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Nutrients Feb 2023Nowadays, developing effective intervention substances for hyperuricemia has become a public health issue. Herein, the therapeutic ability of anserine, a bioactive...
Nowadays, developing effective intervention substances for hyperuricemia has become a public health issue. Herein, the therapeutic ability of anserine, a bioactive peptide, was validated through a comprehensive multiomics analysis of a rat model of hyperuricemia. Anserine was observed to improve liver and kidney function and modulate urate-related transporter expressions in the kidneys. Urine metabolomics showed that 15 and 9 metabolites were significantly increased and decreased, respectively, in hyperuricemic rats after the anserine intervention. Key metabolites such as fructose, xylose, methionine, erythronic acid, glucaric acid, pipecolic acid and trans-ferulic acid were associated with ameliorating kidney injury. Additionally, anserine regularly changed the gut microbiota, thereby ameliorating purine metabolism abnormalities and alleviating inflammatory responses. The integrated multiomics analysis indicated that , and were strongly associated with key differential metabolites. Therefore, we propose that anserine improved hyperuricemia via the gut-kidney axis, highlighting its potential in preventing and treating hyperuricemia.
Topics: Animals; Rats; Anserine; Hyperuricemia; Kidney; Metabolomics; Uric Acid; Intestines
PubMed: 36839325
DOI: 10.3390/nu15040969 -
The Journal of Biological Chemistry Jan 2019Imidazole-containing dipeptides (IDPs), such as carnosine and anserine, are found exclusively in various animal tissues, especially in the skeletal muscles and nerves....
Imidazole-containing dipeptides (IDPs), such as carnosine and anserine, are found exclusively in various animal tissues, especially in the skeletal muscles and nerves. IDPs have antioxidant activity because of their metal-chelating and free radical-scavenging properties. However, the underlying mechanisms that would fully explain IDP antioxidant effects remain obscure. Here, using HPLC-electrospray ionization-tandem MS analyses, we comprehensively investigated carnosine and its related small peptides in the soluble fractions of mouse tissue homogenates and ubiquitously detected 2-oxo-histidine-containing dipeptides (2-oxo-IDPs) in all examined tissues. We noted enhanced production of the 2-oxo-IDPs in the brain of a mouse model of sepsis-associated encephalopathy. Moreover, in SH-SY5Y human neuroblastoma cells stably expressing carnosine synthase, HO exposure resulted in the intracellular production of 2-oxo-carnosine, which was associated with significant inhibition of the HO cytotoxicity. Notably, 2-oxo-carnosine showed a better antioxidant activity than endogenous antioxidants such as GSH and ascorbate. Mechanistic studies indicated that carnosine monooxygenation is mediated through the formation of a histidyl-imidazole radical, followed by the addition of molecular oxygen. Our findings reveal that 2-oxo-IDPs are metal-catalyzed oxidation products present and provide a revised paradigm for understanding the antioxidant effects of the IDPs.
Topics: Animals; Antioxidants; Carnosine; Cell Survival; Dipeptides; Histidine; Humans; Hydrogen Peroxide; Imidazoles; Male; Mice; Mice, Inbred C57BL; Muscle, Skeletal; Neuroblastoma; Oxidants; Oxidation-Reduction; Tumor Cells, Cultured
PubMed: 30504220
DOI: 10.1074/jbc.RA118.006111 -
International Journal of Molecular... Sep 2018In rodents, carnosine treatment improves diabetic nephropathy, whereas little is known about the role and function of anserine, the methylated form of carnosine.
BACKGROUND/AIMS
In rodents, carnosine treatment improves diabetic nephropathy, whereas little is known about the role and function of anserine, the methylated form of carnosine.
METHODS
Antioxidant activity was measured by oxygen radical absorbance capacity and oxygen stress response in human renal tubular cells (HK-2) by RT-PCR and Western-Immunoblotting. In wildtype (WT) and diabetic mice (db/db), the effect of short-term anserine treatment on blood glucose, proteinuria and vascular permeability was measured.
RESULTS
Anserine has a higher antioxidant capacity compared to carnosine ( < 0.001). In tubular cells (HK-2) stressed with 25 mM glucose or 20⁻100 µM hydrogen peroxide, anserine but not carnosine, increased intracellular heat shock protein (Hsp70) mRNA and protein levels. In HK-2 cells stressed with glucose, co-incubation with anserine also increased hemeoxygenase (HO-1) protein and reduced total protein carbonylation, but had no effect on cellular sirtuin-1 and thioredoxin protein concentrations. Three intravenous anserine injections every 48 h in 12-week-old db/db mice, improved blood glucose by one fifth, vascular permeability by one third, and halved proteinuria (all < 0.05).
CONCLUSION
Anserine is a potent antioxidant and activates the intracellular Hsp70/HO-1 defense system under oxidative and glycative stress. Short-term anserine treatment in diabetic mice improves glucose homeostasis and nephropathy.
Topics: Animals; Anserine; Antioxidants; Diabetes Mellitus, Experimental; Diabetic Nephropathies; Hydrogen Peroxide; Kidney Tubules; Male; Mice; Mice, Inbred C57BL; Proteinuria
PubMed: 30217069
DOI: 10.3390/ijms19092751 -
Journal of the Science of Food and... Oct 2019Poultry meat has high levels of histidine-containing dipeptides (HCD) and consumption of meat rich in HCD may elicit certain health benefits. The aim of this work was to... (Comparative Study)
Comparative Study
BACKGROUND
Poultry meat has high levels of histidine-containing dipeptides (HCD) and consumption of meat rich in HCD may elicit certain health benefits. The aim of this work was to compare the HCD content (anserine and carnosine) in the breast and thigh muscles of two broiler strains differing in growth rate, feeding regime, and age at slaughter. A 3 (production system) × 2 (sex) × 2 (age at slaughter) full factorial arrangement was applied with fast-growing Ross 308 chicks fed ad libitum (ROSS-AL), slow-growing Sasso T451 chicks fed ad libitum (SASSO-AL), and Ross 308 chicks given limited feeding (ROSS-LIM). At the age of 40 and 62 days, eight birds per production system × sex combination were randomly selected for sampling of the breast and thigh muscle. Muscle HCD content was determined by high-performance liquid chromatography (HPLC).
RESULTS
Across treatments, levels of anserine were 2.5- and 1.9-fold higher than carnosine in breast and thigh muscle respectively (P < 0.001), and levels of anserine and carnosine were 2.2- and 2.8-fold higher respectively in breast versus thigh muscle (P < 0.001). In breast muscle, SASSO-AL had higher levels of HCD than ROSS-AL and ROSS-LIM (P < 0.001). Considering different market meat types, breast muscle of 62-day-old SASSO-AL birds had more than threefold higher content of HCD compared to thigh muscle of 40-day-old ROSS-AL birds (P < 0.001).
CONCLUSION
Large differences in muscle HCD content were found, varying according to type of muscle and broiler. © 2019 Society of Chemical Industry.
Topics: Animal Feed; Animals; Anserine; Carnosine; Chickens; Female; Histidine; Male; Meat; Muscle, Skeletal
PubMed: 31150113
DOI: 10.1002/jsfa.9829 -
Molecules (Basel, Switzerland) Nov 2022Skin hyperpigmentation is an aesthetic problem that leads to psychosocial issues. Thus, skin whitening agents from agro- and poultry-industrial co-products are...
Skin hyperpigmentation is an aesthetic problem that leads to psychosocial issues. Thus, skin whitening agents from agro- and poultry-industrial co-products are considered high economic value ingredients of interest for sustainable application. Therefore, this study aimed to determine the cosmeceutical potential of anserine/carnosine-rich chicken extract (ACCE) from the Thai native chicken Pradu Hang Dam Mor Kor 55 (PD) meat. The chemical composition was identified and quantified using the HPLC-UV method. Then, the antioxidation potential of the extract was compared to that of L-anserine and L-carnosine, using 1,1-diphenyl-2-picrylhydrazyl assay and shikonin-induced production of reactive oxygen species in CCD-986Sk cell models, and the anti-melanogenesis effect in the MNT-1 melanoma cell line model was investigated. Furthermore, related mechanisms were identified using colorimetric tyrosinase assay and the Western blot technique. The ACCE was composed of L-anserine and L-carnosine as two major constituents. In a dose-dependent manner, ACCE, L-anserine, and L-carnosine manifested significant antioxidation potential and significant reduction of melanin production. Activation of the extracellular signal-regulated kinase (ERK) signaling pathway and inhibition of tyrosinase activity of ACCE were demonstrated as the mechanisms of the anti-melanogenesis effect. In conclusion, ACCE has been revealed as a potential cosmeceutical agent due to its antioxidation and anti-melanogenic activity in association with L-anserine and L-carnosine composition and biomolecular regulating ability. Therefore, further studies and development should be considered to support the utilization of anserine/carnosine-rich chicken extract in the cosmetic industry for economic value creation and sustainability.
Topics: Animals; Anserine; Carnosine; Chickens; Extracellular Signal-Regulated MAP Kinases; Cosmeceuticals; Monophenol Monooxygenase; Thailand; Antioxidants; Signal Transduction
PubMed: 36364267
DOI: 10.3390/molecules27217440 -
Journal of Inherited Metabolic Disease Jan 2018Carnosinase (CN1) is a dipeptidase, encoded by the CNDP1 gene, that degrades histidine-containing dipeptides, such as carnosine, anserine and homocarnosine. Loss of CN1... (Review)
Review
Carnosinase (CN1) is a dipeptidase, encoded by the CNDP1 gene, that degrades histidine-containing dipeptides, such as carnosine, anserine and homocarnosine. Loss of CN1 function (also called carnosinase deficiency or aminoacyl-histidine dipeptidase deficiency) has been reported in a small number of patients with highly elevated blood carnosine concentrations, denoted carnosinaemia; it is unclear whether the variety of clinical symptoms in these individuals is causally related to carnosinase deficiency. Reduced CN1 function should increase serum carnosine concentrations but the genetic basis of carnosinaemia has not been formally confirmed to be due to CNDP1 mutations. A CNDP1 polymorphism associated with low CN1 activity correlates with significantly reduced risk for diabetic nephropathy, especially in women with type 2 diabetes, and may slow progression of chronic kidney disease in children with glomerulonephritis. Studies in rodents demonstrate antiproteinuric and vasculoprotective effects of carnosine, the precise molecular mechanisms, however, are still incompletely understood. Thus, carnosinemia due to CN1 deficiency may be a non-disease; in contrast, carnosine may potentially protect against long-term sequelae of reactive metabolites accumulating, e.g. in diabetes and chronic renal failure.
Topics: Amino Acid Metabolism, Inborn Errors; Animals; Brain Diseases, Metabolic, Inborn; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Dipeptidases; Humans; Mutation; Polymorphism, Genetic; Prognosis; Protective Factors; Risk Factors
PubMed: 29027595
DOI: 10.1007/s10545-017-0099-2 -
Cellular Physiology and Biochemistry :... 2018Reactive dicarbonyl compounds, such as methylglyoxal (MG), contribute to diabetic complications. MG-scavenging capacities of carnosine and anserine, which have been...
BACKGROUND/AIMS
Reactive dicarbonyl compounds, such as methylglyoxal (MG), contribute to diabetic complications. MG-scavenging capacities of carnosine and anserine, which have been shown to mitigate diabetic nephropathy, were evaluated in vitro and in vivo.
METHODS
MG-induced cell toxicity was characterized by MTT and MG-H1-formation, scavenging abilities by Western Blot and NMR spectroscopies, cellular carnosine transport by qPCR and microplate luminescence and carnosine concentration by HPLC.
RESULTS
In vitro, carnosine and anserine dose-dependently reduced N-carboxyethyl lysine (CEL) and advanced glycation end products (AGEs) formation. NMR studies revealed the formation of oligo/polymeric products of MG catalyzed by carnosine or anserine. MG toxicity (0.3-1 mM) was dose-dependent for podocytes, tubular and mesangial cells whereas low MG levels (0.2 mM) resulted in increased cell viability in podocytes (143±13%, p<0.001) and tubular cells (129±3%, p<0.001). Incubation with carnosine/anserine did not reduce MG-induced toxicity, independent of incubation times and across large ranges of MG to carnosine/anserine ratios. Cellular carnosine uptake was low (<0.1% in 20 hours) and cellular carnosine concentrations remained unaffected. The putative carnosine transporter PHT1 along with the taurine transporter (TauT) was expressed in all cell types while PEPT1, PEPT2 and PHT2, also belonging to the proton-coupled oligopeptide transporter (POT) family, were only expressed in tubular cells.
CONCLUSION
While carnosine and anserine catalyze the formation of MG oligo/polymers, the molar ratios required for protection from MG-induced cellular toxicity are not achievable in renal cells. The effect of carnosine in vivo, to mitigate diabetic nephropathy may therefore be independent upon its ability to scavenge MG and/or carnosine is mainly acting extracellularly.
Topics: Animals; Anserine; Carnosine; Cell Line; Cell Survival; Chromatography, High Pressure Liquid; Glutathione; Glutathione Peroxidase; Glycation End Products, Advanced; Humans; Membrane Glycoproteins; Membrane Transport Proteins; Mice; Oxidative Stress; Peptide Transporter 1; Podocytes; Polymers; Pyruvaldehyde; Serum Albumin; Superoxide Dismutase; Symporters
PubMed: 29621776
DOI: 10.1159/000488727 -
The Journal of Physiology Sep 2016Using recombinant DNA technology, the present study provides the first strong and direct evidence indicating that β-alanine is an efficient substrate for the mammalian...
KEY POINTS
Using recombinant DNA technology, the present study provides the first strong and direct evidence indicating that β-alanine is an efficient substrate for the mammalian transaminating enzymes 4-aminobutyrate-2-oxoglutarate transaminase and alanine-glyoxylate transaminase. The concentration of carnosine and anserine in murine skeletal and heart muscle depends on circulating availability of β-alanine, which is in turn controlled by degradation of β-alanine in liver and kidney. Chronic oral β-alanine supplementation is a popular ergogenic strategy in sports because it can increase the intracellular carnosine concentration and subsequently improve the performance of high-intensity exercises. The present study can partly explain why the β-alanine supplementation protocol is so inefficient, by demonstrating that exogenous β-alanine can be effectively routed toward oxidation.
ABSTRACT
The metabolic fate of orally ingested β-alanine is largely unknown. Chronic β-alanine supplementation is becoming increasingly popular for improving high-intensity exercise performance because it is the rate-limiting precursor of the dipeptide carnosine (β-alanyl-l-histidine) in muscle. However, only a small fraction (3-6%) of the ingested β-alanine is used for carnosine synthesis. Thus, the present study aimed to investigate the putative contribution of two β-alanine transamination enzymes, namely 4-aminobutyrate-2-oxoglutarate transaminase (GABA-T) and alanine-glyoxylate transaminase (AGXT2), to the homeostasis of carnosine and its methylated analogue anserine. We found that, when transfected into HEK293T cells, recombinant mouse and human GABA-T and AGXT2 are able to transaminate β-alanine efficiently. The reaction catalysed by GABA-T is inhibited by vigabatrin, whereas both GABA-T and AGXT2 activity is inhibited by aminooxyacetic acid (AOA). Both GABA-T and AGXT2 are highly expressed in the mouse liver and kidney and the administration of the inhibitors effectively reduced their enzyme activity in liver (GABA-T for vigabatrin; GABA-T and AGXT2 for AOA). In vivo, injection of AOA in C57BL/6 mice placed on β-alanine (0.1% w/v in drinking water) for 2 weeks lead to a 3-fold increase in circulating β-alanine levels and to significantly higher levels of carnosine and anserine in skeletal muscle and heart. By contrast, specific inhibition of GABA-T by vigabatrin did not affect carnosine and anserine levels in either tissue. Collectively, these data demonstrate that homeostasis of carnosine and anserine in mammalian skeletal muscle and heart is controlled by circulating β-alanine levels, which are suppressed by hepatic and renal β-alanine transamination upon oral β-alanine intake.
Topics: Aminooxyacetic Acid; Animals; Anserine; Brain; Carnosine; Enzyme Inhibitors; GABA Agents; HEK293 Cells; Homeostasis; Humans; Kidney; Liver; Male; Mice, Inbred C57BL; Muscle, Skeletal; Myocardium; RNA, Messenger; Transaminases; Vigabatrin; beta-Alanine
PubMed: 27062388
DOI: 10.1113/JP272050 -
Journal of Ultrasound in Medicine :... Apr 2020Medial knee pain is commonplace in clinical practice and can be related to several pathologic conditions: ie, medial plica syndrome, saphenous nerve entrapment, pes... (Review)
Review
Medial knee pain is commonplace in clinical practice and can be related to several pathologic conditions: ie, medial plica syndrome, saphenous nerve entrapment, pes anserine syndrome, medial collateral ligament injury, and medial meniscus disorders. Ultrasound (US) imaging represents a valuable first-line diagnostic approach to adequately visualize the superficial structures in the medial compartment of the knee to easily plan for prompt treatment. Currently, the management of chronic degenerative diseases involving the menisci, and causing their extrusion, consists of surgery (arthroscopic partial meniscectomy). This procedure often allows only a partial resolution of pain and functional impairment. In the pertinent literature, US-guided interventions for the medial meniscus are proposed, mainly to decrease pain and inflammation or to induce regeneration. Likewise, this Technical Innovation describes in detail the US findings of medial extrusive meniscopathy and also illustrates a novel US-guided technique to treat the bursa of the medial collateral ligament, the extruded fragment of the medial meniscus, and the synovial parameniscal recesses simultaneously.
Topics: Clinical Protocols; Humans; Joint Diseases; Menisci, Tibial; Tibial Meniscus Injuries; Ultrasonography, Interventional
PubMed: 31617613
DOI: 10.1002/jum.15142 -
Animals : An Open Access Journal From... Aug 2023The beef industry in Poland heavily relies on the Polish Holstein-Friesian (PHF) breed, known for its primary use in dairy production, but which also contributes...
The beef industry in Poland heavily relies on the Polish Holstein-Friesian (PHF) breed, known for its primary use in dairy production, but which also contributes significantly to the beef supply. In contrast, the Limousine (LM), Hereford (HH), and Charolaise (CH) breeds have gained popularity due to their ideal specialized characteristics for beef production. As PHF continues to dominate the beef market, a thorough comparison of its beef quality and nutritional attributes with the three most popular beef breeds in Poland is essential. This study aims to address this knowledge gap by conducting a rigorous comparison. The experiment was carried out on the beef from 67 bulls kept in a free-stall system with standardized feeding. The highest total antioxidant status (TAS) was found in CH and was 147.5% higher than that in PHF. Also, compared with PHF, a large difference of 70% was observed in LM, while in HH it was only 6.25%. For degree of antioxidant potential (DAP), the highest concentration was found in LM, while CH had a slightly lower score than LM. PHF had the lowest scores for each of the analyzed parameters of protein fraction. For anserine, taurine, creatinine, and creatine content, the highest results were found for LM. For carnosine and coenzyme Q10, the highest values were found for CH. Overall, these results highlight the impact of maturity and breed on carcass composition and quality. Late-maturing breeds, such as LM and CH, tend to exhibit leaner carcasses with superior fatty acid profiles and antioxidant properties. This knowledge is valuable for producers, enabling them to make informed decisions regarding breed selection and production strategies to meet specific market demands for beef with the desired composition and quality.
PubMed: 37627394
DOI: 10.3390/ani13162603