treatment groups (P < 0.05). The Cytokinesis Block Micronucleus Cytome assay showed a significant increase in the frequency of both apoptotic and necrotic cells under Zn-deficient conditions (P < 0.05). Furthermore, elevated frequencies of micronuclei (MNi), nucleoplasmic bridges (NPBs) and nuclear buds (NBuds) were observed at 0 and 0.4 μM Zn, whereas these biomarkers were minimised for both Zn compounds at 4 and 16 μM Zn (P < 0.05), suggesting these concentrations are optimal to maintain genome stability. Expression of PARP, p53 and OGG1 measured by western blotting was increased in Zn-depleted cells indicating that DNA repair mechanisms are activated. These results suggest that maintaining Zn concentrations within the range of 4-16 μM is essential for DNA damage prevention in cultured human oral keratinocytes. PMID:21935692

  17. CURRENT STATE OF POULTRy BREEDING AND ITS FUTURE TRENDS

    Directory of Open Access Journals (Sweden)

    Gordana Kralik

    2013-12-01

    Full Text Available Poultry production in eastern Croatia is developed by individual producers mainly in semi intensive way, and within the organized poultry systems where the process is organized in a modern, intensive way. There is a tradition of breeding hens and geese in this area. Poultry products - meat and eggs are important in supplying he population with animal protein, minerals and vitamins. Modern hybrid hens are used for egg production and for meat production in the intensive production. Today geese breeding in these areas are completely neglected. Croatia as a member of European Union, has possibility of the placement ofautochthonous breeds of poultry such as Hrvatica hen, Zagorje turkey and Podravian goose. Financial supports at the national level are allocated for the first two autochthonous breeds of poultry because these breeds can, with good production traits, represent genetic resources and strategic reserves in the future development of domestic poultry genotypes. Poultry production is especial emphasis in accordance with the criteria of welfare and health of poultry. This paper discusses further development of poultry in terms of production of poultry meat and eggs as a functional food. The composition and content of nutricines in meat and eggs can be affected by feed composition. Desired nutricines are installed in muscular tissue of poultry by using feed and adding some components. Consumption of eggs and poultry meat enriched by selenium, lutein and omega-3 fatty acids affects the improvement of the quality of the human diet. The recent researches show that chicken can effectively be enriched in carnosine - ingredients that are now taught as “anti-aging” factor. Enrichment of poultry products with nutricines gives greater importance to these foods in the diet of the population than the former one, mainly based on the nutritional aspect. Greater selection of quality poultry products can be a significant factor in the development of

  18. Study on bioactive di-, and tripeptide content in natural plant sources by HPLC methods with respect to functional food application

    International Nuclear Information System (INIS)

    Complete text of publication follows. Small molecular weight peptides represent an important family of compounds that play significant role in physiological and biochemical processes as well as in clinical and food research. The functional properties can include antioxidant and antimicrobial activity, surfactant and nutritional capabilities, moreover these compounds can contribute to the development of characteristic flavors such as sweetness and bitterness in various types of food. Several publications have dealt with the separation, detection and identification of these compounds, however the published methods carry difficulties in terms of the quantitative analysis, the sensitivity and reproducibility have been proven to be poor mainly because several amino acid moieties have low UV-absorbing properties. Our intention was to develop a reliable and sensitive chromatographic method to detect di-, and tripeptides (Aspartame, L-carnosine, L-glutation, Alanyl-glutamine and γ-glutein) in raw and processed food materials. A HPLC method was developed to analyze peptide containing complex food samples and raw materials using trifluoro-acetic acid-acetonitrile eluent system with gradient elution on a C18 reverse phase chromatographic column. The detection of free peptides was carried out using evaporative light scattering (ELS) detection, while UV detection was accomplished by pre-column derivatization with danzyl-chloride. Pea, rice and garlic samples have been selected for the study, the extraction procedure was optimized with different solvents: 0.1 M phosphoric-acid, 0.1 M hydrochloric-acid, acetic-acid, ethanol and water, the peptide content was analyzed with the newly developed technique. Antioxidant activity (FRAP) was observed only for the sulphur containing derivatives (γ-glutein, L-glutation). Garlic extracts have shown the highest antioxidant activity (46 ppm in ascorbic acid equivalents), pea samples have exhibited lower activity (23 ppm) and the lowest

  19. [Do the glutamate excitotoxicity theory and potential free radicals implication in schizophrenia aetiopathogenesis provide a new enlightenment to links between: genome, environment and biology in the determinism of that disorder?].

    Science.gov (United States)

    Nguimfack Mbodie, P C

    2002-01-01

    radicals a noxious effect on neuronal synapses. This could be due to a failing of their recapture at the presynaptic level in addition to a dysfunctioning of the antioxidizing system (glutathion, carnosine, superoxide dismutase, aspartate) to which dopamine and other monoamines might participate. The question is whether or not this theory contributes to shed light on links between: genome, environmental factors and biology in schizophrenia. Through the review and discussion of genetical aspects of schizophrenia, environmental factors and the biological aspect, we intend to revive debate on that question. The articles and authors were selected with regard to the aptness of their publications on that subject, their evolving ideas and finally the interest of their works for neurosciences. This new approach perhaps is opening the way to new therapeutic perspectives in the treatment of schizophrenia based on the antioxidizing substances as shown for some neurological diseases (amyotrophic lateral sclerosis, Parkinson's disease and Huntington's chorea) for which experiments are going on. PMID:11972141

  20. CURRENT STATE OF POULTRY BREEDING AND ITS FUTURE TRENDS

    Directory of Open Access Journals (Sweden)

    Gordana Kralik

    2013-06-01

    Full Text Available Poultry production in eastern Croatia is developed by individual producers mainly in semi intensive way, and within the organized poultry systems where the process is organized in a modern, intensive way. There is a tradition of breeding hens and geese in this area. Poultry products - meat and eggs are important in supplying the population with animal protein, minerals and vitamins. Modern hybrid hens are used for egg production and for meat production in the intensive production. Today geese breeding in these areas are completely neglected. Croatia as a member of European Union, has possibility of the placement of autochthonous breeds of poultry such as Hrvatica hen, Zagorje turkey and Podravian goose. Financial supports at the national level are allocated for the first two autochthonous breeds of poultry because these breeds can, with good production traits, represent genetic resources and strategic reserves in the future development of domestic poultry genotypes. Poultry production is especial emphasis in accordance with the criteria of welfare and health of poultry. This paper discusses further development of poultry in terms of production of poultry meat and eggs as a functional food. The composition and content of nutricines in meat and eggs can be affected by feed composition. Desired nutricines are installed in muscular tissue of poultry by using feed and adding some components. Consumption of eggs and poultry meat enriched by selenium, lutein and omega-3 fatty acids affects the improvement of the quality of the human diet. The recent researches show that chicken can effectively be enriched in carnosine - ingredients that are now taught as “anti-aging” factor. Enrichment of poultry products with nutricines gives greater importance to these foods in the diet of the population than the former one, mainly based on the nutritional aspect. Greater selection of quality poultry products can be a significant factor in the development of

  1. Spirulina promotes stem cell genesis and protects against LPS induced declines in neural stem cell proliferation.

    Directory of Open Access Journals (Sweden)

    Adam D Bachstetter

    Full Text Available Adult stem cells are present in many tissues including, skin, muscle, adipose, bone marrow, and in the brain. Neuroinflammation has been shown to be a potent negative regulator of stem cell and progenitor cell proliferation in the neurogenic regions of the brain. Recently we demonstrated that decreasing a key neuroinflammatory cytokine IL-1beta in the hippocampus of aged rats reversed the age-related cognitive decline and increased neurogenesis in the age rats. We also have found that nutraceuticals have the potential to reduce neuroinflammation, and decrease oxidative stress. The objectives of this study were to determine if spirulina could protect the proliferative potential of hippocampal neural progenitor cells from an acute systemic inflammatory insult of lipopolysaccharide (LPS. To this end, young rats were fed for 30 days a control diet or a diet supplemented with 0.1% spirulina. On day 28 the rats were given a single i.p. injection of LPS (1 mg/kg. The following day the rats were injected with BrdU (50 mg/kg b.i.d. i.p. and were sacrificed 24 hours after the first injection of BrdU. Quantification of the BrdU positive cells in the subgranular zone of the dentate gyrus demonstrated a decrease in proliferation of the stem/progenitor cells in the hippocampus as a result of the LPS insult. Furthermore, the diet supplemented with spirulina was able to negate the LPS induced decrease in stem/progenitor cell proliferation. In a second set of studies we examined the effects of spirulina either alone or in combination with a proprietary formulation (NT-020 of blueberry, green tea, vitamin D3 and carnosine on the function of bone marrow and CD34+ cells in vitro. Spirulina had small effects on its own and more than additive effects in combination with NT-020 to promote mitochondrial respiration and/or proliferation of these cells in culture. When examined on neural stem cells in culture spirulina increased proliferation at baseline and protected

  2. Reaction of the hydrated electron with amino acids, peptides, and proteins in aqueous solutions

    Energy Technology Data Exchange (ETDEWEB)

    Faraggi, M. (Ohio State Univ., Columbus); Bettelheim, A.

    1977-08-01

    The reaction rate constants of e/sup -//sub aq/ with glycyl-histidine (Gly-His) and ..beta..-alanylhistidine (Carnosine, ..beta..-Ala-His) were determined and compared to those of ..beta..-alanylalanine (..beta..-Ala-Ala), alanyl-alanine ((Ala)/sub 2/), and histidine (His). The rate constants were found to be pH dependent. Below the pK value of the imidazole ring, the rate constants of the histidyl peptides are similar to that of His. This indicates that the main site of the e/sup -//sub aq/ reaction is the protonated ring. Above this pK value the pH dependent rate constants were less in the His amino acids than in the His peptides. This difference was attributed to the presence of the carbonyl grup in the peptides. This group, which is known to react quite rapidly with e/sup -//sub aq/, exhibits its presence when the imidazole ring loses its reactivity after deprotonation. The difference in reactivity toward e/sup -//sub aq/ between the ..cap alpha.. and ..beta.. His peptides is explained by the relative position of the protonated amino groups with respect to the carbonyl groups. A similar difference was also found in (Ala)/sub 2/ and ..beta..-Ala-Ala. The transient absorption spectra resulting from the reaction of e/sup -//sub aq/ with the His peptides were recorded and examined with respect to peptide concentration and pH dependence. Here again, at pH values below the pK of the imidazole, the transient absorption spectra are similar to that of histidine. In alkaline solutions, however, proper experimental conditions could be attained only for Gly-His. In His and ..beta..-Ala-His the interference of the OH radical reaction was observed. In Gly/sup -/His it was found that the band characterizing the imidazole transient (lambda/sub max/ = 360 nm) disappears with a simultaneous appearance of a band at lambda/sub max/ similarly ordered 410 nm.

  3. Identification of Telomerase-activating Blends From Naturally Occurring Compounds.

    Science.gov (United States)

    Ait-Ghezala, Ghania; Hassan, Samira; Tweed, Miles; Paris, Daniel; Crynen, Gogce; Zakirova, Zuchra; Crynen, Stefan; Crawford, Fiona

    2016-06-01

    Context • Telomeres are repeated deoxyribonucleic acid (DNA) sequences (TTAGGG) that are located on the 5' ends of chromosomes, and they control the life span of eukaryotic cells. Compelling evidence has shown that the length of a person's life is dictated by the limited number of times that a human cell can divide. The enzyme telomerase has been shown to bind to and extend the length of telomeres. Thus, strategies for activating telomerase may help maintain telomere length and, thus, may lead to improved health during aging. Objective • The current study intended to investigate the effects of several natural compounds on telomerase activity in an established cell model of telomere shortening (ie, IMR90 cells). Design • The research team designed an in vitro study. Setting • The study was conducted at Roskamp Institute in Sarasota, FL, USA. Intervention • The tested single compounds were (1) α-lipoic acid, (1) green tea extract, (2) dimethylaminoethanol L-bitartrate (DMAE L-bitartrate), (3) N-acetyl-L-cysteine hydrochloride (HCL), (4) chlorella powder, (5) L-carnosine, (6) vitamin D3, (7) rhodiola PE 3%/1%, (8) glycine, (9) French red wine extract, (10) chia seed extract, (11) broccoli seed extract, and (12) Astragalus (TA-65). The compounds were tested singly and as blends. Outcome Measures • Telomerase activity for single compounds and blends of compounds was measured by the TeloTAGGG telomerase polymerase chain reaction (PCR) enzyme-linked immunosorbent assay (ELISA). The 4 most potent blends were investigated for their effects on cancer-cell proliferation and for their potential effects on the cytotoxicity and antiproliferative activity of a chemotherapeutic agent, the topoisomerase I inhibitor topotecan. The benefits of 6 population doublings (PDs) were measured for the single compounds, and the 4 blends were compared to 3 concentrations of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Results • Certain of the compounds increased

  4. Generation of free radicals from model lipid hydroperoxides and H[sub 2]O[sub 2] by Co(II) in the presence of cysteinyl and histidyl chelators

    Energy Technology Data Exchange (ETDEWEB)

    Shi, X.; Kasprzak, K.S. (National Cancer Institute, Frederick, MD (United States)); Dalal, N.S. (West Virginia Univ., Morgantown, WV (United States))

    Electron spin resonance spin trapping was utilized to investigate the generation of free radicals from cumene hydroperoxide (cumene-OOH), tert-butyl hydroperoxide (tert-butyl-OOH), and H[sub 2]O[sub 2] at pH 7.2 by Co(II) in the presence of cysteinyl and histidyl chelating agents. The spin trap used was 5,5-dimethyl-1-pyrroline N-oxide. Incubation of Co(II) with cumene-OOH or tert-butyl-OOH did not generate any detectable amounts of free radicals. However, in the presence of glutathione, cysteine, penicillamine, or N-acetylcysteine, Co(II) generated cumene-OOH-derived carbon-centered radicals, cumene alkoxyl radicals, and hydroxy (OH) radicals. Oxidized glutathione and cysteine used instead of reduced glutathione or cysteine did not generate any free radical, indicating an important role of the -SH group in radical generation. While the addition of diethylenetriaminepentaacetic acid (DTPA) prevented radical generation, deferoxamine had only a slightly inhibitory effect. Similar results to those obtained using cumene-OOH were obtained utilizing tert-butyl-OOH in place of cumene-OOH. The yields of free radicals were in the order of glutathione > cysteine > penicillamine > N-acetylcysteine. Incubation of Co(II) with cumene-OOH or t-butyl-OOH in the presence of the histidyl oligopeptide Gly-Gly-His also generated lipid hydroperoxide-derived free radicals, with the yield being comparable to that obtained using thiols. In contrast, histidine, anserine, homocarnosine, or carnosine did not cause any free radical generation from Co(II) and lipid hydroperoxides. Incubation of Co(II) with H[sub 2]O[sub 2] produced only a small amount of OH radicals. Addition of glutathione to the mixture of Co(II) and H[sub 2]O[sub 2] resulted in generation of both glutathionyl (GS) and OH radicals, which could be inhibited by DTPA and deferoxamine. Deferoxamine nitroxide radical was produced from deferoxamine incubated with Co(II) and H[sub 2]O[sub 2]. 36 refs., 7 figs., 3 tabs.

  5. Use of Awamori-pressed Lees and Tofu Lees as Feed Ingredients for Growing Male Goats.

    Science.gov (United States)

    Nagamine, Itsuki; Sunagawa, Katsunori; Kina, Takashi

    2013-09-01

    the CFG, the total essential and non-essential amino acids in the loin of the AMFG and TMFG were well balanced. Compared to the CFG, the AMFG and TMFG were high in taurine and carnosine. The results indicate dried Awamori-pressed lees and Tofu lees can be used as a feed ingredient for raising male goats. PMID:25049908

  6. Extruded soybean meal increased feed intake and milk production in dairy cows.

    Science.gov (United States)

    Giallongo, F; Oh, J; Frederick, T; Isenberg, B; Kniffen, D M; Fabin, R A; Hristov, A N

    2015-09-01

    The objective of this study was to assess the effects of 2 extruded soybean meals (ESBM) processed at 2 extruder temperatures, 149°C (LTM) and 171°C (HTM), on performance, nutrient digestibility, milk fatty acid and plasma amino acid profiles, and rumen fermentation in lactating dairy cows. Nine multiparous Holstein cows were included in a replicated 3×3 Latin square design experiment with three 28-d periods. The control diet contained 13% solvent-extracted soybean meal (SSBM; 53.5% crude protein with 74.1% ruminal degradability and 1.8% fat), which was replaced with equivalent amount (dry matter basis) of LTM (46.8%, 59.8%, and 10.0%) or HTM (46.9%, 41.1%, and 10.9%, respectively) ESBM in the 2 experimental diets (LTM and HTM, respectively). The diets met or exceeded the nutrient requirements of the cows for net energy of lactation and metabolizable protein. The 2 ESBM diets increased dry matter intake and milk yield compared with SSBM. Feed efficiency and milk composition were not affected by treatment. Milk protein yield tended to be increased by ESBM compared with SSBM. Milk urea N and urinary urea N excretions were increased by the ESBM diets compared with SSBM. Concentration of fatty acids with chain length of up to C17 and total saturated fatty acids in milk fat were generally decreased and that of C18 and total mono- and polyunsaturated fatty acids was increased by the ESBM diets compared with SSBM. Blood plasma concentrations of His, Leu, and Val were increased by HTM compared with LTM and SSBM. Plasma concentration of Met was decreased, whereas that of carnosine was increased by the ESBM diets. Treatments had no effect on rumen fermentation, but the proportion of Fibrobacter spp. in whole ruminal contents was increased by HTM compared with SSBM and LTM. Overall, data from this crossover experiment suggest that substituting SSBM with ESBM in the diet has a positive effect on feed intake and milk yield in dairy cows. PMID:26188569

  7. Cellular stress response: a novel target for chemoprevention and nutritional neuroprotection in aging, neurodegenerative disorders and longevity.

    Science.gov (United States)

    Calabrese, Vittorio; Cornelius, Carolin; Mancuso, Cesare; Pennisi, Giovanni; Calafato, Stella; Bellia, Francesco; Bates, Timothy E; Giuffrida Stella, Anna Maria; Schapira, Tony; Dinkova Kostova, Albena T; Rizzarelli, Enrico

    2008-12-01

    curcumin, acetyl-L-carnitine and carnosine have been demonstrated through the activation of these redox-sensitive intracellular pathways. Although the notion that stress proteins are neuroprotective is broadly accepted, still much work needs to be done in order to associate neuroprotection with specific pattern of stress responses. In this review the importance of vitagenes in the cellular stress response and the potential use of dietary antioxidants in the prevention and treatment of neurodegenerative disorders is discussed. PMID:18629638

  8. Effect of feed restriction on metabolites in cerebrospinal fluid and plasma of dairy cows.

    Science.gov (United States)

    Laeger, T; Görs, S; Metges, C C; Kuhla, B

    2012-03-01

    plasma, whereas free fatty acids and volatile fatty acids were determined in plasma only. Although plasma arginine (132%), leucine (134%), lysine (117%), nonesterified fatty acids (224%), and cholesterol (112%) increased, tryptophan and carnosine decreased (-33% and -20%, respectively) in R animals as compared with AL animals. In CSF, concentrations of these metabolites were not affected after R feeding, suggesting that these identified plasma metabolites have only little potential to contribute to central feed intake regulatory signaling in cows. By contrast, in CSF, serine, threonine, and tyrosine decreased (-20, -24, and -31%, respectively) after R feeding. Therefore, these 3 AA are potential centrally acting anorexigenic signals in cows. PMID:22365204

  9. Exercise but not (-)-epigallocatechin-3-gallate or β-alanine enhances physical fitness, brain plasticity, and behavioral performance in mice.

    Science.gov (United States)

    Bhattacharya, Tushar K; Pence, Brandt D; Ossyra, Jessica M; Gibbons, Trisha E; Perez, Samuel; McCusker, Robert H; Kelley, Keith W; Johnson, Rodney W; Woods, Jeffrey A; Rhodes, Justin S

    2015-06-01

    Nutrition and physical exercise can enhance cognitive function but the specific combinations of dietary bioactives that maximize pro-cognitive effects are not known nor are the contributing neurobiological mechanisms. Epigallocatechin-3-gallate (EGCG) is a flavonoid constituent of many plants with high levels found in green tea. EGCG has anti-inflammatory and anti-oxidant properties and is known to cross the blood brain barrier where it can affect brain chemistry and physiology. β-Alanine (B-ALA) is a naturally occurring β-amino acid that could increase cognitive functioning by increasing levels of exercise via increased capacity of skeletal muscle, by crossing the blood brain barrier and acting as a neurotransmitter, or by free radical scavenging in muscle and brain after conversion into carnosine. The objective of this study was to determine the effects of EGCG (~250mg/kg/day), B-ALA (~550mg/kg/day), and their combination with voluntary wheel running exercise on the following outcome measures: body composition, time to fatigue, production of new cells in the granule layer of the dentate gyrus of the hippocampus as a marker for neuronal plasticity, and behavioral performance on the contextual and cued fear conditioning tasks, as measures of associative learning and memory. Young adult male BALB/cJ mice approximately 2months old were randomized into 8 groups varying the nutritional supplement in their diet and access to running wheels over a 39day study period. Running increased food intake, decreased fat mass, increased time to exhaustive fatigue, increased numbers of new cells in the granule layer of the hippocampus, and enhanced retrieval of both contextual and cued fear memories. The diets had no effect on their own or in combination with exercise on any of the fitness, plasticity, and behavioral outcome measures other than B-ALA decreased percent body fat whereas EGCG increased lean body mass slightly. Results suggest that, in young adult BALB/cJ mice, a 39

  10. Generation of reactive oxygen species in the anterior eye segment. Synergistic codrugs of N-acetylcarnosine lubricant eye drops and mitochondria-targeted antioxidant act as a powerful therapeutic platform for the treatment of cataracts and primary open-angle glaucoma.

    Science.gov (United States)

    Babizhayev, Mark A

    2016-12-01

    -targeted antioxidants might be used to effectively prevent ROS-induced oxidation of lipids and proteins in the inner mitochondrial membrane in vivo. The authors developed and patented the new ophthalmic compositions including N-acetylcarnosine acting as a prodrug of naturally targeted to mitochondria l-carnosine endowed with pluripotent antioxidant activities, combined with mitochondria-targeted rechargeable antioxidant (either MitoVit E, Mito Q or SkQs) as a potent medicine to treat ocular diseases. Such specificity is explained by the fact that developed compositions might be used to effectively prevent ROS-induced oxidation of lipids and proteins in the inner mitochondrial membrane in vivo and outside mitochondria in the cellular and tissue structures of the lens and eye compartments. Mitochondrial targeting of compounds with universal types of antioxidant activity represents a promising approach for treating a number of ROS-related ocular diseases of the aging eye and can be implicated in the management of cataracts and primary open-angle glaucoma. PMID:27413694

  11. Radioprotectors in Radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Nair, C.K.K. [Bhabha Atomic Research Centre, Mumbai (India); Parida, D.K.; Nomura, Taisei

    2001-03-01

    , orientin, and vicinin), DNA-binding ligands (Hoechst 33342), and other compounds (melatonin, carnosin, tempace, and tempol). The article also briefly explains the mechanisms of radiation protection (e.g., suppression of the formation of reactive species, detoxification of radiation-induced species, target stabilization, and enhancement of the repair and recovery processes) and of DNA repair and cell recovery processes. Although a large number of radioprotective compounds have been identified over the last 50 years, most of them have failed to make the transition from laboratory to clinic. Acute toxicity and inability to differentiate between tumor and normal cells are the main reasons for their failure to be applied clinically. The authors conclude the article by describing some approaches to overcoming problems associated with the toxicity of radioprotective agents. Future searches for effective radioprotectors may be directed at compounds that protect normoxic cells but afford no protection in a hypoxic environment, which is a common feature of all solid tumors. Other eandidates are compounds that are enzymatically converted to toxic derivatives in hypoxic tumor cells while remaining unchanged and protecting normal cells. (K.H.). 120 refs.

  12. Molecular dynamics and information on possible sites of interaction of intramyocellular metabolites in vivo from resolved dipolar couplings in localized 1H NMR spectra

    Science.gov (United States)

    Schröder, Leif; Schmitz, Christian; Bachert, Peter

    2004-12-01

    Proton NMR resonances of the endogenous metabolites creatine and phosphocreatine ((P)Cr), taurine (Tau), and carnosine (Cs, β-alanyl- L-histidine) were studied with regard to residual dipolar couplings and molecular mobility. We present an analysis of the direct 1H- 1H interaction that provides information on motional reorientation of subgroups in these molecules in vivo. For this purpose, localized 1H NMR experiments were performed on m. gastrocnemius of healthy volunteers using a 1.5-T clinical whole-body MR scanner. We evaluated the observable dipolar coupling strength SD0 ( S = order parameter) of the (P)Cr-methyl triplet and the Tau-methylene doublet by means of the apparent line splitting. These were compared to the dipolar coupling strength of the (P)Cr-methylene doublet. In contrast to the aliphatic protons of (P)Cr and Tau, the aromatic H2 ( δ = 8 ppm) and H4 ( δ = 7 ppm) protons of the imidazole ring of Cs exhibit second-order spectra at 1.5 T. This effect is the consequence of incomplete transition from Zeeman to Paschen-Back regime and allows a determination of SD0 from H2 and H4 of Cs as an alternative to evaluating the multiplet splitting which can be measured directly in high-resolution 1H NMR spectra. Experimental data showed striking differences in the mobility of the metabolites when the dipolar coupling constant D0 (calculated with the internuclear distance known from molecular geometry in the case of complete absence of molecular dynamics and motion) is used for comparison. The aliphatic signals involve very small order parameters S ≈ (1.4 - 3) × 10 -4 indicating rapid reorientation of the corresponding subgroups in these metabolites. In contrast, analysis of the Cs resonances yielded S ≈ (113 - 137) × 10 -4. Thus, the immobilization of the Cs imidazole ring owing to an anisotropic cellular substructure in human m. gastrocnemius is much more effective than for (P)Cr and Tau subgroups. Furthermore, 1H NMR experiments on aqueous model

  13. From tryptophan to hydroxytryptophan: reflections on a busy life.

    Science.gov (United States)

    Fisher, Hans

    2009-01-01

    Given the very difficult odyssey of my early years, who could have imagined the incredible and successful journey that constituted my life path after age 13? I was born into a Jewish family in Breslau, Germany, right before the rise of Nazism and Hitler's election. After Kristallnacht, when my father was taken to Buchenwald Concentration Camp, we had to leave Germany as soon as possible. The first opportunity came in May of 1939, when we boarded the SS St. Louis bound for Havana, Cuba. Almost all passengers were denied entrance into Cuba, and the ship had to go back to Europe, where I ended up in France. In December of 1939, during World War II, I was fortunate to be able to leave France. This time I made it to Cuba, where my father was already in residence. A year later, my entire family was allowed into the United States. I took advantage of all the educational resources in this land of opportunity. I graduated valedictorian of my high school class and earned a four-year scholarship to Rutgers University, where I obtained a Bachelor of Science degree. I went on to earn a Master's degree from the University of Connecticut and finally a PhD from the University of Illinois. Within two months after graduating from Illinois, I was hired as an assistant professor of nutritional biochemistry at Rutgers, where I enjoyed a most productive research and teaching career. My PhD research involved tryptophan and niacin metabolism in the chick, and upon arrival at Rutgers I continued amino acid studies with the goal of assessing the essential amino acid requirements for egg production. This research was crowned with success and was followed with amino acid requirement studies for maintenance and for growth in rabbits, and ultimately with a reevaluation of requirements in adult humans. An outgrowth of the maintenance requirements led to a series of investigations into the metabolism of histidine, histamine, and carnosine (a histidine-containing dipeptide). Histamine, we found

  14. The Role of Oxidative Stress in Diabetic Neuropathy: Generation of Free Radical Species in the Glycation Reaction and Gene Polymorphisms Encoding Antioxidant Enzymes to Genetic Susceptibility to Diabetic Neuropathy in Population of Type I Diabetic Patients.

    Science.gov (United States)

    Babizhayev, Mark A; Strokov, Igor A; Nosikov, Valery V; Savel'yeva, Ekaterina L; Sitnikov, Vladimir F; Yegorov, Yegor E; Lankin, Vadim Z

    2015-04-01

    pathway are detoxified by the glyoxalase system with reduced glutathione as co-factor. The concentration of reduced glutathione may be decreased by oxidative stress and by decreased in situ glutathione reductase activity in diabetes mellitus. Genetic variations within the antioxidant genes therefore could be implicated in the pathogenesis of DN. In this work, the supporting data about the association between the -262T > C polymorphism of the catalase (CAT) gene and DN were shown. The -262TT genotype of the CAT gene was significantly associated with higher erythrocyte catalase activity in blood of DN patients compared to the -262CC genotype (17.8 ± 2.7 × 10(4) IU/g Hb vs. 13.5 ± 3.2 × 10(4) IU/g Hb, P = 0.0022). The role of these factors in the development of diabetic complications and the prospective prevention of DN by supplementation in formulations of transglycating imidazole-containing peptide-based antioxidants (non-hydrolyzed carnosine, carcinine, n-acetylcarcinine) scavenging ROS in the glycation reaction, modifying the activity of enzymic and non-enzymic antioxidant defenses that participate in metabolic processes with ability of controlling at transcriptional levels the differential expression of several genes encoding antioxidant enzymes inherent to DN in Type I Diabetic patients, now deserve investigation. PMID:25427889

  15. [Novel findings from an animal tourniquet shock model].

    Science.gov (United States)

    Hiraiwa, Kouichi

    2003-09-01

    This article is a review of our experimental results regarding the physiological statuses and roles of chemical mediators in tourniquet shock, and a novel phenomenon, modulation reflex, that is commonly observed in this shock model is discussed. In a rabbit with a tourniquet applied to a hind limb for 24 hrs, blood pressure (BP) gradually falls after release of the tourniquet, but the decline in BP stops when a tourniquet is again applied to the hind limb, indicating that shock mediators are attributed to the hind limb. The levels of dipeptides (anserine and carnosine) and lysosomes in blood samples as well as the levels of leukotrienes (LTD4 and LTE4) in blood and muscle samples from rabbits in tourniquet shock were elevated. However, injection of a large amount of a dipeptide into an ear vein of a rabbit did not reduce BP, suggesting that both peptides may not be directly related with reduction in BP of rabbits in tourniquet shock. Injection of a platelet-activating factor (PAF) antagonist into an ear vein resulted in slight elevation of BP and the elevated level was maintained for about 1 to 4 hrs during the period of decline in BP in tourniquet shock. As for interleukin-6 (IL-6), IL-6-deficient mice at young ages have a significantly greater blood volume than do wild-type mice without concomitant changes in body composition. Therefore, the role for IL-6 in the regulation of peripheral circulation may be to elevate, not reduce BP. In mice in tourniquet shock, superoxide (O2-) production is observed in skeletal muscle cells and these cells correspond to mitochondria-rich cells. However, RT-PCR of muscle samples showed no significant nitric oxide synthase (NOS) mRNA expression after tourniquet release. Pretreatment with NOS inhibitors before tourniquet release reduced O2- production in the skeletal muscle. These results indicate that O2- produced in muscle subjected to ischemia/repefusion may be involved in shock. As for changes in mRNA expression patterns of pro