{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T15:15:22Z","timestamp":1791645322616,"version":"4.3.4"},"reference-count":131,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2022,6,20]],"date-time":"2022-06-20T00:00:00Z","timestamp":1655683200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Cathay General Hospital","award":["CGH-MR-A110025"],"award-info":[{"award-number":["CGH-MR-A110025"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>The most common joint disease in the elderly is knee osteoarthritis (OA). It is distinguished by cartilage degradation, subchondral bone loss, and a decrease in joint space. We studied the effects of carnosine (CA) on knee OA in male Wistar rats. OA is induced by anterior cruciate ligament transection combined with medial meniscectomy (ACLT+MMx) method and in vitro studies are conducted in fibroblast-like synoviocyte cells (FLS). The pain was assessed using weight-bearing and paw-withdrawal tests. CA supplementation significantly reduced pain. The enzyme-linked immunosorbent assay (ELISA) method was used to detect inflammatory proteins in the blood and intra-articular synovial fluid (IASF), and CA reduced the levels of inflammatory proteins. Histopathological studies were performed on knee-tissue samples using toluidine blue and hematoxylin and eosin (H and E) assays. CA treatment improved synovial protection and decreased cartilage degradation while decreasing zonal depth lesions. Furthermore, Western blotting studies revealed that the CA-treated group activated nuclear factor erythroid 2-related factor (Nrf2) and heme oxygenase (HO-1) and reduced the expression of cyclooxygenase-2 (COX-2). FLS cells were isolated from the knee joints and treated with IL-1\u03b2 to stimulate the inflammatory response and increase reactive oxygen species (ROS). The matrix metalloproteinase protein (MMP\u2019s) levels (MMP-3, and MMP-13) were determined using the reverse transcription-polymerase chain reaction (RT-PCR), and CA treatment reduced the MMP\u2019s expression levels. When tested using the 2\u2032,7\u2032-dicholorodihydrofluroscene diacetate (DCFDA) assay and the 5,5\u2032,6,6\u2032-tetracholoro-1,1\u2032,3,3\u2032-tertraethylbenzimidazolcarboc janine iodide (JC-1) assay in augmented ROS FLS cells, CA reduced the ROS levels and improved the mitochondrial membrane permeability. This study\u2019s investigation suggests that CA significantly alleviates knee OA both in vitro and in vivo.<\/jats:p>","DOI":"10.3390\/antiox11061209","type":"journal-article","created":{"date-parts":[[2022,6,21]],"date-time":"2022-06-21T01:43:27Z","timestamp":1655775807000},"page":"1209","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Carnosine Alleviates Knee Osteoarthritis and Promotes Synoviocyte Protection via Activating the Nrf2\/HO-1 Signaling Pathway: An In-Vivo and In-Vitro Study"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5173-7705","authenticated-orcid":false,"given":"Prabhakar","family":"Busa","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Cathay General Hospital, Taipei City 106, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sing-Ong","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Cathay General Hospital, Taipei City 106, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niancih","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Tri-Service General Hospital, Taipei City 114, Taiwan"},{"name":"National Defense Medical Center, Graduate Institute of Medical Sciences, Taipei City 114, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaswanth","family":"Kuthati","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Cathay General Hospital, Taipei City 106, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih-Shung","family":"Wong","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Cathay General Hospital, Taipei City 106, Taiwan"},{"name":"Department of Anesthesiology, Tri-Service General Hospital, Taipei City 114, Taiwan"},{"name":"National Defense Medical Center, Graduate Institute of Medical Sciences, Taipei City 114, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.reth.2020.07.007","article-title":"Degenerative osteoarthritis a reversible chronic disease","volume":"15","year":"2020","journal-title":"Regen. Ther."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"789898","DOI":"10.3389\/fvets.2022.789898","article-title":"Moving Beyond the Limits of Detection: The Past, the Present, and the Future of Diagnostic Imaging in Canine Osteoarthritis","volume":"9","author":"Jones","year":"2022","journal-title":"Front. Vet. Sci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1016\/j.joca.2008.06.025","article-title":"Current concepts in the pathogenesis of osteoarthritis","volume":"16","author":"Krasnokutsky","year":"2008","journal-title":"Osteoarthr. Cartil."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1016\/j.rdc.2008.07.001","article-title":"The role of bone in osteoarthritis pathogenesis","volume":"34","author":"Goldring","year":"2008","journal-title":"Rheum. Dis. Clin. N. Am."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Molnar, V., Matisic, V., Kodvanj, I., Bjelica, R., Jelec, Z., Hudetz, D., Rod, E., Cukelj, F., Vrdoljak, T., and Vidovic, D. (2021). Cytokines and Chemokines Involved in Osteoarthritis Pathogenesis. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22179208"},{"key":"ref_6","first-page":"43","article-title":"Pathogenesis of osteoarthritis","volume":"66","author":"Berenbaum","year":"2007","journal-title":"Ann. Rheum. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/S1063-4584(97)80008-8","article-title":"Detection of interleukin-1 in the cartilage of patients with osteoarthritis: A possible autocrine\/paracrine role in pathogenesis","volume":"5","author":"Towle","year":"1997","journal-title":"Osteoarthr. Cartil."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1054\/bjom.2001.0742","article-title":"Proinflammatory cytokines and arthroscopic findings of patients with internal derangement and osteoarthritis of the temporomandibular joint","volume":"40","author":"Nishimura","year":"2002","journal-title":"Br. J. Oral Maxillofac. Surg."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1431","DOI":"10.1007\/s10067-009-1242-8","article-title":"Correlation of synovial fluid leptin concentrations with the severity of osteoarthritis","volume":"28","author":"Ku","year":"2009","journal-title":"Clin. Rheumatol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1136\/ard.56.3.184","article-title":"Detection of oncostatin M in synovial fluid from patients with rheumatoid arthritis","volume":"56","author":"Hui","year":"1997","journal-title":"Ann. Rheum. Dis."},{"key":"ref_11","first-page":"3620","article-title":"Matrix metalloproteinase-13, NF-kappa B p65 and interleukin-1 beta are associated with the severity of knee osteoarthritis","volume":"19","author":"Zhao","year":"2020","journal-title":"Exp. Ther. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"576","DOI":"10.2174\/138945010791011965","article-title":"Activated Synovial Macrophages as Targets for Osteoarthritis Drug Therapy","volume":"11","author":"Bondeson","year":"2010","journal-title":"Curr. Drug Targets"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"684389","DOI":"10.3389\/fmed.2021.684389","article-title":"Synovial Fibrosis Involvement in Osteoarthritis","volume":"8","author":"Zhang","year":"2021","journal-title":"Front. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"367","DOI":"10.2174\/138161207780163006","article-title":"Inflammatory caspases: Targets for novel therapies","volume":"13","author":"Cornelis","year":"2007","journal-title":"Curr. Pharm. Des."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1016\/j.joca.2006.04.008","article-title":"NF-kappa B as a potential therapeutic target in osteoarthritis and rheumatoid arthritis","volume":"14","author":"Jimenez","year":"2006","journal-title":"Osteoarthr. Cartil."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1177\/0300985814522810","article-title":"Degenerative Joint Disease: In the Beginning","volume":"51","author":"Weisbrode","year":"2014","journal-title":"Vet. Pathol."},{"key":"ref_17","first-page":"S242","article-title":"Anti-inflamatory radiotherapy for refractory degenerative joints (osteoarthritis)","volume":"81","author":"Baquedano","year":"2006","journal-title":"Radiother. Oncol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Ozeki, N., Koga, H., and Sekiya, I. (2022). Degenerative Meniscus in Knee Osteoarthritis: From Pathology to Treatment. Life, 12.","DOI":"10.3390\/life12040603"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1620\/tjem.245.69","article-title":"Altered Wnt and NF-kappa B Signaling in Facet Joint Osteoarthritis: Insights from RNA Deep Sequencing","volume":"245","author":"Chen","year":"2018","journal-title":"Tohoku J. Exp. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1002\/term.3090","article-title":"Saikosaponin D: A potential therapeutic drug for osteoarthritis","volume":"14","author":"Jiang","year":"2020","journal-title":"J. Tissue Eng. Regen. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1830","DOI":"10.1159\/000495684","article-title":"Morin Exhibits Anti-Inflammatory Effects on IL-1 beta-Stimulated Human Osteoarthritis Chondrocytes by Activating the Nrf2 Signaling Pathway","volume":"51","author":"Qu","year":"2018","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Liu, F.C., Wang, C.C., Lu, J.W., Lee, C.H., Chen, S.C., Ho, Y.J., and Peng, Y.J. (2019). Chondroprotective Effects of Genistein against Osteoarthritis Induced Joint Inflammation. Nutrients, 11.","DOI":"10.3390\/nu11051180"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1007\/s12192-020-01079-z","article-title":"Nrf2\/ARE is a key pathway for curcumin-mediated protection of TMJ chondrocytes from oxidative stress and inflammation","volume":"25","author":"Jiang","year":"2020","journal-title":"Cell Stress Chaperones"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3573","DOI":"10.1111\/jcmm.16443","article-title":"Lycopene inhibits IL-1 beta-induced inflammation in mouse chondrocytes and mediates murine osteoarthritis","volume":"25","author":"Zhan","year":"2021","journal-title":"J. Cell. Mol. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"105742","DOI":"10.1016\/j.intimp.2019.105742","article-title":"Activation of Nrf2\/HO-1 signal with Myricetin for attenuating ECM degradation in human chondrocytes and ameliorating the murine osteoarthritis","volume":"75","author":"Pan","year":"2019","journal-title":"Int. Immunopharmacol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e40421","DOI":"10.1590\/fst.44021","article-title":"Polygonatum sibiricum polysaccharide inhibits IL-1 beta-induced inflammation in human chondrocytes","volume":"42","author":"Wu","year":"2022","journal-title":"Food Sci. Technol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"949","DOI":"10.3389\/fphar.2020.00949","article-title":"Cinnamic Aldehyde Inhibits Lipopolysaccharide-Induced Chondrocyte Inflammation and Reduces Cartilage Degeneration by Blocking the Nuclear Factor-Kappa B Signaling Pathway","volume":"11","author":"Chen","year":"2020","journal-title":"Front. Pharmacol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1080\/03008207.2019.1601187","article-title":"Resveratrol inhibits the development of obesity-related osteoarthritis via the TLR4 and PI3K\/Akt signaling pathways","volume":"60","author":"Xu","year":"2019","journal-title":"Connect. Tissue Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1080\/00325481.2021.1949199","article-title":"Treating osteoarthritis pain: Mechanisms of action of acetaminophen, nonsteroidal anti-inflammatory drugs, opioids, and nerve growth factor antibodies","volume":"133","author":"Mantyh","year":"2021","journal-title":"Postgrad. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2564","DOI":"10.1001\/jama.2018.19319","article-title":"Association of Pharmacological Treatments With Long-term Pain Control in Patients With Knee Osteoarthritis A Systematic Review and Meta-analysis","volume":"320","author":"Gregori","year":"2018","journal-title":"JAMA-J. Am. Med. Assoc."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12937-015-0115-z","article-title":"Benefits of antioxidant supplements for knee osteoarthritis: Rationale and reality","volume":"15","author":"Grover","year":"2016","journal-title":"Nutr. J."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1053\/berh.2001.0175","article-title":"Pharmacological therapy of osteoarthritis","volume":"15","author":"Hochberg","year":"2001","journal-title":"Best Pract. Res. Clin. Rheumatol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Jukic, I., Kolobaric, N., Stupin, A., Matic, A., Kozina, N., Mihaljevic, Z., Mihalj, M., Susnjara, P., Stupin, M., and Curic, Z.B. (2021). Carnosine, Small but Mighty-Prospect of Use as Functional Ingredient for Functional Food Formulation. Antioxidants, 10.","DOI":"10.3390\/antiox10071037"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Fresta, C.G., Fidilio, A., Lazzarino, G., Musso, N., Grasso, M., Merlo, S., Amorini, A.M., Bucolo, C., Tavazzi, B., and Lazzarino, G. (2020). Modulation of Pro-Oxidant and Pro-Inflammatory Activities of M1 Macrophages by the Natural Dipeptide Carnosine. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21030776"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Jeong, B.Y., Lee, H.Y., Park, C.G., Kang, J., Yu, S.L., Choi, D.R., Han, S.Y., Park, M.H., Cho, S., and Lee, S.Y. (2018). Oxidative stress caused by activation of NADPH oxidase 4 promotes contrast-induced acute kidney injury. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0191034"},{"key":"ref_36","first-page":"486","article-title":"Hyperoside protects human kidney-2 cells against oxidative damage induced by oxalic acid","volume":"18","author":"Chen","year":"2018","journal-title":"Mol. Med. Rep."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1590\/1517-869220202601158444","article-title":"Carnosine avoids the oxidative damage caused by intense exercise on rat soleus muscle","volume":"26","author":"Bortolatto","year":"2020","journal-title":"Rev. Bras. Med. Esporte"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"864088","DOI":"10.3389\/fphar.2022.864088","article-title":"New Advances on Pathophysiology of Diabetes Neuropathy and Pain Management: Potential Role of Melatonin and DPP-4 Inhibitors","volume":"13","author":"Busa","year":"2022","journal-title":"Front. Pharmacol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2939087","DOI":"10.1155\/2016\/2939087","article-title":"Use of Carnosine for Oxidative Stress Reduction in Different Pathologies","volume":"2016","author":"Prokopieva","year":"2016","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1426","DOI":"10.1139\/cjpp-2016-0647","article-title":"Chelating effects of carnosine in ameliorating nickel-induced nephrotoxicity in rats","volume":"95","author":"Hasanein","year":"2017","journal-title":"Can. J. Physiol. Pharmacol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Calabrese, V., Scuto, M., Salinaro, A.T., Dionisio, G., Modafferi, S., Ontario, M.L., Greco, V., Sciuto, S., Schmitt, C.P., and Calabrese, E.J. (2020). Hydrogen Sulfide and Carnosine: Modulation of Oxidative Stress and Inflammation in Kidney and Brain Axis. Antioxidants, 9.","DOI":"10.3390\/antiox9121303"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Caruso, G., Fresta, C.G., Fidilio, A., O\u2019Donnell, F., Musso, N., Lazzarino, G., Grasso, M., Amorini, A.M., Tascedda, F., and Bucolo, C. (2019). Carnosine Decreases PMA-Induced Oxidative Stress and Inflammation in Murine Macrophages. Antioxidants, 8.","DOI":"10.3390\/antiox8080281"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1038\/s41598-020-80804-1","article-title":"Comparing the protective effects of resveratrol, curcumin and sulforaphane against LPS\/IFN-gamma-mediated inflammation in doxorubicin-treated macrophages","volume":"11","author":"Saleh","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1053\/j.gastro.2008.09.062","article-title":"Dietary Histidine Ameliorates Murine Colitis by Inhibition of Proinflammatory Cytokine Production From Macrophages","volume":"136","author":"Andou","year":"2009","journal-title":"Gastroenterology"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1007\/s10522-006-9038-6","article-title":"Carnosine, taurine and enzyme activities of human skeletal muscle fibres from elderly subjects with osteoarthritis and young moderately active subjects","volume":"8","author":"Tallon","year":"2007","journal-title":"Biogerontology"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Kubota, M., Kobayashi, N., Sugizaki, T., Shimoda, M., Kawahara, M., and Tanaka, K. (2020). Carnosine suppresses neuronal cell death and inflammation induced by 6-hydroxydopamine in an in vitro model of Parkinson\u2019s disease. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0240448"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Pickarski, M., Hayami, T., Zhuo, Y., and Duong, L.T. (2011). Molecular changes in articular cartilage and subchondral bone in the rat anterior cruciate ligament transection and meniscectomized models of osteoarthritis. BMC Musculoskelet. Disord., 12.","DOI":"10.1186\/1471-2474-12-197"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Huang, N.C., Yang, T.S., Busa, P., Lin, C.L., Fang, Y.C., Chen, J., and Wong, C.S. (2021). Detection and Evaluation of Serological Biomarkers to Predict Osteoarthritis in Anterior Cruciate Ligament Transection Combined Medial Meniscectomy Rat Model. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms221910179"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1002\/jor.23069","article-title":"Sulfasalazine attenuates ACL transection and medial menisectomy-induced cartilage destruction by inhibition of cystine\/glutamate antiporter","volume":"34","author":"Tsai","year":"2016","journal-title":"J. Orthop. Res."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Kao, J.H., Lin, S.H., Lai, C.F., Lin, Y.C., Kong, Z.L., and Wong, C.S. (2016). Shea Nut Oil Triterpene Concentrate Attenuates Knee Osteoarthritis Development in Rats: Evidence from Knee Joint Histology. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0162022"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"41","DOI":"10.2147\/JPR.S154038","article-title":"Traumatic osteoarthritis-induced persistent mechanical hyperalgesia in a rat model of anterior cruciate ligament transection plus a medial meniscectomy","volume":"11","author":"Tsai","year":"2018","journal-title":"J. Pain Res."},{"key":"ref_52","first-page":"589","article-title":"Development and characteristics of pannus-like soft tissue in osteoarthritic articular surface in rat osteoarthritis model","volume":"26","author":"Duc","year":"2008","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Silva, J.M.D., Alabarse, P.V.G., Teixeira, V.D.N., Freitas, E.C., de Oliveira, F.H., Chakr, R.M.D., and Xavier, R.M. (2018). Muscle wasting in osteoarthritis model induced by anterior cruciate ligament transection. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0196682"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Szychlinska, M.A., Trovato, F.M., Di Rosa, M., Malaguarnera, L., Puzzo, L., Leonardi, R., Castrogiovanni, P., and Musumeci, G. (2016). Co-Expression and Co-Localization of Cartilage Glycoproteins CHI3L1 and Lubricin in Osteoarthritic Cartilage: Morphological, Immunohistochemical and Gene Expression Profiles. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17030359"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"9518","DOI":"10.1111\/jcmm.15669","article-title":"The emerging role of fibroblast-like synoviocytes-mediated synovitis in osteoarthritis: An update","volume":"24","author":"Han","year":"2020","journal-title":"J. Cell. Mol. Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1002\/biof.5520130104","article-title":"Dietary docosahexaenoic acid does not promote tissue lipid peroxide formation to the extent expected from the peroxidizability index of the lipids","volume":"13","author":"Saito","year":"2000","journal-title":"Biofactors"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1111\/nyas.13407","article-title":"Oxidative stress and chronic inflammation in osteoarthritis: Can NRF2 counteract these partners in crime?","volume":"1401","author":"Marchev","year":"2017","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1007\/s12640-017-9816-8","article-title":"Cholinergic System and Oxidative Stress Changes in the Brain of a Zebrafish Model Chronically Exposed to Ethanol","volume":"33","author":"Agostini","year":"2018","journal-title":"Neurotox. Res."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Bhuvanalakshmi, G., Arfuso, F., Millward, M., Dharmarajan, A., and Warrier, S. (2015). Secreted Frizzled-Related Protein 4 Inhibits Glioma Stem-Like Cells by Reversing Epithelial to Mesenchymal Transition, Inducing Apoptosis and Decreasing Cancer Stem Cell Properties. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0127517"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2071","DOI":"10.1089\/scd.2012.0563","article-title":"Osteoarthritis Prevention Through Meniscal Regeneration Induced by Intra-Articular Injection of Meniscus Stem Cells","volume":"22","author":"Shen","year":"2013","journal-title":"Stem Cells Dev."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1801","DOI":"10.2174\/0929867326666190326111851","article-title":"Carnosine and Diabetic Nephropathy","volume":"27","author":"Peters","year":"2020","journal-title":"Curr. Med. Chem."},{"key":"ref_62","first-page":"1132","article-title":"Effects of beta-alanine supplementation on performance and muscle fatigue in athletes and non-athletes of different sports: A systematic review","volume":"57","author":"Zanela","year":"2017","journal-title":"J. Sports Med. Phys. Fit."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.ejphar.2008.10.002","article-title":"Preventive effect of L-carnosine on changes in the thermal nociceptive threshold in streptozotocin-induced diabetic mice","volume":"600","author":"Kamei","year":"2008","journal-title":"Eur. J. Pharmacol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"srep02005","DOI":"10.1038\/srep02005","article-title":"A TRPA1 antagonist reverts oxaliplatin-induced neuropathic pain","volume":"3","author":"Nativi","year":"2013","journal-title":"Sci. Rep."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Kuthati, Y., Rao, V.N., Busa, P., and Wong, C.S. (2021). Teneligliptin Exerts Antinociceptive Effects in Rat Model of Partial Sciatic Nerve Transection Induced Neuropathic Pain. Antioxidants, 10.","DOI":"10.3390\/antiox10091438"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Caruso, G., Fresta, C.G., Musso, N., Giambirtone, M., Grasso, M., Spampinato, S.E., Merlo, S., Drago, F., Lazzarino, G., and Sortino, M.A. (2019). Carnosine Prevents A beta-Induced Oxidative Stress and Inflammation in Microglial Cells: A Key Role of TGF-beta 1. Cells, 8.","DOI":"10.3390\/cells8010064"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"8470589","DOI":"10.1155\/2016\/8470589","article-title":"Effect of Carnosine in Experimental Arthritis and on Primary Culture Chondrocytes","volume":"2016","author":"Ponist","year":"2016","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/j.joca.2018.09.016","article-title":"Models of osteoarthritis: The good, the bad and the promising","volume":"27","author":"Cope","year":"2019","journal-title":"Osteoarthr. Cartil."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"607764","DOI":"10.3389\/fcell.2020.607764","article-title":"Subchondral Bone Remodeling: A Therapeutic Target for Osteoarthritis","volume":"8","author":"Zhu","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1016\/j.joca.2014.05.023","article-title":"Bone-cartilage interface crosstalk in osteoarthritis: Potential pathways and future therapeutic strategies","volume":"22","author":"Yuan","year":"2014","journal-title":"Osteoarthr. Cartil."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"110023","DOI":"10.1016\/j.biopha.2020.110023","article-title":"Protective effect of a new hyaluronic acid -carnosine conjugate on the modulation of the inflammatory response in mice subjected to collagen-induced arthritis","volume":"125","author":"Impellizzeri","year":"2020","journal-title":"Biomed. Pharmacother."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Siracusa, R., Impellizzeri, D., Cordaro, M., Peritore, A.F., Gugliandolo, E., D\u2019Amico, R., Fusco, R., Crupi, R., Rizzarelli, E., and Cuzzocrea, S. (2020). The Protective Effect of New Carnosine-Hyaluronic Acid Conjugate on the Inflammation and Cartilage Degradation in the Experimental Model of Osteoarthritis. Appl. Sci., 10.","DOI":"10.20944\/preprints202001.0105.v1"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1016\/j.joca.2013.03.018","article-title":"The epidemiology and impact of pain in osteoarthritis","volume":"21","author":"Neogi","year":"2013","journal-title":"Osteoarthr. Cartil."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"2999","DOI":"10.1007\/s10067-016-3401-z","article-title":"Disease-specific pain and function predict future pain impact in hip and knee osteoarthritis","volume":"35","author":"Carlesso","year":"2016","journal-title":"Clin. Rheumatol."},{"key":"ref_75","first-page":"324","article-title":"Prevalence, risk factors, and impact of knee pain suggesting osteoarthritis in Spain","volume":"26","author":"Laffon","year":"2008","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"R201","DOI":"10.1186\/ar3173","article-title":"Perturbation of adhesion molecule-mediated chondrocyte-matrix interactions by 4-hydroxynonenal binding: Implication in osteoarthritis pathogenesis","volume":"12","author":"Welman","year":"2010","journal-title":"Arthritis Res. Ther."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1969","DOI":"10.1002\/jor.23854","article-title":"Metabolomic serum profiling after ACL injury in rats: A pilot study implicating inflammation and immune dysregulation in post-traumatic osteoarthritis","volume":"36","author":"Maerz","year":"2018","journal-title":"J. Orthop. Res."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"6285","DOI":"10.3892\/mmr.2017.7340","article-title":"Articular cartilage degradation is prevented by tanshinone IIA through inhibiting apoptosis and the expression of inflammatory cytokines","volume":"16","author":"Jia","year":"2017","journal-title":"Mol. Med. Rep."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.joca.2005.07.014","article-title":"Osteoarthritis cartilage histopathology: Grading and staging","volume":"14","author":"Pritzker","year":"2006","journal-title":"Osteoarthr. Cartil."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1038\/nrrheum.2011.104","article-title":"Joint instability and OA: Do animal models provide insights?","volume":"7","author":"Pritzker","year":"2011","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1016\/j.joca.2007.04.017","article-title":"Reliability, reproducibility and variability of the traditional Histologic\/Histochemical Grading System vs the new OARSI Osteoarthritis Cartilage Histopathology Assessment System","volume":"15","author":"Custers","year":"2007","journal-title":"Osteoarthr. Cartil."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"598","DOI":"10.3389\/fphar.2018.00598","article-title":"Carnosine Prevents Type 2 Diabetes-Induced Osteoarthritis Through the ROS\/NF-kappa B Pathway","volume":"9","author":"Yang","year":"2018","journal-title":"Front. Pharmacol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"664","DOI":"10.3892\/etm.2017.4571","article-title":"Neuroprotective effect of carnosine against salsolinol-induced Parkinson\u2019s disease","volume":"14","author":"Zhao","year":"2017","journal-title":"Exp. Ther. Med."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1016\/S0271-5317(00)00187-1","article-title":"Carnosine inhibits in vitro low-density lipoprotein oxidation","volume":"20","author":"Bogardus","year":"2000","journal-title":"Nutr. Res."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"552","DOI":"10.3109\/10520295.2014.913811","article-title":"Antioxidant effect of carnosine treatment on renal oxidative stress in streptozotocin-induced diabetic rats","volume":"89","author":"Yay","year":"2014","journal-title":"Biotech. Histochem."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Sirse, M. (2022). Effect of Dietary Polyphenols on Osteoarthritis-Molecular Mechanisms. Life, 12.","DOI":"10.3390\/life12030436"},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Kuthati, Y., Busa, P., Tummala, S., Rao, V.N., Davuluri, V.N.G., Ho, Y.P., and Wong, C.S. (2021). Mesoporous Polydopamine Nanoparticles Attenuate Morphine Tolerance in Neuropathic Pain Rats by Inhibition of Oxidative Stress and Restoration of the Endogenous Antioxidant System. Antioxidants, 10.","DOI":"10.3390\/antiox10020195"},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Chin, K.Y., and Pang, K.L. (2017). Therapeutic Effects of Olive and Its Derivatives on Osteoarthritis: From Bench to Bedside. Nutrients, 9.","DOI":"10.3390\/nu9101060"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"110452","DOI":"10.1016\/j.biopha.2020.110452","article-title":"Oxidative stress and inflammation in osteoarthritis pathogenesis: Role of polyphenols","volume":"129","author":"Ansari","year":"2020","journal-title":"Biomed. Pharmacother."},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Tudorachi, N.B., Totu, E.E., Fifere, A., Ardeleanu, V., Mocanu, V., Mircea, C., Isildak, I., Smilkov, K., and Carausu, E.M. (2021). The Implication of Reactive Oxygen Species and Antioxidants in Knee Osteoarthritis. Antioxidants, 10.","DOI":"10.3390\/antiox10060985"},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Busa, P., Koutavarapu, R., and Kuthati, Y. (2022). Polydopamine-Coated Copper-Substituted Mesoporous Silica Nanoparticles for Dual Cancer Therapy. Coatings, 12.","DOI":"10.3390\/coatings12010060"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/s13075-015-0908-7","article-title":"Targeting oxidative stress to reduce osteoarthritis","volume":"18","author":"Poulet","year":"2016","journal-title":"Arthritis Res. Ther."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Busa, P., Koutavarapu, R., Lee, D.Y., Shim, J., and Kuthati, Y. (2021). Hierarchical Two-Dimensional Layered Double Hydroxide Coated Polydopamine Nanocarriers for Combined Chemodynamic and Photothermal Tumor Therapy. Coatings, 11.","DOI":"10.3390\/coatings11081008"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"119467","DOI":"10.1016\/j.biomaterials.2019.119467","article-title":"Manganese dioxide nanoparticles protect cartilage from inflammation-induced oxidative stress","volume":"224","author":"Kumar","year":"2019","journal-title":"Biomaterials"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"617","DOI":"10.5114\/aoms.2016.59871","article-title":"Lutein prevents osteoarthritis through Nrf2 activation and downregulation of inflammation","volume":"14","author":"Qiao","year":"2018","journal-title":"Arch. Med. Sci."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"106612","DOI":"10.1016\/j.intimp.2020.106612","article-title":"Imperatorin suppresses IL-1 beta-induced iNOS expression via inhibiting ERK-MAPK\/AP1 signaling in primary human OA chondrocytes","volume":"85","author":"Ahmad","year":"2020","journal-title":"Int. Immunopharmacol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.ejphar.2012.02.005","article-title":"Carnosine has antinociceptive properties in the inflammation-induced nociceptive response in mice","volume":"682","author":"Ohsawa","year":"2012","journal-title":"Eur. J. Pharmacol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1306","DOI":"10.1016\/j.peptides.2009.04.003","article-title":"Inhibitory effect of carnosine and N-acetyl carnosine on LPS-induced microglial oxidative stress and inflammation","volume":"30","author":"Apte","year":"2009","journal-title":"Peptides"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"0300060520931609","DOI":"10.1177\/0300060520931609","article-title":"The role of oxidation of low-density lipids in pathogenesis of osteoarthritis: A narrative review","volume":"48","author":"Hashimoto","year":"2020","journal-title":"J. Int. Med. Res."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"8293921","DOI":"10.1155\/2020\/8293921","article-title":"The Role of Inflammation in the Pathogenesis of Osteoarthritis","volume":"2020","author":"Chow","year":"2020","journal-title":"Mediat. Inflamm."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1097\/BOR.0000000000000353","article-title":"Role of low-grade inflammation in osteoarthritis","volume":"29","author":"Scanzello","year":"2017","journal-title":"Curr. Opin. Rheumatol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1080\/13697137.2017.1421926","article-title":"Female hormonal factors and osteoarthritis of the knee, hip and hand: A narrative review","volume":"21","author":"Hussain","year":"2018","journal-title":"Climacteric"},{"key":"ref_103","first-page":"261","article-title":"Macrophages in osteoarthritis: Pathophysiology and therapeutics","volume":"12","author":"Chen","year":"2020","journal-title":"Am. J. Transl. Res."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1831","DOI":"10.3389\/fimmu.2021.678757","article-title":"Synovial Macrophages in Osteoarthritis: The Key to Understanding Pathogenesis?","volume":"12","author":"Thomson","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"4348973","DOI":"10.1155\/2019\/4348973","article-title":"Carnosine Protects Mouse Podocytes from High Glucose Induced Apoptosis through PI3K\/AKT and Nrf2 Pathways","volume":"2019","author":"Zhao","year":"2019","journal-title":"Biomed Res. Int."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1080\/08923973.2017.1344987","article-title":"Zinc L-carnosine suppresses inflammatory responses in lipopolysaccharide-induced RAW 264.7 murine macrophages cell line via activation of Nrf2\/HO-1 signaling pathway","volume":"39","author":"Ooi","year":"2017","journal-title":"Immunopharmacol. Immunotoxicol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"2100406","DOI":"10.1002\/mnfr.202100406","article-title":"l-Carnosine Protects Against Deoxynivalenol-Induced Oxidative Stress in Intestinal Stem Cells by Regulating the Keap1\/Nrf2 Signaling Pathway","volume":"65","author":"Zhou","year":"2021","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1186\/s13075-019-2085-6","article-title":"Inhibition of Nrf2\/HO-1 signaling leads to increased activation of the NLRP3 inflammasome in osteoarthritis","volume":"21","author":"Chen","year":"2019","journal-title":"Arthritis Res. Ther."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"4533","DOI":"10.2147\/DDDT.S258973","article-title":"S-Allylmercaptocysteine Targets Nrf2 in Osteoarthritis Treatment Through NOX4\/NF-kappa B Pathway","volume":"14","author":"Yang","year":"2020","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"8579","DOI":"10.1111\/jcmm.15484","article-title":"Nomilin targets the Keap1-Nrf2 signalling and ameliorates the development of osteoarthritis","volume":"24","author":"Xue","year":"2020","journal-title":"J. Cell. Mol. Med."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"238S","DOI":"10.1177\/19476035211012465","article-title":"Shockwave Treatment Enhanced Extracellular Matrix Production in Articular Chondrocytes Through Activation of the ROS\/MAPK\/Nrf2 Signaling Pathway","volume":"13","author":"Shen","year":"2021","journal-title":"Cartilage"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"4079","DOI":"10.2147\/JIR.S310831","article-title":"Nrf2 Regulates CHI3L1 to Suppress Inflammation and Improve Post-Traumatic Osteoarthritis","volume":"14","author":"Song","year":"2021","journal-title":"J. Inflamm. Res."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"194","DOI":"10.3892\/etm.2021.9627","article-title":"Ergosterol limits osteoarthritis development and progression through activation of Nrf2 signaling","volume":"21","author":"Cai","year":"2021","journal-title":"Exp. Ther. Med."},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Peng, Y.J., Lu, J.W., Lee, C.H., Lee, H.S., Chu, Y.H., Ho, Y.J., Liu, F.C., Huang, C.J., Wu, C.C., and Wang, C.C. (2021). Cardamonin Attenuates Inflammation and Oxidative Stress in Interleukin-1 beta-Stimulated Osteoarthritis Chondrocyte through the Nrf2 Pathway. Antioxidants, 10.","DOI":"10.3390\/antiox10060862"},{"key":"ref_115","doi-asserted-by":"crossref","unstructured":"Kim, E.H., Kim, E.S., Shin, D., Kim, D., Choi, S., Shin, Y.J., Kim, K.A., Noh, D., Caglayan, A.B., and Rajanikant, G.K. (2021). Carnosine Protects against Cerebral Ischemic Injury by Inhibiting Matrix-Metalloproteinases. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22147495"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1002\/psc.2658","article-title":"Inhibitory effect of the carnosine-gallic acid synthetic peptide on MMP-2 and MMP-9 in human fibrosarcoma HT1080 cells","volume":"20","author":"Kim","year":"2014","journal-title":"J. Pept. Sci."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1080\/01635580801911787","article-title":"L-carnosine inhibits metastasis of SK-Hep-1 cells by inhibition of matrix metaoproteinase-9 expression and induction of an antimetastatic gene, nm23-H1","volume":"60","author":"Chuang","year":"2008","journal-title":"Nutr. Cancer-Int. J."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1111\/j.0105-2896.2009.00859.x","article-title":"Fibroblast-like synoviocytes: Key effector cells in rheumatoid arthritis","volume":"233","author":"Bartok","year":"2010","journal-title":"Immunol. Rev."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"14376","DOI":"10.18632\/aging.103480","article-title":"MicroRNA-15a\/16\/SOX5 axis promotes migration, invasion and inflammatory response in rheumatoid arthritis fibroblast-like synoviocytes","volume":"12","author":"Wei","year":"2020","journal-title":"Aging"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1186\/s13075-020-02204-0","article-title":"The effect of nicotinamide adenine dinucleotide phosphate oxidase 4 on migration and invasion of fibroblast-like synoviocytes in rheumatoid arthritis","volume":"22","author":"Lee","year":"2020","journal-title":"Arthritis Res. Ther."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1007\/s00726-019-02713-6","article-title":"Carnosine\u2019s inhibitory effect on glioblastoma cell growth is independent of its cleavage","volume":"51","author":"Oppermann","year":"2019","journal-title":"Amino Acids"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.neulet.2009.04.047","article-title":"Inhibition of 6-hydroxydopamine-induced endoplasmic reticulum stress by L-carnosine in SH-SY5Y cells","volume":"459","author":"Oh","year":"2009","journal-title":"Neurosci. Lett."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1007\/s10571-007-9235-0","article-title":"Carnosine protects against A beta 42-induced neurotoxicity in differentiated rat PC12 cells","volume":"28","author":"Fu","year":"2008","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"C26","DOI":"10.1159\/000106509","article-title":"Antiglycation and antioxidant effect of carnosine against glucose degradation products in peritoneal mesothelial cells","volume":"107","author":"Alhamdani","year":"2007","journal-title":"Nephron Clin. Pract."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"e2565","DOI":"10.1038\/cddis.2016.490","article-title":"IL-17-mediated mitochondrial dysfunction impairs apoptosis in rheumatoid arthritis synovial fibroblasts through activation of autophagy","volume":"8","author":"Kim","year":"2017","journal-title":"Cell Death Dis."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1002\/jmr.2541","article-title":"Therapeutic efficacy of natural dipeptide carnosine against human cervical carcinoma cells","volume":"29","author":"Pandurangan","year":"2016","journal-title":"J. Mol. Recognit."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1055\/a-1017-5085","article-title":"The Nephroprotective Role of Carnosine Against Ifosfamide-Induced Renal Injury and Electrolytes Imbalance is Mediated Via the Regulation of Mitochondrial Function and Alleviation of Oxidative Stress","volume":"70","author":"Ommati","year":"2020","journal-title":"Drug Res."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1080\/1028415X.2018.1552399","article-title":"The neuroprotective properties of carnosine in a mouse model of manganism is mediated via mitochondria regulating and antioxidative mechanisms","volume":"23","author":"Ommati","year":"2020","journal-title":"Nutr. Neurosci."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"S21","DOI":"10.1016\/j.freeradbiomed.2017.04.098","article-title":"Copper(II)-induced Cytotoxicity and Oxidative Stress in Human Blood Cells and its Attenuation by Carnosine","volume":"108","author":"Husain","year":"2017","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1111\/1440-1681.12019","article-title":"Carnosine protects brain microvascular endothelial cells against rotenone-induced oxidative stress injury through histamine H-1 and H-2 receptors in vitro","volume":"39","author":"Zhang","year":"2012","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"93","DOI":"10.3233\/CH-2008-1072","article-title":"Impaired erythrocytes deformability in H2O2-induced oxidative stress: Protective effect of L-carnosine","volume":"39","author":"Aydogan","year":"2008","journal-title":"Clin. Hemorheol. Microcirc."}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/11\/6\/1209\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:35:56Z","timestamp":1760139356000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/11\/6\/1209"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,20]]},"references-count":131,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2022,6]]}},"alternative-id":["antiox11061209"],"URL":"https:\/\/doi.org\/10.3390\/antiox11061209","relation":{},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,20]]}}}