Amino Acids最新文献

{"title":"Proteins and peptides as antigen candidates for the immunodiagnosis of hepatitis D.","authors":"Sandra Rodrigues Xavier, Isabelle Caroline Dos Santos Barcelos, Isadora Braga Gandra, Sabrina Paula Pereira, Anna Julia Ribeiro, Kamila Alves Silva, Carlos Ananias Aparecido Resende, Lucas da Silva Lopes, Rafaela Camargo Rodrigues Machado, Leonardo Maciel Santos Silva, Líria Souza Silva, Lívia Corrêa Ferreira, Luiz Fellype Alves de Souza, Rutilene Barbosa Souza, Ana Maísa Passos-Silva, Mariana Campos da Paz, Miguel Angel Chávez Fumagalli, Eduardo Antônio Ferraz Coelho, Rodolfo Cordeiro Giunchetti, Juliana Martins Machado, Ana Alice Maia Gonçalves, Soraya Dos Santos Pereira, Daniel Archimedes da Matta, Deusilene Souza Vieira, Alexsandro Sobreira Galdino","doi":"10.1007/s00726-025-03465-2","DOIUrl":"https://doi.org/10.1007/s00726-025-03465-2","url":null,"abstract":"<p><p>Designing innovative, accurate, universal, and accessible diagnostic tests is mandatory to improve screening, prevention, and management of hepatitis D (HD), especially in endemic areas with poor infrastructure and restricted access to public health care. Recombinant proteins (RP), recombinant multiepitope proteins (RMP), and synthetic peptides have been extensively reported as tools for efficient immunodiagnosis of several diseases. This review aimed to discuss the use of these antigens for the immunodiagnosis of HD. To this end, a bibliographic study was conducted in the PubMed database by searching the primary (\"Hepatitis D\" and \"Hepatitis Delta\"), secondary (\"Detection\", \"Diagno*\", \"Diagnosis\", \"Immunodiagnosis\", and \"Serodiagnosis\"), and tertiary (\"Chimera\", \"Epitope\", \"Peptide\"; \"Protein\" and \"Recombinant\") descriptors, including papers published up to January 2025. Review articles and case reports were excluded. Only nine articles (five for RP, three for synthetic peptides, and one for RMP) met the inclusion criteria, revealing that there are very few studies on this subject, particularly when compared to the advances made in the diagnosis of hepatitis A, B, and C. Despite the scarcity of articles published in the literature, six of the nine analyzed studies corroborate the potential of these antigens to effectively replace traditional diagnostic methods, including development of rapid tests. These data highlight the need for further studies to assess the potential of RP, RMP, and synthetic peptides for immunodiagnosis of HD, aiming to increase the accuracy of diagnosis, as well as improve monitoring and prevention.</p>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"57 1","pages":"35"},"PeriodicalIF":3.0,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144558863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transport of the uremic toxin symmetric dimethylarginine (SDMA) by renal transport proteins.","authors":"Lorenz A Scherpinski, Martin F Fromm, Renke Maas, Jörg König","doi":"10.1007/s00726-025-03466-1","DOIUrl":"10.1007/s00726-025-03466-1","url":null,"abstract":"<p><p>The L-arginine derivative and uremic toxin symmetric dimethylarginine (SDMA) is an independent risk marker for total mortality and cardiovascular events. Interferences with L-arginine- or L-homoarginine-related signaling, metabolism, or transport have been proposed as underlying mechanisms. SDMA is endogenously formed and predominantly eliminated via the kidney. Whereas for L-arginine and other L-arginine derivatives such as L-homoarginine and asymmetric dimethylarginine (ADMA) key transport proteins involved in the cellular uptake and release have been characterized, comparable data for the transport of SDMA are lacking.Using HEK cell lines overexpressing the transport proteins OCT2, OATP4C1, MATE1, OAT4, and OAT10, which are all expressed in renal proximal tubule cells, and the ubiquitously-expressed transport protein CAT1 we performed uptake experiments demonstrating that SDMA is a substrate for CAT1, OATP4C1, OCT2, and MATE1 in physiological concentrations, but not of OAT4 and OAT10. K_m values for OATP4C1-, CAT1-, and MATE1-mediated SDMA uptake were 70 µM, 246 µM, and 1 973 µM, respectively. For OCT2-mediated uptake, no saturation could be reached, precluding the determination of a K_m value. Uptake of SDMA by these transporters could be inhibited by known substrates of the respective transport proteins. Furthermore, CAT1 and OATP4C1 also mediate the efflux of SDMA out of cells.These results show that SDMA is a substrate of renally-expressed transport proteins OATP4C1, OCT2, and MATE1 and of CAT1 demonstrating that these transporters are involved in the homeostasis of this uremic toxin and possible sites of interactions with related compounds.</p>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"57 1","pages":"34"},"PeriodicalIF":3.0,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12187869/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144482904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhanced γ-aminobutyric acid levels promote degeneration of silk glands following spermidine supplementation in Bombyx mori.","authors":"Brinda Goda Lakshmi Didugu, Anitha Mamillapalli","doi":"10.1007/s00726-025-03462-5","DOIUrl":"10.1007/s00726-025-03462-5","url":null,"abstract":"<p><p>Silk glands are modified labial glands that produce silk which has immense commercial importance. Silk is extruded out in liquid form after which the glands undergo autophagy and apoptosis during larval to pupal transition. Biogenic amines, specially spermidine and γ-aminobutyric acid (GABA) are known to play an important role in autophagy. Yet, GABA is not identified in the silk glands till now and therefore its role in autophagy remains unknown. Current study aimed to evaluate role of biogenic amines in the autophagy of silk glands. Fifth instar silkworms were fed with control and spermidine supplemented mulberry leaves under controlled conditions. Qualitative and quantitative analysis of biogenic amines were analyzed in silk glands of control and spermidine fed groups at the end of feeding stage, spinning and pre-pupal stages. Biogenic amines were significantly decreased in the silk glands from feeding stage to non-feeding prepupal stages. Elevated levels of biogenic amines; putrescine, spermidine, and spermine were observed in silk glands at pre-pupal stage in the spermidine fed group. The unknown biogenic amine whose levels were significantly elevated during silk gland degeneration in both control and spermidine fed groups was identified as GABA by spectroscopic techniques. This is the first report of the identification of GABA in the silk glands of Bombyx mori which increased significantly following spermidine supplementation, resulting in elevated levels of calcium deposits, contributing to the early degeneration of the silk glands.</p>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"57 1","pages":"33"},"PeriodicalIF":3.0,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12166014/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of potential inhibitors of interleukin-2-inducible T-cell kinase: insights from docking, molecular dynamics, MMPBSA and free energy landscape studies.","authors":"Shazia Ahmed, Arunabh Choudhury, Mohammad Umar Saeed, Taj Mohammad, Afzal Hussain, Mohamed F Alajmi, Dharmendra Kumar Yadav, Anas Shamsi, Md Imtaiyaz Hassan","doi":"10.1007/s00726-025-03457-2","DOIUrl":"10.1007/s00726-025-03457-2","url":null,"abstract":"<p><p>Interleukin-2-inducible T-cell kinase (ITK) is an essential enzyme that plays a key role in both the activation and differentiation of T-cells. As a member of the Tec family of non-receptor tyrosine kinases, ITK is predominantly expressed in T cells, exerting a critical influence on T-cell receptor signaling and downstream pathways. Moreover, ITK regulates cytokine production, notably interleukin-2 (IL-2), and the differentiation of Th2 cells. In the context of immunology, ITK has garnered significant attention, particularly for its potential to address immune-related conditions such as cancer and autoimmune diseases, including lymphoproliferative diseases. In this study, we performed a structure-based virtual screening utilizing a library of plant-based small molecules to identify inhibitors of ITK. The initial selection of phytochemicals was guided by adherence to the Lipinski rule of five. After molecular docking, top-ranked hits in terms of binding affinity underwent screening for physicochemical and pharmacokinetic properties and PASS analyses. The three selected phytochemicals, Withanolide A, Amorphispironon E, and 27-Deoxy-14-hydroxywithaferin A (27-DHA) demonstrated remarkable binding affinity to ITK with a docking score of - 9.2, - 9.1, and - 9.1 kcal/mol, respectively. All the phytochemicals showed specific binding to the ATP-binding site of ITK as revealed by protein structure network analysis. These selected phytoconstituents underwent all-atom molecular dynamics (MD) simulations, spanning 100 ns each. The simulation results showed that ITK with elucidated compounds exhibited stability with minimal dynamics. In addition, we performed an MM-PBSA analysis, which indicated a strong binding affinity. This study highlights the potential of Withanolide A, Amorphispironon E, and 27-DHA as preliminary leads for further experimental validation and preclinical investigation toward therapeutic development.</p>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"57 1","pages":"32"},"PeriodicalIF":3.0,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12137478/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144214635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of safe utilization of l-threonine for supplementation in healthy adults: a randomized double blind controlled trial","authors":"Hideki Matsumoto,&nbsp;Naoki Miura,&nbsp;Masaki Naito,&nbsp;Rajavel Elango","doi":"10.1007/s00726-025-03461-6","DOIUrl":"10.1007/s00726-025-03461-6","url":null,"abstract":"<div><p><span>l</span>-threonine is used in dietary supplements and nutritional products ingested by healthy consumers. The objective of this study was to determine in a randomized double blind controlled clinical trial the safety and tolerability of <span>l</span>-threonine used as graded doses in supplements for 4 weeks. Healthy male adults (age 42.9) ingested randomly placebo or different doses of L-threonine (0, 3, 6, 9, 12 g/day) for 4 weeks using a crossover design. At the end of supplementation period, the subjects visited the clinic for medical examination, anthropometric parameter measurements, blood sampling for biochemical tests including amino acid concentrations in plasma, measurement of blood pressure and heart rate, and dietary intake evaluation. Adverse events were recorded all along the trial. None of the anthropometric parameters measured, dietary intake and the biochemical parameters were affected by <span>l</span>-threonine supplementation except a non-specific minor increase in plasma aspartate amino transferase and creatine kinase which was measured in the group supplemented with 9 g <span>l</span>-threonine per day but not with the 12 g per day dose. Also, the concentration of L-threonine as well as the concentration of its metabolite L-2-amino butylate were found to be increased in plasma after supplementation with 6, 9, 12 g/day L-threonine. The moderate and mild adverse events were found to occur at random. All symptoms disappeared during the supplementation period despite continuous L-threonine supplementation. These results of this study indicate a no-observed-adverse-effect-level (NOAEL) value for L-threonine to be 12 g/day in healthy adult males. This study was registered at jRCT as jRCT1050230137.</p></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"57 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00726-025-03461-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144140247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis of novel bisazlactones and their applications in the synthesis of a new family of pseudo-peptide enamides with anti-cancer properties","authors":"Azim Ziyaei Halimehjani,&nbsp;Farzaneh Noorakhtar","doi":"10.1007/s00726-025-03459-0","DOIUrl":"10.1007/s00726-025-03459-0","url":null,"abstract":"<div><p>Pseudo-peptides are an important category of biologically active artificial small molecules. To access these important molecules, a novel series of bisazlactones was synthesized via the Erlenmeyer-Plöchl reaction, using glycine- and terephthaloyl-based diacid with aldehydes. These bisazlactones were then utilized as efficient intermediates in reactions with primary and secondary amines, providing novel pseudo-peptides containing enamide groups in high to excellent yields. The selected pseudo-peptide enamides exhibited selective cytotoxicity against hepatocarcinoma cells, while exhibiting negligible impact on normal mammalian cells. Notably, compound <b>6y</b> displayed superior anti-cancer activity compared to the others.</p></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"57 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00726-025-03459-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144140246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dietary exposure to creatine-precursor amino acids in the general population","authors":"David Nedeljkovic,&nbsp;Sergej M. Ostojic","doi":"10.1007/s00726-025-03460-7","DOIUrl":"10.1007/s00726-025-03460-7","url":null,"abstract":"<div><h3>Background</h3><p>Creatine is a semi-essential nutrient that plays a critical role in energy metabolism, with dietary intake and endogenous synthesis contributing to overall creatine availability. While dietary creatine intake has been studied extensively, limited data exist on the dietary exposure to its precursor amino acids—glycine, arginine, and methionine—and their contribution to endogenous creatine synthesis. This study aimed to assess the dietary intake of these precursors in U.S. children and adults using data from the Third National Health and Nutrition Examination Survey (NHANES III) and to compare endogenous creatine synthesis with direct dietary creatine intake.</p><h3>Methods</h3><p>We analyzed NHANES III dietary recall data from 29,945 individuals aged 2 years and older. Intakes of glycine, arginine, methionine, and creatine were calculated per kilogram of body weight. The contribution of precursor amino acids to endogenous creatine synthesis was estimated using established metabolic conversion factors.</p><h3>Results</h3><p>The mean daily intakes of glycine, arginine, methionine, and creatine were 59.6 ± 0.4 mg/kg, 77.2 ± 0.5 mg/kg, 31.9 ± 0.2 mg/kg, and 15.5 ± 0.1 mg/kg, respectively. Estimated endogenous creatine synthesis from precursor amino acids was significantly greater than dietary creatine intake across all age groups (<i>P</i> &lt; 0.01), with precursor-derived creatine production averaging 41.9 ± 0.3 mg/kg body weight per day, approximately 2.7 times higher than dietary creatine intake. Creatine precursor availability declined with age, with the lowest values observed in individuals aged ≥ 65 years.</p><h3>Conclusion</h3><p>This study provides the first comprehensive evaluation of total creatine availability in a representative U.S. population, highlighting the predominance of endogenous synthesis over direct dietary intake. These findings suggest that creatine metabolism is largely dependent on precursor amino acid intake and that certain populations, particularly older adults, may be at higher risk for reduced creatine availability. Future research should explore the physiological implications of these findings and potential dietary interventions to optimize creatine status across the lifespan.</p></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"57 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00726-025-03460-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144131501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cationic antimicrobial peptide CC34 potential anticancer and apoptotic induction on cancer cells","authors":"Liqiang Dong,&nbsp;Yunhe Li,&nbsp;Yaguang Zhang,&nbsp;Shi Su","doi":"10.1007/s00726-025-03458-1","DOIUrl":"10.1007/s00726-025-03458-1","url":null,"abstract":"<div><p>To evaluate the potential of antimicrobial peptide CC34 for use as therapeutic agents for gastric cancer SGC-7901 and hepatocellular carcinoma HepG-2. In this study, the antibacterial activity and antibacterial mechanism were tested by the minimum inhibitory concentration (MIC) analysis, minimal bactericidal concentration (MBC) analysis, bacterial biofilm and NaCl permeability assays. Then, we assessed the hemolytic activity and cytotoxicity of CC34 for red blood cells and cancer cells, respectively. Apoptosis assay, cell cycle analysis, determination of intracellular ROS, western blot analysis caspase activity assay and ATP assay were further performed to investigate the mechanism of CC34 affected cancer cells. The novel peptide could inhibit Gram-negative and Gram-positive bacteria, with low hemolytic activity against mouse and chicken erythrocytes. Moreover, CC34 exhibited higher inhibitory activity against biofilm formation. In addition, our data showed that CC34 significantly suppressed cell proliferation, in a dose dependent manner. CC34 induced apoptosis, induced reactive oxygen species (ROS) generation, inhibited B-cell lymphoma-2 (Bcl-2) expression, increase B-cell lymphoma protein 2 associated X protein (Bax) expression, release of cytochrome c (Cyt C), promoted caspase-3 and − 9 activities and reduced cellular ATP levels in cancer cells. Our results indicate that CC34 with antimicrobial activity have a highly potent ability to induced apoptosis via mitochondrial-mediated apoptotic pathway in cancer cells.</p></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"57 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00726-025-03458-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144131502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting LAT1 with JPH203 to reduce TNBC proliferation and reshape suppressive immune microenvironment by blocking essential amino acid uptake","authors":"Yajie Zhao,&nbsp;Chunrui Pu,&nbsp;Kangdong Liu,&nbsp;Zhenzhen Liu","doi":"10.1007/s00726-025-03456-3","DOIUrl":"10.1007/s00726-025-03456-3","url":null,"abstract":"<div><p>The competitive uptake of essential amino acids (EAAs) by breast cancer cells is associated with poor patient prognosis and the development of an immunosuppressive tumor microenvironment. L-type amino acid transporters, LAT1 (<i>SLC7 A5</i>) and LAT2 (<i>SLC7 A8</i>) are major mediators of EAAs transmembrane uptake and are overexpressed in some tumor tissues. However, the distribution and functional roles of these transporters across breast cancer subtypes have not been fully elucidated. This study aims to investigate the therapeutic potential of targeting EAA transporters, particularly LAT1, in triple-negative breast cancer (TNBC) and its role in remodeling the tumor immune microenvironment. The distribution of EAA transporters across breast cancer subtypes was analyzed using multi-omics data. The effects of LAT1 targeting on TNBC cell proliferation and EAA uptake were evaluated using <i>SLC7 A5</i> knockout and LAT1 inhibitors in vitro experiments. A 4T1-BALB/c tumor-bearing mouse model with normal immune function was constructed to investigate the effects of LAT1 targeting on tumor growth and immune microenvironment remodeling in vivo. TNBC demonstrated a strong dependence on LAT1-mediated EAAs uptake. Targeting LAT1 limited the exogenous supply of EAAs, leading to amino acid starvation, cell cycle arrest, and increased apoptosis in TNBC cells. The in vivo experiments, using a 4T1-BALB/c tumor-bearing mouse model, showed that LAT1 targeting inhibited tumor growth and remodeled the immunosuppressive tumor microenvironment. Targeting LAT1 improved PD-L1-associated immune suppression and improved the efficacy of PD-1 antibody treatment, producing synergistic anti-tumor effects. This study highlights the therapeutic potential of targeting LAT1 in TNBC, particularly in remodeling the tumor immune microenvironment. The findings provide a promising strategy for immune combination therapy in TNBC.</p><h3>Graphical abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"57 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00726-025-03456-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144074115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of histidine and carnosine on haemoglobin recovery in anaemia induced-kidney damage and iron-loading mouse models","authors":"Mayra Vera-Aviles,&nbsp;Jorge Moreno-Fernandez,&nbsp;Tugba Kose,&nbsp;Robert Hider,&nbsp;Gladys O. Latunde-Dada","doi":"10.1007/s00726-025-03451-8","DOIUrl":"10.1007/s00726-025-03451-8","url":null,"abstract":"<div><p>Histidine and carnosine can form complexes with divalent metal ions such as Fe²⁺, potentially providing stability to intracellular labile iron. Anaemia is a common comorbidity in the late stages of kidney disease, and patients are treated with erythropoiesis-stimulating agents (ESAs) and iron supplementation. However, iron supplementation is also associated with worse long-term outcomes. The purpose of this study is to investigate how histidine and carnosine supplementation can reduce symptoms of anaemia of chronic kidney disease (CKD) and the effects associated with iron-overloaded conditions. Adenine-induced chronic kidney disease mice were treated with histidine and carnosine by oral gavage for 10 days. Additionally, a model involving iron overload in mice was established, and these mice received concurrent treatment with histidine and carnosine. Haemoglobin, non-haem iron, malondialdehyde (MDA) and iron parameters were measured. Carnosine increased erythropoietin (EPO) levels (35.62 µg/ml ± 11.43) and resulted in haemoglobin repletion (16.7 g/dL ± 3.4). When iron was supplemented alongside with histidine or carnosine, there were better effects on haemoglobin repletion (14.22 ± 1.7 and 13.82 ± 2.15 g/ dL respectively), ferritin (59.5 ± 16.4, 52 ± 29.5 µg/ml) and non-haem iron (0.8 ± 0.21, 0.7 ± 0.38 nmol/mg), than the group receiving iron alone (<i>p</i> &lt; 0.05). Furthermore, histidine and carnosine reduced non-haem iron and MDA, in iron-loaded conditions (<i>p</i> &lt; 0.05). These positive effects observed in histidine and carnosine could be associated with reactive oxygen species (ROS) scavenging. EPO restoring levels in CKD model and the increment in haemoglobin and ferritin in carnosine treatments suggested the potential formation of a ternary complex with iron-glutathione. In conclusion, our results indicate the beneficial effect of histidine and carnosine in the context of iron supplementation for the correction of haemoglobin and protection against iron-loaded conditions.</p></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"57 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00726-025-03451-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143938550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}